The current state of optometric education worldwide

Optometric practice has been shown to vary greatly between countries. Previous data has suggested much disparity between the level of optometric education and the scope of practice. There currently exists no comprehensive comparative data on the standards · and scope of optometric education throughout the world. The goal of this project was to establish such a data source. A two-tiered survey was sent to various countries to establish a comprehensive computer database describing optometric education at vanous institutions and numerous countries worldwide. The general scope of optometric education is summarized for each country

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: A GENFI study

Objective: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age. Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD

Os retratos de Maria Isabel e Maria Francisca de Bragança, de Nicolas-Antoine Taunay

Nicolas-Antoine Taunay, French landscape painter, produced also several portraits during his stay at the Rio de Janeiro Court. In this city, in 1816, he paints the queen Carlota Joaquina and all her daughters. In this group, two portraits have a very special way: the paintings still today catalogued as Maria Francisca and Maria Teresa, but probably being Maria Isabel and Maria Francisca de Assis - princesses that, in this year, left Brazil to marry the Spanish King Fernando VII, and his brother Carlos Maria Isidro de Bourbon. In this article, beyond to describe these portraits (and analyse the identities of the portrayed princesses), I analyse their functions in the Court society and the mains artists of this gender in Europe. I will discuss, as well, the hypothesis about the Taunay choices. In this sense, I will analyse the possible circulation of the typologies of portrait between Italy, Portugal, Spain and France, understanding these productions by Taunay and the functions occupied by these portraits in the political relations between Brazil and Europe.Nicolas-Antoine Taunay, pintor de paisagens francês, também realizou alguns retratos durante sua estadia na corte do Rio de Janeiro. Nessa cidade, em 1816, ele pinta a rainha Carlota Joaquina e todas as suas filhas. Nesse conjunto, dois retratos sobressaem-se de modo especial: os hoje ainda inventariados como de Maria Francisca e de Maria Teresa, mas que provavelmente são o de Maria Isabel e o de Maria Francisca de Assis - princesas que, nesse ano, deixavam o Brasil para casar-se, respectivamente, com Fernando VII, o rei espanhol, e com seu irmão Carlos Isidro de Bourbon. Neste artigo, além de descrevermos os retratos (e analisarmos a questão da identidade das princesas retratadas), abordamos suas funções na sociedade das cortes e os principais artistas do gênero na Europa. Discutimos, também, as hipóteses que permeiam as escolhas de Taunay para sua execução. Nesse sentido, tratamos da possível circulação de tipologias entre Itália, Portugal, Espanha e França, buscando entender a forma como Taunay os realizou e as funções que doravante tais retratos ocupariam nas relações entre o Brasil e a Europa.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

The theory of the firm and its critics: a stocktaking and assessment

Includes bibliographical references."Prepared for Jean-Michel Glachant and Eric Brousseau, eds. New Institutional Economics: A Textbook, Cambridge, Cambridge University Press.""This version: August 22, 2005."Since its emergence in the 1970s the modern economic or Coasian theory of the firm has been discussed and challenged by sociologists, heterodox economists, management scholars, and other critics. This chapter reviews and assesses these critiques, focusing on behavioral issues (bounded rationality and motivation), process (including path dependence and the selection argument), entrepreneurship, and the challenge from knowledge-based theories of the firm

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

Background Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs. Principal Findings The CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2 and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual tumors. In vitro, SBT-1214 (100nM-1µM; for 72 hr) induced about 60% cell death in CD133high/CD44+/high cells cultured on collagen I in stem cell medium (in contrast, the same doses of paclitaxel increased proliferation of these cells). The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24. A stem cell-specific PCR array assay revealed that this drug combination mediated massive inhibition of multiple constitutively up-regulated stem cell-related genes, including key pluripotency transcription factors. Importantly, this drug combination induced expression of p21 and p53, which were absent in CD133high/CD44high cells. Viable cells that survived this treatment regimen were no longer able to induce secondary spheroids, exhibited significant morphological abnormalities and died in 2-5 days. Conclusions We report here that the SBT-1214 alone, or in combination with CMC2.24, possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells. This drug combination efficiently inhibits expression of the majority of stem cell-related genes and pluripotency transcription factors. In addition, it induces a previously absent expression of p21 and p53 (“gene wake-up”), which can potentially reverse drug resistance by increasing sensitivity to anti-cancer drugs

An Exploration of the Paradigm for the 2-3 Hour Period Gap in Cataclysmic Variables

We critically examine the basic paradigm for the origin of the 2-3 hr period gap in cataclysmic variables (CVs). We carry out an extensive population synthesis study of CVs starting from ~ 3 x 10^6 primordial binaries, and evolving some ~ 2 x 10^4 surviving systems through their CV phase. In particular we study current-epoch distributions of CVs in the $\dot M-P_{orb}$, R_{2}-P_{orb}, M_{2}-P_{orb}, q-P_{orb}, T_{eff}-P_{orb}, and L_{2}-P_{orb} planes, where $\dot M$ is the mass transfer rate, q is the mass ratio M_2/M_1, and M_2, R_2, T_{eff}, and L_2 are the donor star mass, radius, effective temperature, and luminosity, respectively. This work presents a new perspective on theoretical studies of the long-term evolution of CVs. In particular, we show that if the current paradigm is correct, the secondary masses in CVs just above the period gap should be as much as ~ 50% lower than would be inferred if one assumes a main-sequence radius-mass relation for the donor star.Comment: Accepted in Ap

Therapy development for the mucopolysaccharidoses : updated consensus recommendations for neuropsychological endpoints

Neurological dysfunction represents a significant clinical component of many of the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment of neuropsychological function is essential to gain a greater understanding of the precise natural history of these conditions and to design effective clinical trials to evaluate the impact of therapies on the brain. In 2017, an International MPS Consensus Panel published recommendations for best practice in the design and conduct of clinical studies investigating the effects of therapies on cognitive function and adaptive behavior in patients with neuronopathic mucopolysaccharidoses. Based on an International MPS Consensus Conference held in February 2020, this article provides updated consensus recommendations and expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses