PAX6, brain structure and function in human adults: Advanced MRI in aniridia

Objective PAX6 is a pleiotropic transcription factor essential for the development of several tissues including the eyes, central nervous system, and some endocrine glands. Recently it has also been shown to be important for the maintenance and functioning of corneal and pancreatic tissues in adults. We hypothesized that PAX6 is important for the maintenance of brain integrity in humans, and that adult heterozygotes may have abnormalities of cortical patterning analogous to those found in mouse models. Methods We used advanced magnetic resonance imaging techniques, including surface-based morphometry and region-of-interest analysis in adult humans heterozygously mutated for PAX6 mutations (n = 19 subjects and n = 21 controls). Using immunohistochemistry, we also studied PAX6 expression in the adult brain tissue of healthy subjects (n = 4) and patients with epilepsy (n = 42), some of whom had focal injuries due to intracranial electrode track placement (n = 17). Results There were significant reductions in frontoparietal cortical area after correcting for age and intracranial volume. A greater decline in thickness of the frontoparietal cortex with age, in subjects with PAX6 mutations compared to controls, correlated with age-corrected, accelerated decline in working memory. These results also demonstrate genotypic effects: those subjects with the most severe genotypes have the most widespread differences compared with controls. We also demonstrated significant increases in PAX6-expressing cells in response to acute injury in the adult human brain. Interpretation These findings suggest a role for PAX6 in the maintenance and consequent functioning of the adult brain, homologous to that found in other tissues. This has significant implications for the understanding and treatment of neurodegenerative diseases

Factors related to tinnitus and hyperacusis handicap in older people.

OBJECTIVE: The aim was to assess factors related to tinnitus and hyperacusis handicap in older people. DESIGN: Retrospective cross-sectional. STUDY SAMPLE: Data were gathered for 184 patients with an average age of 69 years. RESULTS: Tinnitus handicap as measured via the Tinnitus Handicap Inventory (THI) was significantly predicted by tinnitus annoyance as measured via the visual analogue scale (VAS) (regression coefficient, b = 2.9, p < 0.001) and the effect of tinnitus on the patient's life as measured via the VAS (b = 3.9, p < 0.001). Hyperacusis handicap as measured via the Hyperacusis Questionnaire (HQ) was significantly predicted by the score on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) (b = 0.8, p < 0.001) and to a small extent by the THI score (b = 0.07, p = 0.048). Insomnia scores as measured via the Insomnia Severity Index (ISI) were significantly predicted by scores on the depression subscale of the HADS (b = 0.46, p = 0.007). CONCLUSIONS: Since tinnitus annoyance significantly predicts tinnitus handicap, it is important to explore factors associated with annoyance that may be useful in designing appropriate rehabilitative interventions aimed at reducing tinnitus handicap in older people. Future studies should explore whether hyperacusis and insomnia in older people with tinnitus need to be managed in conjunction with treatment for depression

Vortex states in 2D superconductor at high magnetic field in a periodic pinning potential

The effect of a periodic pinning array on the vortex state in a 2D superconductor at low temperatures is studied within the framework of the Ginzburg-Landau approach. It is shown that attractive interaction of vortex cores to a commensurate pin lattice stabilizes vortex solid phases with long range positional order against violent shear fluctuations. Exploiting a simple analytical method, based on the Landau orbitals description, we derive a rather detailed picture of the low temperatures vortex state phase diagram. It is predicted that for sufficiently clean samples application of an artificial periodic pinning array would enable one to directly detect the intrinsic shear stiffness anisotropy characterizing the ideal vortex lattice.Comment: 8 pages, 5 figure

TITAN's Digital RFQ Ion Beam Cooler and Buncher, Operation and Performance

We present a description of the Radio Frequency Quadrupole (RFQ) ion trap built as part of the TITAN facility. It consists of a gas-filled, segmented, linear Paul trap and is the first stage of the TITAN setup with the purpose of cooling and bunching radioactive ion beams delivered from ISAC-TRIUMF. This is the first such device to be driven digitally, i.e., using a high voltage ($V_{pp} = \rm{400 \, V}$), wide bandwidth ($0.2 < f < 1.2 \, \rm{MHz}$) square-wave as compared to the typical sinusoidal wave form. Results from the commissioning of the device as well as systematic studies with stable and radioactive ions are presented including efficiency measurements with stable $^{133}$Cs and radioactive $^{124, 126}$Cs. A novel and unique mode of operation of this device is also demonstrated where the cooled ion bunches are extracted in reverse mode, i.e., in the same direction as previously injected.Comment: 34 pages, 17 figure

Alcohol Use Disorder and Recent Alcohol Use and HIV Viral Non-Suppression Among People Engaged in HIV Care in an Urban Clinic, 2014–2018

We estimated joint associations between having history of alcohol use disorder (AUD) (based on prior ICD-9/ICD-10 codes) and recent self-reported alcohol use and viral non-suppression (≥ 1 viral load measurement > 20 copies/mL in the same calendar year as alcohol consumption was reported) among patients on ART enrolled in routine care, 2014–2018, in an urban specialty clinic. Among 1690 patients, 26% had an AUD, 21% reported high-risk alcohol use, and 39% had viral non-suppression. Relative to person-years in which people without AUD reported not drinking, prevalence of viral non-suppression was higher in person-years when people with AUD reported drinking at any level; prevalence of viral non-suppression was not significantly higher in person-years when people with AUD reported not drinking or person-years when people without AUD reported drinking at any level. No level of alcohol use may be “safe” for people with a prior AUD with regard to maintaining viral suppression

Fractional Quantum Hall States of Clustered Composite Fermions

The energy spectra and wavefunctions of up to 14 interacting quasielectrons (QE's) in the Laughlin nu=1/3 fractional quantum Hall (FQH) state are investigated using exact numerical diagonalization. It is shown that at sufficiently high density the QE's form pairs or larger clusters. This behavior, opposite to Laughlin correlations, invalidates the (sometimes invoked) reapplication of the composite fermion picture to the individual QE's. The series of finite-size incompressible ground states are identified at the QE filling factors nu_QE=1/2, 1/3, 2/3, corresponding to the electron fillings nu=3/8, 4/11, 5/13. The equivalent quasihole (QH) states occur at nu_QH=1/4, 1/5, 2/7, corresponding to nu=3/10, 4/13, 5/17. All these six novel FQH states were recently discovered experimentally. Detailed analysis indicates that QE or QH correlations in these states are different from those of well-known FQH electron states (e.g., Laughlin or Moore-Read states), leaving the origin of their incompressibility uncertain. Halperin's idea of Laughlin states of QP pairs is also explored, but is does not seem adequate.Comment: 14 pages, 9 figures; revision: 1 new figure, some new references, some new data, title chang

Determining the density of states for classical statistical models: A random walk algorithm to produce a flat histogram

We describe an efficient Monte Carlo algorithm using a random walk in energy space to obtain a very accurate estimate of the density of states for classical statistical models. The density of states is modified at each step when the energy level is visited to produce a flat histogram. By carefully controlling the modification factor, we allow the density of states to converge to the true value very quickly, even for large systems. This algorithm is especially useful for complex systems with a rough landscape since all possible energy levels are visited with the same probability. In this paper, we apply our algorithm to both 1st and 2nd order phase transitions to demonstrate its efficiency and accuracy. We obtained direct simulational estimates for the density of states for two-dimensional ten-state Potts models on lattices up to $200 \times 200$ and Ising models on lattices up to $256 \times 256$. Applying this approach to a 3D $\pm J$ spin glass model we estimate the internal energy and entropy at zero temperature; and, using a two-dimensional random walk in energy and order-parameter space, we obtain the (rough) canonical distribution and energy landscape in order-parameter space. Preliminary data suggest that the glass transition temperature is about 1.2 and that better estimates can be obtained with more extensive application of the method.Comment: 22 pages (figures included

Dysfunctional LAT2 Amino Acid Transporter Is Associated With Cataract in Mouse and Humans.

Cataract, the loss of ocular lens transparency, accounts for ∼50% of worldwide blindness and has been associated with water and solute transport dysfunction across lens cellular barriers. We show that neutral amino acid antiporter LAT2 (Slc7a8) and uniporter TAT1 (Slc16a10) are expressed on mouse ciliary epithelium and LAT2 also in lens epithelium. Correspondingly, deletion of LAT2 induced a dramatic decrease in lens essential amino acid levels that was modulated by TAT1 defect. Interestingly, the absence of LAT2 led to increased incidence of cataract in mice, in particular in older females, and a synergistic effect was observed with simultaneous lack of TAT1. Screening SLC7A8 in patients diagnosed with congenital or age-related cataract yielded one homozygous single nucleotide deletion segregating in a family with congenital cataract. Expressed in HeLa cells, this LAT2 mutation did not support amino acid uptake. Heterozygous LAT2 variants were also found in patients with cataract some of which showed a reduced transport function when expressed in HeLa cells. Whether heterozygous LAT2 variants may contribute to the pathology of cataract needs to be further investigated. Overall, our results suggest that defects of amino acid transporter LAT2 are implicated in cataract formation, a situation that may be aggravated by TAT1 defects