The Effects of Class Size on the Long Run Growth in Reading Abilities and Early Adult Outcomes in the Christchurch Health and Development Study

This paper utilizes the feature of the CHDS data from New Zealand that children are sampled for extremely long individual histories of their class size experiences as well as their scholastic and early labor market outcomes. Our interest is to explore the full set of empirical implications of the recent experimental evidence on class size effects on student achievement from the United States in Project STAR for observational data. We argue that one implication of Project STAR is that only persistent class size reduction policies may have detectable effects, and so the longitudinal aspect of CHDS is necessary to detect class size effects. We account for the observational nature of the CHDS (in that children were not randomly assigned to different class sizes) by examining the long-run trends in test score growth, rather than levels. Consistent with the experimental evidence, we find statistically and economically significant effects of children being assigned to persistently smaller classes on both childhood test score growth as well as on early adult outcomes. Our analysis points the way towards the unification of experimental and observational evidence on class size effects, as well as highlighting several possible pitfalls in the analysis of observational data on this topic.School Quality; Value-Added Model; Experimental Evidence

Retrofitting O'Raifeartaigh Models with Dynamical Scales

We provide a method for obtaining simple models of supersymmetry breaking, with all small mass scales generated dynamically, and illustrate it with explicit examples. We start from models of perturbative supersymmetry breaking, such as O'Raifeartaigh and Fayet models, that would respect an $R$ symmetry if their small input parameters transformed as the superpotential does. By coupling the system to a pure supersymmetric Yang-Mills theory (or a more general supersymmetric gauge theory with dynamically small vacuum expectation values), these parameters are replaced by powers of its dynamical scale in a way that is naturally enforced by the symmetry. We show that supersymmetry breaking in these models may be straightforwardly mediated to the supersymmetric Standard Model, obtain complete models of direct gauge mediation, and comment on related model building strategies that arise in this simple framework.Comment: 15 pages, harvmac bi

Safety of overlapping inpatient orthopaedic surgery: A multicenter study

BackgroundAlthough overlapping surgery is used to maximize efficiency, more empirical data are needed to guide patient safety. We conducted a retrospective cohort study to evaluate the safety of overlapping inpatient orthopaedic surgery, as judged by the occurrence of perioperative complications.MethodsAll inpatient orthopaedic surgical procedures performed at 5 academic institutions from January 1, 2015, to December 31, 2015, were included. Overlapping surgery was defined as 2 skin incisions open simultaneously for 1 surgeon. In comparing patients who underwent overlapping surgery with those who underwent non-overlapping surgery, the primary outcome was the occurrence of a perioperative complication within 30 days of the surgical procedure, and secondary outcomes included all-cause 30-day readmission, length of stay, and mortality. To determine if there was an association between overlapping surgery and a perioperative complication, we tested for non-inferiority of overlapping surgery, assuming a null hypothesis of an increased risk of 50%. We used an inverse probability of treatment weighted regression model adjusted for institution, procedure type, demographic characteristics (age, sex, race, comorbidities), admission type, admission severity of illness, and clustering by surgeon.ResultsAmong 14,135 cases, the frequency of overlapping surgery was 40%. The frequencies of perioperative complications were 1% in the overlapping surgery group and 2% in the non-overlapping surgery group. The overlapping surgery group was non-inferior to the non-overlapping surgery group (odds ratio [OR], 0.61 [90% confidence interval (CI), 0.45 to 0.83]; p < 0.001), with reduced odds of perioperative complications (OR, 0.61 [95% CI, 0.43 to 0.88]; p = 0.009). For secondary outcomes, there was a significantly lower chance of all-cause 30-day readmission in the overlapping surgery group (OR, 0.67 [95% CI, 0.52 to 0.87]; p = 0.003) and shorter length of stay (e, 0.94 [95% CI, 0.89 to 0.99]; p = 0.012). There was no difference in mortality.ConclusionsOur results suggest that overlapping inpatient orthopaedic surgery does not introduce additional perioperative risk for the complications that we evaluated. The suitability of this practice should be determined by individual surgeons on a case-by-case basis with appropriate informed consent.Level of evidenceTherapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

Formation and removal of alkylthiolate self-assembled monolayers on gold in aqueous solutions

We report the development of novel reagents and approaches for generating recyclable biosensors. The use of aqueous media for the formation of protein binding alkylthiolate monolayers on Au surfaces results in accelerated alkylthiolate monolayer formation and improvement in monolayer integrity as visualized by fluorescence microscopy and CV techniques. We have also developed an electrocleaning protocol that is compatible with microfluidics devices, and this technique serves as an on-chip method for cleaning Au substrates both before and after monolayer formation. The techniques for the formation and dissociation of biotinylated SAMs from aqueous solvents reported here may be applied towards the development of Au-based sensor devices and microfluidics chips in the future. A potential use of these devices includes the specific capture and triggered release of target cells, proteins, or small molecules from liquid samples

Examining the reversibility of long-term behavioral disruptions in progeny of maternal SSRI exposure

Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring. It is unclear from these studies whether ASD susceptibility is purely related to maternal psychiatric diagnosis, or if treatment poses additional risk. We sought to determine whether maternal SSRI treatment alone or in combination with genetically vulnerable background was sufficient to induce offspring behavior disruptions relevant to ASD. We exposed C57BL/6J or Celf6(+/-) mouse dams to fluoxetine (FLX) during different periods of gestation and lactation and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations (USVs) and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity. Celf6 mutant mice demonstrate social communicative deficits and perseverative behaviors, without further interaction with FLX. FLX re-exposure in adulthood ameliorates the tactile hypersensitivity yet exacerbates the dominance phenotype. This suggests acute deficiencies in serotonin levels likely underlie the abnormal responses to sensory stimuli, while the social alterations are instead due to altered development of social circuits. These findings indicate maternal FLX treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy

Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons

CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying 3D chromatin structure. Human mutations inCTCFcause intellectual disability and autistic features. Knocking outCtcfin mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked outCtcfpostnatally in glutamatergic forebrain neurons under the control ofCamk2a-Cre. CtcfloxP/loxP;Camk2a-Cre+(CtcfCKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor coordination, and decreased sociability by 4 months of age.CtcfCKO mice also had reduced dendritic spine density in the hippocampus and cerebral cortex. Microarray analysis of mRNA fromCtcfCKO mouse hippocampus identified increased transcription of inflammation-related genes linked to microglia. Separate microarray analysis of mRNA isolated specifically fromCtcfCKO mouse hippocampal neurons by ribosomal affinity purification identified upregulation of chemokine signaling genes, suggesting crosstalk between neurons and microglia inCtcfCKO hippocampus. Finally, we found that microglia inCtcfCKO mouse hippocampus had abnormal morphology by Sholl analysis and increased immunostaining for CD68, a marker of microglial activation. Our findings confirm thatCtcfKO in postnatal neurons causes a neurobehavioral phenotype in mice and provide novel evidence that CTCF depletion leads to overexpression of inflammation-related genes and microglial dysfunction.SIGNIFICANCE STATEMENTCCCTC-binding factor (CTCF) is a DNA-binding protein that organizes nuclear chromatin topology. Mutations inCTCFcause intellectual disability and autistic features in humans. CTCF deficiency in embryonic neurons is lethal in mice, but mice with postnatal CTCF depletion are less well studied. We find that mice lackingCtcfinCamk2a-expressing neurons (CtcfCKO mice) have spatial learning/memory deficits, impaired fine motor skills, subtly altered social interactions, and decreased dendritic spine density. We demonstrate thatCtcfCKO mice overexpress inflammation-related genes in the brain and have microglia with abnormal morphology that label positive for CD68, a marker of microglial activation. Our findings suggest that inflammation and dysfunctional neuron–microglia interactions are factors in the pathology of CTCF deficiency.</jats:p

Planetary Collisions outside the Solar System: Time Domain Characterization of Extreme Debris Disks

Luminous debris disks of warm dust in the terrestrial planet zones around solar-like stars are recently found to vary, indicative of ongoing large-scale collisions of rocky objects. We use Spitzer 3.6 and 4.5 {\mu}m time-series observations in 2012 and 2013 (extended to 2014 in one case) to monitor 5 more debris disks with unusually high fractional luminosities ("extreme debris disk"), including P1121 in the open cluster M47 (80 Myr), HD 15407A in the AB Dor moving group (80 Myr), HD 23514 in the Pleiades (120 Myr), HD 145263 in the Upper Sco Association (10 Myr), and the field star BD+20 307 (>1 Gyr). Together with the published results for ID8 in NGC 2547 (35 Myr), this makes the first systematic time-domain investigation of planetary impacts outside the solar system. Significant variations with timescales shorter than a year are detected in five out of the six extreme debris disks we have monitored. However, different systems show diverse sets of characteristics in the time domain, including long-term decay or growth, disk temperature variations, and possible periodicity.Comment: 50 pages, 14 figures, 9 tables; Accepted for publication in the Astrophysical Journa

Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells

The Sp/Kriippel-like factor (Sp/KIf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated basic Kruppel-like factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, erythroid Kruppel-like factor (Eklf/Kif1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf-null murine embryos. We find that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, la, and an erythroid downstream promoter, 1b. Transcripts from the two promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo

A deep X-ray observation of NGC 4258 and its surrounding field

We present a deep X-ray observation of the low-luminosity active galactic nucleus in NGC4258 (M106) using ASCA. The soft X-ray spectrum <2keV is dominated by thermal emission from optically-thin plasma with kT~0.5keV. The hard X-ray emission is clearly due to a power-law component with photon index Gamma=1.8 absorbed by a column density of N_H=8x10^22/cm^2. The power-law is readily identified with primary X-ray emission from the AGN central engine. We also clearly detect a narrow iron K-alpha emission line at 6.4keV. No broad component is detected. We suggest that the bulk of this narrow line comes from the accretion disk and, furthermore, that the power-law X-ray source which excites this line emission (which is typically identified with a disk corona) must be at least 100GM/c^2 in extent. This is in stark contrast to many higher-luminosity Seyfert galaxies which display a broad iron line indicating a small 10 GM/c^2 X-ray emitting region. It must be stressed that this study constrains the size of the X-ray emitting corona rather than the presence/absence of a radiatively efficient accretion disk in the innermost regions. If, instead, a substantial fraction of the observed narrow line originates from material not associated with the accretion disk, limits can be placed on the parameter space of possible allowed relativistically broad iron lines. By comparing our data with previous ASCA observations, we find marginal evidence for a change in absorbing column density through to the central engine, and good evidence for a change in the AGN flux.Comment: 11 pages, 9 postscript figures. Accepted for publication in Ap