2013 Koiter Medal Paper: Crack-Tip Fields and Toughness of Two-Dimensional Elasto-Plastic Lattices

The dependence of the fracture toughness of two dimensional elasto-plastic lattices upon relative density and ductility of cell wall material is obtained for four topologies: the triangular lattice, kagome lattice, diamond lattice, and the hexagonal lattice. Crack tip fields are explored, including the plastic zone size and crack opening displacement. The cell walls are treated as beams, with a material response given by the Ramberg-Osgood law. There is choice in the criterion for crack advance, and two extremes are considered: (i) the maximum local tensile strain anywhere in the lattice attains the failure strain, or (ii) the average tensile strain across the cell wall attains the failure strain (which can be identified with the necking strain). The dependence of macroscopic fracture toughness upon failure strain, strain hardening exponent and relative density are obtained for each lattice, and scaling laws are derived. The role of imperfections in degrading the fracture toughness is assessed by random movement of the nodes. The paper provides a strategy for obtaining lattices of high toughness at low density, thereby filling gaps in material property space

Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

Explicit Model Checking of Very Large MDP using Partitioning and Secondary Storage

The applicability of model checking is hindered by the state space explosion problem in combination with limited amounts of main memory. To extend its reach, the large available capacities of secondary storage such as hard disks can be exploited. Due to the specific performance characteristics of secondary storage technologies, specialised algorithms are required. In this paper, we present a technique to use secondary storage for probabilistic model checking of Markov decision processes. It combines state space exploration based on partitioning with a block-iterative variant of value iteration over the same partitions for the analysis of probabilistic reachability and expected-reward properties. A sparse matrix-like representation is used to store partitions on secondary storage in a compact format. All file accesses are sequential, and compression can be used without affecting runtime. The technique has been implemented within the Modest Toolset. We evaluate its performance on several benchmark models of up to 3.5 billion states. In the analysis of time-bounded properties on real-time models, our method neutralises the state space explosion induced by the time bound in its entirety.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-24953-7_1

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer

<p>Abstract</p> <p>Background</p> <p>Understanding what constitutes an important difference on a HRQL measure is critical to its interpretation. The aim of this study was to provide a range of estimates of minimally important differences (MIDs) in EQ-5D scores in cancer and to determine if estimates are comparable in lung cancer.</p> <p>Methods</p> <p>A retrospective analysis was conducted on cross-sectional data collected from 534 cancer patients, 50 of whom were lung cancer patients. A range of minimally important differences (MIDs) in EQ-5D index-based utility (UK and US) scores and VAS scores were estimated using both anchor-based and distribution-based (1/2 standard deviation and standard error of the measure) approaches. Groups were anchored using Eastern Cooperative Oncology Group performance status (PS) ratings and FACT-G total score-based quintiles.</p> <p>Results</p> <p>For UK-utility scores, MID estimates based on PS ranged from 0.10 to 0.12 both for all cancers and for lung cancer subgroup. Using FACT-G quintiles, MIDs were 0.09 to 0.10 for all cancers, and 0.07 to 0.08 for lung cancer. For US-utility scores, MIDs ranged from 0.07 to 0.09 grouped by PS for all cancers and for lung cancer; when based on FACT-G quintiles, MIDs were 0.06 to 0.07 in all cancers and 0.05 to 0.06 in lung cancer. MIDs for VAS scores were similar for lung and all cancers, ranging from 8 to 12 (PS) and 7 to 10 (FACT-G quintiles).</p> <p>Discussion</p> <p>Important differences in EQ-5D utility and VAS scores were similar for all cancers and lung cancer, with the lower end of the range of estimates closer to the MID, i.e. 0.08 for UK-index scores, 0.06 for US-index scores, and 0.07 for VAS scores.</p

Secondary contact and admixture between independently invading populations of the Western corn rootworm, diabrotica virgifera virgifera in Europe

The western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is one of the most destructive pests of corn in North America and is currently invading Europe. The two major invasive outbreaks of rootworm in Europe have occurred, in North-West Italy and in Central and South-Eastern Europe. These two outbreaks originated from independent introductions from North America. Secondary contact probably occurred in North Italy between these two outbreaks, in 2008. We used 13 microsatellite markers to conduct a population genetics study, to demonstrate that this geographic contact resulted in a zone of admixture in the Italian region of Veneto. We show that i) genetic variation is greater in the contact zone than in the parental outbreaks; ii) several signs of admixture were detected in some Venetian samples, in a Bayesian analysis of the population structure and in an approximate Bayesian computation analysis of historical scenarios and, finally, iii) allelic frequency clines were observed at microsatellite loci. The contact between the invasive outbreaks in North-West Italy and Central and South-Eastern Europe resulted in a zone of admixture, with particular characteristics. The evolutionary implications of the existence of a zone of admixture in Northern Italy and their possible impact on the invasion success of the western corn rootworm are discussed

Reproducibility and responsiveness of the Symptom Severity Scale and the hand and finger function subscale of the Dutch arthritis impact measurement scales (Dutch-AIMS2-HFF) in primary care patients with wrist or hand problems

BACKGROUND: To determine the clinimetric properties of two questionnaires assessing symptoms (Symptom Severity Scale) and physical functioning (hand and finger function subscale of the AIMS2) in a Dutch primary care population. METHODS: The first 84 participants in a 1-year follow-up study on the diagnosis and prognosis of hand and wrist problems completed the Symptom Severity Scale and the hand and finger function subscale of the Dutch-AIMS2 twice within 1 to 2 weeks. The data were used to assess test-retest reliability (ICC) and smallest detectable change (SDC, based on the standard error of measurement (SEM)). To assess responsiveness, changes in scores between baseline and the 3 month follow-up were related to an external criterion to estimate the minimal important change (MIC). We calculated the group size needed to detect the MIC beyond measurement error. RESULTS: The ICC for the Symptom Severity Scale was 0.68 (95% CI: 0.54–0.78). The SDC was 1.00 at individual level and 0.11 at group level, both on a 5-point scale. The MIC was 0.23, exceeding the SDC at group level. The group size required to detect a MIC beyond measurement error was 19 for the Symptom Severity Scale. The ICC for the hand and finger function subscale of the Dutch-AIMS2 was 0.62 (95% CI: 0.47–0.74). The SDC was 3.80 at individual level and 0.42 at group level, both on an 11-point scale. The MIC was 0.31, which was less than the SDC at group level. The group size required to detect a MIC beyond measurement error was 150. CONCLUSION: In our heterogeneous primary care population the Symptom Severity Scale was found to be a suitable instrument to assess the severity of symptoms, whereas the hand and finger function subscale of the Dutch-AIMS2 was less suitable for the measurement of physical functioning in patients with hand and wrist problems

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response