Introduction to the Analysis of Survival Data in the Presence of Competing Risks

Competing risks occur frequently in the analysis of survival data. A competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. In a study examining time to death attributable to cardiovascular causes, death attributable to noncardiovascular causes is a competing risk. When estimating the crude incidence of outcomes, analysts should use the cumulative incidence function, rather than the complement of the Kaplan-Meier survival function. The use of the Kaplan-Meier survival function results in estimates of incidence that are biased upward, regardless of whether the competing events are independent of one another. When fitting regression models in the presence of competing risks, researchers can choose from 2 different families of models: modeling the effect of covariates on the cause-specific hazard of the outcome or modeling the effect of covariates on the cumulative incidence function. The former allows one to estimate the effect of the covariates on the rate of occurrence of the outcome in those subjects who are currently event free. The latter allows one to estimate the effect of covariates on the absolute risk of the outcome over time. The former family of models may be better suited for addressing etiologic questions, whereas the latter model may be better suited for estimating a patient’s clinical prognosis. We illustrate the application of these methods by examining cause-specific mortality in patients hospitalized with heart failure. Statistical software code in both R and SAS is provided

A distinct mechanism for the ABC transporter BtuCD–BtuF revealed by the dynamics of complex formation

ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a diverse array of substrates across cell membranes. We present here the dynamics of complex formation of three structurally characterized ABC transporters—the BtuCD vitamin B_(12) importer and MetNI d/l-methionine importer from Escherichia coli and the Hi1470/1 metal-chelate importer from Haemophilus influenzae—in complex with their cognate binding proteins. Similarly to other ABC importers, MetNI interacts with its binding protein with low affinity (K_d ~10^(−4) M). In contrast, BtuCD–BtuF and Hi1470/1–Hi1472 form stable, high-affinity complexes (K_d ~10^(−13) and 10^(−9) M, respectively). In BtuCD–BtuF, vitamin B_(12) accelerates the complex dissociation rate ~10^7-fold, with ATP having an additional destabilizing effect. The findings presented here highlight substantial mechanistic differences between BtuCD–BtuF, and likely Hi1470/1–Hi1472, and the better-characterized maltose and related ABC transport systems, indicating that there is considerable mechanistic diversity within this large protein super-family

Lower Levels of Glutathione (GSH) in the Brains of Secondary Progressive Multiple Sclerosis Patients Measured by 1H Magnetic Resonance Chemical Shift Imaging at 3 T

BACKGROUND: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. OBJECTIVE: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. METHODS: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4±7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. RESULTS: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p=0.001). CONCLUSION: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS

Developing points-based risk-scoring systems in the presence of competing risks.

Predicting the occurrence of an adverse event over time is an important issue in clinical medicine. Clinical prediction models and associated points-based risk-scoring systems are popular statistical methods for summarizing the relationship between a multivariable set of patient risk factors and the risk of the occurrence of an adverse event. Points-based risk-scoring systems are popular amongst physicians as they permit a rapid assessment of patient risk without the use of computers or other electronic devices. The use of such points-based risk-scoring systems facilitates evidence-based clinical decision making. There is a growing interest in cause-specific mortality and in non-fatal outcomes. However, when considering these types of outcomes, one must account for competing risks whose occurrence precludes the occurrence of the event of interest. We describe how points-based risk-scoring systems can be developed in the presence of competing events. We illustrate the application of these methods by developing risk-scoring systems for predicting cardiovascular mortality in patients hospitalized with acute myocardial infarction. Code in the R statistical programming language is provided for the implementation of the described methods. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd

A Catalog of Very Isolated Galaxies from the SDSS Data Release 1

We present a new catalog of isolated galaxies obtained through an automated systematic search. These 2980 isolated galaxies were found in approximately 2099 sq deg of sky in the Sloan Digital Sky Survey Data Release 1 (SDSS DR1) photometry. The selection algorithm, implementing a variation on the criteria developed by Karachentseva in 1973, proved to be very efficient and fast. This catalog will be useful for studies of the general galaxy characteristics. Here we report on our results.Comment: 67 pages, which includes 14 figures. Accepted for publication by A

High-Pressure Phase Transitions of Morphologically Distinct Zn2SnO4 Nanostructures

Many aspects of nanostructured materials at high pressures are still unexplored. We present here, high-pressure structural behavior of two Zn2SnO4 nanomaterials with inverse spinet type, one a particle with size of similar to 7 nm zero dimensional (0-D)] and the other with a chain-like one dimensional (1-D)] morphology. We performed in situ micro-Raman and synchrotron X-ray diffraction measurements and observed that the cation disordering of the O-D nanoparticle is preserved up to similar to 40 GPa, suppressing the reported martensitic phase transformation. On the other hand, an irreversible phase transition is observed from the 1-D nanomaterial into a new and dense high-pressure orthorhombic CaFe2O4-type structure at similar to 40 GPa. The pressure-treated 0-D and 1-D nanomaterials have distinct diffuse reflectance and emission properties. In particular, a heterojunction between the inverse spinet and quenchable orthorhombic phases allows the use of 1-D Zn2SnO4 nanomaterials as efficient photocatalysts as shown by the degradation of the textile pollutant methylene blue

A study of blood contamination of Siqveland matrix bands

AIMS To use a sensitive forensic test to measure blood contamination of used Siqveland matrix bands following routine cleaning and sterilisation procedures in general dental practice. MATERIALS AND METHODS: Sixteen general dental practices in the West of Scotland participated. Details of instrument cleaning procedures were recorded for each practice. A total of 133 Siqveland matrix bands were recovered following cleaning and sterilisation and were examined for residual blood contamination by the Kastle-Meyer test, a well-recognised forensic technique. RESULTS: Ultrasonic baths were used for the cleaning of 62 (47%) bands and retainers and the remainder (53%) were hand scrubbed prior to autoclaving. Overall, 21% of the matrix bands and 19% of the retainers gave a positive Kastle-Meyer test, indicative of residual blood contamination, following cleaning and sterilisation. In relation to cleaning method, 34% of hand-scrubbed bands and 32% of hand-scrubbed retainers were positive for residual blood by the Kastle-Meyer test compared with 6% and 3% respectively of ultrasonically cleaned bands and retainers (P less than 0.001). CONCLUSIONS: If Siqveland matrix bands are re-processed in the assembled state, then adequate pre-sterilisation cleaning cannot be achieved reliably. Ultrasonic baths are significantly more effective than hand cleaning for these items of equipment