JointAI: Joint Analysis and Imputation of Incomplete Data in R

Missing data occur in many types of studies and typically complicate the analysis. Multiple imputation, either using joint modelling or the more flexible fully conditional specification approach, are popular and work well in standard settings. In settings involving non-linear associations or interactions, however, incompatibility of the imputation model with the analysis model is an issue often resulting in bias. Similarly, complex outcomes such as longitudinal or survival outcomes cannot be adequately handled by standard implementations. In this paper, we introduce the R package JointAI, which utilizes the Bayesian framework to perform simultaneous analysis and imputation in regression models with incomplete covariates. Using a fully Bayesian joint modelling approach it overcomes the issue of uncongeniality while retaining the attractive flexibility of fully conditional specification multiple imputation by specifying the joint distribution of analysis and imputation models as a sequence of univariate models that can be adapted to the type of variable. JointAI provides functions for Bayesian inference with generalized linear and generalized linear mixed models and extensions thereof as well as survival models and joint models for longitudinal and survival data, that take arguments analogous to corresponding well known functions for the analysis of complete data from base R and other packages. Usage and features of JointAI are described and illustrated using various examples and the theoretical background is outlined.Comment: imputation, Bayesian, missing covariates, non-linear, interaction, multi-level, survival, joint model R, JAG

Carbon-poor stellar cores as supernova progenitors

Exploring stellar models which ignite carbon off-center (in the mass range of about 1.05 - 1.25 Msun, depending on the carbon mass fraction) we find that they may present an interesting SN I progenitor scenario, since whereas in the standard scenario runaway always takes place at the same density of about 2 X 10^9 gr/cm^3, in our case, due to the small amount of carbon ignited, we get a whole range of densities from 1 X 10^9 up to 6 X 10^9 gr/cm^3. These results could contribute in resolving the emerging recognition that at least some diversity among SNe I exists, since runaway at various central densities is expected to yield various outcomes in terms of the velocities and composition of the ejecta, which should be modeled and compared to observations.Comment: 49 pages, 20 figure

Summarising salient information on historical controls: A structured assessment of validity and comparability across studies

BACKGROUND: While placebo-controlled randomised controlled trials remain the standard way to evaluate drugs for efficacy, historical data are used extensively across the development cycle. This ranges from supplementing contemporary data to increase the power of trials to cross-trial comparisons in estimating comparative efficacy. In many cases, these approaches are performed without in-depth review of the context of data, which may lead to bias and incorrect conclusions. METHODS: We discuss the original 'Pocock' criteria for the use of historical data and how the use of historical data has evolved over time. Based on these factors and personal experience, we created a series of questions that may be asked of historical data, prior to their use. Based on the answers to these questions, various statistical approaches are recommended. The strategy is illustrated with a case study in colorectal cancer. RESULTS: A number of areas need to be considered with historical data, which we split into three categories: outcome measurement, study/patient characteristics (including setting and inclusion/exclusion criteria), and disease process/intervention effects. Each of these areas may introduce issues if not appropriately handled, while some may preclude the use of historical data entirely. We present a tool (in the form of a table) for highlighting any such issues. Application of the tool to a colorectal cancer data set demonstrates under what conditions historical data could be used and what the limitations of such an analysis would be. CONCLUSION: Historical data can be a powerful tool to augment or compare with contemporary trial data, though caution is required. We present some of the issues that may be considered when involving historical data and what (if any) statistical approaches may account for differences between studies. We recommend that, where historical data are to be used in analyses, potential differences between studies are addressed explicitly

Sulphur-bearing molecules in diffuse molecular clouds: new results from SOFIA/GREAT and the IRAM 30 m telescope

We have observed five sulphur-bearing molecules in foreground diffuse molecular clouds lying along the sight-lines to five bright continuum sources. We have used the GREAT instrument on SOFIA to observe the 1383 GHz $^2\Pi_{3/2} J=5/2-3/2$ transitions of SH towards the star-forming regions W31C, G29.96-0.02, G34.3+0.1, W49N and W51, detecting foreground absorption towards all five sources; and the EMIR receivers on the IRAM 30m telescope at Pico Veleta to detect the H$_2$S 1(10)-1(01), CS J=2-1 and SO 3(2)-2(1) transitions. In nine foreground absorption components detected towards these sources, the inferred column densities of the four detected molecules showed relatively constant ratios, with N(SH)/N(H$_2$S) in the range 1.1 - 3.0, N(CS)/N(H$_2$S) in the range 0.32 - 0.61, and N(SO)/N(H$_2$S) in the range 0.08 - 0.30. The observed SH/H$_2$ ratios - in the range (0.5-2.6) $\times 10^{-8}$ - indicate that SH (and other sulphur-bearing molecules) account for << 1% of the gas-phase sulphur nuclei. The observed abundances of sulphur-bearing molecules, however, greatly exceed those predicted by standard models of cold diffuse molecular clouds, providing further evidence for the enhancement of endothermic reaction rates by elevated temperatures or ion-neutral drift. We have considered the observed abundance ratios in the context of shock and turbulent dissipation region (TDR) models. Using the TDR model, we find that the turbulent energy available at large scale in the diffuse ISM is sufficient to explain the observed column densities of SH and CS. Standard shock and TDR models, however, fail to reproduce the column densities of H$_2$S and SO by a factor of about 10; more elaborate shock models - in which account is taken of the velocity drift, relative to H$_2$, of SH molecules produced by the dissociative recombination of H$_3$S$^+$ - reduce this discrepancy to a factor ~ 3.Comment: 30 pages, accepted for publication in A&

Low-velocity shocks: signatures of turbulent dissipation in diffuse irradiated gas

Context. Large-scale motions in galaxies (supernovae explosions, galaxy collisions, galactic shear etc.) generate turbulence, which allows a fraction of the available kinetic energy to cascade down to small scales before it is dissipated. Aims. We establish and quantify the diagnostics of turbulent dissipation in mildly irradiated diffuse gas in the specific context of shock structures. Methods. We incorporated the basic physics of photon-dominated regions into a state-of-the-art steady-state shock code. We examined the chemical and emission properties of mildly irradiated (G_0 = 1) magnetised shocks in diffuse media (n_H = 10^2 to 10^4 cm^(-3)) at low- to moderate velocities (from 3 to 40 km s^(-1)). Results. The formation of some molecules relies on endoergic reactions. Their abundances in J-type shocks are enhanced by several orders of magnitude for shock velocities as low as 7 km s^(-1). Otherwise most chemical properties of J-type shocks vary over less than an order of magnitude between velocities from about 7 to about 30 km s^(-1), where H_2 dissociation sets in. C-type shocks display a more gradual molecular enhancement with increasing shock velocity. We quantified the energy flux budget (fluxes of kinetic, radiated and magnetic energies) with emphasis on the main cooling lines of the cold interstellar medium. Their sensitivity to shock velocity is such that it allows observations to constrain statistical distributions of shock velocities. We fitted various probability distribution functions (PDFs) of shock velocities to spectroscopic observations of the galaxy-wide shock in Stephan’s Quintet and of a Galactic line of sight which samples diffuse molecular gas in Chamaeleon. In both cases, low velocities bear the greatest statistical weight and the PDF is consistent with a bimodal distribution. In the very low velocity shocks (below 5 km s^(-1)), dissipation is due to ion-neutral friction and it powers H_2 low-energy transitions and atomic lines. In moderate velocity shocks (20 km s^(-1) and above), the dissipation is due to viscous heating and accounts for most of the molecular emission. In our interpretation a significant fraction of the gas in the line of sight is shocked (from 4% to 66%). For example, C^+ emission may trace shocks in UV irradiated gas where C^+ is the dominant carbon species. Conclusions. Low- and moderate velocity shocks are important in shaping the chemical composition and excitation state of the interstellar gas. This allows one to probe the statistical distribution of shock velocities in interstellar turbulence

Towards quantitative tissue absorption imaging by combining photoacoustics and acousto-optics

We propose a strategy for quantitative photoacoustic mapping of chromophore concentrations that can be performed purely experimentally. We exploit the possibility of acousto-optic modulation using focused ultrasound, and the principle that photons follow trajectories through a turbid medium in two directions with equal probability. A theory is presented that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters. Proof of the validity of the theory is given with Monte Carlo simulations.Comment: 14 pages, 5 figure

Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography

We propose an original adaptive wavefront holographic setup based on the photorefractive effect (PR), to make real-time measurements of acousto-optic signals in thick scattering media, with a high flux collection at high rates for breast tumor detection. We describe here our present state of art and understanding on the problem of breast imaging with PR detection of the acousto-optic signal

An Application of the Multivariate Linear Mixed Model to the Analysis of Shoulder Complexity in Breast Cancer Patients

In this study, four major muscles acting on the scapula were investigated in patients who had been treated in the last six years for unilateral carcinoma of the breast. Muscle activity was assessed by electromyography during abduction and adduction of the affected and unaffected arms. The main principal aim of the study was to compare shoulder muscle activity in the affected and unaffected shoulder during elevation of the arm. A multivariate linear mixed model was introduced and applied to address the principal aims. The result of fitting this model to the data shows a huge improvement as compared to the alternatives

Dynamic prediction of outcome for patients with severe aortic stenosis: Application of joint models for longitudinal and time-to-event data

Background: Physicians utilize different types of information to predict patient prognosis. For example: confronted with a new patient suffering from severe aortic stenosis (AS), the cardiologist considers not only the severity of the AS but also patient characteristics, medical history, and markers such as BNP. Intuitively, doctors adjust their prediction of prognosis over time, with the change in clinical status, aortic valve area and BNP at each outpatient clinic visit. With the help of novel statistical approaches to model outcomes, it is now possible t