Scrotal Swelling After Penetrating Chest Trauma

A 16-year-old male was brought to the emergency department by ambulance after being found lying unresponsive on an overturned motorcycle. He was orotracheally intubated. He had palpable subcutaneous crepitus over the chest and abdomen with massive scrotal swelling, and his back exam revealed multiple penetrating wounds (Figure 1). Autopsy results found five rightsided posterior thoracic gunshot wounds. The path of one bullet shattered the right seventh rib, entering the right lung and exiting though the main pulmonary artery before ending at the left clavicle. The presence of intra-scrotal air or gas is a rare clinical entity formed when air reaches the scrotum through tissue planes and cavities via the path of least resistance. The air source may be remote from the scrotum. Known causes include infections from gas-producing organisms, intestinal or gastric perforation and pneumothorax. 1,2 Three common routes could allow air t

Towards dynamic genome scale models

Copyright © The Author(s) 2017. Background Advances in bioinformatic techniques and analyses have led to the availability of genome-scale metabolic reconstructions. The size and complexity of such networks often means that their potential behaviour can only be analysed with constraint-based methods. Whilst requiring minimal experimental data, such methods are unable to give insight into cellular substrate concentrations. Instead, the long-term goal of systems biology is to use kinetic modelling to characterize fully the mechanics of each enzymatic reaction, and to combine such knowledge to predict system behaviour. Results We describe a method for building a parameterized genome-scale kinetic model of a metabolic network. Simplified linlog kinetics are used and the parameters are extracted from a kinetic model repository. We demonstrate our methodology by applying it to yeast metabolism. The resultant model has 956 metabolic reactions involving 820 metabolites, and, whilst approximative, has considerably broader remit than any existing models of its type. Control analysis is used to identify key steps within the system. Conclusions Our modelling framework may be considered a stepping-stone toward the long-term goal of a fully-parameterized model of yeast metabolism. The model is available in SBML format from the BioModels database (BioModels ID: MODEL1001200000) and at http://www.mcisb.org/resources/genomescale/

Fidelity and level correlations in the transition from regularity to chaos

Mean fidelity amplitude and parametric energy--energy correlations are calculated exactly for a regular system, which is subject to a chaotic random perturbation. It turns out that in this particular case under the average both quantities are identical. The result is compared with the susceptibility of chaotic systems against random perturbations. Regular systems are more susceptible against random perturbations than chaotic ones.Comment: 7 pages, 1 figur

Structural Analysis to Determine the Core of Hypoxia Response Network

The advent of sophisticated molecular biology techniques allows to deduce the structure of complex biological networks. However, networks tend to be huge and impose computational challenges on traditional mathematical analysis due to their high dimension and lack of reliable kinetic data. To overcome this problem, complex biological networks are decomposed into modules that are assumed to capture essential aspects of the full network's dynamics. The question that begs for an answer is how to identify the core that is representative of a network's dynamics, its function and robustness. One of the powerful methods to probe into the structure of a network is Petri net analysis. Petri nets support network visualization and execution. They are also equipped with sound mathematical and formal reasoning based on which a network can be decomposed into modules. The structural analysis provides insight into the robustness and facilitates the identification of fragile nodes. The application of these techniques to a previously proposed hypoxia control network reveals three functional modules responsible for degrading the hypoxia-inducible factor (HIF). Interestingly, the structural analysis identifies superfluous network parts and suggests that the reversibility of the reactions are not important for the essential functionality. The core network is determined to be the union of the three reduced individual modules. The structural analysis results are confirmed by numerical integration of the differential equations induced by the individual modules as well as their composition. The structural analysis leads also to a coarse network structure highlighting the structural principles inherent in the three functional modules. Importantly, our analysis identifies the fragile node in this robust network without which the switch-like behavior is shown to be completely absent

Derivation of a biomass proxy for dynamic analysis of whole genome metabolic models

A whole genome metabolic model (GEM) is essentially a reconstruction of a network of enzyme-enabled chemical reactions representing the metabolism of an organism, based on information present in its genome. Such models have been designed so that flux balance analysis (FBA) can be applied in order to analyse metabolism under steady state. For this purpose, a biomassfunctionisaddedtothesemodelsasanoverallindicatorofthemodel’s viability. Our objective is to develop dynamic models based on these FBA models in order to observe new and complex behaviours, including transient behaviour. There is however a major challenge in that the biomass function does not operate under dynamic simulation. An appropriate biomass function would enable the estimation under dynamic simulation of the growth of both wildtype and genetically modified bacteria under different, possibly dynamically changing growth conditions. Using data analytics techniques, we have developed a dynamic biomass function which acts as a faithful proxy for the FBA equivalent for a reduced GEM for E. coli. This involved consolidating data for reaction rates and metabolite concentrations generated under dynamic simulation with gold standard target data for biomass obtained by steady state analysis using FBA. It also led to a number of interesting insights regarding biomass fluxes for pairs of conditions. These findings were reproduced in our dynamic proxy function

The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies.</p

Corporate identity at the stakeholder group level

There is a paucity of literature regarding the construction and operation of corporate identity at the stakeholder group level. This article examines corporate identity from the perspective of an individual stakeholder group, namely, front-line employees. A stakeholder group that is central to the development of an organization’s corporate identity as it spans an organization’s boundaries, frequently interacts with both internal and external stakeholders, and influences a firm’s financial performance by building customer loyalty and satisfaction. The article reviews the corporate identity, branding, services and social identity literatures to address how corporate identity manifests within the front-line employee stakeholder group, identifying what components comprise front-line employee corporate identity and assessing what contribution front-line employees make to constructing a strong and enduring corporate identity for an organization. In reviewing the literature the article develops propositions that, in conjunction with a conceptual model, constitute the generation of theory that is recommended for empirical testing