Results of this randomized, double-masked clinical trial demonstrate the effectiveness of the MiSight soft contact lens in slowing myopia progression over multiple years.
The purpose of this study ...was to quantify the effectiveness of MiSight daily disposable soft contact lens in slowing the progression of juvenile-onset myopia.
Myopic children (spherical equivalent refraction, -0.75 to -4.00 D; astigmatism, <1.00 D) aged 8 to 12 years with no prior contact lens experience were enrolled in a 3-year, double-masked, randomized clinical trial at four investigational sites in four countries. Subjects in each group were matched for age, sex, and ethnicity and were randomized to either a MiSight 1-day contact lens (test) or Proclear 1-day (control; omafilcon A) and worn on a daily disposable basis. Primary outcome measures were the change in cycloplegic spherical equivalent refraction and axial length.
Of the subjects enrolled, 75.5% (109/144) completed the clinical trial (53 test, 56 control). Unadjusted change in spherical equivalent refraction was -0.73 D (59%) less in the test group than in the control group (-0.51 ± 0.64 vs. -1.24 ± 0.61 D, P < .001). Mean change in axial length was 0.32 mm (52%) less in the test group than in the control group (0.30 ± 0.27 vs. 0.62 ± 0.30 mm, P < .001). Changes in spherical equivalent refraction and axial length were highly correlated (r = -0.90, P < .001). Over the course of the study, there were no cases of serious ocular adverse events reported. Four asymptomatic corneal infiltrative (one test, three control) events were observed at scheduled study visits.
Results of this clinical trial demonstrate the effectiveness of the MiSight daily disposable soft contact lens in slowing change in spherical equivalent refraction and axial length.
Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in ...children switched from a single vision control to treatment lenses (3 years in each lens).
This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3.
Part 1 was a 3-year clinical trial comparing DFCLs with a control contact lens (Proclear 1 day) at four investigational sites. In part 2, subjects completing part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated T6 and control T3 groups, respectively). Eighty-five subjects (45 T3 and 40 T6) completed part 2. Cyclopleged spherical equivalent refractive errors (SEREs) and axial lengths (ALs) were monitored, and a linear mixed model was used to compare their adjusted change annually.
Average ages at part 2 baseline were 13.2 ± 1.3 and 13.0 ± 1.5 years for the T6 and T3 groups, respectively. Slowed myopia progression in the T6 group observed during part 1 was sustained throughout part 2 (mean ± standard error of the mean: change from baseline SERE in diopters, -0.52 ± 0.076 vs. -0.51 ± 0.076; change in AL in millimeters, 0.28 ± 0.033 vs. 0.23 ± 0.033; both P > .05). Comparing progression rates in part 2 for the T6 and T3 groups, respectively, indicates that prior treatment does not influence efficacy (SERE, -0.51 ± 0.076 vs. -0.34 ± 0.077; AL, 0.23 ± 0.03 vs. 0.18 ± 0.03; both P > .05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3 years older than part 1) and further revealed a small subset of eyes (10%) that did not respond to treatment.
Dual-focus soft contact lenses continue to slow the progression of myopia in children over a 6-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period.
ABSTRACT
We investigate the accuracy and precision of triaxial dynamical orbit models by fitting 2D mock observations of a realistic N-body merger simulation resembling a massive early-type galaxy ...with a supermassive black hole. We show that we can reproduce the triaxial N-body merger remnant’s correct black hole mass, stellar mass-to-light ratio and total enclosed mass (inside the half-light radius) for several different tested orientations with an unprecedented accuracy of 5–10 per cent. Our dynamical models use the entire non-parametric line-of-sight velocity distribution (LOSVD) rather than parametric LOSVDs or velocity moments as constraints. Our results strongly suggest that state-of-the-art integral-field projected kinematic data contain only minor degeneracies with respect to the mass and anisotropy recovery. Moreover, this also demonstrates the strength of the Schwarzschild method in general. We achieve the proven high recovery accuracy and precision with our newly developed modelling machinery by combining several advancements: (i) our new semiparametric deprojection code probes degeneracies and allows us to constrain the viewing angles of a triaxial galaxy; (ii) our new orbit modelling code SMART uses a 5-dim orbital starting space to representatively sample in particular near-Keplerian orbits in galaxy centres; (iii) we use a generalized information criterion AICp to optimize the smoothing and to compare different mass models to avoid biases that occur in χ2-based models with varying model flexibilities.
Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. ...Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTEN haploinsufficiency in humans.
We measured insulin sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness.
Measures of insulin resistance were lower in the patients with a PTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter range, 9 to 99 vs. 74 pmol per liter range, 22 to 185; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index the weight in kilograms divided by the square of the height in meters, 32 range, 23 to 42 vs. 26 range, 15 to 48; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution.
PTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.).
Abstract
Background
Breast cancer (BC) risk is increased among Hodgkin lymphoma (HL) survivors treated with chest radiotherapy. Case-control studies showed a linear radiation dose-response ...relationship for estimated dose to the breast tumor location. However, these relative risks cannot be used for absolute risk prediction of BC anywhere in the breasts. Furthermore, the independent and joint effects of radiation dose and irradiated volumes are unclear. Therefore, we examined the effects of mean breast dose and various dose-volume parameters on BC risk in HL patients.
Methods
We conducted a nested case-control study of BC among 5-year HL survivors (173 case patients, 464 matched control patients). Dose-volume histograms were obtained from reconstructed voxel-based 3-dimensional dose distributions. Summary parameters of dose-volume histograms were studied next to mean and median breast dose, Gini index, and the new dose metric mean absolute difference of dose, using categorical and linear excess odds ratio (EOR) models. Interactions between dose-volume parameters and mean dose were also examined.
Results
Statistically significant linear dose-response relationships were observed for mean breast dose (EOR per Gy = 0.19, 95% confidence interval CI = 0.05 to 1.06) and median dose (EOR/Gy = 0.06, 95% CI = 0.02 to 0.19), with no statistically significant curvature. All metrics except Gini and mean absolute difference were positively correlated with each other. These metrics all showed similar patterns of dose-response that were no longer statistically significant when adjusting for mean dose. No statistically significant modification of the effect of mean dose was observed.
Conclusion
Mean breast dose predicts subsequent BC risk in long-term HL survivors.
Several Avian paramyxoviruses 1 (synonymous with Newcastle disease virus or NDV, used hereafter) classification systems have been proposed for strain identification and differentiation. These systems ...pioneered classification efforts; however, they were based on different approaches and lacked objective criteria for the differentiation of isolates. These differences have created discrepancies among systems, rendering discussions and comparisons across studies difficult. Although a system that used objective classification criteria was proposed by Diel and co-workers in 2012, the ample worldwide circulation and constant evolution of NDV, and utilization of only some of the criteria, led to identical naming and/or incorrect assigning of new sub/genotypes. To address these issues, an international consortium of experts was convened to undertake in-depth analyses of NDV genetic diversity. This consortium generated curated, up-to-date, complete fusion gene class I and class II datasets of all known NDV for public use, performed comprehensive phylogenetic neighbor-Joining, maximum-likelihood, Bayesian and nucleotide distance analyses, and compared these inference methods. An updated NDV classification and nomenclature system that incorporates phylogenetic topology, genetic distances, branch support, and epidemiological independence was developed. This new consensus system maintains two NDV classes and existing genotypes, identifies three new class II genotypes, and reduces the number of sub-genotypes. In order to track the ancestry of viruses, a dichotomous naming system for designating sub-genotypes was introduced. In addition, a pilot dataset and sub-trees rooting guidelines for rapid preliminary genotype identification of new isolates are provided. Guidelines for sequence dataset curation and phylogenetic inference, and a detailed comparison between the updated and previous systems are included. To increase the speed of phylogenetic inference and ensure consistency between laboratories, detailed guidelines for the use of a supercomputer are also provided. The proposed unified classification system will facilitate future studies of NDV evolution and epidemiology, and comparison of results obtained across the world.
•An international consortium phylogenetically studied the diversity of NDV.•Consensus objective NDV classification and nomenclature system was developed.•Optimal phylogenetic inference method with guidelines is recommended.•Curated, up-to-date, complete fusion gene datasets for public use were created.•Three new NDV genotypes were identified.
Six rhizobacteria isolated from common bean and able to protect bean plants from the common bacterial blight (CBB) causal agent, were in vitro evaluated for their potential antifungal effects toward ...different plant pathogenic fungi, mostly soil-borne. By dual culture assays, the above bacteria resulted producing diffusible and volatile metabolites which inhibited the growth of the majority of the pathogens under study. In particular, the latter substances highly affected the mycelium growth of Sclerotinia sclerotiorum strains, one of which was selected for further studies either on mycelium or sclerotia. Gas chromatographic analysis of the bacterial volatiles led to the identification of an array of volatile organic compounds (VOCs). Time course studies showed the modification of the VOCs profile along a period of 5 days. In order to evaluate the single detected VOC effects on fungal growth, some of the pure compounds were tested on S. sclerotiorum mycelium and their minimal inhibitory quantities were determined. Similarly, the minimal inhibitory quantities on sclerotia germination were also defined. Moreover, observations by light and transmission electron microscopes highlighted hyphae cytoplasm granulation and ultrastructural alterations at cell organelles, mostly membranes, mitochondria, and endoplasmic reticulum. The membranes appeared one of the primary targets of bacterial volatiles, as confirmed by hemolytic activity observed for the majority of pure VOCs. However, of interest is the alteration observed on mitochondria as well.
Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Increased gene dosage has been observed in males ...with non-syndromic mild to moderate ID with speech delay. Missense variants reported previously appear to be associated with severe ID in males and mild or no ID in obligate carrier females. Here, we report the largest cohort of patients with HUWE1 variants, consisting of 14 females and 7 males, with 15 different missense variants and one splice site variant. Clinical assessment identified common clinical features consisting of moderate to profound ID, delayed or absent speech, short stature with small hands and feet and facial dysmorphism consisting of a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures, and a short philtrum. We describe for the first time that females can be severely affected, despite preferential inactivation of the affected X chromosome. Three females with the c.329 G > A p.Arg110Gln variant, present with a phenotype of mild ID, specific facial features, scoliosis and craniosynostosis, as reported previously in a single patient. In these females, the X inactivation pattern appeared skewed in favour of the affected transcript. In summary, HUWE1 missense variants may cause syndromic ID in both males and females.
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