Correcting for measurement error in fractional polynomial models using Bayesian modelling and regression calibration,with an application to alcohol and mortality

Exposure measurement error can result in a biased estimate of the association between an exposure and outcome. When the exposure–outcome relationship is linear on the appropriate scale (e.g. linear, logistic) and the measurement error is classical, that is the result of random noise, the result is attenuation of the effect. When the relationship is non‐linear, measurement error distorts the true shape of the association. Regression calibration is a commonly used method for correcting for measurement error, in which each individual's unknown true exposure in the outcome regression model is replaced by its expectation conditional on the error‐prone measure and any fully measured covariates. Regression calibration is simple to execute when the exposure is untransformed in the linear predictor of the outcome regression model, but less straightforward when non‐linear transformations of the exposure are used. We describe a method for applying regression calibration in models in which a non‐linear association is modelled by transforming the exposure using a fractional polynomial model. It is shown that taking a Bayesian estimation approach is advantageous. By use of Markov chain Monte Carlo algorithms, one can sample from the distribution of the true exposure for each individual. Transformations of the sampled values can then be performed directly and used to find the expectation of the transformed exposure required for regression calibration. A simulation study shows that the proposed approach performs well. We apply the method to investigate the relationship between usual alcohol intake and subsequent all‐cause mortality using an error model that adjusts for the episodic nature of alcohol consumption.     

Reversible Hypomagnesaemia-Induced Subacute Cerebellar Syndrome

Magnesium is the second most abundant intracellular cation and is a fundamental cofactor in a multitude of cellular enzymatic reactions. Magnesium deficiency causes diverse clinical features predominantly due to cardio- and neurotoxicity. We describe a case of severe hypomagnesaemia associated with intermittent downbeat nystagmus, cerebellar ataxia, generalised convulsions and a supraventricular tachycardia. On MRI imaging, a transient lesion of the cerebellar nodulus was observed, which has not, to our knowledge, been previously described in isolated hypomagnesaemia.     

Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research

Despite the desire to delve deeper into hallucinations of all types, methodological obstacles have frustrated development of more rigorous quantitative experimental techniques, thereby hampering research progress. Here, we discuss these obstacles and, with reference to visual phenomena, argue that experimentally induced phenomena (e.g. hallucinations induced by flickering light and classical conditioning) can bring hallucinations within reach of more objective behavioural and neural measurement. Expanding the scope of hallucination research raises questions about which phenomena qualify as hallucinations, and how to identify phenomena suitable for use as laboratory models of hallucination. Due to the ambiguity inherent in current hallucination definitions, we suggest that the utility of phenomena for use as laboratory hallucination models should be represented on a continuous spectrum, where suitability varies with the degree to which external sensory information constrains conscious experience. We suggest that existing strategies that group pathological hallucinations into meaningful subtypes based on hallucination characteristics (including phenomenology, disorder and neural activity) can guide extrapolation from hallucination models to other hallucinatory phenomena. Using a spectrum of phenomena to guide scientific hallucination research should help unite the historically separate fields of psychophysics, cognitive neuroscience and clinical research to better understand and treat hallucinations, and inform models of consciousness.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.     

Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development

Ecdysone 20-monooxygenase activity and the factors which may regulate this steroid hydroxylase were examined in the midgut of the tobacco hornworm, Manduca sexta, during the last larval stadium. Radioassay experiments revealed that midgut ecdysone 20-monooxygenase undergoes a single 50-fold increase in activity temporally coincident with the onset of the wandering stage. The increase in midgut monooxygenase activity was prevented by actinomycin D and cycloheximide, and could be elicited in head (but not thoracic) ligated animals by a brain-retrocerebral complex factor(s) released at the same time as prothoracicotropic hormone. In contrast, ecdysone or 20-hydroxyecdysone could elicit the increase in enzyme activity in both head and thoracic ligated animals. These data suggest the operation of a neuroendocrine-endocrine axis in the regulation of midgut ecdysone 20-monooxygenase activity.     

Triterpenes of Sarcostemma asclepiadaceae

A mixture of n-alkanes, four pentacyclic triterpenes, and the butyrate of germanicol were isolated and their structures established.