Modulation of the GABAergic pathway for the treatment of fragile X syndrome.

Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins. The metabotropic glutamate receptor (mGluR) hypothesis states that the neurological deficits in individuals with FXS are due mainly to downstream consequences of overstimulation of the mGluR pathway. The main efforts have focused on mGluR5 targeted treatments; however, investigation on the gamma-aminobutyric acid (GABA) system and its potential as a targeted treatment is less emphasized. The fragile X mouse models (Fmr1-knock out) show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain. Consequences of the reduced GABAergic input in FXS include oversensitivity to sensory stimuli, seizures, and anxiety. Deficits in the GABA receptors in different regions of the brain are associated with behavioral and attentional processing deficits linked to anxiety and autistic behaviors. The understanding of the neurobiology of FXS has led to the development of targeted treatments for the core behavioral features of FXS, which include social deficits, inattention, and anxiety. These symptoms are also observed in individuals with autism and other neurodevelopmental disorders, therefore the targeted treatments for FXS are leading the way in the treatment of other neurodevelopmental syndromes and autism. The GABAergic system in FXS represents a target for new treatments. Herein, we discuss the animal and human trials of GABAergic treatment in FXS. Arbaclofen and ganaxolone have been used in individuals with FXS. Other potential GABAergic treatments, such as riluzole, gaboxadol, tiagabine, and vigabatrin, will be also discussed. Further studies are needed to determine the safety and efficacy of GABAergic treatments for FXS

Using Matching, Instrumental Variables and Control Functions to Estimate Economic Choice Models

This paper investigates four topics. (1) It examines the different roles played by the propensity score (probability of selection) in matching, instrumental variable and control functions methods. (2) It contrasts the roles of exclusion restrictions in matching and selection models. (3) It characterizes the sensitivity of matching to the choice of conditioning variables and demonstrates the greater robustness of control function methods to misspecification of the conditioning variables. (4) It demonstrates the problem of choosing the conditioning variables in matching and the failure of conventional model selection criteria when candidate conditioning variables are not exogenous.

Border Enforcement and Selection of Mexican Immigrants in the United States

Since 1986 the United States has made considerable efforts to curb illegal immigration. This has resulted in an increase in migration costs for undocumented immigrants. More stringent border enforcement either deters potential illegal immigrants from coming to the U.S., or moves the point of crossing for illegal immigrants from traditional crossing routes to more inhospitable routes. These changes are likely to place a heavier burden on illegal immigrant women as they are more likely to be kidnapped, smuggled, or raped when crossing illegally. If migration costs are not the same for all migrants, higher migrating costs may result in a change in the number and in the composition of immigrants to the United States. In the face of higher migration costs, only immigrants with relatively high expected benefits of migration will choose to migrate. Based on our theoretical model, we test for three empirical results that are associated with a stronger selection of immigrant women from Mexico relative to men as a result of higher migration costs: 1) A decrease in the relative flow of older and highly educated undocumented immigrant women relative to men; 2) A change in the skill composition of immigrant women to men; and 3) An increase in the average earnings of those groups most affected by increased migration costs. Using data from the 1990, 2000 Decennial Census, and from the 2006-2008 American Community Survey we empirically confirm these predictions.selection, gender, immigration, border enforcement