Historical and future trends in emergency pituitary referrals: a machine learning analysis.

PURPOSE: Acute pituitary referrals to neurosurgical services frequently necessitate emergency care. Yet, a detailed characterisation of pituitary emergency referral patterns, including how they may change prospectively is lacking. This study aims to evaluate historical and current pituitary referral patterns and utilise state-of-the-art machine learning tools to predict future service use. METHODS: A data-driven analysis was performed using all available electronic neurosurgical referrals (2014-2021) to the busiest U.K. pituitary centre. Pituitary referrals were characterised and volumes were predicted using an auto-regressive moving average model with a preceding seasonal and trend decomposition using Loess step (STL-ARIMA), compared against a Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) algorithm, Prophet and two standard baseline forecasting models. Median absolute, and median percentage error scoring metrics with cross-validation were employed to evaluate algorithm performance. RESULTS: 462 of 36,224 emergency referrals were included (referring centres = 48; mean patient age = 56.7 years, female:male = 0.49:0.51). Emergency medicine and endocrinology accounted for the majority of referrals (67%). The most common presentations were headache (47%) and visual field deficits (32%). Lesions mainly comprised tumours or haemorrhage (85%) and involved the pituitary gland or fossa (70%). The STL-ARIMA pipeline outperformed CNN-LSTM, Prophet and baseline algorithms across scoring metrics, with standard accuracy being achieved for yearly predictions. Referral volumes significantly increased from the start of data collection with future projected increases (p < 0.001) and did not significantly reduce during the COVID-19 pandemic. CONCLUSION: This work is the first to employ large-scale data and machine learning to describe and predict acute pituitary referral volumes, estimate future service demands, explore the impact of system stressors (e.g. COVID pandemic), and highlight areas for service improvement.

Phantasia, aphantasia, and hyperphantasia: Empirical data and conceptual considerations.

Within the past decade, the term "phantasia" has been increasingly used to describe the human capacity, faculty, or power of visual mental imagery, with extremes of imagery vividness characterised as "aphantasia" and "hyperphantasia". A substantial volume of empirical research addressing these constructs has now been published, including attempts to find inductive correlates of behaviourally defined aphantasia, for example using research questionnaires and functional magnetic resonance imaging. Mental imagery has long been noted as a source of conceptual confusions but no specific conceptual analysis of the new formulation of phantasia, aphantasia, and hyperphantasia has been undertaken hitherto. We offer some conceptual considerations on phantasia, noting the ongoing confusion of perceptual with mental images, and the ubiquitous use of unvalidated subjective assessment instruments such as the Vividness of Visual Imagery Questionnaire (VVIQ) in diagnosis and assessment, development of which was predicated on these conceptual confusions. We offer some suggestions for a conceptual framework for future empirical studies in this field, circumventing these conceptual confusions.

Cognitive processes in saccade generation.

The analysis of saccades offers an opportunity to study a number of different cognitive processes, such as visuospatial attention, working memory, and volitional conflict. A study of saccades in patients with visuospatial hemineglect, who performed a visual search task, showed repeated fixations on targets previously discovered, yet they often failed to retain the information that a particular target had previously been discovered. High-resolution structural brain scanning showed that this abnormality was due either to a lesion in the right intraparietal sulcus or the right inferior frontal lobe. Detailed analysis of the scanpaths suggested that the former location was associated with an accumulating impairment in remapping target locations across saccades or impaired memory of previously inspected target locations, whereas the latter location was more consistent with a failure to inhibit responses to rightward locations. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often reexamine rightward targets, at the expense of items to their left. The functions of the supplementary eye field (SEF), in the medial frontal lobe, in relation to saccade generation are controversial. A series of studies in a patient with a focal lesion of the right SEF has indicated an important role for the SEF in the rapid self-control of saccadic eye movements and in set-switching (i.e., implementing control in situations of response conflict when ongoing saccadic plans have to be changed rapidly), rather than monitoring errors. In a recent fMRI study of normal subjects, it was shown that the SEF is involved in implementing the resolution of any volitional conflict, whereas other presupplementary motor areas are involved in the generation of volitional plans and processing volitional conflict.

Covert cognition in the persistent vegetative state.

Brain damage can sometimes render a patient persistently unresponsive and yet apparently awake, admitting the possibility that the absence of overt voluntary behaviour might conceal a retained capacity for covert cognition. When given instructions to perform a cognitive task, a minority of patients in such a so-called persistent vegetative state (PVS) has recently been found to exhibit patterns of brain activation closely matching those observed in normal subjects obeying the same instructions. These data have been widely interpreted as implying the detection of covert "consciousness". Here we show that this inference is not supported by the extant data because it relies on critical assumptions, obscured by conceptual unclarities, that are either untested or untestable. We set out the proper grounds for ascribing psychological attributes to PVS patients from physiological evidence of any kind, and offer a perspicuous conceptual framework for future empirical studies in the field.

Effects of proteolytic encymes on uremic serum inhibition of hepatic and renal transport functions.

Dialysates of rat uremic serum were incubated with Pronase, Carboxypeptidase A, Leucine Aminopeptidase, or Trypsin to investigate whether these enzymes might destroy the inhibitory effects of the dialysates on the uptake of paraaminohippurate by rat renal cortical slices or the uptake of purines by rat liver slices. Of these enzymes, Pronase produced the greatest destruction (63.2 +/- 4.5%) of the inhibitory action on renal transport, with a much smaller destruction (17.8 +/- 2.1%) of the inhibitory effect on hepatic transport.

Uremic inhibition of purine uptake by rat hepatic slices.

Measurements were made of the production of allantoin by liver slices prepared either from bilaterally nephrectomized rats or from normal, control rats in flasks containing either a) no added substrate, b) hypoxanthine, or c) xanthine. Uremic liver slices showed a 72.3% inhibition of augmented allantoin production with hypoxanthine as substrate and a 68.3% inhibition with xanthine as substrate. Next, uremic rat serum was added to liver slices prepared from normal rats along with either a) no added substrate, b) hypoxanthine, or c) xanthine. Normal rat serum replaced uremic rat serum in control experiments. In these paired experiments, uremic serum exerted an inhibitory effect on allantoin production of 78.0% when hypoxanthine was the substrate and of 83.6% when xanthine was the substrate. Studies on possible underlying mechanisms showed that the observed uremic inhibition of allantoin production by hepatic slices, in the presence of substrate (e.g., hypoxanthine), represents a decreased production of uric acid, secondary to the decreased hepatic uptake of substrate.

[Stability of antilipidemic etofibrate and its metabolites towards gastrointestinal and blood hydrolases (author's transl)]. / Zur Stabilität des Blutlipidsenkers Etofibrat und seiner Metabolite gegenüber Hydrolasen des Gastrointestinaltraktes und des Blutes.

Etofibrate is preferentially cleaved in its clofibrinic acid ester group by the hydrolases of the blood. The formed nicotinic acid 2-hydroxyethyl ester is considerably more stable than the 2-(4-chlorophenoxy)-2-methylpropionic acid (2-hydroxyethyl)-ester. Against artificial gastric and intestinal juice (USP XIX), the nicotinic acid 2-hydroxyethyl ester is almost completely stable. Etofibrate is bound to plasma albumin substantially more tightly than is clofibrate.