The Emergence of Forensic Nursing and Advanced Nursing Practice in Switzerland: An Innovative Case Study Consultation.

BACKGROUND AND METHODS:: The objectives of this article were to systematically describe and examine the novel roles and responsibilities assumed by nurses in a forensic consultation for victims of violence at a University Hospital in French-speaking Switzerland. Utilizing a case study methodology, information was collected from two main sources: (a) discussion groups with nurses and forensic pathologists and (b) a review of procedures and protocols. Following a critical content analysis, the roles and responsibilities of the forensic nurses were described and compared with the seven core competencies of advanced nursing practice as outlined by Hamric, Spross, and Hanson (2009). RESULTS:: Advanced nursing practice competencies noted in the analysis included "direct clinical practice," "coaching and guidance," and "collaboration." The role of the nurse in terms of "consultation," "leadership," "ethics," and "research" was less evident in the analysis. DISCUSSION AND CONCLUSION:: New forms of nursing are indeed practiced in the forensic clinical setting, and our findings suggest that nursing practice in this domain is following the footprints of an advanced nursing practice model. Further reflections are required to determine whether the role of the forensic nurse in Switzerland should be developed as a clinical nurse specialist or that of a nurse practitioner.

A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Stratégies thérapeutiques pour le traitement des gliomes [Therapeutic strategies for the management of gliomas]

The management of gliomas remains challenging and requires a multidisciplinary approach that involves neurosurgeons, radiation therapists and oncologists. For patients with glioblastomas, progress has been made in recent years with the introduction of a combined modality treatment associating radiation therapy and concomitant chemotherapy with the novel alkylating agent temozolomide. This combination resulted in a significant prolongation of survival and increase in the number of patients with survival well beyond two years. Since then, interest in developing new agents in this disease has dramatically increased. In parallel, molecular markers, such as methylation status of MGMT or identification of the translocation of 1p and 19q in oligodendrogliomas have allowed to identify distinct subtypes with exquisite response to treatment or different prognosis. These developments have implications for the development of clinical trials of new potential drug treatments. In this article, we provide a review of the current management of low- and high-grade gliomas, including astrocytomas, oligodendrogliomas and glioblastomas and provide an outlook into future potential therapies.

Novel Bioconjugates of Aminolevulinic Acid with Nucleosides

Esters and amino acid derivatives of 5-aminolevulinic acid (ALA) are efficient prodrugs for the production of protoporphyrin IX (PpIX), which has been used in photodynamic cancer therapy (PDT). The synthesis of novel bioconjugates combining ALA with adenosine and thymidine is reported. The novel bioconjugates have been made using a robust methodology. The new class of prodrugs contains one, two, or three ALA per molecule. Preliminary cell tests in human cancer cell lines indicate that the thymidine conjugate of ALA is an efficient prodrug for PDT.

New insights into the mechanisms of organ-specific breast cancer metastasis.

Despite the substantial advances obtained in the treatment of localized malignancies, metastatic disease still lacks effective treatment and remains the primary cause of cancer mortality, including in breast cancer. Thus, in order to improve the survival of cancer patients it is necessary to effectively improve prevention or treatment of metastasis. To achieve this goal, complementary strategies can be envisaged: the first one is the eradication of established metastases by adding novel modalities to current treatments, such as immunotherapy or targeted therapies. A second one is to prevent tumor cell dissemination to secondary organs by targeting specific steps governing the metastatic cascade and organ-specific tropism. A third one is to block the colonization of secondary organs and subsequent cancer cell growth by impinging on the ability of disseminated cancer cells to adapt to the novel microenvironment. To obtain optimal results it might be necessary to combine these strategies. The development of therapeutic approaches aimed at preventing dissemination and organ colonization requires a deeper understanding of the specific genetic events occurring in cancer cells and of the host responses that co-operate to promote metastasis formation. Recent developments in the field disclosed novel mechanisms of metastasis. In particular the crosstalk between disseminated cancer cells and the host microenvironment is emerging as a critical determinant of metastasis. The identification of tissue-specific signals involved in metastatic progression will open the way to new therapeutic strategies. Here, we will review recent progress in the field, with particular emphasis on the mechanisms of organ specific dissemination and colonization of breast cancer.

The parties' voices in a therapeutic interview

Drawing on a dialogical approach inspired by Bakhtin, we start from the assumptionthat a concrete discussion is an intermingling between dialogue in praesentia and dialogue inabsentia, and we refer to the notion of 'enunciative positioning' to account for the variousrelations that a speaker may express towards the voices that he or she invokes. Our data arebased on a first therapeutic interview between a therapist, a mother and a child in a counselingcenter for children and adolescents. We identify the various voices invoked in this interviewand show that three levels of discursive process were involved: (a) the speakers invokedabsent speakers; (b) at the same time they developed their own discourse on the basis of theirinterlocutors' discourse which (c) itself drew on absent speakers or voices. We highlight thevarious discursive processes through which the speakers integrate their own voice into absentvoices, or integrate a distant voice so that it loses its property of being a distant (andborrowed) voice. As a theoretical and methodological contribution to dialogism, our resultsshow that absent voices and their specific intermingling with hic et nunc exchanges were amajor resource for therapeutic changes.

The Effects of a Nematode Lungworm (Rhabdias hylae) on its Natural and Invasive Anuran Hosts.

Biological invasions can bring both the invader and native taxa into contact with novel parasites. As cane toads ( Rhinella marina ) have spread through Australia, they have encountered lungworms (Rhabdias hylae) that occur in native frogs. Field surveys suggest that these lungworms have not host-switched to toads. In our laboratory studies, R. hylae infected cane toads as readily as it infected native frogs, but failed to reach the lungs of the novel host (i.e., were killed by the toads' immune response). Plausibly, then, R. hylae might reduce the viability both of their native hosts (frogs, that can exhibit high parasite burdens) and cane toads (that must deal with infective larvae traveling through the host body). Our laboratory trials suggest, however, that the impacts of the parasite on infected anuran hosts (both frogs and toads) were minimal, with no significant decrements to host survival, activity, growth, or locomotor performance. Ironically, the lack of impact of the parasite on its native hosts appears to be an outcome of co-evolution (frogs tolerate the lungworm), whereas the lack of impact on the novel host is due to a lack of co-evolution (toads can recognize and eliminate the lungworm).

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications.

OBJECTIVES: The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS: The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS: The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION: In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE: Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

A novel set of DIP-STR markers for improved analysis of challenging DNA mixtures.

Currently available molecular biology tools allow forensic scientists to characterize DNA evidence found at crime scenes for a large variety of samples, including those of limited quantity and quality, and achieve high levels of individualization. Yet, standard forensic markers provide limited or no results when applied to mixed DNA samples where the contributors are present in very different proportions (unbalanced DNA mixtures). This becomes an issue mostly for the analysis of trace samples collected on the victim or from touched objects. To this end, we recently proposed an innovative type of genetic marker, named DIP-STR that relies on pairing deletion/insertion polymorphisms (DIP) with standard short tandem repeats (STR). This novel compound marker allows detection of the minor DNA contributor in a DNA mixture of any gender and cellular origin with unprecedented resolution (beyond a DNA ratio of 1:1000). To provide a novel analytical tool useful in practice to common forensic laboratories, this article describes the first set of 10 DIP-STR markers selected according to forensic technical standards. The novel DIP-STR regions are short (between 146 and 271 bp), include only highly polymorphic tri-, tetra- and pentanucleotide tandem repeats and are located on different chromosomes or chromosomal arms to provide statistically independent results. This novel set of DIP-STR can target the amplification of 0.03-0.1 ng of DNA when mixed with a 1000-fold excess of major DNA. DIP-STR relative allele frequencies are estimated based on a survey of 103 Swiss individuals. Finally, this study provides an estimate of the occurrence of informative alleles and a calculation of the corresponding random match probability of the detected minor DIP-STR genotype assessed across 10,506 pairwise conceptual mixtures.

The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNFα-mediated in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Second mitochondria-derived activator of caspase (SMAC)-mimetics are a new class of targeted drugs that specifically induce apoptotic cancer cell death and block pro-survival signaling by antagonizing selected members of the inhibitor of apoptosis protein (IAP) family. MATERIAL AND METHODS: The present study was designed to investigate the radiosensitizing effect and optimal sequence of administration of the novel SMAC-mimetic Debio 1143 in vitro and in vivo. Apoptosis, alteration of DNA damage repair (DDR), and tumor necrosis factor-alpha (TNF-α) signaling were examined. RESULTS: In vitro, Debio 1143 displayed anti-proliferative activity and enhanced intrinsic radiation sensitivity in 5/6 head and neck squamous cell carcinoma (HNSCC) cell lines in a synergistic manner. In vivo, Debio 1143 dose-dependently radio-sensitized FaDu and SQ20B xenografts, resulting in complete tumor regression in 8/10 FaDu-xenografted mice at the high dose level. At the molecular level, Debio 1143 combined with radiotherapy (RT) induced enhancement of caspase-3 activity, increase in Annexin V-positive cells and karyopyknosis, and increase in TNF-α mRNA levels. Finally, in a neutralization experiment using a TNF-α-blocking antibody and a caspase inhibitor, it was shown that the radiosensitizing effect of Debio 1143 is mediated by caspases and TNF-α. CONCLUSIONS: These results demonstrate that the novel SMAC-mimetic Debio 1143 is a radiosensitizing agent that is worthy of further investigation in clinical trials in combination with radiotherapy.

The effect of learning on the evolution of new courtship behavior: a simulation model

The fact that individuals learn can change the relationship between genotype and phenotype in the population, and thus affect the evolutionary response to selection. Here we ask how male ability to learn from female response affects the evolution of a novel male behavioral courtship trait under pre-existing female preference (sensory drive). We assume a courtship trait which has both a genetic and a learned component, and a two-level female response to males. With individual-based simulations we show that, under this scenario, learning generally increases the strength of selection on the genetic component of the courtship trait, at least when the population genetic mean is still low. As a consequence, learning not only accelerates the evolution of the courtship trait, but also enables it when the trait is costly, which in the absence of learning results in an adaptive valley. Furthermore, learning can enable the evolution of the novel trait in the face of gene flow mediated by immigration of males that show superior attractiveness to females based on another, non-heritable trait. However, rather than increasing monotonically with the speed of learning, the effect of learning on evolution is maximized at intermediate learning rates. This model shows that, at least under some scenarios, the ability to learn can drive the evolution of mating behaviors through a process equivalent to Waddington's genetic assimilation.

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Aspects de la représentation de l'autre dans les romans grecs et "Les Métamorphoses" d'Apulée

Les romans grecs et les Métamorphoses d'Apulée - même si les modalités sont différentes pour ce dernier - sont des fictions en prose qui fonctionnent autour de topoi auxquels la figure de l'Autre n'échappe pas. Bien que le monde grec soit alors radicalement différent de ce qu'il était au Ve siècle avant J.-C, période à laquelle l'identité grecque est construite par opposition à la figure du barbare, les romanciers qui prennent la plume à partir du 1er siècle avant notre ère utilisent un certain nombre de stéréotypes hérités de l'époque classique, alors mise à l'honneur par le mouvement de la Seconde Sophistique. Il s'agit d'étudier dans le détail certains éléments de la représentation de l'Autre pour déterminer qui il est, comment il se comporte, ce qui le constitue en Autre. Puis, à partir de cette esquisse, nécessairement incomplète, d'évaluer ce que cette représentation peut induire sur l'image de l'identité grecque à l'époque impériale, par le jeu de miroir que F. Hartog a décelé dans l'oeuvre d'Hérodote. Une première partie est consacrée aux rapports entre l'homme et l'animal ainsi qu'à l'image de la sauvagerie, ce qui permet d'explorer les bornes romanesques de l'humanité. La seconde partie s'attache à des éléments que l'époque classique a plus particulièrement mis en avant pour distinguer les Grecs des non-Grecs : le critère de la langue, l'art de faire la guerre et le discours politique qui est tenu sur les institutions barbares. La troisième partie étudie la place des dieux et des pratiques religieuses dans la définition de l'Autre. J'espère ainsi contribuer à la compréhension du genre romanesque et des représentations culturelles de l'empire « gréco-romain ». -- The Greek novels and The Metamorphoses of Apuleius, even if it is in different terms for the last, are prose fictions which are based on topoi, and the figure of the Other is one of them. Although the Greek world was radically different of what it was in the fifth century BC, time during which Greek identity is contructed as opposed to the figure of the barbaros, the authors of novels, who wrote from the first century BC onward, used some stereotypes inherited from classical period, which was celebrated by the Second Sophistic movement. The aim of this thesis is to study in detail some elements of the representation of the Other to determine who it is, how he behaves, what makes him other. Then, from this sketch, necessarily incomplete, to evaluate what this representation says about the image of Greek identity in the imperial age, according to the play of the mirror detected by F. Hartog in the text of Herodotus. The first part of the thesis is dedicated to the relationship between man and animal and to the image of savagery, in order to explore the novelistic limits of humanity. The second part concentrates on elements that classical period had particularly insisted on to promote the distinction between Greeks and non-Greeks : the linguistic criterion, the way to make war, and the politic discourse on the barbaric institutions. The third part study the place of the gods and of religious practices in the definition of the Other. I hope to contribute to the understanding of novel genre and of cultural representations of the « greco- roman- empire ».