The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.Peer reviewedFinal Accepted Versio

Can a stress management programme reduce stress and improve quality of life in people diagnosed with multiple sclerosis?

Background Despite evidence of perceived stress as a risk factor for multiple sclerosis activity, the evidence for managing stress is limited. Objective To evaluate a stress management programme on perceived stress and quality of life, over 6 months. Methods One hundred people with multiple sclerosis were randomly assigned to either a stress management programme of mindfulness, meditation and progressive muscle relaxation, or wait list. Perceived stress and quality of life were assessed at three intervals across 6 months. Salivary cortisol levels were assessed at two intervals: baseline and first follow-up. Results The stress management programme did not significantly reduce perceived stress, when comparing mean scores. Secondary analysis using median scores found a significant improvement for quality of life, favouring the intervention group. Conclusion Stress management had no significant effect on the primary outcome of perceived stress but did improve quality of life in a secondary analysis of median scores

The growth and form of knowledge networks by kinesthetic curiosity

Throughout life, we might seek a calling, companions, skills, entertainment, truth, self-knowledge, beauty, and edification. The practice of curiosity can be viewed as an extended and open-ended search for valuable information with hidden identity and location in a complex space of interconnected information. Despite its importance, curiosity has been challenging to computationally model because the practice of curiosity often flourishes without specific goals, external reward, or immediate feedback. Here, we show how network science, statistical physics, and philosophy can be integrated into an approach that coheres with and expands the psychological taxonomies of specific-diversive and perceptual-epistemic curiosity. Using this interdisciplinary approach, we distill functional modes of curious information seeking as searching movements in information space. The kinesthetic model of curiosity offers a vibrant counterpart to the deliberative predictions of model-based reinforcement learning. In doing so, this model unearths new computational opportunities for identifying what makes curiosity curious

Theoretical stellar models for old galactic clusters

We present new evolutionary stellar models suitable for old Population I clusters, discussing both the consequences of the most recent improvements in the input physics and the effect of element diffusion within the stellar structures. Theoretical cluster isochrones are presented, covering the range of ages from 1 to 9 Gyr for the four selected choices on the metallicity Z= 0.007, 0.010, 0.015 and 0.020. Theoretical uncertainties on the efficiency of superadiabatic convection are discussed in some details. Isochrone fitting to the CM diagrams of the two well observed galactic clusters NGC2420 and M67 indicates that a mixing length parameter alpha = 1.9 appears adequate for reproducing the observed color of cool giant stars. The problems in matching theoretical preditions to the observed slope of MS stars are discussed.Comment: 7 pages, 14 postscript figures, accepted for publication on MNRA

Steroid receptor coactivator 2 is required for female fertility and mammary morphogenesis: insights from the mouse, relevance to the human

Although the importance of the progesterone receptor (PR) to female reproductive and mammary gland biology is firmly established, the coregulators selectively co-opted by PR in these systems have not been clearly delineated. A selective gene-knockout approach applied to the mouse, which abrogates gene function only in cell types that express PR, recently disclosed steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) to be an indispensable coregulator for uterine and mammary gland responses that require progesterone. Uterine cells positive for PR (but devoid of SRC-2) were found to be incapable of facilitating embryo implantation, a necessary first step toward the establishment of the materno-fetal interface. Importantly, such an implantation defect is not exhibited by knockouts for SRC-1 or SRC-3, underscoring the unique coregulator importance of SRC-2 in peri-implantation biology. Moreover, despite normal levels of PR, SRC-1 and SRC-3, progesterone-dependent branching morphogenesis and alveologenesis fails to occur in the murine mammary gland in the absence of SRC-2, thereby establishing a critical coregulator role for SRC-2 in signaling cascades that mediate progesterone-induced mammary epithelial proliferation. Finally, the recent detection of SRC-2 in the human endometrium and breast suggests that this coregulator may represent a new clinical target for the future management of female reproductive health and/or breast cancer

Development and field testing of a vision-based displacement system using a low cost wireless action camera

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThis paper describes development of a contactless, low cost vision-based system for displacement measurement of civil structures. Displacement measurements provide a valuable insight into the structural condition and service behaviour of bridges under live loading. Conventional displacement gauges or GPS based systems have limitations in terms of access to the infrastructure and accuracy. The system introduced in this paper provides a low cost durable alternative which is rapidly deployable in the field and does not require direct contact or access to the infrastructure or its vicinity. A commercial action camera was modified to facilitate the use of a telescopic lens and paired with the development of robust displacement identification algorithms based on pattern matching. Performance was evaluated first in a series of controlled laboratory tests and validated against displacement measurements obtained using a fibre optic displacement gauge. The efficiency of the system for field applications was then demonstrated by capturing the validated bridge response of two structures under live loading including the iconic peace bridge. Located in the City of Derry, Northern Ireland, the Peace Bridge is a 310 m curved self-anchored suspension pedestrian bridge structure. The vision-based results of the field experiment were confirmed against displacements calculated from measured accelerations during a dynamic assessment of the structure under crowd loading. In field applications the developed system can achieve a root mean square error (RMSE) of 0.03 mm against verified measurements

Multiscale and multimodal network dynamics underpinning working memory

Working memory (WM) allows information to be stored and manipulated over short time scales. Performance on WM tasks is thought to be supported by the frontoparietal system (FPS), the default mode system (DMS), and interactions between them. Yet little is known about how these systems and their interactions relate to individual differences in WM performance. We address this gap in knowledge using functional MRI data acquired during the performance of a 2-back WM task, as well as diffusion tensor imaging data collected in the same individuals. We show that the strength of functional interactions between the FPS and DMS during task engagement is inversely correlated with WM performance, and that this strength is modulated by the activation of FPS regions but not DMS regions. Next, we use a clustering algorithm to identify two distinct subnetworks of the FPS, and find that these subnetworks display distinguishable patterns of gene expression. Activity in one subnetwork is positively associated with the strength of FPS-DMS functional interactions, while activity in the second subnetwork is negatively associated. Further, the pattern of structural linkages of these subnetworks explains their differential capacity to influence the strength of FPS-DMS functional interactions. To determine whether these observations could provide a mechanistic account of large-scale neural underpinnings of WM, we build a computational model of the system composed of coupled oscillators. Modulating the amplitude of the subnetworks in the model causes the expected change in the strength of FPS-DMS functional interactions, thereby offering support for a mechanism in which subnetwork activity tunes functional interactions. Broadly, our study presents a holistic account of how regional activity, functional interactions, and structural linkages together support individual differences in WM in humans