Comparison of Oxygen Flux in Hydrogel and Silicone Hydrogel Contact Lenses

The prevalence of contact lens use has been continuously growing for their convenience and for cosmetic reasons. Although contact lenses do offer many advantages over glasses, the major concern for many contact lens users is dryness that results from a lack of oxygen that goes through the contact lens to meet the demand of eye tissue. A new type of contact lens, made out of silicone hydrogel, has been introduced in the market which has garnered much attention from many contact users. The silicone hydrogel is different from the traditional hydrogel contact lens since oxygen is permeable through silicone, which was not possible through hydrogels. The hydrogel contact lenses must have high water content for oxygen delivery, silicone hydrogel contacts depends on their high oxygen diffusivity while having low water content. Night and day contact lenses are made out of silicone hydrogel whereas traditional ones for day use are often made out of hydrogel. A model was developed to validate the advantage of wearing silicone hydrogel contact lenses in both day and night conditions. By analyzing the center area of the eye around the pupil as a thin slab, the performance of these two types of contact lenses were compared by computing average oxygen concentrations in the stroma, which is the largest layer of cornea. Using COMSOL Multiphysics, the simplified geometry that included the layers of contact lens, tear, endothelium, and stroma was used as our model to find the oxygen concentration after eight hours of use either with eyes open or closed. The thickness of 80/mu m was used for both hydrogel and silicone hydrogel, the average oxygen concentration was found to be 9.100219x10-8mol/cm3 and 4.198608x10-8 mol/cm3 respectively for day setting with eyes open for eight hours and 3.536442x10-8 mol/cm3 and 2.119774x10-8 mol/cm3 respectively for night setting with eyes closed. Variations of other parameters in modeling also showed the same trend that silicone hydrogel contact lenses ended up with less oxygen in the cornea than hydrogel. Thus, the modeling showed how the silicone hydrogel did not offer any increase in oxygen delivery in both day and night settings

A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease

Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases characterized by movement disorders, psychiatric disturbances and cognitive decline. Brain tissue from HD and HDL2 patients shows degeneration of the striatum and ubiquitinated inclusions immunoreactive for polyglutamine (polyQ) antibodies. Despite these similarities, the diseases result from different genetic mutations. HD is caused by a CAG repeat expansion in the huntingtin (HTT) gene, while HDL2 results from an expansion at the junctophilin 3 (JPH3) locus. Recent evidence indicates that the HDL2 expansion may give rise to a toxic polyQ protein translated from an antisense mRNA derived from the JPH3 locus. To investigate this hypothesis, we generated and characterized a Drosophila HDL2 model and compared it with a previously established HD model. We find that neuronal expression of HDL2-Q15 is not toxic, while the expression of an expanded HDL2-Q138 protein is lethal. HDL2-Q138 forms large nuclear aggregates, with only smaller puncta observed in the cytoplasm. This is in contrast to what is observed in a Drosophila model of HD, where polyQ aggregates localize exclusively to the cytoplasm. Altering localization of HLD2 with the addition of a nuclear localization or nuclear export sequence demonstrates that nuclear accumulation is required for toxicity in the Drosophila HDL2 model. Directing HDL2-Q138 to the nucleus exacerbates toxicity in multiple tissue types, while confining HDL2-Q138 to the cytoplasm restores viability to control levels. We conclude that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms are likely to drive toxicity in Drosophila models of these disorders.National Institutes of Health (U.S.) (Grants NS40296 and MH104536)JPB Foundatio

Food Security & Civil Society

Findings from an in-depth qualitative investigation of Food Security with people from civil society organisations. A ‘boots on the ground’ perspective, which reveals the concerns about food security, and stakeholder evaluations of what they think needs to be done

High-Frequency and Below Bandgap Anisotropic Dielectric Constants in \u3cem\u3eα\u3c/em\u3e-(Al\u3csub\u3ex\u3c/sub\u3eGa\u3csub\u3e1-x\u3c/sub\u3e)\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e (0≤x≤1)

A Mueller matrix spectroscopic ellipsometry approach was used to investigate the anisotropic dielectric constants of corundum α-(AlxGa1-x)2O3 thin films in their below bandgap spectral regions. The sample set was epitaxially grown using plasma-assisted molecular beam epitaxy on m-plane sapphire. The spectroscopic ellipsometry measurements were performed at multiple azimuthal angles to resolve the uniaxial dielectric properties. A Cauchy dispersion model was applied, and high-frequency dielectric constants are determined for polarization perpendicular (ε∞,⟂) and parallel (ε∞,∥) to the thin film c-axis. The optical birefringence is negative throughout the composition range, and the overall index of refraction substantially decreases upon incorporation of Al. We find small bowing parameters of the high-frequency dielectric constants with b⟂=0.386 and b∥=0.307

Patterns of substance use across the first year of college and associated risk factors

Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N = 2056, 1240 females) of the “Spit for Science” sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains – including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety – were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: (1) use of all four substances; (2) alcohol, tobacco, and cannabis use; and (3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use

Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model

Abstract Background Adoptive cell transfer (ACT) is a promising cancer immunotherapeutic strategy that remains ineffective for a large subset of patients. ACT with memory CD8+ T cells (Tmem) has been shown to have superior efficacy compared to traditional ACT with effector CD8+ T cells (Teff). Teff and Tmem have complementary physiological advantages for immunotherapy, but previous publications have not examined ACT using a combination of Teff and Tmem. Methods Splenocytes harvested from Ly5.1+/C57BL/6 mice during and after infection with lymphocytic choriomeningitis virus (LCMV) were used to generate bona fide effector and memory CD8+ T cells specific for the LCMV epitope peptide GP33. Congenic Ly5.2+/C57BL/6 mice were inoculated with B16F10 melanoma cells transfected to express very low levels of GP33, then treated with ACT 7 days later with GP33-specific Teff, Tmem, or a combination of Teff + Tmem. Results Inhibition of melanoma growth was strongest in mice receiving combinatorial ACT. Although combinatorial ACT and memory ACT resulted in maximal intratumoral infiltration of CD8+ T cells, combinatorial ACT induced stronger infiltration of endogenous CD8+ T cells than Tmem ACT and a stronger systemic T cell responsiveness to tumor antigen. In vitro assays revealed rapid but transient melanoma inhibition with Teff and gradual but prolonged melanoma inhibition with Tmem; the addition of Tmem enhanced the ability of Teff to inhibit melanoma in a manner that could be reproduced using conditioned media from activated Tmem and blocked by the addition of anti-IL-2 blocking antibody. Conclusions These findings suggest that a novel combinatorial approach that takes advantage of the unique and complementary strengths of tumor-specific Teff and Tmem may be a way to optimize the efficacy of adoptive immunotherapy.https://deepblue.lib.umich.edu/bitstream/2027.42/143864/1/40425_2018_Article_358.pd

The Effect of Neutrophil-lymphocyte Ratio on 10-year Survival Outcomes Following Elective Open and EVAR Procedures

Objectives: The neutrophil-lymphocyte ratio (NLR) is a useful and inexpensive inflammatory marker associated with surgical outcomes. This study evaluates the effects of NLR on survival after elective endovascular (EVAR) and open aortic repair (OAR) of abdominal aortic aneurysm. Methods: We retrospectively reviewed patients from 1989 to 2019 who underwent elective OAR or EVAR at two separate academic centers. Baseline comorbidities were assessed. A receiver operating characteristic (ROC) curve was used to determine a cutoff point where NLR was associated with outcome. Kaplan-Meier survival analysis was used to compare survival through 10-year follow-up. Results: Overall, 437 patients (mean age, 72.0 6 10.1 years; 74.1% male) underwent 213 EVARs and 224 OARs. Median duration of follow-up was 4.55 years. The analysis of the ROC curve yielded an NLR of 3.94 with the highest specificity and sensitivity for 10-year survival. Baseline characteristics were similar between groups, except for an increased age in the group with NLR \u3e3.94 (73.5 vs 70.9 years; P ¼ .008) (Table). KaplanMeier analysis revealed that patients with NLR \u3e3.94 had decreased 10-year survival (37.2% vs 54.2%; P ¼ .0001) (Fig). By univariate analysis, NLR \u3e3.94 (P ¼ .0001), chronic obstructive pulmonary disease (P ¼ .006), and increased age (P ¼ .0001) were associated with increased mortality. On multivariable cox regression analysis, an NLR \u3e3.94 (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.19-2.40), increased age (OR, 1.05; 95% CI, 1.03-1.07), and chronic obstructive pulmonary disease (OR, 1.44; 95% CI, 1.01-2.07) were associated with increased risk of mortality. Between OAR and EVAR, no difference in late survival was noted (49.9% vs 43.5%; P ¼ .24). Conclusions: An NLR \u3e3.94 is associated with increased mortality over a 10-year follow-up period after open and endovascular aortic repair. Future studies to further understand the driving force between an elevated NLR and increased mortality are warranted

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Anisotropic Dielectric Functions, Band-to-Band Transitions, and Critical Points in \u3cem\u3eα\u3c/em\u3e-Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e

We use a combined generalized spectroscopic ellipsometry and density functional theory approach to determine and analyze the anisotropic dielectric functions of an α-Ga2O3 thin film. The sample is grown epitaxially by plasma-assisted molecular beam epitaxy on m-plane sapphire. Generalized spectroscopic ellipsometry data from multiple sample azimuths in the spectral range from 0.73 eV to 8.75 eV are simultaneously analyzed. Density functional theory is used to calculate the valence and conduction band structure. We identify, for the indirect-bandgap material, two direct band-to-band transitions with M0-type van Hove singularities for polarization perpendicular to the c axis, E0,⊥=5.46(6) eV and E0,⊥=6.04(1) eV, and one direct band-to-band transition with M1-type van Hove singularity for polarization parallel to E0,∥=5.44(2) eV. We further identify excitonic contributions with a small binding energy of 7 meV associated with the lowest ordinary transition and a hyperbolic exciton at the M1-type critical point with a large binding energy of 178 meV