Assessment of the face validity, feasibility and utility of a patient-completed questionnaire for polymyalgia rheumatica: a postal survey using the QQ-10 questionnaire.

BACKGROUND: The development of a patient-reported outcome measure (PROM) for polymyalgia rheumatica (PMR), a condition that causes pain, stiffness and disability, is necessary as there is no current validated disease-specific measure. Initial literature synthesis and qualitative research established a conceptual framework for the condition along with a list of symptoms and effects of PMR that patients felt were important to them. These findings were used to derive the candidate items for a patient-completed questionnaire. We aim to establish the face validity of this initial "long form" of a PROM. METHODS: People with a current or previous diagnosis of PMR were recruited both from the community and from rheumatology clinics. They were asked to complete the PMR questionnaire along with the QQ-10 questionnaire, which is a measure used to assess the face validity, feasibility and utility of patient healthcare questionnaires. RESULTS: A total of 28 participants with an age range of 59-85 years and a length of time since diagnosis from 4 months to 18 years completed the QQ-10. The overall mean "value" score was 79% (SD 12), and the mean "burden" score was 21% (SD 18). The free-text comments were analysed thematically and were found to focus on layout, content, where in the clinical pathway the questionnaire would be most beneficial, specific items missing and other areas for consideration. CONCLUSIONS: The high mean value score and low burden score indicate that the questionnaire has good face validity and is acceptable to patients. The questionnaire now needs to undergo further psychometric evaluation and refinement to develop the final tool for use in clinical practice and research

Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats

YesIt has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats’ performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia

Evolutionary diversification of the RomR protein of the invasive deltaproteobacterium, Bdellovibrio bacteriovorus

This is the final version. Available on open access from Nature Research via the DOI in this recordBdellovibrio bacteriovorus is a predatory deltaproteobacterium that encounters individual Gram-negative prey bacteria with gliding or swimming motility, and then is able to invade such prey cells via type IVa pilus-dependent mechanisms. Movement control (pili or gliding) in other deltaproteobacteria, such as the pack hunting Myxococcus xanthus, uses a response regulator protein, RomRMx (which dynamically relocalises between the cell poles) and a GTPase, MglAMx, previously postulated as an interface between the FrzMx chemosensory system and gliding or pilus-motility apparatus, to produce regulated bidirectional motility. In contrast, B. bacteriovorus predation is a more singular encounter between a lone predator and prey; contact is always via the piliated, non-flagellar pole of the predator, involving MglABd, but no Frz system. In this new study, tracking fluorescent RomRBd microscopically during predatory growth shows that it does not dynamically relocalise, in contrast to the M. xanthus protein; instead having possible roles in growth events. Furthermore, transcriptional start analysis, site-directed mutagenesis and bacterial two-hybrid interaction studies, indicate an evolutionary loss of RomRBd activation (via receiver domain phosphorylation) in this lone hunting bacterium, demonstrating divergence from its bipolar role in motility in pack-hunting M. xanthus and further evolution that may differentiate lone from pack predators.Leverhulme TrustMedical Research Council (MRC)Biotechnology and Biological Sciences Research Council (BBSRC

Predicting clinical diagnosis in Huntington's disease: An imaging polymarker

Objective Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real‐life clinical diagnosis in HD. Method A multivariate machine learning approach was applied to resting‐state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross‐group comparisons between preHD and controls, and within the preHD group in relation to “estimated” and “actual” proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy. Results Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models. Interpretation We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials

Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

Further properties on the core partial order and other matrix partial orders

This paper carries further the study of core partial order initiated by Baksalary and Trenkler [Core inverse of matrices, Linear Multilinear Algebra. 2010;58:681-697]. We have extensively studied the core partial order, and some new characterizations are obtained in this paper. In addition, simple expressions for the already known characterizations of the minus, the star (and one-sided star), the sharp (and one-sided sharp) and the diamond partial orders are also obtained by using a Hartwig-Spindelbck decomposition.This author was partially supported by Ministry of Education of Spain [grant number DGI MTM2010-18228] and by Universidad Nacional de La Pampa, Argentina, Facultad de Ingenieria [grant number Resol. No 049/11].Malik, SB.; Rueda, LC.; Thome, N. (2014). Further properties on the core partial order and other matrix partial orders. Linear and Multilinear Algebra. 62(12):1629-1648. https://doi.org/10.1080/03081087.2013.839676S162916486212Mitra, S. K., & Bhimasankaram, P. (2010). MATRIX PARTIAL ORDERS, SHORTED OPERATORS AND APPLICATIONS. SERIES IN ALGEBRA. doi:10.1142/9789812838452Baksalary, J. K., & Hauke, J. (1990). A further algebraic version of Cochran’s theorem and matrix partial orderings. Linear Algebra and its Applications, 127, 157-169. doi:10.1016/0024-3795(90)90341-9Baksalary, O. M., & Trenkler, G. (2010). Core inverse of matrices. Linear and Multilinear Algebra, 58(6), 681-697. doi:10.1080/03081080902778222Baksalary, J. K., Baksalary, O. M., & Liu, X. (2003). Further properties of the star, left-star, right-star, and minus partial orderings. Linear Algebra and its Applications, 375, 83-94. doi:10.1016/s0024-3795(03)00609-8Groβ, J., Hauke, J., & Markiewicz, A. (1999). Partial orderings, preorderings, and the polar decomposition of matrices. Linear Algebra and its Applications, 289(1-3), 161-168. doi:10.1016/s0024-3795(98)10108-8Mosić, D., & Djordjević, D. S. (2012). Reverse order law for the group inverse in rings. Applied Mathematics and Computation, 219(5), 2526-2534. doi:10.1016/j.amc.2012.08.088Patrício, P., & Costa, A. (2009). On the Drazin index of regular elements. Open Mathematics, 7(2). doi:10.2478/s11533-009-0015-6Rakić, D. S., & Djordjević, D. S. (2012). Space pre-order and minus partial order for operators on Banach spaces. Aequationes mathematicae, 85(3), 429-448. doi:10.1007/s00010-012-0133-2Tošić, M., & Cvetković-Ilić, D. S. (2012). Invertibility of a linear combination of two matrices and partial orderings. Applied Mathematics and Computation, 218(9), 4651-4657. doi:10.1016/j.amc.2011.10.052Hartwig, R. E., & Spindelböck, K. (1983). Matrices for whichA∗andA†commute. Linear and Multilinear Algebra, 14(3), 241-256. doi:10.1080/03081088308817561Baksalary, O. M., Styan, G. P. H., & Trenkler, G. (2009). On a matrix decomposition of Hartwig and Spindelböck. Linear Algebra and its Applications, 430(10), 2798-2812. doi:10.1016/j.laa.2009.01.015Mielniczuk, J. (2011). Note on the core matrix partial ordering. Discussiones Mathematicae Probability and Statistics, 31(1-2), 71. doi:10.7151/dmps.1134Meyer, C. (2000). Matrix Analysis and Applied Linear Algebra. doi:10.1137/1.978089871951

Access to recreational physical activities by car and bus : an assessment of socio-spatial inequalities in mainland Scotland

Obesity and other chronic conditions linked with low levels of physical activity (PA) are associated with deprivation. One reason for this could be that it is more difficult for low-income groups to access recreational PA facilities such as swimming pools and sports centres than high-income groups. In this paper, we explore the distribution of access to PA facilities by car and bus across mainland Scotland by income deprivation at datazone level. GIS car and bus networks were created to determine the number of PA facilities accessible within travel times of 10, 20 and 30 minutes. Multilevel negative binomial regression models were then used to investigate the distribution of the number of accessible facilities, adjusting for datazone population size and local authority. Access to PA facilities by car was significantly (p<0.01) higher for the most affluent quintile of area-based income deprivation than for most other quintiles in small towns and all other quintiles in rural areas. Accessibility by bus was significantly lower for the most affluent quintile than for other quintiles in urban areas and small towns, but not in rural areas. Overall, we found that the most disadvantaged groups were those without access to a car and living in the most affluent areas or in rural areas