Do State Laws Affect the Age of Marriage? A Cautionary Tale About Avoidance Behavior

This paper investigates the response of young people in the United States to state laws dictating the minimum age at which individuals could marry, with and without parental consent. We use variation across states and over time to document behavioral responses to laws governing the age of marriage using both administrative records from the Vital Statistics and retrospective reports from the U.S. Census. We find evidence that state laws delayed the marriages of some young people, but the effects are much smaller in Census data than in Vital Statistics records. This discrepancy appears to be driven by systematic avoidance behavior of two kinds. First, some young people marry outside their state of residence, in states with less restrictive laws. Second, many young people appear to have evaded minimum age of marriage laws by misrepresenting age on their marriage certificate. This avoidance was especially pronounced in earlier years, when few states required documented proof of age and when there was greater gain to marrying out of state because of wider variation in laws. Our results have important implications about the quality of administrative data when it is poorly monitored; about the effect of laws when agents can avoid them; and about the validly of estimates using cross-state variation in laws as an instrumental variable. By contrasting two data sources, we achieve a more complete picture of behavioral response than would be possible with either one alone.

Biofilm-specific extracellular matrix proteins of nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi), a human respiratory tract pathogen, can form colony biofilms in vitro. Bacterial cells and the amorphous extracellular matrix (ECM) constituting the biofilm can be separated using sonication. The ECM from 24- and 96-h NTHi biofilms contained polysaccharides and proteinaceous components as detected by nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) spectroscopy. More conventional chemical assays on the biofilm ECM confirmed the presence of these components and also DNA. Proteomics revealed eighteen proteins present in biofilm ECM that were not detected in planktonic bacteria. One ECM protein was unique to 24-h biofilms, two were found only in 96-h biofilms, and fifteen were present in the ECM of both 24- and 96-h NTHi biofilms. All proteins identified were either associated with bacterial membranes or cytoplasmic proteins. Immunocytochemistry showed two of the identified proteins, a DNA-directed RNA polymerase and the outer membrane protein OMP P2, associated with bacteria and biofilm ECM. Identification of biofilm-specific proteins present in immature biofilms is an important step in understanding the in vitro process of NTHi biofilm formation. The presence of a cytoplasmic protein and a membrane protein in the biofilm ECM of immature NTHi biofilms suggests that bacterial cell lysis may be a feature of early biofilm formation

Quantitative Mapping of Pore Fraction Variations in Silicon Nitride Using an Ultrasonic Contact Scan Technique

An ultrasonic scan procedure using the pulse-echo contact configuration was employed to obtain maps of pore fraction variations in sintered silicon nitride samples in terms of ultrasonic material properties. Ultrasonic velocity, attenuation coefficient, and reflection coefficient images were obtained simultaneously over a broad band of frequencies (e.g., 30 to 110 MHz) by using spectroscopic analysis. Liquid and membrane (dry) coupling techniques and longitudinal and shear-wave energies were used. The major results include the following: Ultrasonic velocity (longitudinal and shear wave) images revealed and correlated with the extent of average through-thickness pore fraction variations in the silicon nitride disks. Attenuation coefficient images revealed pore fraction nonuniformity due to the scattering that occurred at boundaries between regions of high and low pore fraction. Velocity and attenuation coefficient images were each nearly identical for machined and polished disks, making the method readily applicable to machined materials. Velocity images were similar for wet and membrane coupling. Maps of apparent Poisson's ratio constructed from longitudinal and shear-wave velocities quantified Poisson's ratio variations across a silicon nitride disk. Thermal wave images of a disk indicated transient thermal behavior variations that correlated with observed variations in pore fraction and velocity and attenuation coefficients

Genome wide association mapping in <i>Arabidopsis thaliana</i> identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense

A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis

Natural genetic variation in <i>Arabidopsis thaliana</i> defense metabolism genes modulates field fitness

Natural populations persist in complex environments, where biotic stressors, such as pathogen and insect communities, fluctuate temporally and spatially. These shifting biotic pressures generate heterogeneous selective forces that can maintain standing natural variation within a species. To directly test if genes containing causal variation for the Arabidopsis thaliana defensive compounds, glucosinolates (GSL) control field fitness and are therefore subject to natural selection, we conducted a multi-year field trial using lines that vary in only specific causal genes. Interestingly, we found that variation in these naturally polymorphic GSL genes affected fitness in each of our environments but the pattern fluctuated such that highly fit genotypes in one trial displayed lower fitness in another and that no GSL genotype or genotypes consistently out-performed the others. This was true both across locations and within the same location across years. These results indicate that environmental heterogeneity may contribute to the maintenance of GSL variation observed within Arabidopsis thaliana. DOI: http://dx.doi.org/10.7554/eLife.05604.00

3 dimensional modelling of early human brain development using optical projection tomography

BACKGROUND: As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped. RESULTS: Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (~300 μm by ~150 μm) to the rootlets of cranial nerve XII (~20 μm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is ~30 μm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated. CONCLUSION: In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of ~20 μm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development

Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population

ABSTRACT Objective: To evaluate the effectiveness of a selective serotonin reuptake inhibitor (SSRI) (sertraline) in decreasing hot flashes in a general population of women. Design: A double-blind, placebo-controlled, crossover trial was conducted in a southwestern urban setting. A total of 102 women aged 40 to 65 who were experiencing hot flashes and not taking any hormone therapy were recruited. After 1 week of baseline hot flash data collection, study participants were randomized to receive placebo or active drug (sertraline 50 mg) for 4 weeks. This intervention was followed by a 1-week washout and cross over to the opposite treatment for 4 weeks. The number and severity of hot flashes were measured. Results: One hundred two women were enrolled in the study. Five dropped out before providing baseline data. Of the 97 remaining, 52 were randomized to active drug first and 45 to placebo first. Ten dropped out of the study before completing all 10 weeks, leaving 46 in the active drug-first arm and 41 in the placebo-first arm. At baseline, the mean number of hot flashes reported was 45.6 per week (SD = 29.6), ranging from 2 to 148. During the sertraline phase of the study, women experienced five fewer hot flashes per week than they did on the placebo (P = 0.002). The severity of hot flashes was not significantly different; however, the hot flash score (number  average severity) was significantly improved during the sertraline phase. Conclusion: Sertraline reduced the number of hot flashes and improved the hot flash score relative to placebo and may be an acceptable alternative treatment for women experiencing hot flashes

Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD

This study forms part of the first complete characterization of the dose-response curve for glycopyrrolate (GP) delivered using Co-Suspension™ Delivery Technology via a metered dose inhaler (MDI). We examined the lower GP MDI dose range to determine an optimal dose for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD)

Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti-inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

During pathological pain, the actions of the endocannabinoid system, including the cannabinoid 2 receptor (CB2R), leads to effective anti-allodynia and modifies a variety of spinal microglial and astrocyte responses. Here, following spinal administration of the CB2R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen-activated protein kinase, interleukin-1β (IL-1β), the anti-inflammatory cytokine, interleukin-10 (IL-10) as well as degradative endocannabinoid enzymes, and markers for altered glial responses in neuropathic rats. In these studies, the dorsal horn of the spinal cord and dorsal root ganglia were examined. AM1241 produced profound anti-allodynia with corresponding immunoreactive levels of p38 mitogen-activated kinase, IL-1β, IL-10, the endocannabinoid enzyme monoacylglycerol lipase, and astrocyte activation markers that were similar to nonneuropathic controls. In contrast, spinal AM1241 did not suppress the increased microglial responses observed in neuropathic rats. The differences in fluorescent markers were determined within discrete anatomical regions by applying spectral analysis methods, which virtually eliminated nonspecific signal during the quantification of specific immunofluorescent intensity. These data reveal expression profiles that support the actions of intrathecal AM1241 control pathological pain through anti-inflammatory mechanisms by modulating critical glial factors, and additionally decrease expression levels of endocannabinoid degradative enzymes