Biochemical and pharmacological studies of amygdaloid kindling in the rat

The kindling effect was investigated in the rat amygdala in an attempt to iden¬ tify the biochemical correlates of the long-la-strng-Thanges in neuronal excitability which are characteristic of this phenomenon. The hypothesis that cholinergic mechanisms are facilitatory and catecholaminergic systems are inhibitor}' in amygdaloid kindling was tested. The cholinergic muscarinic antagonist atropine was found to be without effect on kindling and mus¬ carinic receptor sites and sodium-dependent,high affinity choline uptake were not perturbed one month after a kindled convulsion, even though the epileptogenic effect of kindling is known to persist for over 1 year. From these results it was concluded that there was not a signifi¬ cant cholinergic contribution to the development or maintenance of kindling. The involvement of noradrenaline and dopamine in kindling was assessed by measuring the turnover rates of these amines. At the site of stimulus the basal level of noradrenaline was found to be reduced and the rate of depletion of dopamine was increased when compared with the contralateral unstimulated amygdala. Cyclic GMP levels in slices prepared from the amygdala was higher in kindled than in sham-operated animals, whilst an impaired res¬ ponse of cyclic GMP to depolarization or to media containing dopamine or haloperidol was recorded. These findings suggest a role for catecholamines in kindling and support the view that the long-term changes in kindling are associated with dopamine receptor subs ens itivity accompanied by a compensating increase in presynaptic dopamine release. During the course of these experiments it became apparent that the very presence of metal electrodes in the amygdala, for periods of up to 4 weeks, caused enhancement in the rate of kindling. This observation, which has some implications for theories about kindling, was confirmed using both stainless steel and platinum/iridium metal implants. Finally, a comparison of regional metabolic requirements during kindling induced con¬ vulsions, electroshock convulsions and partial kindling were compared and contrasted with regional requirements in sham-operated and unope rated control animals using a deoxyglucose technique for estimating regional glucose utilization. Changes observed in glucose consumption were always bilateral and in no area did rats which had been kindled but not convulsed at the time of the deoxyglucose experiment, differ from sham operated controls. In two regions the hypothalamus and septal nuclei unoperated controls showed a significantly lower uptake than in sham operated rats. Since these groups differed only in the placement of an elec¬ trode into the amygdala the results were taken to imply that the presence of an electrode caused increased neuronal activity in those regions. Kindled induced convulsions were associated with an increase in neuronal activity in the amygdalae, hippocampi, superior colliculi, substantia nigra and septal nuclei. Partial kindling caused increased glucose consumption in the amygdalae hippocampi and superior colliculi. Electro -convulsions led to increased neuronal activity in the amygdalae, hippocampi, hypothalami, substantia nigra, septal nuclei thalamus, striata, cerebellar nuclei, cerebellar hemispheres and reticular formation, Theories about the anatomy of spread of epileptic seizures are discussed

Views and Practices of Anaesthetists Towards End of Life Decisions and Advance Care Planning

Background: Despite low mortality rates, ~2%, the high volume of surgery now conducted in the UK means that around 100,000 people die each year within 90 days of having an operation. It is probable that these patients would have benefited from a discussion about their wishes and preferences prior to the operation via a process of advance care planning. Pre-operative assessment clinics, commonly operated by anaesthetists, offer an opportunity for this prior to surgery. Aim: This thesis aims to describe the most important components of end-of-life and advance care planning discussions as well as barriers which may prevent anaesthetists from engaging in these conversations pre-operatively. Methods: A mixed methods study was carried out to outline the knowledge, attitudes, and practices of UK anaesthetists towards end-of-life decisions and advance care planning in the perioperative setting. This involved multiple workstreams: two systematic reviews; two national surveys of UK anaesthetists; and a qualitative component involving semi-structured interviews and participant observation. Results: UK anaesthetists were found to be knowledgeable and have a good understanding of advance care planning. They have positive attitudes towards the concept both generally and perioperatively, and strongly support the principle of autonomy. When considering their own end-of-life care the themes which emerged were: ‘patient engagement’; ‘intensity of treatment’; ‘family and friends’; a ‘transition point’; ‘care’; and plans for ‘after death’. Perioperative advance care planning was not a routine part of anaesthetists’ practice as the treatment limitations implied were not felt to align with surgical care. The structure and organisation of pre-operative care also creates barriers to anaesthetists having these discussions. Conclusion: This study has demonstrated that advance care planning is not a routine part of UK anaesthetists’ practice for patient’s approaching surgery and outlines particular attitudinal and practical barriers. It describes a process for a modified advance care planning discussion appropriate for surgical patients

A 4q35.2 subtelomeric deletion identified in a screen of patients with co-morbid psychiatric illness and mental retardation

BACKGROUND: Cryptic structural abnormalities within the subtelomeric regions of chromosomes have been the focus of much recent research because of their discovery in a percentage of people with mental retardation (UK terminology: learning disability). These studies focused on subjects (largely children) with various severities of intellectual impairment with or without additional physical clinical features such as dysmorphisms. However it is well established that prevalence of schizophrenia is around three times greater in those with mild mental retardation. The rates of bipolar disorder and major depressive disorder have also been reported as increased in people with mental retardation. We describe here a screen for telomeric abnormalities in a cohort of 69 patients in which mental retardation co-exists with severe psychiatric illness. METHODS: We have applied two techniques, subtelomeric fluorescence in situ hybridisation (FISH) and multiplex amplifiable probe hybridisation (MAPH) to detect abnormalities in the patient group. RESULTS: A subtelomeric deletion was discovered involving loss of 4q in a patient with co-morbid schizoaffective disorder and mental retardation. CONCLUSION: The precise region of loss has been defined allowing us to identify genes that may contribute to the clinical phenotype through hemizygosity. Interestingly, the region of 4q loss exactly matches that linked to bipolar affective disorder in a large multiply affected Australian kindred

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

Control design for the SERC experimental testbeds

Viewgraphs on control design for the Space Engineering Research Center experimental testbeds are presented. Topics covered include: SISO control design and results; sensor and actuator location; model identification; control design; experimental results; preliminary LAC experimental results; active vibration isolation problem statement; base flexibility coupling into isolation feedback loop; cantilever beam testbed; and closed loop results

The Lynx X-Ray Observatory: Concept Study Overview and Status

Lynx, one of four strategic mission concepts under study for the 2020 Astrophysics Decadal Survey, will provide leaps in capability over previous and planned X-ray missions, and will provide synergistic observations in the 2030s to a multitude of space- and ground-based observatories across all wavelengths. Lynx will have orders of magnitude improvement in sensitivity, on-axis sub-arcsecond imaging with arcsecond angular resolution over a large field of view, and high-resolution spectroscopy for point-like and extended sources. The Lynx architecture enables a broad range of unique and compelling science, to be carried out mainly through a General Observer Program. This Program is envisioned to include detecting the very first supermassive black holes, revealing the high-energy drivers of galaxy and structure formation, characterizing the mechanisms that govern stellar activity - including effects on planet habitability, and exploring the highest redshift galaxy clusters. An overview and status of the Lynx concept are summarized

DNA sequence level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes

Assessment of an undergraduate psychiatry course in an African setting

<p>Abstract</p> <p>Background</p> <p>International reports recommend the improvement in the amount and quality of training for mental health workers in low and middle income countries. The Scotland-Malawi Mental Health Education Project (SMMHEP) has been established to support the teaching of psychiatry to medical students in the University of Malawi. While anecdotally supportive medical educational initiatives appear of value, little quantitative evidence exists to demonstrate whether such initiatives can deliver comparable educational standards. This study aimed to assess the effectiveness of an undergraduate psychiatry course given by UK psychiatrists in Malawi by studying University of Malawi and Edinburgh University medical students' performance on an MCQ examination paper.</p> <p>Methods</p> <p>An undergraduate psychiatry course followed by an MCQ exam was delivered by the SMMHEP to 57 Malawi medical students. This same MCQ exam was given to 71 Edinburgh University medical students who subsequently sat their own Edinburgh University examination.</p> <p>Results</p> <p>There were no significant differences between Edinburgh students' performance on the Malawi exam and their own Edinburgh University exam. (p = 0.65). This would suggest that the Malawi exam is a comparable standard to the Edinburgh exam. Malawi students marks ranged from 52.4%–84.6%. Importantly 84.4% of Malawi students scored above 60% on their exam which would equate to a hypothetical pass by UK university standards.</p> <p>Conclusion</p> <p>The support of an undergraduate course in an African setting by high income country specialists can attain a high percentage pass rate by UK standards. Although didactic teaching has been surpassed by more novel educational methods, in resource poor countries it remains an effective and cost effective method of gaining an important educational standard.</p