Material parameter estimation and hypothesis testing on a 1D viscoelastic stenosis model: Methodology

This is the post-print version of the final published paper that is available from the link below. Copyright @ 2013 Walter de Gruyter GmbH.Non-invasive detection, localization and characterization of an arterial stenosis (a blockage or partial blockage in the artery) continues to be an important problem in medicine. Partial blockage stenoses are known to generate disturbances in blood flow which generate shear waves in the chest cavity. We examine a one-dimensional viscoelastic model that incorporates Kelvin–Voigt damping and internal variables, and develop a proof-of-concept methodology using simulated data. We first develop an estimation procedure for the material parameters. We use this procedure to determine confidence intervals for the estimated parameters, which indicates the efficacy of finding parameter estimates in practice. Confidence intervals are computed using asymptotic error theory as well as bootstrapping. We then develop a model comparison test to be used in determining if a particular data set came from a low input amplitude or a high input amplitude; this we anticipate will aid in determining when stenosis is present. These two thrusts together will serve as the methodological basis for our continuing analysis using experimental data currently being collected.National Institute of Allergy and Infectious Diseases, Air Force Office of Scientific Research, Department of Education, and Engineering and Physical Sciences Research Council

High-order space-time finite element schemes for acoustic and viscodynamic wave equations with temporal decoupling

Copyright @ 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.We revisit a method originally introduced by Werder et al. (in Comput. Methods Appl. Mech. Engrg., 190:6685–6708, 2001) for temporally discontinuous Galerkin FEMs applied to a parabolic partial differential equation. In that approach, block systems arise because of the coupling of the spatial systems through inner products of the temporal basis functions. If the spatial finite element space is of dimension D and polynomials of degree r are used in time, the block system has dimension (r + 1)D and is usually regarded as being too large when r > 1. Werder et al. found that the space-time coupling matrices are diagonalizable over inline image for r ⩽100, and this means that the time-coupled computations within a time step can actually be decoupled. By using either continuous Galerkin or spectral element methods in space, we apply this DG-in-time methodology, for the first time, to second-order wave equations including elastodynamics with and without Kelvin–Voigt and Maxwell–Zener viscoelasticity. An example set of numerical results is given to demonstrate the favourable effect on error and computational work of the moderately high-order (up to degree 7) temporal and spatio-temporal approximations, and we also touch on an application of this method to an ambitious problem related to the diagnosis of coronary artery disease

Experiences of the ‘Nearest Relative’ provisions in the compulsory detention of people under the Mental Health Act: rapid systematic review

This is the final version. Available from NIHR Journals Library via the DOI in this record.Background Service users detained for assessment and/or treatment under the Mental Health Act 1983 are allocated a ‘Nearest Relative’. The Nearest Relative has access to confidential information about the service user, and can make decisions about their care and treatment. Tensions exist regarding the identification, displacement and powers of the Nearest Relative. Objectives To examine the experiences of service users, carers and relevant professionals of the Nearest Relative provisions of the Mental Health Act 1983, and the equivalent Named Person provisions in Scotland. Five research objectives were defined, understanding the experiences of and issues associated with i) identification of the Nearest Relative, ii) displacement of the Nearest Relative, iii) confidentiality and information sharing iv) access to support from carers and v) making decisions about treatment or care. Data sources Seven bibliographic databases: MEDLINE (via Ovid), MEDLINE In-Process & Other Non-Indexed Citations (via Ovid), PsycINFO (via Ovid), Social Policy and Practice (via Ovid), HMIC (via Ovid), CINAHL (via EBSCO) and ASSIA (via ProQuest). Citation searching, author contact and grey literature searches were conducted. Review methods A rapid systematic review was conducted in six weeks. Evidence published after 1998 was sought from the UK, pertaining to the experiences of those involved in compulsory detention under the Mental Health Act 1983 (or UK variants), including service users, carers, family members, Nearest Relatives, Named Persons, mental health professionals, policy makers and lawyers. Study selection, data extraction and critical appraisal were completed independently by two reviewers. We sought data about experiences obtained through qualitative means or surveys. Included studies containing several paragraphs of participant quotes and/or author interpretations were entered into a framework synthesis; the rest were summarised descriptively. The framework synthesis was based upon the five research objectives and refined using the findings of key studies from England and Scotland and inductive thematic analysis. Findings Twenty studies were included with 12 prioritised for framework synthesis. Four themes emerged i) issues regarding the identification of the Nearest Relative/Named Person, ii) confidentiality and information sharing, iii) enabling use of the Nearest Relative/Named Person role and iv) importance of maintaining relationships. The involvement of service users in choosing their representative and the role of services in supporting the Nearest Relative/Named Person was identified as important. Limitations There is little recent evidence to inform this important and complex discussion. The review was rigorously conducted despite the short timescale; however a more in-depth, iterative thematic analysis of all the included studies may have provided additional insights into the mechanisms underpinning the issues. Conclusions The Nearest Relative provisions of the Mental Health Act 1983 are complex and of significant importance to individuals detained under the Act and their carers. This rapid review provides specific examples of issues that individuals may experience. More research is needed to aid understanding of this complex topic. Future work Primary research specifically focussed on the perceived and actual use and impact of the Nearest Relative provisions in England and Scotland.This report was commissioned by the Department of Health and Social Care via the NIHR HS&DR programme as a review project within NIHR HS&DR programme project number 16/47/22

Multi-objective shop floor scheduling using monitored energy data

Modern factories will become more and more directly connected to intermittent energy sources like solar systems or wind turbines as part of a smart grid or a self-sufficient supply. However, solar systems or wind turbines are not able to provide a continuous energy supply over a certain time period. In order to enable an effective use of these intermittent energy sources without using temporary energy storages, it is necessary to rapidly and flexibly adapt the energy demand of the factory to the constantly changing requirements of the energy supply. The adaption of the energy demand to the intermittent supply results in different energy-related objectives for the production system of the factory, such as reducing energy consumption, avoiding power peaks, or achieving a power use within the available power supply. Shop Floor Scheduling can help to pursue these objectives within the production system. For this purpose, a solution methodology based on a meta-heuristic will be described for Flexible Job Shop Scheduling taking into account different energy- as well as productivity-related objectives

Improving the cost-effectiveness of visual devices for the control of Riverine tsetse flies, the major vectors of Human African Trypanosomiasis

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 161 m black targets and small 25625 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness

New investigations into the stability of Mesna using LC-MS/MS and NMR

Both LC-MS/MS and NMR analyses confirmed the instability of Mesna and its conversion into Dimesna

Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities

Identifying patients at risk of traumatic brain injury (TBI) is important because research suggests prophylactic treatments to reduce risk of long-term sequelae. Blast pressure waves can cause TBI without penetrating wounds or blunt force trauma. Similarly, bullet impacts distant from the brain can produce pressure waves sufficient to cause mild to moderate TBI. The fluid percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the thigh produce pressure waves in the brain of 18-45 psi and measurable injury to neurons and neuroglia. Analyses of research in goats and epidemiological data from shooting events involving humans show high correlations (r > 0.9) between rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case study has documented epilepsy resulting from a pressure wave without the bullet directly hitting the brain. Taken together, these results support the hypothesis that bullet impacts distant from the brain produce pressure waves that travel to the brain and can retain sufficient magnitude to induce brain injury. The link to long-term sequelae could be investigated via epidemiological studies of patients who were gunshot in the chest to determine whether they experience elevated rates of epilepsy and other neurological sequelae

Comparison and relative utility of inequality measurements: as applied to Scotland’s child dental health

This study compared and assessed the utility of tests of inequality on a series of very large population caries datasets. National cross-sectional caries datasets for Scotland’s 5-year-olds in 1993/94 (n = 5,078); 1995/96 (n = 6,240); 1997/98 (n = 6,584); 1999/00 (n = 6,781); 2002/03 (n = 9,747); 2003/04 (n = 10,956); 2005/06 (n = 10,945) and 2007/08 (n = 12,067) were obtained. Outcomes were based on the d3mft metric (i.e. the number of decayed, missing and filled teeth). An area-based deprivation category (DepCat) measured the subjects’ socioeconomic status (SES). Simple absolute and relative inequality, Odds Ratios and the Significant Caries Index (SIC) as advocated by the World Health Organization were calculated. The measures of complex inequality applied to data were: the Slope Index of Inequality (absolute) and a variety of relative inequality tests i.e. Gini coefficient; Relative Index of Inequality; concentration curve; Koolman and Doorslaer’s transformed Concentration Index; Receiver Operator Curve and Population Attributable Risk (PAR). Additional tests used were plots of SIC deciles (SIC10) and a Scottish Caries Inequality Metric (SCIM10). Over the period, mean d3mft improved from 3.1(95%CI 3.0–3.2) to 1.9(95%CI 1.8–1.9) and d3mft = 0% from 41.1(95%CI 39.8–42.3) to 58.3(95%CI 57.8–59.7). Absolute simple and complex inequality decreased. Relative simple and complex inequality remained comparatively stable. Our results support the use of the SII and RII to measure complex absolute and relative SES inequalities alongside additional tests of complex relative inequality such as PAR and Koolman and Doorslaer’s transformed CI. The latter two have clear interpretations which may influence policy makers. Specialised dental metrics (i.e. SIC, SIC10 and SCIM10) permit the exploration of other important inequalities not determined by SES, and could be applied to many other types of disease where ranking of morbidity is possible e.g. obesity. More generally, the approaches described may be applied to study patterns of health inequality affecting worldwide populations

Needle to needle robot-assisted manufacture of cell therapy products

Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapies for untreatable diseases, generating the need for large volumes of high-quality, clinically-compliant GMP cells to replace costly, high-risk and limited scale manual expansion processes. We present the design of a fully automated, robot-assisted platform incorporating the use of multiliter stirred tank bioreactors for scalable production of adherent human stem cells. The design addresses a needle-to-needle closed process incorporating automated bone marrow collection, cell isolation, expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular, adaptable, fully closed system ensures no direct operator interaction with biological material; all commands are performed through a graphic interface. Seeding of source material, process monitoring, feeding, sampling, harvesting and cryopreservation are automated within the closed platform, comprising two clean room levels enabling both open and closed processes. A bioprocess based on human MSCs expanded on microcarriers was used for proof of concept. Utilizing equivalent culture parameters, the AUTOSTEM robot-assisted platform successfully performed cell expansion at the liter scale, generating results comparable to manual production, while maintaining cell quality postprocessing

Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man