On the Role of Body Size in a Tri-Trophic Metapopulation Model

A particular tri-trophic (resource, prey, predator) metapopulation model with dispersal of preys and predators is considered in this paper. The analysis is carried out numerically, by finding the bifurcations of the equilibria and of the limit cycles with respect to prey and predator body sizes. Two routes to chaos are identified. One is characterized by an intriguing cascade of flip and tangent bifurcations of limit cycles, while the other corresponds to the crisis of a strange attractor. The results are summarized by partitioning the space of body sizes in eight subregions, each one of which is associated to a different asymptotic behavior of the system. Emphasis is put on the possibility of having different modes of coexistence (stationary, cyclic, and chaotic) and/or extinction of the predator population

Design of a low band gap oxide ferroelectric: Bi6_6Ti4_4O17_{17}

A strategy for obtaining low band gap oxide ferroelectrics based on charge imbalance is described and illustrated by first principles studies of the hypothetical compound Bi$_6$Ti$_4$O$_{17}$, which is an alternate stacking of the ferroelectric Bi$_4$Ti$_3$O$_{12}$. We find that this compound is ferroelectric, similar to Bi$_4$Ti$_3$O$_{12}$ although with a reduced polarization. Importantly, calculations of the electronic structure with the recently developed functional of Tran and Blaha yield a much reduced band gap of 1.83 eV for this material compared to Bi$_4$Ti$_3$O$_{12}$. Therefore, Bi$_6$Ti$_4$O$_{17}$ is predicted to be a low band gap ferroelectric material

Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training

Introduction: The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT. Materials and Methods: Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women. Results: Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect. Conclusions: Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management

Dose dependence of efficacy and safety of subcutaneous immunotherapy

A number of experimental and clinical evidence has shown that exposure to high amounts of allergen molecules favours the development of tolerance. This is true also for subcutaneous immunotherapy (SCIT), for which a dose dependence of clinical efficacy was clearly demonstrated. The effective doses, measured as μg of major allergens, to be administered during maintenance treatment were established for the main allergens. Regarding pollens, the range of effectiveness corresponds to 25-41 and 13-20 μg of major allergens Phl p 5 and Phl p 6 for grasses, to 10-47 μg of Amb a 1 for ragweed, to 12 μg of Bet v 1 for birch, and to 6.2 μg of Par j 1 for Parietaria. With house dust mites, a maintenance dose of 5-11.5 μg of the major allergen from Dermatophagoides pteronyssinus Der p 1 is associated to clinically relevant effects, and with cat epithelium the clinical success is observed using a dose of 13-15 μg of Fel d 1. Nevertheless, there are adverse reactions facing SCIT, which are related to the amount of injected allergen. In fact, the safety decreases when the administered doses increase. This has led to “optimal doses” being defined which show a good balance between efficacy and safety (corresponding for example to a dose of 7 μg for Der p 1 and of 13 μg for Fel d 1). The dose dependency with respect to both efficacy and safety makes essential to accurately consider the risk/benefit ratio in each patient eligible for SCIT

Developing Central Nervous System and Vulnerability to Platinum Compounds

Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability

Messy entanglements: research assemblages in heart transplantation discourses and practices

The paper engages with a variety of data around a supposedly single biomedical event, that of heart transplantation. In conventional discourse, organ transplantation constitutes an unproblematised form of spare part surgery in which failing biological components are replaced by more efficient and enduring ones, but once that simple picture is complicated by employing a radically interdisciplinary approach, any biomedical certainty is profoundly disrupted. Our aim, as a cross-sectorial partnership, has been to explore the complexities of heart transplantation by explicitly entangling research from the arts, biosciences and humanities without privileging any one discourse. It has been no easy enterprise yet it has been highly productive of new insights. We draw on our own ongoing funded research with both heart donor families and recipients to explore our different perceptions of what constitutes data and to demonstrate how the dynamic entangling of multiple data produces a constitutive assemblage of elements in which no one can claim priority. Our claim is that the use of such research assemblages and the collaborations that we bring to our project breaks through disciplinary silos to enable a fuller comprehension of the significance and experience of heart transplantation in both theory and practice

A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term sideeffects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant cells. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanoparticles coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated/deleted leukemia cells expressing a low amount of CD20, but also circulating primary cells isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders. [Figure not available: see fulltext.

Dose dependence of efficacy but not of safety in sublingual immunotherapy

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies

Ab initio simulation of photoemission spectroscopy in solids: Plane-wave pseudopotential approach, with applications to normal-emission spectra of Cu(001) and Cu(111)

We introduce a new method for simulating photoemission spectra from bulk crystals in the ultra-violet energy range, within a three-step model. Our method explicitly accounts for transmission and matrix-element effects, as calculated from state-of-the-art plane-wave pseudopotential techniques within density-functional theory. Transmission effects, in particular, are included by extending to the present problem a technique previously employed with success to deal with ballistic conductance in metal nanowires. The spectra calculated for normal emission in Cu(001) and Cu(111) are in fair agreement with previous theoretical results and with experiments, including a newly determined spectrum. The residual discrepancies between our results and the latter are mainly due to the well-known deficiencies of density-functional theory in accounting for correlation effects in quasi-particle spectra. A significant improvement is obtained by the LDA+U method. Further improvements are obtained by including surface-optics corrections, as described by Snell's law and Fresnel's equations.Comment: 25 pages, 7 figures, accepted in PR