Multiple imputation in data that grow over time:A comparison of three strategies

Multiple imputation is a recommended technique to deal with missing data. We study the problem where the investigator has already created imputations before the arrival of the next wave of data. The newly arriving data contain missing values that need to be imputed. The standard method (RE-IMPUTE) is to combine the new and old data before imputation, and re-impute all missing values in the combined data. We study the properties of two methods that impute the missing data in the new part only, thus preserving the historic imputations. Method NEST multiply imputes the new data conditional on each filled-in old data (Formula presented.) times. Method APPEND is the special case of NEST with (Formula presented.) thus appending each filled-in data by single imputation. We found that NEST and APPEND have the same validity as RE-IMPUTE for monotone missing data-patterns. NEST and APPEND also work well when relations within waves are stronger than between waves and for moderate percentages of missing data. We do not recommend the use of NEST or APPEND when relations within time points are weak and when associations between time points are strong

Multiple imputation in data that grow over time:A comparison of three strategies

Multiple imputation is a highly recommended technique to deal with missing data, but the application to longitudinal datasets can be done in multiple ways. When a new wave of longitudinal data arrives, we can treat the combined data of multiple waves as a new missing data problem and overwrite existing imputations with new values (re-imputation). Alternatively, we may keep the existing imputations, and impute only the new data. We may do either a full multiple imputation (nested) or a single imputation (appended) on the new data per imputed set. This study compares these three strategies by means of simulation. All techniques resulted in valid inference under a monotone missingness pattern. A non-monotone missingness pattern led to biased and non-confidence valid regression coefficients after nested and appended imputation, depending on the correlation structure of the data. Correlations within timepoints must be stronger than correlations between timepoints to obtain valid inference. In an empirical example, the three strategies performed similarly.We conclude that appended imputation is especially beneficial in longitudinal datasets that suffer from dropout

The Efficiency of Globular Cluster Formation

(Abridged): The total populations of globular cluster systems (GCSs) are discussed in terms of their connection to the efficiency of globular cluster formation---the mass fraction of star-forming gas that was able to form bound stellar clusters rather than isolated stars or unbound associations---in galaxy halos. Observed variations in GCS specific frequencies (S_N=N_gc/L_gal), both as a function of galactocentric radius in individual systems and globally between entire galaxies, are reviewed in this light. It is argued that trends in S_N do not reflect any real variation in the underlying efficiency of cluster formation; rather, they result from ignoring the hot gas in many large ellipticals. This claim is checked and confirmed in each of M87, M49, and NGC 1399, for which existing data are combined to show that the volume density profile of globular clusters, rho_cl, is directly proportional to the sum of (rho_gas+rho_stars) at large radii. The constant of proportionality is the same in each case: epsilon=0.0026 +/- 0.0005 in the mean. This is identified with the globular cluster formation efficiency. The implication that epsilon might have had a universal value is supported by data on the GCSs of 97 early-type galaxies, on the GCS of the Milky Way, and on the ongoing formation of open clusters. These results have specific implications for some issues in GCS and galaxy formation, and they should serve as a strong constraint on more general theories of star and cluster formation.Comment: 36 pages with 11 figures; accepted for publication in The Astronomical Journa

Vasopressors and Inotropes in the Treatment of Human Septic Shock: Effect on Innate Immunity?

Catecholamines have been suggested to modulate innate immune responses in experimental settings. The significance hereof in the treatment of human septic shock is unknown. We therefore sought if and how vasopressor/inotropic doses relate to pro-inflammatory mediators during treatment of septic shock. We prospectively studied 20 consecutive septic shock patients. For 3 days after admission, hemodynamic variables, lactate and plasma levels of interleukins (IL)-6 and 8, tumor necrosis factor (TNF)-α, and elastase-α1-antitrypsin were measured six hourly. Doses of vasoactive drugs were recorded. Of the 20 patients, nine died in the intensive care unit. Dobutamine doses were positively associated and related to TNF-α plasma levels, independently of disease severity, hemodynamics, and outcome, in multivariable models. Dopamine doses were positively associated with IL-6, and norepinephrine was inversely associated with IL-8 and TNF-α levels. Our observations suggest that catecholamines used in the treatment of human septic shock differ in their potential modulation of the innate immune response to sepsis in vivo. Dobutamine treatment may contribute to circulating TNF-α and dopamine to IL-6, independently of activated neutrophils. Conversely, norepinephrine may lack pro-inflammatory actions

A Search for sub-km KBOs with the Method of Serendipitous Stellar Occultations

The results of a search for sub-km Kuiper Belt Objects (KBOs) with the method of serendipitous stellar occultations are reported. Photometric time series were obtained on the 1.8m telescope at the Dominion Astrophysical Observatory (DAO) in Victoria, BC, and were analyzed for the presence of occultation events. Observations were performed at 40 Hz and included a total of 5.0 star-hours for target stars in the ecliptic open cluster M35 (beta=0.9deg), and 2.1 star-hours for control stars in the off-ecliptic open cluster M34 (beta=25.7deg). To evaluate the recovery fraction of the analysis method, and thereby determine the limiting detectable size, artificial occultation events were added to simulated time series (1/f scintillation-like power-spectra), and to the real data. No viable candidate occultation events were detected. This limits the cumulative surface density of KBOs to 3.5e10 deg^{-2} (95% confidence) for KBOs brighter than m_R=35.3 (larger than ~860m in diameter, assuming a geometric albedo of 0.04 and a distance of 40 AU). An evaluation of TNO occultations reported in the literature suggests that they are unlikely to be genuine, and an overall 95%-confidence upper limit on the surface density of 2.8e9 deg^{-2} is obtained for KBOs brighter than m_R=35 (larger than ~1 km in diameter, assuming a geometric albedo of 0.04 and a distance of 40 AU) when all existing surveys are combined.Comment: Accepted for publication in A

Globular cluster luminosity function as distance indicator

Globular clusters are among the first objects used to establish the distance scale of the Universe. In the 1970-ies it has been recognized that the differential magnitude distribution of old globular clusters is very similar in different galaxies presenting a peak at M_V ~ -7.5. This peak magnitude of the so-called Globular Cluster Luminosity Function has been then established as a secondary distance indicator. The intrinsic accuracy of the method has been estimated to be of the order of ~0.2 mag, competitive with other distance determination methods. Lately the study of the Globular Cluster Systems has been used more as a tool for galaxy formation and evolution, and less so for distance determinations. Nevertheless, the collection of homogeneous and large datasets with the ACS on board HST presented new insights on the usefulness of the Globular Cluster Luminosity Function as distance indicator. I discuss here recent results based on observational and theoretical studies, which show that this distance indicator depends on complex physics of the cluster formation and dynamical evolution, and thus can have dependencies on Hubble type, environment and dynamical history of the host galaxy. While the corrections are often relatively small, they can amount to important systematic differences that make the Globular Cluster Luminosity Function a less accurate distance indicator with respect to some other standard candles.Comment: Accepted for publication in Astrophysics and Space Science. Review paper based on the invited talk at the conference "The Fundamental Cosmic Distance Scale: State of the Art and Gaia Perspective", Naples, May 2011. (13 pages, 8 figures

Ovine Fetal Thymus Response to Lipopolysaccharide-Induced Chorioamnionitis and Antenatal Corticosteroids

RATIONALE: Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development. METHODS: Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term = 150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated. RESULTS: Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes. CONCLUSION: Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus

The expansion field: The value of H_0

Any calibration of the present value of the Hubble constant requires recession velocities and distances of galaxies. While the conversion of observed velocities into true recession velocities has only a small effect on the result, the derivation of unbiased distances which rest on a solid zero point and cover a useful range of about 4-30 Mpc is crucial. A list of 279 such galaxy distances within v<2000 km/s is given which are derived from the tip of the red-giant branch (TRGB), from Cepheids, and from supernovae of type Ia (SNe Ia). Their random errors are not more than 0.15 mag as shown by intercomparison. They trace a linear expansion field within narrow margins from v=250 to at least 2000 km/s. Additional 62 distant SNe Ia confirm the linearity to at least 20,000 km/s. The dispersion about the Hubble line is dominated by random peculiar velocities, amounting locally to <100 km/s but increasing outwards. Due to the linearity of the expansion field the Hubble constant H_0 can be found at any distance >4.5 Mpc. RR Lyr star-calibrated TRGB distances of 78 galaxies above this limit give H_0=63.0+/-1.6 at an effective distance of 6 Mpc. They compensate the effect of peculiar motions by their large number. Support for this result comes from 28 independently calibrated Cepheids that give H_0=63.4+/-1.7 at 15 Mpc. This agrees also with the large-scale value of H_0=61.2+/-0.5 from the distant, Cepheid-calibrated SNe Ia. A mean value of H_0=62.3+/-1.3 is adopted. Because the value depends on two independent zero points of the distance scale its systematic error is estimated to be 6%. Typical errors of H_0 come from the use of a universal, yet unjustified P-L relation of Cepheids, the neglect of selection bias in magnitude-limited samples, or they are inherent to the adopted models.Comment: 44 pages, 4 figures, 6 tables, accepted for publication in the Astronony and Astrophysics Review 15