Properties of developmental gene regulatory networks

The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. We survey examples of such subcircuits and relate their structures to corresponding developmental functions. These relations transcend organisms and genes, as illustrated by the similar structures of the subcircuits controlling the specification of the mesectoderm in the Drosophila embryo and the endomesoderm in the sea urchin, even though the respective subcircuits are composed of nonorthologous regulatory genes

High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

BackgroundMultiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity.MethodsA retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality.ResultsA total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05).ConclusionHigh-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV

Location, Location, Location: Contrasting Roles of Synaptic and Extrasynaptic NMDA Receptors in Huntington's Disease

Abnormally enhanced N-methyl-D-aspartate (NMDA) receptor function is implicated in Huntington's disease (HD). In this issue of Neuron and a recent issue of Nature Medicine, an abnormal balance between the activity of NMDA receptors at synaptic (prosurvival) and extrasynaptic (proapoptotic) sites has been uncovered in a cellular and a mouse model of HD

The Effect of Discovery Systems on Online Journal Usage: A Longitudinal Study

Many academic libraries are implementing discovery services as a way of giving their users a single comprehensive search option for all library resources. These tools are designed to change the research experience, yet very few studies have investigated the impact of discovery service implementation. This study examines one aspect of that impact by asking whether usage of publisher-hosted journal content changes after implementation of a discovery tool. Libraries that have begun using the four major discovery services have seen an increase in usage of this content, suggesting that for this particular type of material, discovery services have a positive impact on use. Though all discovery services significantly increased usage relative to a no discovery service control group, some had a greater impact than others, and there was extensive variation in usage change among libraries using the same service. Future phases of this study will look at other types of content

The Effect of Discovery Systems on Online Journal Usage: A Longitudinal Study

Many academic libraries are implementing discovery services as a way of giving their users a single comprehensive search option for all library resources. These tools are designed to change the research experience, yet very few studies have investigated the impact of discovery service implementation. This study examines one aspect of that impact by asking whether usage of publisher-hosted journal content changes after implementation of a discovery tool. Libraries that have begun using the four major discovery services have seen an increase in usage of this content, suggesting that for this particular type of material, discovery services have a positive impact on use. Though all discovery services significantly increased usage relative to a no discovery service control group, some had a greater impact than others, and there was extensive variation in usage change among libraries using the same service. Future phases of this study will look at other types of content

Improving Regulatory Effectiveness through Better Targeting: Evidence from OSHA

We study how a regulator can best allocate its limited inspection resources. We direct our analysis to a US Occupational Safety and Health Administration (OSHA) inspection program that targeted dangerous establishments and allocated some inspections via random assignment. We find that inspections reduced serious injuries by an average of 9% over the following five years. We use new machine learning methods to estimate the effects of counterfactual targeting rules OSHA could have deployed. OSHA could have averted over twice as many injuries if its inspections had targeted the establishments where we predict inspections would avert the most injuries. The agency could have averted nearly as many additional injuries by targeting the establishments predicted to have the most injuries. Both of these targeting regimes would have generated over $1 billion in social value over the decade we examine. Our results demonstrate the promise, and limitations, of using machine learning to improve resource allocation. JEL Classifications: I18; L51; J38; J

Gain Modulation by Corticostriatal and Thalamostriatal Input Signals during Reward-Conditioned Behavior.

The cortex and thalamus send excitatory projections to the striatum, but little is known about how these inputs, either individually or collectively, regulate striatal dynamics during behavior. The lateral striatum receives overlapping input from the secondary motor cortex (M2), an area involved in licking, and the parafascicular thalamic nucleus (PF). Using neural recordings, together with optogenetic terminal inhibition, we examine the contribution of M2 and PF projections on medium spiny projection neuron (MSN) activity as mice performed an anticipatory licking task. Each input has a similar contribution to striatal activity. By comparing how suppressing single or multiple projections altered striatal activity, we find that cortical and thalamic input signals modulate MSN gain and that this effect is more pronounced in a temporally specific period of the task following the cue presentation. These results demonstrate that cortical and thalamic inputs synergistically regulate striatal output during reward-conditioned behavior