Catatonia Psychopathology and Phenomenology in a Large Dataset

Background: The external clinical manifestations (psychopathology) and internal subjective experience (phenomenology) of catatonia are of clinical importance but have received little attention. This study aimed to use a large dataset to describe the clinical signs of catatonia; to assess whether these signs are associated with underlying diagnosis and prognosis; and to describe the phenomenology of catatonia, particularly with reference to fear. // Methods: A retrospective descriptive cross-sectional study was conducted using the electronic healthcare records of a large secondary mental health trust in London, United Kingdom. Patients with catatonia were identified in a previous study by screening records using natural language processing followed by manual validation. The presence of items of the Bush-Francis Catatonia Screening Instrument was coded by the investigators. The presence of psychomotor alternation was assessed by examining the frequency of stupor and excitement in the same episode. A cluster analysis and principal component analysis were conducted on catatonic signs. Principal components were tested for their associations with demographic and clinical variables. Where text was available on the phenomenology of catatonia, this was coded by two authors in an iterative process to develop a classification of the subjective experience of catatonia. // Results: Searching healthcare records provided 1,456 validated diagnoses of catatonia across a wide range of demographic groups, diagnoses and treatment settings. The median number of catatonic signs was 3 (IQR 2–5) and the most commonly reported signs were mutism, immobility/stupor and withdrawal. Stupor was present in 925 patients, of whom 105 (11.4%) also exhibited excitement. Out of 196 patients with excitement, 105 (53.6%) also had immobility/stupor. Cluster analysis produced two clusters consisting of negative and positive clinical features. From principal component analysis, three components were derived, which may be termed parakinetic, hypokinetic and withdrawal. The parakinetic component was associated with women, neurodevelopmental disorders and longer admission duration; the hypokinetic component was associated with catatonia relapse; the withdrawal component was associated with men and mood disorders. 68 patients had phenomenological data, including 49 contemporaneous and 24 retrospective accounts. 35% of these expressed fear, but a majority (72%) gave a meaningful narrative explanation for the catatonia, which consisted of hallucinations, delusions of several different types and apparently non-psychotic rationales. // Conclusion: The clinical signs of catatonia can be considered as parakinetic, hypokinetic and withdrawal components. These components are associated with diagnostic and prognostic variables. Fear appears in a large minority of patients with catatonia, but narrative explanations are varied and possibly more common

Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts

New Techniques for Analysing Axisymmetric Gravitational Systems. 1. Vacuum Fields

A new framework for analysing the gravitational fields in a stationary, axisymmetric configuration is introduced. The method is used to construct a complete set of field equations for the vacuum region outside a rotating source. These equations are under-determined. Restricting the Weyl tensor to type D produces a set of equations which can be solved, and a range of new techniques are introduced to simplify the problem. Imposing the further condition that the solution is asymptotically flat yields the Kerr solution uniquely. The implications of this result for the no-hair theorem are discussed. The techniques developed here have many other applications, which are described in the conclusions.Comment: 30 pages, no figure

Shear-Mediated Dilation of the Internal Carotid Artery Occurs Independent of Hypercapnia.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial carbon dioxide was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined the hypothesis that, following a 30-second transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants the partial pressures of end-tidal O2 and CO2, ventilation (pneumotachography), blood pressure (finger-photoplethysmography), heart-rate (electrocardiogram), internal carotid artery flow, diameter and shear stress (high resolution duplex ultrasound) and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-minute steady state and transient 30-second hypercapnic tests (both +9mmHg CO2). Internal carotid artery dilation was lower in the transient, compared to the steady state hypercapnia (3.3±1.9% vs. 5.3±2.9%, respectively; P<0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both the transient (time: 16.8±13.2s vs. 59.4±60.3s; P<0.01) and steady state (time: 18.2±14.2s vs. 110.3±79.6s; P<0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient (r(2)=0.44; P<0.01), but not steady state (r(2)=0.02; P=0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans

Results of the EUROTeV Post Collision Line Design (PCDL) Task

This paper is the deliverable of the EUROTeV Post Collision Line Design (PCDL) task and gives an overview of the published results

Transformation of Cs-IONSIV® into a ceramic wasteform by hot isostatic pressing

A simple method to directly convert Cs-exchanged IONSIV® IE-911 into a ceramic wasteform by hot isostatic pressing (1100 °C/190 MPa/2 hr) is presented. Two major Cs-containing phases, Cs2TiNb6O18 and Cs2ZrSi6O15, and a series of mixed oxides form. The microstructure and phase assemblage of the samples as a function of Cs content were examined using XRD, XRF, SEM and TEM/EDX. The chemical aqueous durability of the materials was investigated using the MCC-1 and PCT-B standard test methods. For HIPed Cs-IONSIV® samples, the MCC-1 normalised release rates of Cs were <1.57 × 10−1 g m−2 d−1 at 0–28 days, and <3.78 × 10−2 g m−2 d−1 for PCT-B at 7 days. The low rates are indicative of a safe long-term immobilisation matrix for Cs formed directly from spent IONSIV®. It was also demonstrated that the phase formation can be altered by adding Ti metal due to a controlled redox environment

Changes in gene expression in space and time orchestrate environmentally mediated shaping of root architecture

Shaping of root architecture is a quintessential developmental response that involves the concerted action of many different cell types, is highly dynamic and underpins root plasticity. To determine to what extent the environmental regulation of lateral root development is a product of cell type preferential activities, we tracked transcriptomic responses to two different treatments that both change root development in Arabidopsis thaliana, at an unprecedented level of temporal detail. We found that individual transcripts are expressed with a very high degree of temporal and spatial specificity, yet biological processes are commonly regulated, in a mechanism we term response nonredundancy. Using causative gene network inference to compare the genes regulated in different cell types and during responses to nitrogen and a biotic interaction we found that common transcriptional modules often regulate the same gene families, but control different individual members of these families, specific to response and cell type. This reinforces that the activity of a gene cannot be defined simply as molecular function; rather, it is a consequence of spatial location, expression timing and environmental responsiveness

Enantioselective carbohydrate recognition by synthetic lectins in water

These chiral “synthetic lectins” are the first to discriminate between carbohydrate enantiomers, and also show unprecedented affinities for monosaccharide substrates.</p

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)Supported by grants from the U.K. Department of Health, the British Retinitis Pigmentosa Society, and the Special Trustees of Moorfields Eye Hospital, and by the Sir Jules Thorn Charitable Trust, the Wellcome Trust, the European Union (EVI-Genoret and Clinigene programs), the Medical Research Council, Foundation Fighting Blindness, Fight for Sight, the Ulverscroft Foundation, Fighting Blindness (Ireland), Moorfields Eye Hospital, and Institute of Ophthalmology Biomedical Research Centre for Ophthalmology, University College London