Observations of the intracluster medium (ICM) in the outskirts of galaxy clusters reveal shocks associated with gas accretion from the cosmic web. Previous work based on non-radiative cosmological hydrodynamical simulations have defined the shock radius, $r_{\text{shock}}$, using the ICM entropy, $K \propto T/{n_\mathrm{e}}^{2/3}$, where T and $n_{\text{e}}$ are the ICM temperature and electron density, respectively; the $r_{\text{shock}}$ is identified with either the radius at which K is a maximum or at which its logarithmic slope is a minimum. We investigate the relationship between $r_{\text{shock}}$, which is driven by gravitational hydrodynamics and shocks, and the splashback radius, $r_{\text{splash}}$, which is driven by the gravitational dynamics of cluster stars and dark matter and is measured from their mass profile. Using 324 clusters from The Three Hundred project of cosmological galaxy formation simulations, we quantify statistically how $r_{\text{shock}}$ relates to $r_{\text{splash}}$. Depending on our definition, we find that the median $r_{\text{shock}} \simeq 1.38 r_{\text{splash}} (2.58 R_{200})$ when K reaches its maximum and $r_{\text{shock}} \simeq 1.91 r_{\text{splash}} (3.54 R_{200})$ when its logarithmic slope is a minimum; the best-fit linear relation increases as $r_{\text{shock}} \propto 0.65 r_{\text{splash}}$. We find that $r_{\text{shock}}/R_{200}$ and $r_{\text{splash}}/R_{200}$ anti-correlate with virial mass, $M_{200}$, and recent mass accretion history, and $r_{\text{shock}}/r_{\text{splash}}$ tends to be larger for clusters with higher recent accretion rates. We discuss prospects for measuring $r_{\text{shock}}$ observationally and how the relationship between $r_{\text{shock}}$ and $r_{\text{splash}}$ can be used to improve constraints from radio, X-ray, and thermal Sunyaev-Zeldovich surveys that target the interface between the cosmic web and clusters.

We investigate the relationship between a galaxy cluster’s hydrostatic equilibrium state, the entropy profile, K, of the intracluster gas, and the system’s non-thermal pressure (NTP), within an analytic model of cluster structures. When NTP is neglected from the cluster’s hydrostatic state, we find that the gas’ logarithmic entropy slope, $k\equiv \mathrm{d}\ln K/\mathrm{d}\ln r$, converges at large halocentric radius, r, to a value that is systematically higher than the value $k\simeq1.1$ that is found in observations and simulations. By applying a constraint on these ‘pristine equilibrium’ slopes, $k_\mathrm{eq}$, we are able to predict the required NTP that must be introduced into the hydrostatic state of the cluster. We solve for the fraction, $\mathcal{F}\equiv p_\mathrm{nt}/p$, of NTP, $p_\mathrm{nt}$, to total pressure, p, of the cluster, and we find $\mathcal{F}(r)$ to be an increasing function of halocentric radius, r, that can be parameterised by its value in the cluster’s core, $\mathcal{F}_0$, with this prediction able to be fit to the functional form proposed in numerical simulations. The minimum NTP fraction, as the solution with zero NTP in the core, $\mathcal{F}_0=0$, we find to be in excellent agreement with the mean NTP predicted in non-radiative simulations, beyond halocentric radii of $r\gtrsim0.7r_{500}$, and in tension with observational constraints derived at similar radii. For this minimum NTP profile, we predict $\mathcal{F}\simeq0.20$ at $r_{500}$, and $\mathcal{F}\simeq0.34$ at $2r_{500}$; this amount of NTP leads to a hydrostatic bias of $b\simeq0.12$ in the cluster mass $M_{500}$ when measured within $r_{500}$. Our results suggest that the NTP of galaxy clusters contributes a significant amount to their hydrostatic state near the virial radius and must be accounted for when estimating the cluster’s halo mass using hydrostatic equilibrium approaches.

We investigate the connection between a cluster’s structural configuration and observable measures of its gas emission that can be obtained in X-ray and Sunyaev–Zeldovich (SZ) surveys. We present an analytic model for the intracluster gas density profile: parameterised by the dark matter halo’s inner logarithmic density slope, $\alpha$, the concentration, c, the gas profile’s inner logarithmic density slope, $\varepsilon$, the dilution, d, and the gas fraction, $\eta$, normalised to cosmological content. We predict four probes of the gas emission: the emission-weighted, $T_\mathrm{X}$, and mean gas mass-weighted, $T_\mathrm{m_g}$, temperatures, and the spherically, $Y_\mathrm{sph}$, and cylindrically, $Y_\mathrm{cyl}$, integrated Compton parameters. Over a parameter space of clusters, we constrain the X-ray temperature scaling relations, $M_{200} - T_\mathrm{X}$ and $M_{500} - T_\mathrm{X}$, within $57.3\%$ and $41.6\%$, and $M_{200} - T_\mathrm{m_g}$ and $M_{500} - T_\mathrm{m_g}$, within $25.7\%$ and $7.0\%$, all respectively. When excising the cluster’s core, the $M_{200} - T_\mathrm{X}$ and $M_{500} - T_\mathrm{X}$ relations are further constrained, to within $31.3\%$ and $17.1\%$, respectively. Similarly, we constrain the SZ scaling relations, $M_{200} - Y_\mathrm{sph}$ and $M_{500} - Y_\mathrm{sph}$, within $31.1\%$ and $17.7\%$, and $M_{200} - Y_\mathrm{cyl}$ and $M_{500} - Y_\mathrm{cyl}$, within $25.2\%$ and $22.0\%$, all respectively. The temperature observable $T_\mathrm{m_g}$ places the strongest constraint on the halo mass, whilst $T_\mathrm{X}$ is more sensitive to the parameter space. The SZ constraints are sensitive to the gas fraction, whilst insensitive to the form of the gas profile itself. In all cases, the halo mass is recovered with an uncertainty that suggests the cluster’s structural profiles only contribute a minor uncertainty in its scaling relations.

Operational Risk is one of the most difficult risks to model. It is a large and diverse category covering anything from cyber losses to mis-selling fines; and from processing errors to HR issues. Data is usually lacking, particularly for low frequency, high impact losses, and consequently there can be a heavy reliance on expert judgement. This paper seeks to help actuaries and other risk professionals tasked with the challenge of validating models of operational risks. It covers the loss distribution and scenario-based approaches most commonly used to model operational risks, as well as Bayesian Networks. It aims to give a comprehensive yet practical guide to how one may validate each of these and provide assurance that the model is appropriate for a firm’s operational risk profile.

OBJECTIVES/GOALS: Current COVID-19 rapid molecular tests require cartridge-reader detection, expensive circuitry, and complex microfluidics making the most accurate tests unavailable to the masses. Here we present a rapid molecular diagnostic leveraging isothermal amplification and paper-based microfluidics for a low-cost ultra-sensitive COVID-19 assay. METHODS/STUDY POPULATION: We designed a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of SARS-CoV-2 and bacteriophage MS2 RNA. RT-RPA is a sequence specific, ultrasensitive, rapid isothermal DNA amplification technique that is well suited to home based testing due to its rapid assay time, robustness, ease of use, and readout options. RT-RPA reagents are added to a tube and incubated at 39°C in a fluorometer. Realtime fluorometer data gives results in under 15 minutes. This assay also provides visual detection via lateral flow readout with results in 23 minutes. RESULTS/ANTICIPATED RESULTS: We have developed a rapid multiplexed nucleic acid amplification assay with an internal process control for SARS-CoV-2 using single-pot RT-RPA. We screened 21 primer combinations to select primers that demonstrated excellent performance and target specificity against common respiratory viruses. We demonstrate the ability to multiplex SARS-CoV-2 and MS2 detection, utilizing MS2 as an internal process control for lysis, reverse transcription, amplification, and readout. We show duplexed detection using both fluorescence readout and visual readout using lateral flow strips. Duplexed fluorescence detection shows a limit of detection of 25 copies per reaction. Duplexed lateral flow readout shows a limit of detection of 50 copies per reaction DISCUSSION/SIGNIFICANCE: We developed a duplexed RT-RPA assay for SARS-CoV-2 with fluorescence or lateral flow readout. Our assay does not re-quire expensive reader, circuity, or fluid handling. The low material cost, temperature, and robustness make it ideal for a more accurate home-based COVID-19 diagnostic.

Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.

The mainstream commercialization of colloidal quantum dots (QDs) for light-emitting applications has begun: Sony televisions emitting QD-enhanced colors are now on sale. The bright and uniquely size-tunable colors of solution-processable semiconducting QDs highlight the potential of electroluminescent QD light-emitting devices (QLEDs) for use in energy-efficient, high-color-quality thin-film display and solid-state lighting applications. Indeed, this year’s report of record-efficiency electrically driven QLEDs rivaling the most efficient molecular organic LEDs, together with the emergence of full-color QLED displays, foreshadow QD technologies that will transcend the optically excited QD-enhanced products already available. In this article, we discuss the key advantages of using QDs as luminophores in LEDs and outline the 19-year evolution of four types of QLEDs that have seen efficiencies rise from less than 0.01% to 18%. With an emphasis on the latest advances, we identify the key scientific and technological challenges facing the commercialization of QLEDs. A quantitative analysis, based on published small-scale synthetic procedures, allows us to estimate the material costs of QDs typical in light-emitting applications when produced in large quantities and to assess their commercial viability.

The aim of this study was to investigate familial influences and their dependence on sex for panic disorder and/or agoraphobia, social phobia, generalized anxiety disorder and major depression. Data from Australian (N = 2287) and Dutch (N = 1185) twins and siblings who were selected for a linkage study and participated in clinical interviews to obtain lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnoses were used. In a liability model, tetrachoric correlations were estimated in sibling pairs and sex differences between sibling correlations were tested. For each diagnosis, the sibling correlations could be constrained to be equal across the Australian and Dutch samples. With the exception of panic disorder and/or agoraphobia, all sibling correlations were the same for brother, sister and opposite-sex sibling pairs and were around .20. For panic disorder and/or agoraphobia, the correlation was .23 in brother and sister pairs, but absent in opposite-sex sibling pairs. From these results it can be concluded that upper heritability estimates, based on twice the correlations in the sibling pairs, vary between 36% (major depression) and 50% (social phobia). Furthermore, different genetic risk factors appear to contribute to the vulnerability for panic disorder and/or agoraphobia in men and women. No other sex differences were found.

People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this dimension of personality can therefore give insights into the etiology of important psychiatric disorders. Neuroticism can be assessed easily via self-report questionnaires in large population samples. We have examined the genetic and phenotypic stability of neuroticism, measured up to 4 times over 22 years, on different scales, on a data set of 4999 families with over 20,000 individuals completing at least 1 neuroticism questionnaire. The neuroticism scales used were the Eysenck Personality Questionnaire revised (EPQ-R), the EPQ-R shortened form, and the NEO 5 factor inventory personality questionnaire. The estimates of heritability of the individual measures ranged from .26 ± .04 to .36 ± .03. Genetic, environmental, and phenotypic correlations averaged .91, .42, and .57 respectively. Despite the range in heritabilities, a more parsimonious ‘repeatability model’ of equal additive genetic variances and genetic correlations of unity could not be rejected. Use of multiple measures increases the effective heritability from .33 for a single measure to .43 for mean score because of the reduction in the estimate of the environmental variance, and this will increase power in genetic linkage or association studies of neuroticism.

The Cosmic Infrared Background ExpeRiment (CIBER) is a rocket-borne absolute photometry imaging and spectroscopy experiment optimized to detect signatures of first-light galaxies present during reionization in the unresolved IR background. CIBER-I consists of a wide-field two-color camera for fluctuation measurements, a low-resolution absolute spectrometer for absolute EBL measurements, and a narrow-band imaging spectrometer to measure and correct scattered emission from the foreground zodiacal cloud. CIBER-I was successfully flown in February 2009 and July 2010 and four more flights are planned by 2014, including an upgrade (CIBER-II). We propose, after several additional flights of CIBER-I, an improved CIBER-II camera consisting of a wide-field 30 cm imager operating in 4 bands between 0.5 and 2.1 microns. It is designed for a high significance detection of unresolved IR background fluctuations at the minimum level necessary for reionization. With a FOV 50 to 2000 times larger than existing IR instruments on satellites, CIBER-II will carry out the definitive study to establish the surface density of sources responsible for reionization.

The effect of the dietary n-3 long-chain PUFA, DHA (22 : 6n-3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2–0·3 % DHA) in a randomised controlled trial. Infants born < 33 weeks gestation (n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g). The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids. The intervention was from day 2 to 5 of life until the infant's expected date of delivery (EDD). Growth was assessed at EDD, and at 4, 12 and 18 months corrected age. There was no effect of higher DHA on weight or head circumference at any age, but infants fed higher DHA were 0·7 cm (95 % CI 0·1, 1·4 cm; P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight (P = 0·01) and length (P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.