Standard item response theory (IRT) models fit to dichotomous examination responses ignore the fact that sets of items (testlets) often come from a single common stimuli (e.g. a reading comprehension passage). In this setting, all items given to an examinee are unlikely to be conditionally independent (given examinee proficiency). Models that assume conditional independence will overestimate the precision with which examinee proficiency is measured. Overstatement of precision may lead to inaccurate inferences such as prematurely ending an examination in which the stopping rule is based on the estimated standard error of examinee proficiency (e.g., an adaptive test). To model examinations that may be a mixture of independent items and testlets, we modified one standard IRT model to include an additional random effect for items nested within the same testlet. We use a Bayesian framework to facilitate posterior inference via a Data Augmented Gibbs Sampler (DAGS; Tanner & Wong, 1987). The modified and standard IRT models are both applied to a data set from a disclosed form of the SAT. We also provide simulation results that indicates that the degree of precision bias is a function of the variability of the testlet effects, as well as the testlet design.

Disordered eating (DE) is associated with elevated cardiometabolic risk (CMR) factors, yet little is known about this association in non-Western countries. We examined the association between DE characteristics and CMR and tested the potential mediating role of BMI. This cross-sectional study included 2005 Chinese women (aged 18–50 years) from the 2015 China Health and Nutrition Survey. Loss of control, restraint, shape concern and weight concern were assessed using selected questions from the SCOFF questionnaire and the Eating Disorder Examination-Questionnaire. Eight CMR were measured by trained staff. Generalised linear models examined associations between DE characteristics with CMR accounting for dependencies between individuals in the same household. We tested whether BMI potentially mediated significant associations using structural equation modelling. Shape concern was associated with systolic blood pressure (β (95 % CI) 0·06 (0·01, 0·10)), diastolic blood pressure (DBP) (0·07 (95 % CI 0·03, 0·11)) and high-density lipoprotein (HDL)-cholesterol (–0·08 (95 % CI –0·12, −0·04)). Weight concern was associated with DBP (0·06 (95 % CI 0·02, 0·10)), triglyceride (0·06 (95 % CI 0·02, 0·10)) and HDL-cholesterol (–0·10 (95 % CI –0·14, −0·07)). Higher scores on DE characteristics were associated with higher BMI, and higher BMI was further associated with lower HDL-cholesterol and higher other CMR. In summary, we observed significant associations between shape and weight concerns with some CMR in Chinese women, and these associations were potentially partially mediated by BMI. Our findings suggest that prevention and intervention strategies focusing on addressing DE could potentially help reduce the burden of CMR in China, possibly through controlling BMI.

Presented is a novel way to combine snapshot compressive imaging and lateral shearing interferometry in order to capture the spatio-spectral phase of an ultrashort laser pulse in a single shot. A deep unrolling algorithm is utilized for snapshot compressive imaging reconstruction due to its parameter efficiency and superior speed relative to other methods, potentially allowing for online reconstruction. The algorithm’s regularization term is represented using a neural network with 3D convolutional layers to exploit the spatio-spectral correlations that exist in laser wavefronts. Compressed sensing is not typically applied to modulated signals, but we demonstrate its success here. Furthermore, we train a neural network to predict the wavefronts from a lateral shearing interferogram in terms of Zernike polynomials, which again increases the speed of our technique without sacrificing fidelity. This method is supported with simulation-based results. While applied to the example of lateral shearing interferometry, the methods presented here are generally applicable to a wide range of signals, including Shack–Hartmann-type sensors. The results may be of interest beyond the context of laser wavefront characterization, including within quantitative phase imaging.

ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.

ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

In this paper, the lateral migration of a neutrally buoyant spherical particle in the pressure-driven rectangular channel flow of an Oldroyd-B fluid is numerically investigated with a fictitious domain method. The aspect ratio of the channel cross-section considered is 1 and 2, respectively. The particle lateral motion trajectories are shown for the bulk Reynolds number ranging from 1 to 100, the ratio of the solvent viscosity to the total viscosity being 0.5, and a Weissenberg number up to 1.5. Our results indicate that the lateral equilibrium positions located on the cross-section midline, diagonal line, corner and channel centreline occur successively as the fluid elasticity is increased, for particle migration in square channel flow with finite fluid inertia. The transition of the equilibrium position depends strongly on the elasticity number (the ratio of the Weissenberg number to the Reynolds number) and weakly on the Reynolds number. The diagonal-line equilibrium position occurs at an elasticity number ranging from roughly 0.001 to 0.02, and can coexist with the midline and corner equilibrium positions. When the fluid inertia is negligibly small, particles migrate towards the channel centreline, or the closest corner, depending on their initial positions and the Weissenberg number, and the corner attractive area first increases and then decreases as the Weissenberg number increases. For particle migration in a rectangular channel with an aspect ratio of 2, the transition of the equilibrium position from the midline, ‘diagonal line’ (the line where two lateral shear rates are equal to each other), off-centre long midline and channel centreline takes place as the Weissenberg number increases at moderate Reynolds numbers. An off-centre equilibrium position on the long midline is observed for a large blockage ratio of 0.3 (i.e. the ratio of the particle diameter to the channel height is 0.3) at a low Reynolds number. This off-centre migration is driven by shear forces, unlike the elasticity-induced rapid inward migration, which is driven by the normal force (pressure or first normal stress difference).

Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.

During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.

Insulating silicon dioxide (SiO2) films can be produced by hydrolysis of metal alkoxide tetraethylorthosilicate (TEOS) in the presence of an acid catalyst in supercritical fluid CO2 (sc-CO2). In this study, SiO2 films are formed on different substrates using TEOS as a source of silicon, and acetic acid (HAc) as a catalyst. Water required for the hydrolysis reaction is from in situ generation of esterification and condensation reactions involving HAc and the alcohol produced. The acid catalyzed deposition reaction actually starts at room temperature but produces decent films in sc-CO2 at moderately high temperatures (e.g. 50 °C). Supercritical fluid CO2 is known to have near zero surface tension and provides an ideal medium for fabrication of SiO2 films. Formation of SiO2 films via hydrolysis reaction in sc-CO2 is more rapid compared to the traditional hydrolysis reaction at room temperature. In general, metal alkoxide hydrolysis reactions carried out in a closed sc-CO2 system is not affected by moisture in air compared with traditional open-air hydrolysis systems. Using sc-CO2 as a reaction medium can eliminate undesirable organic solvents utilized in traditional alkoxide hydrolysis reactions.

X-ray diffraction (XRD) and electron diffraction (ED) measurements demonstrated that the SiO2 films produced are amorphous. Energy dispersive spectroscopy (EDS), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopy show elemental compositions of the films formed on the substrate surfaces to be SiO2. Film thickness formation by controlling the amount of the catalyst is discussed.

We use Raman scattering to study the spatially-resolved strain and stress in a complex zinc blende GaAs/GaP heterostructured nanowire which contains both axial and radial interfaces. The nanowires are grown by metal-organic chemical vapor deposition in the [111] direction with Au nano particles as catalysts, High spatial resolution Raman scans along the nanowires show the GaAs/GaP interface is clearly identifiable. We interpret the phonon energy shifts in each material as one approaches the interface.

Objective: To study when and how an urgent public health message about a boil-water order reached an urban population after the Massachusetts water main break.

Methods: In-person surveys were conducted in waiting areas of clinics and emergency departments at a large urban safety net hospital within 1 week of the event.

Results: Of 533 respondents, 97% were aware of the order; 34% of those who lived in affected cities or towns were potentially exposed to contaminated water. Among those who were aware, 98% took action. Respondents first received the message through word of mouth (33%), television (25%), cellular telephone calls (20%), landline calls (10%), and other modes of communication (12%). In multivariate analyses, foreign-born respondents and those who lived outside the city of Boston had a higher risk of exposure to contaminated water. New modes (eg, cellular telephones) were used more commonly by females and younger individuals (ages 18 to 34). Individuals who did not speak English at home were more likely to receive the message through their personal networks.

Conclusions: Given the increasing prevalence of cellular telephone use, public officials should encourage residents to register landline and cellular telephone for emergency alerts and must develop creative ways to reach immigrants and non–English-speaking groups quickly via personal networks.

(Disaster Med Public Health Preparedness. 2011;5:235–241)

Context: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. Objective: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Design, Setting, and Participants: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12–26; N = 2,128). Main Outcome Measures: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. Results: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Conclusions: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.

Molecular dynamic simulations of helium atoms escaping from a helium-filled nanobubble near the surface of crystalline palladium reveal unexpected behavior. Significant deformation and cracking near the helium bubble occur initially, and then a channel forms between the bubble and the surface, providing a pathway for helium atoms to propagate toward the surface. The helium atoms erupt from the bubble in an instantaneous and volcano-like process, which leads to surface deformation consisting of cavity formation on the surface, along with modification and atomic rearrangement at the periphery of the cavity. The present simulation results show that, near the palladium surface, there is a helium-bubble-free zone, or denuded zone, with a typical thickness of about 3.0 nm. Combined with experimental measurements and continuum-scale evolutionary model predictions, the present atomic simulations demonstrate that the thickness of the denuded zone, which contains a low concentration of helium atoms, is somewhat larger than the diameter of the helium bubbles in the metal tritide. Furthermore, a relationship between the tensile strength and thickness of metal film is also determined.

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer’s disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype. (JINS, 2010, 16, 278–286.)

Three Harwich P sublines with different P-element activity potential were used to investigate the influence of P-derived chromosomes on snω mutability and vg suppression and to relate the induction of these dysgenic traits to the number and structure of P elements. Destabilization of the snω allele, a measure of P transposase activity, was differentially influenced by the major autosomes. Chromosome 2 of the standard Harwich subline, Hw, induced only 60% of the level of mutability relative to chromosome 3, whereas chromosome 3 of the weakest Harwich subline, Hf, induced only 50% of the mutability relative to chromosome 2. In somatic suppression of the vg21–3 allele, chromosome 3 of the Hf subline produced a lower level of complete suppression as compared to chromosome 3 of the Hw or the Hs subline (the high hybrid-dysgenesis-inducing subline). The level of these dysgenic traits and GD sterility, was not correlated with the number of P elements per individual (67–68) or per chromosome arm which was very similar among the sublines. The number of complete P elements per genome, based on Southern blot analysis of the X and major autosomes, ranged from 15 to 19. Destabilization of the snω allele and vg suppression by chromosome 3 was correlated with a greater number of complete P elements. Two novel unexpected observations emerged from these studies: both snω mutability and vg suppression data demonstrated high P-element activity in hybrids derived from non-dysgenic crosses irrespective of Harwich subline, indicating a lack of P-cytotype regulation. Mutability in non-dysgenic males ranged from 40 to 60% of the level found in dysgenic males. The high snω mutability and low GD sterility in non-dysgenic hybrids suggests that these traits may arise by a different mechanism.