Malaria in Northern Ireland

The clinical features, parasitology and prophylactic history of 67 patients who imported malaria to Northern Ireland between 1974 and 1983 are reported. P. falciparum infections were encountered more frequently than anticipated from current United Kingdom experience. The clinical implications of these findings are discussed

Meningitis in an Irish community

A series of 26 cases of meningitis occurring in one year in a defined area is presented. The clinical features, and complications are reviewed. Neisseria meningitidis occurred twice as commonly as Haemophilus influenzae, suggesting that the pattern of infection differs from that reported in England and Wales. An incidence of 4·6/100,000 for N. meningitidis is reported exceeding rates of infection in previous UK “epidemics”

Number of adaptive steps to a local fitness peak

We consider a population of genotype sequences evolving on a rugged fitness landscape with many local fitness peaks. The population walks uphill until it encounters a local fitness maximum. We find that the statistical properties of the walk length depend on whether the underlying fitness distribution has a finite mean. If the mean is finite, all the walk length cumulants grow with the sequence length but approach a constant otherwise. Experimental implications of our analytical results are also discussed

Improved power for TB phase IIa trials using a model-based pharmacokinetic-pharmacodynamic approach compared with commonly used analysis methods

The research leading to these results has received funding from the Swedish Research Council (grant number 521-2011-3442) in addition to the Innovative Medicines Initiative Joint Undertaking (www.imi.europe.eu) under grant agreement no. 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in kind contribution.Background : The demand for new anti-TB drugs is high, but development programmes are long and costly. Consequently there is a need for new strategies capable of accelerating this process. Objectives : To explore the power to find statistically significant drug effects using a model-based pharmacokinetic–pharmacodynamic approach in comparison with the methods commonly used for analysing TB Phase IIa trials. Methods : Phase IIa studies of four hypothetical anti-TB drugs (labelled A, B, C and D), each with a different mechanism of action, were simulated using the multistate TB pharmacometric (MTP) model. cfu data were simulated over 14 days for patients taking once-daily monotherapy at four different doses per drug and a reference (10 mg/kg rifampicin). The simulated data were analysed using t-test, ANOVA, mono- and bi-exponential models and a pharmacokinetic–pharmacodynamic model approach (MTP model) to establish their respective power to find a drug effect at the 5% significance level. Results : For the pharmacokinetic–pharmacodynamic model approach, t-test, ANOVA, mono-exponential model and bi-exponential model, the sample sizes needed to achieve 90% power were: 10, 30, 75, 20 and 30 (drug A); 30, 75, 245, 75 and 105 (drug B); 70, >1250, 315, >1250 and >1250 (drug C); and 30, 110, 710, 170 and 185 (drug D), respectively. Conclusions : A model-based design and analysis using a pharmacokinetic–pharmacodynamic approach can reduce the number of patients required to determine a drug effect at least 2-fold compared with current methodologies. This could significantly accelerate early-phase TB drug development.Publisher PDFPeer reviewe

The detection of geothermal areas from Skylab thermal data

Skylab-4 X-5 thermal data of the geysers area was analyzed to determine the feasibility of using midday Skylab images to detect geothermal areas. The hottest ground areas indicated on the Skylab image corresponded to south-facing barren or sparsely vegetated slopes. A geothermal area approximately 15 by 30 m coincided with one of the hottest areas indicated by Skylab. This area could not be unambiguously distinguished from the other areas which are believed to be hotter than their surroundings as a result of their topography, and micrometeorological conditions. A simple modification of a previous thermal model was performed and the predicted temperatures for the hottest slopes using representative values was in general agreement with the observed data. It is concluded that data from a single midday Skylab pass cannot be used to locate geothermal areas

Escaping from nonhyperbolic chaotic attractors

We study the noise-induced escape process from chaotic attractors in nonhyperbolic systems. We provide a general mechanism of escape in the low noise limit, employing the theory of large fluctuations. Specifically, this is achieved by solving the variational equations of the auxiliary Hamiltonian system and by incorporating the initial conditions on the chaotic attractor unambiguously. Our results are exemplified with the H{\'e}non and the Ikeda map and can be implemented straightforwardly to experimental data.Comment: replaced with published versio

Stronger computational modelling of signalling pathways using both continuous and discrete-state methods

Starting from a biochemical signalling pathway model expresses in a process algebra enriched with quantitative information, we automatically derive both continuous-space and discrete-space representations suitable for numerical evaluation. We compare results obtained using approximate stochastic simulation thereby exposing a flaw in the use of the differentiation procedure producing misleading results

The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits

Recent work has suggested a high level of congruence between normative personality, most typically represented by the big five factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-S-Norwegian Brief Form (PID-5NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-S-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-S-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI

Calibrating AIS images using the surface as a reference

A method of evaluating the initial assumptions and uncertainties of the physical connection between Airborne Imaging Spectrometer (AIS) image data and laboratory/field spectrometer data was tested. The Tuscon AIS-2 image connects to lab reference spectra by an alignment to the image spectral endmembers through a system gain and offset for each band. Images were calibrated to reflectance so as to transform the image into a measure that is independent of the solar radiant flux. This transformation also makes the image spectra directly comparable to data from lab and field spectrometers. A method was tested for calibrating AIS images using the surface as a reference. The surface heterogeneity is defined by lab/field spectral measurements. It was found that the Tuscon AIS-2 image is consistent with each of the initial hypotheses: (1) that the AIS-2 instrument calibration is nearly linear; (2) the spectral variance is caused by sub-pixel mixtures of spectrally distinct materials and shade, and (3) that sub-pixel mixtures can be treated as linear mixtures of pure endmembers. It was also found that the image can be characterized by relatively few endmembers using the AIS-2 spectra

Preparing the foundations for video-based, practice-placement support: establishing the role from a students’ perspective

Currently, many placement-based health programme students within the UK are supported through face-to-face visits from university staff. Whilst cited in literature as being of value, the face-to-face nature of this contact is not supported. Alternatives including video-based communications methods offer the potential for cost effective, environmentally responsible support. However, in order to establish the fitness for purpose of alternative approaches, the content and purpose of current support needs to be understood. This project aimed to investigate student perceptions of the ideal content and purpose of clinical support visits, and alternatives to the current face-to-face approach. Fifty-six Physiotherapy undergraduate students responded to questionnaires with a further nine participating in a follow-up focus group. Participants emphasised the value of the visit in guiding learning, ensuring progression and resolving arising issues, and highlighted concerns over alternative approaches. Focus group participants discussed the importance of personal and professional confidence in directing requirements for support, and went on to propose a menu of options for methods of communication.Whilst limited in some applications, video technologies may be one of the options. Overall, however, this project supports the need for consideration of individualised learning journeys within curriculum planning