A Mathematical Model for Lymphangiogenesis in Normal and Diabetic Wounds

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis) very few have been proposed for the regeneration of the lymphatic network. Moreover, lymphangiogenesis is markedly distinct from angiogenesis, occurring at different times and in a different manner. Here a model of five ordinary differential equations is presented to describe the formation of lymphatic capillaries following a skin wound. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from experimental and clinical data. The system is then solved numerically and the results are compared with the available biological literature. Finally, a parameter sensitivity analysis of the model is taken as a starting point for suggesting new therapeutic approaches targeting the enhancement of lymphangiogenesis in diabetic wounds. The work provides a deeper understanding of the phenomenon in question, clarifying the main factors involved. In particular, the balance between TGF-$\beta$ and VEGF levels, rather than their absolute values, is identified as crucial to effective lymphangiogenesis. In addition, the results indicate lowering the macrophage-mediated activation of TGF-$\beta$ and increasing the basal lymphatic endothelial cell growth rate, \emph{inter alia}, as potential treatments. It is hoped the findings of this paper may be considered in the development of future experiments investigating novel lymphangiogenic therapies

Adding Adhesion to a Chemical Signaling Model for Somite Formation

Somites are condensations of mesodermal cells that form along the two sides of the neural tube during early vertebrate development. They are one of the first instances of a periodic pattern, and give rise to repeated structures such as the vertebrae. A number of theories for the mechanisms underpinning somite formation have been proposed. For example, in the “clock and wavefront” model (Cooke and Zeeman in J. Theor. Biol. 58:455– 476, 1976), a cellular oscillator coupled to a determination wave progressing along the anterior-posterior axis serves to group cells into a presumptive somite. More recently, a chemical signaling model has been developed and analyzed by Maini and coworkers (Collier et al. in J. Theor. Biol. 207:305–316, 2000; Schnell et al. in C. R. Biol. 325:179– 189, 2002; McInerney et al. in Math. Med. Biol. 21:85–113, 2004), with equations for two chemical regulators with entrained dynamics. One of the chemicals is identified as a somitic factor, which is assumed to translate into a pattern of cellular aggregations via its effect on cell–cell adhesion. Here, the authors propose an extension to this model that includes an explicit equation for an adhesive cell population. They represent cell adhesion via an integral over the sensing region of the cell, based on a model developed previousl

A comparison of the ballistic behaviour of conventionally sintered and additively manufactured alumina

Production of ceramic armour solutions on-demand/in-theatre would have significant logistical and military advantages. However, even assuming that such technologies could be successfully deployed in the field, such near net-shape manufacturing technology is relatively immature compared to conventional sintering of ceramics. In this study, the ballistic performance of a series of additively manufactured (AM)/rapidly-prototyped (RP) alumina tiles of 97.2% of the density of Sintox FA™ were investigated using both forward- and reverse-ballistic experiments. These experiments, undertaken with compressed gas-guns, employed the depth-of-penetration technique and flash X-ray as primary diagnostics to interrogate both efficiency of penetration and projectile-target interaction, respectively. The RP alumina was found to exhibit useful ballistic properties, successfully defeating steel-cored (AP) 7.62 × 39 mm BXN rounds at velocities of up-to c.a. 850 m/s, while exhibiting comparable failure modes to conventionally sintered armour-grade Sintox FA™. However, where a <1% by vol. Cu dopant was introduced into the RP material failure modes changed dramatically with performance dropping below that of conventionally sintered alumina. Overall, the results from both sets of experiments were complimentary and clearly indicated the potential of such RP materials to play an active role in provision of real-world body armour solutions provided quality control of the RP material can be maintained

Survival of sharp force trauma in burnt bones: effects of environmental factors

This study investigates how environmental variables, such as temperature and rainfall, affect previously induced cut marks on burnt bones. This research used non-serrated and serrated blade knives to inflict trauma on Sus scrofa ribs (n = 240). The bones were later burnt and left for 1 month in a taphonomic experimental facility. Qualitative and quantitative examinations were conducted using macroscopic and microscopic techniques to assess specific characteristics of the cut marks. Any changes to the dimension and morphology of the cut marks as well as their level of fragmentation were recorded. This study has led to three important outcomes: (1) identification of pre-existing cut marks is possible in reconstructed burnt bone fragments; (2) cut marks from different types of knife blades showed dissimilar responses to heat and the environment; and (3) specific environmental variables affect burnt bone fragmentation. These results have implications for trauma analysis on burnt remains in forensic anthropology casework

Knife cut marks inflicted by different blade types and the changes induced by heat: a dimensional and morphological study

Detailed information on skeletal trauma analysis of burned bone is important to ascertain the manner and cause of death in forensic casework. This research used three different knife types, one with a non-serrated blade, one a fine-serrated blade, and one a coarse-serrated blade, to inflict trauma to manually macerated Sus scrofa ribs (n = 240), and these ribs were later exposed to heat. Qualitative and quantitative analyses were conducted using macroscopic and microscopic techniques to assess specific characteristics of the cut marks. Differences in cut mark dimension and morphology of the ribs were investigated. After heat exposure, the cut marks on the rib samples remained recognisable and did not alter considerably. A level of dimensional and morphological preservation was reliant on the cutting action and the features of the knife blade as well as surrounding bone injury. The cut marks inflicted by the non-serrated blade remained recognisable despite exposure to the burning process. However, the cut marks inflicted by the coarse-serrated blade were likely to change significantly when exposed to heat. This study leads to two important results: (1) identification of pre-existing cut marks prior to heat exposure is possible in reconstructed burned bone fragments, and (2) cut marks from different types of knife blades showed dissimilar responses to heat. The outcomes obtained in this study stressed the need to adopt great care with the effects of heat on skeletal trauma analysis

A scanning electron microscopy study of projectile entry fractures in cortical bone; genesis and microarchitectural features

The present paper presents a scanning electron microscope (SEM) analysis of the genesis and microarchitecture of experimentally induced cortical entry fractures in porcine scapulae impacted at velocities ranging from 54 to 897 m/s. SEM observation was conducted on polyurethane replicas cast from negative silicone moulds. Analysis of the sequence of fracture processes operative during projectile impact revealed the presence of ring cracks at the site of impact, confirming that penetration in sandwich bones is achieved by cone crack propagation. Despite impulsive loading, two forms of plastic deformation were identified in the cortical bone surrounding the entry fracture up to a maximum velocity of 871 m/s. Microscopic radial and concentric cracks were associated with projectile impact, and the role of pores and pits as stress concentrators was captured. Possible underlying mechanisms for the observed plastic deformation are described, and the diagnostic utility of SEM analysis is presented

Advancing Pharmacist Collaborative Care within Academic Health Systems.

INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system

Multi-impact response of CR4 mild steel: Characterising the transition from absorption to failure

Single impact perforation shots are well understood for various target materials and different shaped projectiles. Although considered a rare case, localised multi-impacts are not well understood as they involve both perforating and non-perforating impacts on the target. The lack of understanding of non-perforating impact on metallic materials makes it tough to predict the change in the material’s mechanical performance. Given the widespread use of metallic materials for protective applications, it is important to understand the material response when subject to multiple impacts. To determine the effect of a non-perforating shot on CR4 mild steel and establish a minimum energy impact that will define the transition point whereby the metal can no longer absorb energy a series of impact experiments were conducted. Results show a subsequent perforation event occurs at a lower than the experimentally determined perforation velocity. Results suggest that there could be a direct correlation between the material thickness and the critical crater depth (the depth of crater required to affect the materials ability to absorb energy, the measure of materials performance). As the crater depth increased from 3mm to 8.5mm for the first shot, the energy absorption of the steel plate reduced by 25%. This allowed the residual performance for CR4 mild steel to be quantified for a known impact crater, giving a 7% performance loss for every millimetre the critical crater depth grows beyond 3mm until the point of failure

Comparison of high and low intensity contact between secondary and primary care to detect people at ultra-high risk for psychosis: study protocol for a theory-based, cluster randomized controlled trial.

BACKGROUND: The early detection and referral to specialized services of young people at ultra-high risk (UHR) for psychosis may reduce the duration of untreated psychosis and, therefore, improve prognosis. General practitioners (GPs) are usually the healthcare professionals contacted first on the help-seeking pathway of these individuals. METHODS/DESIGN: This is a cluster randomized controlled trial (cRCT) of primary care practices in Cambridgeshire and Peterborough, UK. Practices are randomly allocated into two groups in order to establish which is the most effective and cost-effective way to identify people at UHR for psychosis. One group will receive postal information about the local early intervention in psychosis service, including how to identify young people who may be in the early stages of a psychotic illness. The second group will receive the same information plus an additional, ongoing theory-based educational intervention with dedicated liaison practitioners to train clinical staff at each site. The primary outcome of this trial is count data over a 2-year period: the yield - number of UHR for psychosis referrals to a specialist early intervention in psychosis service - per primary care practice. DISCUSSION: There is little guidance on the essential components of effective and cost-effective educational interventions in primary mental health care. Furthermore, no study has demonstrated an effect of a theory-based intervention to help GPs identify young people at UHR for psychosis. This study protocol is underpinned by a robust scientific rationale that intends to address these limitations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70185866.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are