Investigation of a role for noradrenaline in the neurochemical and behavioural effects of an established and putative target for antianxiety/antidepressant drugs: a microdialysis and behavioural study in rats and NK1 receptor knockout mice.

The precise neurochemical effects of antidepressants that underlie their efficacy remain unclear. Many antidepressants modulate noradrenaline transmission in vivo. However, the selective serotonin reuptake inhibitors (SSRIs) and NK1 receptor antagonists target 5-HT and substance P transmission, respectively. Whether effects on noradrenaline neurones contribute to the efficacy of these drugs has been largely neglected. This study investigates modulation of central NA transmission by an SSRI (fluoxetine) in rats and by NK1 receptor ablation in mice. NK1 'knockout' mice are used as a model for lifelong inhibition of the NK1 receptor. Changes in noradrenaline transmission were determined using in vivo microdialysis to sample the extracellular noradrenaline concentration (efflux). Noradrenaline-related behavioural effects of these treatments were determined using a modified light/dark exploration test. Systemic fluoxetine increased noradrenaline efflux in two brain regions (frontal cortex and hypothalamus). The effect was inconsistent, echoing the 5-HT response to SSRIs. Fluoxetine reduced noradrenaline efflux after partial lesioning of noradrenergic axon terminals (by DSP-4), suggesting an inhibitory action upstream of these terminals. Locally infused (retrodialysis) fluoxetine augmented noradrenaline efflux in the terminal field. Whereas 50uM fluoxetine elevated efflux in both regions, 5uM infusion increased efflux in the frontal cortex only. This effect was 5-HT-dependent (i.e. 5-HT synthesis inhibition with pCPA blocked the response). However, this increase was not secondary to inhibition of 5-HT reuptake (since the more potent and selective SSRI, citalopram, did not change noradrenaline efflux). Thus, fluoxetine has opposing effects on noradrenaline efflux, probably at cell bodies and terminals. The balance of processes could underlie its variable effects. Fluoxetine reduced locomotor activity of DSP-4-pretreated rats in the novel compartment of the exploration box, suggesting a noradrenaline-related effect on behaviour. A 5-HT-related effect of fluoxetine was also found (reduced locomotor activity in the dark compartment), since this was abolished by pCPA

Reduction of critical temperatures in pure and thoriated UBe13 by columnar defects

We investigate the influence of columnar defects on the superconducting transition temperatures of pure and thoriated UBe13. The defects cause all the transitions to widen and to drop slightly in temperature. Quantitatively, the single UBe13 transition resembles the lower transition in a sample with 3% thorium more closely than the upper thoriated transition.Comment: 3 pages, 1 figure. To be presented at M2S-HTSC-V

The Johannesburg cardiac rehabilitation programme

Cardiac rehabilitation has become a generally accepted mode of treatment for patients suffering from coronary artery disease. The Johannesburg cardiac rehabilitation programme has started in 1982 and has rapidly grown to become one of the largest programmes in southern Africa. This paper describes the 387 patients admitted to the unit l;Ietween June 1986 and July 1988 and evaluates the effects of a combined exercise training and lifestyle modification programme. The mean age on admission was 55 years for males and 58 years for females. Most patients were from social classes I and 11. Myocardial infarction, coronary artery bypass graft and a combination of both were the most common reasons for admission (35,4%. 23% and 21,2% respectively). On admission 72,9% of patients were smokers, 26,3% had hypertension and 34,3% had hypercholesterolaemia. A 50% drop-out rate within 12 months of starting the programme was noted. An increase in peak oxygen uptake, weight and skinfold thickness reduction, and improvement in the lipogram were seen after 6 months in patients who complied well with the programme. Cardiac rehabilitation is a secondary preventive strategy that can complement traditional medical and surgical therapies

Blueprints for Green Communities: Climate change visioning and participatory landscape planning for resilient low-carbon communities

Emerging 3D visualization tools and future visioning methods offer new ways to make climate change impacts and potential responses explicit, and accelerate holistic solutions. Previous research at UBC’s Collaborative for Advanced Landscape Planning (CALP) and elsewhere confirms that 4D visioning processes using landscape visualizations of recognizable places under alternative future conditions can improve community engagement and awareness on complex environmental and planning issues (Tress and Tress, 2002; Sheppard and Meitner, 2005; Schroth, 2007). This paper examines a visioning process (Sheppard, 2008) that applies visualization and other landscape planning methods to explore high and low-carbon futures of the affluent, sub-urban hillside community of North Vancouver with climate change, and its surrounding scenic North Shore sub region of Metro Vancouver, BC, Canada

On Power Suppressed Operators and Gauge Invariance in SCET

The form of collinear gauge invariance for power suppressed operators in the soft-collinear effective theory is discussed. Using a field redefinition we show that it is possible to make any power suppressed ultrasoft-collinear operators invariant under the original leading order gauge transformations. Our manipulations avoid gauge fixing. The Lagrangians to O(lambda^2) are given in terms of these new fields. We then give a simple procedure for constructing power suppressed soft-collinear operators in SCET_II by using an intermediate theory SCET_I.Comment: 15 pages, journal versio

Pretreatment with beta-blockers and the frequency of hypokalemia in patients with acute chest pain

Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on P blockers before admission. The potassium concentrations of patients admitted early (within four hours of onsetof symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with , B blockers. This was not seen in patients who had been on P blockers before admission. Nonselective, B blockers were more effective than cardioselective agents in maintaining concentrationsof plasma potassium. These findings suggest a mechanism for the beneficial effects of ,B blockers on morbidity and mortality in acute myocardial infarction

Natural language processing to extract symptoms of severe mental illness from clinical text: the Clinical Record Interactive Search Comprehensive Data Extraction (CRIS-CODE) project.

OBJECTIVES: We sought to use natural language processing to develop a suite of language models to capture key symptoms of severe mental illness (SMI) from clinical text, to facilitate the secondary use of mental healthcare data in research. DESIGN: Development and validation of information extraction applications for ascertaining symptoms of SMI in routine mental health records using the Clinical Record Interactive Search (CRIS) data resource; description of their distribution in a corpus of discharge summaries. SETTING: Electronic records from a large mental healthcare provider serving a geographic catchment of 1.2 million residents in four boroughs of south London, UK. PARTICIPANTS: The distribution of derived symptoms was described in 23 128 discharge summaries from 7962 patients who had received an SMI diagnosis, and 13 496 discharge summaries from 7575 patients who had received a non-SMI diagnosis. OUTCOME MEASURES: Fifty SMI symptoms were identified by a team of psychiatrists for extraction based on salience and linguistic consistency in records, broadly categorised under positive, negative, disorganisation, manic and catatonic subgroups. Text models for each symptom were generated using the TextHunter tool and the CRIS database. RESULTS: We extracted data for 46 symptoms with a median F1 score of 0.88. Four symptom models performed poorly and were excluded. From the corpus of discharge summaries, it was possible to extract symptomatology in 87% of patients with SMI and 60% of patients with non-SMI diagnosis. CONCLUSIONS: This work demonstrates the possibility of automatically extracting a broad range of SMI symptoms from English text discharge summaries for patients with an SMI diagnosis. Descriptive data also indicated that most symptoms cut across diagnoses, rather than being restricted to particular groups

Cardiovascular disease treatment among patients with severe mental illness: a data linkage study between primary and secondary care

Background Suboptimal treatment of cardiovascular diseases (CVD) among patients with severe mental illness (SMI) may contribute to physical health disparities. Aim To identify SMI characteristics associated with meeting CVD treatment and prevention guidelines. Design and setting Population-based electronic health record database linkage between primary care and the sole provider of secondary mental health care services in south east London, UK. Method Cardiovascular disease prevalence, risk factor recording, and Quality and Outcomes Framework (QOF) clinical target achievement were compared among 4056 primary care patients with SMI whose records were linked to secondary healthcare records and 270 669 patients without SMI who were not known to secondary care psychiatric services, using multivariate logistic regression modelling. Data available from secondary care records were then used to identify SMI characteristics associated with QOF clinical target achievement. Results Patients with SMI and with coronary heart disease and heart failure experienced reduced prescribing of beta blockers and angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARB). A diagnosis of schizophrenia, being identified with any indicator of risk or illness severity, and being prescribed with depot injectable antipsychotic medication was associated with the lowest likelihood of prescribing. Conclusion Linking primary and secondary care data allows the identification of patients with SMI most at risk of undertreatment for physical health problems

Angular 21 cm Power Spectrum of a Scaling Distribution of Cosmic String Wakes

Cosmic string wakes lead to a large signal in 21 cm redshift maps at redshifts larger than that corresponding to reionization. Here, we compute the angular power spectrum of 21 cm radiation as predicted by a scaling distribution of cosmic strings whose wakes have undergone shock heating.Comment: 13 pages, 6 figures; v2: minor modifications, journal versio

Searching for Signatures of Cosmic Superstrings in the CMB

Because cosmic superstrings generically form junctions and gauge theoretic strings typically do not, junctions may provide a signature to distinguish between cosmic superstrings and gauge theoretic cosmic strings. In cosmic microwave background anisotropy maps, cosmic strings lead to distinctive line discontinuities. String junctions lead to junctions in these line discontinuities. In turn, edge detection algorithms such as the Canny algorithm can be used to search for signatures of strings in anisotropy maps. We apply the Canny algorithm to simulated maps which contain the effects of cosmic strings with and without string junctions. The Canny algorithm produces edge maps. To distinguish between edge maps from string simulations with and without junctions, we examine the density distribution of edges and pixels crossed by edges. We find that in string simulations without Gaussian noise (such as produced by the dominant inflationary fluctuations) our analysis of the output data from the Canny algorithm can clearly distinguish between simulations with and without string junctions. In the presence of Gaussian noise at the level expected from the current bounds on the contribution of cosmic strings to the total power spectrum of density fluctuations, the distinction between models with and without junctions is more difficult. However, by carefully analyzing the data the models can still be differentiated.Comment: 15 page