The development and assessment of behavioural markers to support counter-IED training

This article describes the method used to develop and test a checklist of behavioural markers designed to support UK military forces during Counter-Improvised Explosive Device (C-IED) training. IEDs represent a significant threat to UK and allied forces. Effective C-IED procedures and techniques are central to reducing risk to life in this safety critical role. Behavioural markers have been developed to characterise and assess non-technical skills which have been shown to be important in maintaining high performance in other safety critical domains. The aims of this study were two-fold. Firstly to develop a method which could be used to capture and assess operationally relevant behavioural markers for use in C-IED training relating primarily to non-technical skills. Secondly, to test the user acceptance of the behavioural marker checklist during military training activities. Through engagement with military subject matter experts, operationally relevant and observable behaviours seen in C-IED training have been identified and their links to stronger and weaker performance have been established. Using a card-sort technique, the content validity of each of the markers was assessed in addition to their detectability in an operational context. Following this assessment, a selection of the most operationally relevant and detectable behaviours were assimilated into a checklist and this checklist was tested in C-IED training activities. The results of the study show that the method used was effective in generating and assessing the behavioural markers using military subject matter experts. The study also broadly supports the utility and user-acceptance of the use of behavioural markers during training activities. The checklist developed using this methodology will provide those responsible for delivering instruction in C-IED techniques and procedures with a straightforward process for identifying good and poor performance with respect to non-technical skills. In addition it will provide a basis for the provision of focussed feedback to trainees during debrief

The effect of surgical approach on the histology of the femoral head following resurfacing of the hip : analysis of retrieval specimens

Objectives: We aimed to determine the effect of surgical approach on the histology of the femoral head following resurfacing of the hip. Methods: We performed a histological assessment of the bone under the femoral component taken from retrieval specimens of patients having revision surgery following resurfacing of the hip. We compared the number of empty lacunae in specimens from patients who had originally had a posterior surgical approach with the number in patients having alternative surgical approaches. Results: We found a statistically significant increase in the percentage of empty lacunae in retrieval specimens from patients who had the posterior approach compared with other surgical approaches (p < 0.001). Conclusions: This indicates that the vascular compromise that occurs during the posterior surgical approach does have long-term effects on the bone of the femoral head, even if it does not cause overt avascular necrosis

Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway

A colorimetric CMOS-based platform for rapid total serum cholesterol quantification

Elevated cholesterol levels are associated with a greater risk of developing cardiovascular disease and other illnesses, making it a prime candidate for detection on a disposable biosensor for rapid point of care diagnostics. One of the methods to quantify cholesterol levels in human blood serum uses an optically mediated enzyme assay and a bench top spectrophotometer. The bulkiness and power hungry nature of the equipment limits its usage to laboratories. Here, we present a new disposable sensing platform that is based on a complementary metal oxide semiconductor process for total cholesterol quantification in pure blood serum. The platform that we implemented comprises readily mass-manufacturable components that exploit colorimetric changes of cholesterol oxidase and cholesterol esterase reactions. We have shown that our quantification results are comparable to that obtained by a bench top spectrophotometer. Using the implemented device, we have measured cholesterol concentration in human blood serum as low as 29 μM with a limit of detection at 13 μM, which is approximately 400 times lower than average physiological range, implying that our device also has the potential to be used for applications that require greater sensitivity

Contest behaviour of maize weevil larvae when competing within seeds

Food limitation induces severe competition for obligate seed-feeding insect larvae that are unable to leave the seed selected by their mother. The number of eggs laid per seed and the number of larvae hatched from the eggs are important determinants of whether larval behaviour within the seed will be of the scramble or the contest type. In maize weevils, Sitophilus zeamais, few adults emerge per seed regardless of the number of eggs laid, which may arise from scramble competition, if the optimum egg density (i.e. egg density leading to maximum total larval fitness) is low compared to the number of eggs laid per seed, or from contest competition due to direct interference among the larvae. The behavioural process and the ecological outcome of competition were assessed in two strains of the maize weevil. Neither strain showed a reduction in body mass with increased competition, and they had similar optimal egg densities (two eggs per seed). There was a hump in the larval fitness curve suggesting a scramble competition, but this conclusion is compromised because the optimum egg density was small (two eggs per seed). X-ray imaging of seeds was used to observe interactions of larvae within the seed and showed direct interference, with aggression among the larvae. This provides evidence of contest-like competition within seeds even when egg density was low. Hence, one should be cautious in inferring the underlying type of competitive behaviour from variables such as body mass and initial egg density per seed. Direct observation of behaviour is required to make such an inference

Contest behaviour of maize weevil larvae when competing within seeds

Food limitation induces severe competition for obligate seed-feeding insect larvae that are unable to leave the seed selected by their mother. The number of eggs laid per seed and the number of larvae hatched from the eggs are important determinants of whether larval behaviour within the seed will be of the scramble or the contest type. In maize weevils, Sitophilus zeamais, few adults emerge per seed regardless of the number of eggs laid, which may arise from scramble competition, if the optimum egg density (i.e. egg density leading to maximum total larval fitness) is low compared to the number of eggs laid per seed, or from contest competition due to direct interference among the larvae. The behavioural process and the ecological outcome of competition were assessed in two strains of the maize weevil. Neither strain showed a reduction in body mass with increased competition, and they had similar optimal egg densities (two eggs per seed). There was a hump in the larval fitness curve suggesting a scramble competition, but this conclusion is compromised because the optimum egg density was small (two eggs per seed). X-ray imaging of seeds was used to observe interactions of larvae within the seed and showed direct interference, with aggression among the larvae. This provides evidence of contest-like competition within seeds even when egg density was low. Hence, one should be cautious in inferring the underlying type of competitive behaviour from variables such as body mass and initial egg density per seed. Direct observation of behaviour is required to make such an inference

Reframing How Physical Activity Reduces The Incidence of Clinically-Diagnosed Cancers: Appraising Exercise-Induced Immuno-Modulation As An Integral Mechanism

Undertaking a high volume of physical activity is associated with reduced risk of a broad range of clinically diagnosed cancers. These findings, which imply that physical activity induces physiological changes that avert or suppress neoplastic activity, are supported by preclinical intervention studies in rodents demonstrating that structured regular exercise commonly represses tumour growth. In Part 1 of this review, we summarise epidemiology and preclinical evidence linking physical activity or regular structured exercise with reduced cancer risk or tumour growth. Despite abundant evidence that physical activity commonly exerts anti-cancer effects, the mechanism(s)-of-action responsible for these beneficial outcomes is undefined and remains subject to ongoing speculation. In Part 2, we outline why altered immune regulation from physical activity - specifically to T cells - is likely an integral mechanism. We do this by first explaining how physical activity appears to modulate the cancer immunoediting process. In doing so, we highlight that augmented elimination of immunogenic cancer cells predominantly leads to the containment of cancers in a ‘precancerous’ or ‘covert’ equilibrium state, thus reducing the incidence of clinically diagnosed cancers among physically active individuals. In seeking to understand how physical activity might augment T cell function to avert cancer outgrowth, in Part 3 we appraise how physical activity affects the determinants of a successful T cell response against immunogenic cancer cells. Using the cancer immunogram as a basis for this evaluation, we assess the effects of physical activity on: (i) general T cell status in blood, (ii) T cell infiltration to tissues, (iii) presence of immune checkpoints associated with T cell exhaustion and anergy, (iv) presence of inflammatory inhibitors of T cells and (v) presence of metabolic inhibitors of T cells. The extent to which physical activity alters these determinants to reduce the risk of clinically diagnosed cancers – and whether physical activity changes these determinants in an interconnected or unrelated manner – is unresolved. Accordingly, we analyse how physical activity might alter each determinant, and we show how these changes may interconnect to explain how physical activity alters T cell regulation to prevent cancer outgrowth

NURBS modeling and structural shape optimization of cardiovascular stents

Cardiovascular stents have been used since the 1990s to treat atherosclerosis, one of leading causes of death in the western world, and structural optimization has led to significant improvements in stent performance. Much of the potential variation in stent geometry, however, has remained unconsidered. This paper presents a non-uniform rational basis spline (NURBS) parameterization of a stent, the inclusion of structural fatigue resistance as a design consideration, and the results of a design optimization based on response surface techniques. Results show the feasibility and merits of the NURBS approach, which models a much broader range of shapes than was previously possible. Multi-objective optimization produces a range of geometrically diverse Pareto-optimal designs; these can be used to develop future clinical design guides, accounting for the variation observed across patients. We conclude by motivating future work with increasingly complex physical modeling and optimization capabilities

An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 216 sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2 – 12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM – 231 mM, encompassing glucose’s physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine

Using a virtual reality cricket simulator to explore the effects of pressure, competition anxiety on batting performance in cricket

Virtual reality (VR) has created opportunities to innovatively re-imagine the way we examine the relations between pressure, competition anxiety and performance. This study aimed to determine the efficacy of VR as a means of measuring the effects of competition anxiety when pressure manipulations are applied while participants bat in a cricket batting VR simulator. The twenty-eight male participants who took part in two experiments were divided into a high (14, mean age: 22.94, SD: 5.4) and a low skill group (14; mean age: 23.55, SD: 9.9). The aim of the first experiment was to validate the VR simulator as a tool that could capture differences in batting performance between a high and low skilled group. The results showed that high skill participants not only scored significantly higher run rates than low skill participants, but they outperformed the low skill group in all performance measures including higher incidences of correct foot placements that reflect better anticipatory responses. Having established the VR batting simulator as being a reliable tool for capturing batting dynamics, experiment 2 aimed to explore the effects of a pressure manipulation on competition anxiety and batting performance. All measures of competition anxiety were significantly greater for both groups in the high-pressure condition compared to the two low-pressure conditions (p &lt; 0.001). The magnitude of this effect was greater in the low skill group for cognitive (0.59) and somatic (0.794) anxiety. Despite anxiety levels significantly increasing in the high-pressure condition, no significant negative changes to batting performance were found for either group, with both groups actually demonstrating performance improvements. Overall, the findings show how a cricket batting virtual reality simulator can be used as a tool to measure the effects of pressure on competition anxiety and batting performance in tasks involving dynamic skill execution.</p