Cellular xenotransplantation of animal cells into people: benefits and risk

The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need. Recently, pig islet cells have been utilised in clinical trials, with safety being demonstrated. Indeed, pig-derived cells present several advantages: i) porcine cells have a stable function and differentiation pattern and are not tumorigenic; ii) pig cells have been shown to meet the physiological needs in large animal models; iii) the source of pig cells can be scaled up to meet demands in a highly standardised manner, and with respect to animal welfare regulations; iv) ‘designated-pathogen-free’ (DPF) pig lines can be produced, which could result in a higher safety profile than allotransplantation itself; v) the risk of zoonosis, which was raised years ago as the major hurdle, has been recently circumvented and is actually viewed as a controlled risk; and vi) immune risks are being circumvented via the use of genetically modified donor animals and encapsulation of porcine cells, particularly for the treatment of diabetes. Overall, the benefit appears to outweigh potential risks with respect to cellular xenotransplantation and this is discussed further in this review

Metrics For Quantifying Interdependencies

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Towards a More Inclusive Society: The Social Return on Investment (SROI) of an Innovative Ankle–Foot Orthosis for Hemiplegic Children

Hemiplegia is a form of disability that affects one side of the body and has a prevalence of 0.5–0.7 per 1000 live births. It has consequences not only at the medical level but also on psychological, cognitive, and social aspects, and it prevents children from social participation, especially in sports settings. The studies demonstrating the social impact of sports on the hemiplegic population and, in particular, children, are limited. In addition, previous evaluations of healthcare sports initiatives in the hemiplegic population are not available, and traditional methods of evaluation, which are mostly focused on economic outcomes, are not applicable. Thus, this article employs the social return on investment (SROI) methodology, which is able to determine the socio-economic impacts of an initiative, to evaluate the impact of an innovative ankle–foot orthosis (AFO) for hemiplegic children that was created to promote the possibility of “sports for all”. The model was designed with the involvement of stakeholders in all the phases and with mixed methods to assess the input, outcomes, and impact indicators. The final SROI, computed for a time horizon of three years and with a focus on the Lombardy Region, was equal to 3.265:1. Based on this result, the initiative turned out to be worthy of investment

Re-designing the substrate binding pocket of laccase for enhanced oxidation of sinapic acid

Iterative saturation mutagenesis was performed over six residues delimiting the substrate binding pocket of a high-redox potential chimeric laccase with the aim of enhancing its activity over sinapic acid, a lignin-related phenol of industrial interest. In total, more than 15000 clones were screened and two selected variants, together with the parent-type laccase, were purified and characterized. The new variants presented shifted pH activity profiles and enhanced turnover rates on sinapic acid and its methyl ester, whereas the oxidation of related phenols was not significantly enhanced. Neither the enzyme's redox potential nor the mechanism of the reaction were affected. Thus, quantum mechanics and molecular dynamics calculations were done to rationalize the effect of the selected mutations, revealing the critical role of the residues of the enzyme pocket to provide the precise binding of the substrate that enables an efficient electron transfer to the T1 copper. The results presented highlight the power of combining directed evolution and computational approaches to give novel solutions in enzyme engineering and to understand the mechanistic reasons behind them, offering new insights for further rational design towards specific targets

The Multi Crane Scheduling Problem: A Comparison Between Genetic Algorithm and Neural Network Approaches based on Simulation Modeling

The internal logistics for warehouses of many industrial applications, based on the movement of heavy goods, is commonly solved by the installment of a multi-crane system. The job scheduling of a multi-crane system is an interesting problem of optimization, solved in many ways in the past. This paper describes a comparison between the optimization by the use of Genetic Algorithms (GA) and introduce a framework for the solution of the problem using machine learning driven by Neural Networks (NN). Even though this last approach is not implemented in this paper, performances very close to GA ones are expected with NN. A case-study for steel coil production is proposed as a test frame for two different simulation software tools, one based on a heuristic solution and one on machine learning; performances and data achieved from reviews and simulations are compared

Localized pigmented villonodular synovitis of the anterior cruciate ligament of the knee: an exceptional presentation of a rare disease with neoplastic and inflammatory features.

Pigmented villonodular synovitis (PVNS) is a rare condition, most commonly involving the knee joint. PVNS is locally aggressive and can invade and destroy surrounding soft tissue and bone, leading to anatomical and functional deterioration of the affected joint. Localized PVNS is an unusual presentation of the disease, generally consisting of a nodular lesion protruding into the articular cavity. Localized PVNS of the knee can mimic other joint disorders which may pose a challenge for a correct diagnosis. Given the locally aggressive behavior of PVNS, prompt identification and excision of the lesion are instrumental to avoid complications. Here, we report a rare case of localized cystic PVNS involving the anterior cruciate ligament of the knee in a 32-year-old woman with persistent knee pain, in whom magnetic resonance imaging was inconclusive. The diagnosis was achieved via arthroscopy and histology. We also present a concise review of the literature on this pathological entity as well as a discussion on the differential diagnosis between localized PVNS and other intra-articular cystic lesions

Definition of an automated Content-Based Image Retrieval (CBIR) system for the comparison of dermoscopic images of pigmented skin lesions

<p>Abstract</p> <p>Background</p> <p>New generations of image-based diagnostic machines are based on digital technologies for data acquisition; consequently, the diffusion of digital archiving systems for diagnostic exams preservation and cataloguing is rapidly increasing. To overcome the limits of current state of art text-based access methods, we have developed a novel content-based search engine for dermoscopic images to support clinical decision making.</p> <p>Methods</p> <p>To this end, we have enrolled, from 2004 to 2008, 3415 caucasian patients and collected 24804 dermoscopic images corresponding to 20491 pigmented lesions with known pathology. The images were acquired with a well defined dermoscopy system and stored to disk in 24-bit per pixel TIFF format using interactive software developed in C++, in order to create a digital archive.</p> <p>Results</p> <p>The analysis system of the images consists in the extraction of the low-level representative features which permits the retrieval of similar images in terms of colour and texture from the archive, by using a hierarchical multi-scale computation of the Bhattacharyya distance of all the database images representation with respect to the representation of user submitted (query).</p> <p>Conclusion</p> <p>The system is able to locate, retrieve and display dermoscopic images similar in appearance to one that is given as a query, using a set of primitive features not related to any specific diagnostic method able to visually characterize the image. Similar search engine could find possible usage in all sectors of diagnostic imaging, or digital signals, which could be supported by the information available in medical archives.</p

Reversible Holmes Tremor due to Middle Cerebral Artery Giant Aneurysm

A 40-year-old man presented with a 6-month history of mild but worsening tremor of variable intensity. The patient had a focal, irregular, rest and action tremor of middle amplitude and low frequency (about 4 Hz), limited to his right arm with oscillatory motion around the elbow. It was present inconsistently at rest, particularly during emotional activation, and enhanced by posture maintenance. It was evoked by various positions and tasks. Particularly, the tremor was present during fine motor skills such as writing, and it was increased by drinking and shaving, showing a minimal intentional component. The patient also reported slight loss in manual dexterity in his right hand

The role of HD cooling in primordial star formation

The role of HD cooling in the formation of primordial objects is examined by means of a great number of 1-D models of the collapse of halos, exploring a wide range of masses and virialization redshifts. We find that HD has very little effect upon the critical mass separating the objects which are likely to form stars from those which are not. We also find that, once the proto-stellar collapse has started, HD effects are quite negligible. Instead, HD effects can be important during the intermediate stage of gas fragmentation: objects below a certain mass scale (~3x10^5 Msun at z_vir=20 in our ``fiducial'' case) can be cooled by HD down to T~50-100 K, whereas H2 cooling never takes the gas below T~200 K. The lower temperature implies a reduction of a factor ~10 in the Jeans mass of the fragmenting gas, and stars forming in such low-mass halos are probably less massive than their counterparts in larger halos. We estimate the importance of this mode of star formation through a variation of the Press-Schechter formalism, and find that it never exceeds the contribution of halos which are cooled by H2 only. Halos where HD is important account at best for a fraction ~0.25 of the total primordial star formation. However, HD cooling might provide a channel through which long-lived low mass stars could be formed in primordial conditions.Comment: 11 pages, 7 figures. Accepted for publication on MNRA

Split Attractor Flow in N=2 Minimally Coupled Supergravity

We classify the stability region, marginal stability walls (MS) and split attractor flows for two-center extremal black holes in four-dimensional N=2 supergravity minimally coupled to n vector multiplets. It is found that two-center (continuous) charge orbits, classified by four duality invariants, either support a stability region ending on a MS wall or on an anti-marginal stability (AMS) wall, but not both. Therefore, the scalar manifold never contains both walls. Moreover, the BPS mass of the black hole composite (in its stability region) never vanishes in the scalar manifold. For these reasons, the "bound state transformation walls" phenomenon does not necessarily occur in these theories. The entropy of the flow trees also satisfies an inequality which forbids "entropy enigma" decays in these models. Finally, the non-BPS case, due to the existence of a "fake" superpotential satisfying a triangle inequality, can be treated as well, and it can be shown to exhibit a split attractor flow dynamics which, at least in the n=1 case, is analogous to the BPS one.Comment: 1+29 pages, 2 figures; v2: minor changes, especially in Sects. 1 and 2; Sect. 6 changed. To appear on NP