Gender differences in high-stakes performance and college admission policies

The Gale-Shapley algorithm is one of the most popular college allocation mechanism around the world. A crucial policy question in its setting is designing admission priorities for students, understanding how they disadvantage certain demographic groups, and whether these di_erences are related to di_erences in college performance potential (i.e., whether these di_erences are fair). Studying a policy change in Spain, we find a negative e_ect of increasing the weight of standardized high-stakes exams on female college admission scores, driven by students expected to be at the top. The effect on admission scores does not affect enrolment, but the percentage of female students in the most selective degrees declines, along with their career prospects. Using data on college performance of pre-reform cohorts, we find that female students most likely to lose from the reform tend to do better in college than male students expected to benefit from the reform. The results show that rewarding high-stakes performance in selection processes may come along with gender differences unrelated to the determinants of subseqüent performance

Learning Loss One Year After School Closures: Evidence From The Basque Country

We use census data on external assessments in primary and secondary school in the Basque Country (Spain) to estimate learning losses due to the COVID-19 pandemic in March 2021, one year after school closures, which lasted from March to June 2020. Differences-in-differences with student and school-by-grade fixed effects show an average learning loss of 0.045 standard deviations, an effect which is smaller than short run effects estimated by previous papers, and estimated after 6 months of one of the most successful school reopening campaigns among OECD countries. The effect is larger in Mathematics, moderate in Basque language, and none in Spanish language. Controlling for socioeconomic differences, learning losses are especially large in public schools, and also in private schools with a high percentage of low-performing students. On the other hand, we find a regression to the mean within schools, possibly due to a compressed curriculum during the whole period. Finally, we show that students’ with higher learning losses self-report significantly worse levels of socio-emotional well- being due to the pandemi

What is a stake without high-stakes exams? Students’ evaluation and admission to college at the time of Covid-19

The outbreak of COVID-19 in 2020 inhibited face-to-face education and constrained exam taking. In many countries worldwide, high-stakes exams happening at the end of the school year determine college admissions. This paper investigates the impact of using historical data of school and high-stakes exams results to train a model to predict high-stakes exams given the available data in the Spring. The most transparent and accurate model turns out to be a linear regression model with high school GPA as the main predictor. Further analysis of the predictions reflect how high-stakes exams relate to GPA in high school for different subgroups in the population. Predicted scores slightly advantage females and low SES individuals, who perform relatively worse in high-stakes exams than in high school. Our preferred model accounts for about 50% of the out-of-sample variation in the high-stakes exam. On average, the student rank using predicted scores differs from the actual rank by almost 17 percentiles. This suggests that either high-stakes exams capture individual skills that are not measured by high school grades or that high-stakes exams are a noisy measure of the same skill

Els dilemes democràtics de la COVID-19

La pandèmia provocada per la COVID-19 planteja un seguit de dilemes per als sistemes democràtics. En primer lloc, la governança d'un problema complex com aquest requereix molta coordinació entre diferents nivells i àrees de govern. Aquesta coordinació pot derivar en processos de concentració del poder en els executius estatals, i, per tant, en un afebliment de la separació de poders horitzontal i vertical. Així mateix, el control de la pandèmia exigeix mesures que poden representar limitacions importants de drets i llibertats fonamentals. En aquest article, analitzem aquests dilemes i estudiem com hi responen els ciutadans. Mitjançant l'anàlisi d'una enquesta panel duta a terme durant els mesos de gener, març i juny de 2020, observem una tendència molt marcada, en primera instància, a demanar lideratges forts, tecnocràtics i centralitzats, així com a acceptar restriccions de llibertats. Passada la primera onada de contagis, aquesta tendència es va matisar significativament, amb l'excepció de les preferències tecnocràtiques, que es mantenen en uns nivells significativament més elevats que abans de la pandèmia

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies

McArdle disease; Glycogen phosphorylase; Research modelsEnfermedad de McArdle; Glucógeno fosforilasa; Modelos de investigaciónMalaltia de McArdle; Glicogen fosforilasa; Models de recercaMcArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the PYGM gene, which encodes the skeletal muscle-specific isoform of glycogen phosphorylase. Clinical symptoms are mainly characterized by transient acute “crises” of early fatigue, myalgia and contractures, which can be accompanied by rhabdomyolysis. Owing to the difficulty of performing mechanistic studies in patients that often rely on invasive techniques, preclinical models have been used for decades, thereby contributing to gain insight into the pathophysiology and pathobiology of human diseases. In the present work, we describe the existing in vitro and in vivo preclinical models for McArdle disease and review the insights these models have provided. In addition, despite presenting some differences with the typical patient’s phenotype, these models allow for a deep study of the different features of the disease while representing a necessary preclinical step to assess the efficacy and safety of possible treatments before they are tested in patients.The present manuscript was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, grant PI19/01313 and PI17/2052) and co-funded by “Fondos FEDER”

Expression of Glycogen Phosphorylase Isoforms in Cultured Muscle from Patients with McArdle's Disease Carrying the p.R771PfsX33 PYGM Mutation

Mutations in the PYGM gene encoding skeletal muscle glycogen phosphorylase (GP) cause a metabolic disorder known as McArdle's disease. Previous studies in muscle biopsies and cultured muscle cells from McArdle patients have shown that PYGM mutations abolish GP activity in skeletal muscle, but that the enzyme activity reappears when muscle cells are in culture. The identification of the GP isoenzyme that accounts for this activity remains controversial

Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model

Altres ajuts: The present study was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, grant PI16/01492 and PI15/00558) and cofunded by 'Fondos FEDER'. Gisela Nogales-Gadea is supported by a Trampoline Grant #21108 from AMF Telethon.McArdle disease is an autosomal recessive disorder caused by the absence of the muscle glycogen phosphorylase, which leads to impairment of glycogen breakdown. The McArdle mouse, a model heavily affected by glycogen accumulation and exercise intolerance, was used to characterize disease progression at three different ages. The molecular and histopathological consequences of the disease were analyzed in five different hind-limb muscles (soleus, extensor digitorum longus, tibialis anterior, gastrocnemius and quadriceps) of young (8-week-old), adult (35-week-old) and old (70-week-old) mice. We found that McArdle mice have a high perinatal and post-weaning mortality. We also observed a progressive muscle degeneration, fibrosis and inflammation process that was not associated with an increase in muscle glycogen content during aging. Additionally, this progressive degeneration varied among muscle and fiber types. Finally, the lack of glycogen content increase was associated with the inactivation of glycogen synthase and not with compensatory expression of the Pygl and/or Pygb genes in mature muscle

A Transcriptomic Approach to Search for Novel Phenotypic Regulators in McArdle Disease

McArdle disease is caused by lack of glycogen phosphorylase (GP) activity in skeletal muscle. Patients experience exercise intolerance, presenting as early fatigue and contractures. In this study, we investigated the effects produced by a lack of GP on several genes and proteins of skeletal muscle in McArdle patients. Muscle tissue of 35 patients and 7 healthy controls were used to identify abnormalities in the patients' transcriptomic profile using low-density arrays. Gene expression was analyzed for the influence of variables such as sex and clinical severity. Differences in protein expression were studied by immunoblotting and 2D electrophoresis analysis, and protein complexes were examined by two-dimensional, blue native gel electrophoresis (BN-PAGE). A number of genes including those encoding acetyl-coA carboxylase beta, m-cadherin, calpain III, creatine kinase, glycogen synthase (GS), and sarcoplasmic reticulum calcium ATPase 1 (SERCA1), were found to be downregulated in patients. Specifically, compared to controls, GS and SERCA1 proteins were reduced by 50% and 75% respectively; also, unphosphorylated GS and SERCA1 were highly downregulated. On BN-PAGE analysis, GP was present with GS in two muscle protein complexes. Our findings revealed some issues that could be important in understanding the physiological consequences of McArdle disease: (i) SERCA1 downregulation in patients could result in impaired calcium transport in type II (fast-twitch) muscle fibers, leading to early fatigability during exercise tasks involving type II fibers (which mostly use glycolytic metabolism), i.e. isometric exercise, lifting weights or intense dynamic exercise (stair climbing, bicycling, walking at a very brisk pace), (ii) GP and GS were found together in two protein complexes, which suggests a new regulatory mechanism in the activity of these glycogen enzymes

Preclinical research in glycogen storage diseases : a comprehensive review of current animal models

Altres ajuts: The present manuscript was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, grant; Instituto de Salud Carlos III) and cofunded by 'Fondos FEDER'. M.V.-S. is funded by a personal grant for doctoral studies from CONACYT (Consejo Nacional de Ciencia y Tecnología México).GSD are a group of disorders characterized by a defect in gene expression of specific enzymes involved in glycogen breakdown or synthesis, commonly resulting in the accumulation of glycogen in various tissues (primarily the liver and skeletal muscle). Several different GSD animal models have been found to naturally present spontaneous mutations and others have been developed and characterized in order to further understand the physiopathology of these diseases and as a useful tool to evaluate potential therapeutic strategies. In the present work we have reviewed a total of 42 different animal models of GSD, including 26 genetically modified mouse models, 15 naturally occurring models (encompassing quails, cats, dogs, sheep, cattle and horses), and one genetically modified zebrafish model. To our knowledge, this is the most complete list of GSD animal models ever reviewed. Importantly, when all these animal models are analyzed together, we can observe some common traits, as well as model specific differences, that would be overlooked if each model was only studied in the context of a given GSD

Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment?

[Background]: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO2peak)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. [Methods]: We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO2peak in patients (both sexes, N = 145) and healthy controls (N = 133). [Results]: Besides corroborating very poor VO2peak values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. [Conclusions]: In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses.The present study was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, PI17/02052, PI18/00139, PI19/01313, and PI20/00645) and cofunded by ‘Fondos FEDER’. Gisela Nogales-Gadea and Carmen Fiuza-Luces are supported by the Miguel Servet research contracts (ISCIII CD14/00032 and CP18/00034, respectively and cofounded by Fondos FEDER′). Research by Pedro L. Valenzuela is funded by a postdoctoral contract granted by Instituto de Salud Carlos III (Sara Borrell, CD21/00138). Monica Villarreal Salazar is supported by the Mexican National Council for Science and Technology (CONACYT)