DScentTrail: A new way of viewing deception

The DScentTrail System has been created to support and demonstrate research theories in the joint disciplines of computational inference, forensic psychology and expert decision-making in the area of counter-terrorism. DScentTrail is a decision support system, incorporating artificial intelligence, and is intended to be used by investigators. The investigator is presented with a visual representation of a suspect‟s behaviour over time, allowing them to present multiple challenges from which they may prove the suspect guilty outright or receive cognitive or emotional clues of deception. There are links into a neural network, which attempts to identify deceptive behaviour of individuals; the results are fed back into DScentTrail hence giving further enrichment to the information available to the investigator

A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK

Introduction: Venous leg ulceration causes significant pain and suffering for patients, additionally it places considerable financial and service burden on the National Health Service (NHS). A large proportion of venous leg ulceration do not heal within the standard time frames of 16 – 24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. Static wounds can have significant negative impact on the patients quality of life, the wound bed and periwound skin, increased risk of infection all of which results in delayed wound healing and increased health service costs. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce cost and release nursing time whilst maintaining standards of care. Cutimed® Sorbion® Sachet S is a treatment option for the management of patients with a venous leg ulceration. The objective of this study was to provide an update of the health economic analysis of Cutimed® Sorbion® Sachet S in comparison to relevant comparators in the UK with current cost data. Methods: Cutimed® Sorbion® Sachet S was compared against Zetuvit Plus, DryMax extra, KerraMax Care and Eclypse from a cost effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilized based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed venous leg ulcer. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: First, all patients start in a static health state with a non-healed but non-progressing venous leg ulcer. It is assumed in the model that patients can transition to a deteriorating health state where a wound is improving or the wound could progress. Additionally, venous leg ulcers could be healed from a progressed wound (i.e. improved wound), they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. Results: The cost-effectiveness analysis demonstrates health economic dominance of Cutimed® Sorbion® Sachet S being more effective and cost-saving against all analysed comparators. When using literature-based input values the incrementally higher healing rates for Cutimed® Sorbion® Sachet S are 11.04 months (versus Zetuvit Plus), 29.04 months (versus DryMax extra), 1.68 months (versus KerraMax Care) and 11.04 months (versus Eclypse). Cost savings per patient were 37.60£ (versus Zetuvit Plus), 171.68£ (versus DryMax extra), 3.13£ (versus KerraMax Care) and 43.63£ (versus Eclypse). Clinical benefits and cost savings are increasing when real life practice assumptions based on expert opinion are included. Conclusions: Based on the underlying health economic model, Cutimed® Sorbion® Sachet S is more effective and less costly than other comparative products in venous leg ulcers in the UK

Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.

BACKGROUND: Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic. METHODS: Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing. RESULTS: No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes' transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells' gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed. CONCLUSION: The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions - a pilot study

Background: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Methods: Four adult warmblood horses received a unilateral injection of 10 × 106 autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. Results: AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Conclusions: Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 106 AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT

Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity

The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells. No objective clinical responses were observed. CAR T cell engraftment in patients within cohort 4 was significantly higher. However, engraftment was short-lived with a rapid decline of systemic CAR T cells within 14 days. Patients in cohort 4 had transient, acute respiratory toxicity which, in combination with lack of prolonged CAR T cell persistence, resulted in the premature closure of the trial. Elevated levels of systemic IFNγ and IL-6 implied that the CEACAM5-specific T cells had undergone immune activation in vivo but only in patients receiving high-intensity pre-conditioning. Expression of CEACAM5 on lung epithelium may have resulted in this transient toxicity. Raised levels of serum cytokines including IL-6 in these patients implicate cytokine release as one of several potential factors exacerbating the observed respiratory toxicity. Whilst improved CAR designs and T cell production methods could improve the systemic persistence and activity, methods to control CAR T 'on-target, off-tissue' toxicity are required to enable a clinical impact of this approach in solid malignancies

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

The weight-loss experience : qualitative exploration

BACKGROUND: Long-term weight management consists of weight-loss, weight-loss maintenance, and weight-gain stages. Qualitative insights into weight management are now appearing in the literature however research appears to be biased towards explorations of weight-loss maintenance. The qualitative understanding of weight loss, which begets weight-loss maintenance and might establish the experiences and behaviours necessary for successful long-term weight management, is comparatively under-investigated. The aim of this study was to investigate the weight-loss experiences of a sample of participants not aligned to clinical intervention research, in order to understand the weight-loss experiences of a naturalistic sample. METHODS: Participants (n=8) with weight-loss (n=4) and weight-maintenance experiences (n=4) were interviewed using a semi-structured interview to understand the weight-loss experience. Interview data was analysed thematically using Framework Analysis and was underpinned by realist meta-theory. RESULTS: Weight loss was experienced as an enduring challenge, where factors that assisted weight loss were developed and experienced dichotomously to factors that hindered it. Participants described barriers to (dichotomous thinking, environments, social pressures and weight centeredness) and facilitators of (mindfulness, knowledge, exercise, readiness to change, structure, self-monitoring and social support) their weight-loss goals in rich detail, highlighting that weight loss was a complex experience. CONCLUSIONS: Weight loss was a difficult task, with physical, social, behavioural and environmental that appeared to assist and inhibit weight-loss efforts concurrently. Health professionals might need to better understand the day-to-day challenges of dieters in order to provide more effective, tailored treatments. Future research should look to investigate the psycho-social consequences of weight-loss dieting, in particular self-imposed social exclusion and spousal sabotage and flexible approaches to treatment