Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

Aging reduces left atrial performance during adrenergic stress in middle aged and older patients

Background: During adrenergic stress, the influence of age on left atrial (LA) function is unknown. We hypothesized that aging decreases LA total emptying fraction (LAEF) during maximal adrenergic stress. The aim of the study was to determine the influence of aging on LA function during adrenergic stress in middle aged and older patients. Methods: We enrolled 167 middle aged and elderly participants, and measured LA and left ventricular (LV) volumes using a multi-slice three-dimensional cine white blood cardiovascular magnetic resonance (CMR) technique before and during intravenous dobutamine infused to achieve 80% of the maximum heart rate response for age. Paired sample t-test was used to detect differences in LA and LV volumes between baseline and peak dose stage of dobutamine stress CMR, and multivariable linear regression was used to identify predictors of LA function. Results: Participants averaged 68 ± 8 years in age, 53% were men, 25% exhibited coronary artery disease, 35% had diabetes, 9% had a remote history of atrial fibrillation, 90% had hypertension, and 11% had inducible LV wall motion abnormalities indicative of ischemia during dobutamine CMR. Increasing age correlated with LA volumes (maximal and minimal) and inversely correlated with LAEF at rest and after peak adrenergic stress. Age was an independent predictor of LAEF during adrenergic stress, even after accounting for gender, LV volumes, and other co-morbidities including inducible ischemia. Conclusions: Age is associated with a decrease in LA function during adrenergic stress even after adjusting for co-morbidities associated with cardiovascular disease and LV function. (Cardiol J 2012; 19, 1: 45–52

Thrombin-induced Ca2+ mobilization in vascular smooth muscle utilizes a slowly ribosylating pertussis toxin-sensitive G protein: evidence for the involvement of a G protein in inositol trisphosphate-dependent Ca2+ release

The role of pertussis toxin (PT)-sensitive and -insensitive guanine nucleotide-binding proteins (G proteins) in the stimulation of Ca mobilization by thrombin was investigated in cultured rat aortic smooth muscle cells. Characterization using immunoblotting with specific antisera indicated the presence in isolated membranes of the Gα(i2), Gα(i3), Gα(s), Gβ, and Gβ protein subunits as well as a lower molecular weight species of unknown identity. To assess the importance of G proteins in the coupling of thrombin receptors to Ca mobilization, we investigated the effect of PT on Ca responses using fluorescence spectroscopy and the Ca indicator dye Fura-2. Pretreatment of cells for 2 h with PT (1 μg/ml), which produced 91.3% ADP-ribosylation of PT-sensitive G proteins, did not affect the magnitude of thrombin-induced release of Ca from internal stores, suggesting that the residual 8.7% of PT-sensitive G proteins, or PT-insensitive mechanisms, was responsible for Ca release. However, after an 18-h pretreatment with PT, which produced ADP-ribosylation of the total complement of PT-sensitive G proteins, the thrombin-induced peak Ca response was inhibited by approximately 72%, suggesting that the major fraction of the Ca response was mediated by a slowly ribosylating component. The delayed effect of the toxin was not caused by down-regulation of the β-subunit of G proteins because quantitative immunoblots showed that levels of the β-subunit remained constant throughout the period of PT pretreatment. It was also not caused by a reduction in the size of the thrombin-releasable Ca pool because Ca release induced by agents that release Ca directly from internal stores, 2,5-di-tert-butylhydroquinone or thapsigargin, was not affected. In addition, the delayed effect of PT could not be explained in terms of differences in thrombin-induced [H]inositol trisphosphate (IP) formation because the level of inhibition of IP formation after a 2-h PT treatment was similar to that present after an 18-h pretreatment. The results indicate that a slowly ribosylating PT- sensitive species is the major G protein pathway that couples thrombin- receptor activation to Ca mobilization. This G protein appears to be involved not in the mechanisms that generate IP but rather possibly in coupling at the level of the intracellular Ca store

NASA Exploration Mission 2 Mission Design

Exploration Mission 2 (EM-2) will be NASAs first manned flight on the Space Launch System (SLS) and Orion Spacecraft. The mission has been changed from an SLS Block 1B configuration to Block 1. This change has necessitated a reexamination of the flight profile to determine what changes must be made in order to accommodate the reduced launch vehicle performance on the Block 1. Launch availability and orbital debris risk will be traded to find the best flight profile for both SLS and Orion

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Inducing social self‐sorting in organic cages to tune the shape of the internal cavity

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host–guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low-symmetry imine cages. Whether a low-energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high-symmetry cages-and the same aldehyde generates low-symmetry socially self-sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low-symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self-sorting

A longitudinal study of adolescents’ judgments of the attractiveness of facial symmetry, averageness and sexual dimorphism

Adolescents have been found to differ by age in their attraction to facial symmetry, averageness, and sexual dimorphism. However, it has not been demonstrated that attraction to these facial characters changes over time as a consequence of age-linked development. We aimed to extend previous cross-sectional findings by examining whether facial attractiveness judgments change over time during adolescence as a consequence of increasing age, in a within-subjects study of two cohorts of adolescents aged 11–16. Consistent with previous findings, we find that adolescents (often particularly females) judged faces with increased averageness, symmetry and femininity to be more attractive than original, asymmetric and masculine faces, respectively. However, we do not find longitudinal changes in face preference judgments across the course of a year, leading us to question the extent to which some of the previously reported differences in facial attractiveness judgments between younger and older adolescents were due to age-linked changes