The Applicability of Two Strengths-based Systemic Psychotherapy Models for Young People Following Type 1 Trauma

This paper will consider the inter-relationship of a number of overlapping disciplinary theoretical concepts relevant to a strengths-based orientation, including well-being, salutogenesis, sense of coherence, quality of life and resilience. Psychological trauma will be referenced and the current evidence base for interventions with children and young people outlined and critiqued. The relational impact of trauma on family relationships is emphasised, providing a rationale for systemic psychotherapeutic interventions as part of a holistic approach to managing the effects of trauma. The congruence between second-order systemic psychotherapy models and a strengths-based philosophy is noted, with particular reference to solution-focused brief therapy and narrative therapy, and illustrated; via a description of the process of helping someone move from a victim position to a survivor identity using solution-focused brief therapy, and through a case example applying a narrative therapy approach to a teenage boy who suffered a serious assault. The benefits of a strength-based approach to psychological trauma for the clients and therapists will be summarised and a number of potential pitfalls articulated.

Imaging intracellular and systemic in vivo gold nanoparticles to enhance radiotherapy

Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both kilo-electron-volt and mega-electronvolt X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumours. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumour samples. Spatially accurate imaging on the nanoscale poses a serious challenge requiring high- or super-resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitizers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our own work, we have used multiphoton excited plasmon resonance imaging to map the AuNP intracellular distribution. The benefits and limitations of this approach will also be discussed in some detail. In some cases, the same "excitation" mechanism as is used in an imaging modality can be harnessed tomake it also a part of therapymodality (e.g. phototherapy)-such examples are discussed in passing as extensions to the imaging modality concerned.

Systemic risk for financial institutions in UK

Marginal Expected Shortfall (MES) is an approach used to measure the systemic risk financial institutions face. It estimates how significantly systemic events (poor market performance, out of 1.6 times Standard Deviation borders) are expected to affect market capitalization of a particular firm. The concept was developed in the late 2000s and is widely used for cross-country comparisons of financial firms. For the purposes of generalization of this technique it is often used with market data containing non-domestic currencies for some financial firms. That may lead to results having currency noise in them as it is shown for 77 UK financial firms in our analysis between 2001 and 2014.

Normative, systemic and procedural aspects: a review of indicator‐based sustainability assessments in agriculture

Several methods for assessing the sustainability of agricultural systems have been developed. These methods do not fully: (i) take into account the multi‐functionality of agriculture; (ii) include multidimensionality; (iii) utilize and implement the assessment knowledge; and (iv) identify conflicting goals and trade‐offs. This paper reviews seven recently developed multidisciplinary indicator‐based assessment methods with respect to their contribution to these shortcomings. All approaches include (1) normative aspects such as goal setting, (2) systemic aspects such as a specification of scale of analysis, (3) a reproducible structure of the approach. The approaches can be categorized into three typologies. The top‐down farm assessments focus on field or farm assessment. They have a clear procedure for measuring the indicators and assessing the sustainability of the system, which allows for benchmarking across farms. The degree of participation is low, potentially affecting the implementation of the results negatively. The top‐down regional assessment assesses the on‐farm and the regional effects. They include some participation to increase acceptance of the results. However, they miss the analysis of potential trade‐offs. The bottom‐up, integrated participatory or transdisciplinary approaches focus on a regional scale. Stakeholders are included throughout the whole process assuring the acceptance of the results and increasing the probability of implementation of developed measures. As they include the interaction between the indicators in their system representation, they allow for performing a trade‐off analysis. The bottom‐up, integrated participatory or transdisciplinary approaches seem to better overcome the four shortcomings mentioned above.

Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx Mice

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.

Normative, systemic and procedural aspects: a review of indicator-based sustainability assessments in agriculture

Methods for assessing the sustainability of agricultural systems do often not fully (i) take into account the multifunctionality of agriculture, (ii) include multidimensionality, (iii) utilize and implement the assessment knowledge and (iv) identify conflicting goals and trade-offs. This chapter reviews seven recently developed multidisciplinary indicator-based assessment methods with respect to their contribution to these shortcomings. All approaches include (1) normative aspects such as goal setting, (2) systemic aspects such as a specification of scale of analysis and (3) a reproducible structure of the approach. The approaches can be categorized into three typologies: first, top-down farm assessments, which focus on field or farm assessment; second, top-down regional assessments, which assess the on-farm and the regional effects; and third, bottom-up, integrated participatory or transdisciplinary approaches, which focus on a regional scale. Our analysis shows that the bottom-up, integrated participatory or transdisciplinary approaches seem to better overcome the four shortcomings mentioned above.

Black-box decomposition approach for computational hemodynamics: One-dimensional models

Increasing efforts exist in integrating different levels of detail in models of the cardiovascular system. For instance, one-dimensional representations are employed to model the systemic circulation. In this context, effective and black-box-type decomposition strategies for one-dimensional networks are needed, so as to: (i) employ domain decomposition strategies for large systemic models (1D-1D coupling) and (ii) provide the conceptual basis for dimensionally-heterogeneous representations (1D-3D coupling, among various possibilities). The strategy proposed in this article works for both of these two scenarios, though the several applications shown to illustrate its performance focus on the 1D-1D coupling case. A one-dimensional network is decomposed in such a way that each coupling point connects two (and not more) of the sub-networks. At each of the M connection points two unknowns are defined: the flow rate and pressure. These 2M unknowns are determined by 2M equations, since each sub-network provides one (non-linear) equation per coupling point. It is shown how to build the 2M x 2M non-linear system with arbitrary and independent choice of boundary conditions for each of the sub-networks. The idea is then to solve this non-linear system until convergence, which guarantees strong coupling of the complete network. In other words, if the non-linear solver converges at each time step, the solution coincides with what would be obtained by monolithically modeling the whole network. The decomposition thus imposes no stability restriction on the choice of the time step size. Effective iterative strategies for the non-linear system that preserve the black-box character of the decomposition are then explored. Several variants of matrix-free Broyden`s and Newton-GMRES algorithms are assessed as numerical solvers by comparing their performance on sub-critical wave propagation problems which range from academic test cases to realistic cardiovascular applications. A specific variant of Broyden`s algorithm is identified and recommended on the basis of its computer cost and reliability. (C) 2010 Elsevier B.V. All rights reserved.

In vitro basal cytotoxicity assay applied to estimate acute oral systemic toxicity of grandisin and its major metabolite

Preclinical investigations can start with preliminary in vitro studies before using animal models. Following this approach, the number of animals used in preclinical acute toxicity testing can be reduced. In this study, we employed an in-house validated in vitro cytotoxicity test based on the Spielmann approach for toxicity evaluation of the lignan grandisin, a candidate anticancer agent, and its major metabolite. the 4-O-demethylgrandisin, by neutral red uptake (NRU) assay, on mouse fibroblasts Balb/c 3T3 cell line. Using different concentrations of grandisin and its major metabolite (2.31; 1.16; 0.58; 0.29; 0.14; 0.07; 0.04; 0.002 mu M) in Balb/c 3T3-A31 NRU cytotoxicity assay, after incubation for 48 h, we obtained IC(50) values for grandisin and its metabolite of 0.078 and 0.043 mu M, respectively. The computed LD(50) of grandisin and 4-O-demethylgrandisin were 617.72 and 429.95 mg/kg, respectively. Both were classified under the Globally Harmonized System as category 4. Since pharmacological and toxicological data are crucial in the developmental stages of drug discovery, using an in vitro assay we demonstrated that grandisin and its metabolite exhibit distinct toxicity profiles. Furthermore, results presented in this work can contribute to reduce the number of animals required in subsequent pharmacological/toxicological studies. (C) 2010 Elsevier GmbH. All rights reserved.

Re-framing risk transfer to assess integrative partnership opportunities: the S.A.R. approach and the AIG/BID/CNO regional surety bond facility of 2007

Identificar, compartilhar e gerenciar os riscos de contratar são preocupações que impedem o estabelicmento e a administração das Parcerias Públicos Particulares (PPP). Porem, gerentes das entidades públicas, bancos de formento, construtoras e seguradoras pesquisam e utilizam muitas técnicas para enfrentar a avaliação e gerenciamento dos riscos. A transferência de risco é uma indicação dos chamados benefícios que são inspirados pelos PPP, contudo devido às realidades contratuais e conceptuais, a entidade de cede o risco (o partido público) permanece quase sempre como o portador final do risco. Conseqüentemente, o partido público retem um interesse de resistência na gerência total destes riscos cedidos. Esta dissertação explora alguns defeitos das aproximações comuns a conceituar a gestão de risco no contexto de um PPP. Focalizando os conceitos da interdependência e da reciprocidade e usando na decisão para transferir o risco do projeto, esta dissertação molda a decisão para transferir o risco nos termos das realidades interdependentes de relacionamentos sistemáticos, alargam os conceitos técnicos do risco e da avaliação de risco, considerando o uso reflexivo das diferenças na analise de um estudo de caso. O autor explora estes conceitos em uma análise da decisão de um gerente de risco da empresa de construção civil brasileira Construtora Norberto Odebrecht (ODB) para projetar uma facilidade inovadora da ligação de garantia com Inter-American Development Bank (BID) e uma seguradora, American International Group (AIG), um negócio que ganhe o reconhecimento Trade Finance Magazine’s 2007 deal of the year. O autor mostra que por compreender a transferência de risco nos termos abordados nesta dissertação, um atore que transfere o risco pode identificar e criar mais oportunidades de estabelecer relacionamentos em longo prazo, através dos processos que a literatura atual do PPP ainda não considere. Os resultados devem fornecer contribuições para a pesquisas sobre a transferência do risco do projeto, na cooperação entre organizações e na seleção do sócio do projeto do potencial.

Systemic governance and development in Latin America

Includes bibliography

Systemic risk in dynamical networks with stochastic failure criterion

Complex non-linear interactions between banks and assets we model by two time-dependent Erdos-Renyi network models where each node, representing a bank, can invest either to a single asset (model I) or multiple assets (model II). We use a dynamical network approach to evaluate the collective financial failure -systemic risk- quantified by the fraction of active nodes. The systemic risk can be calculated over any future time period, divided into sub-periods, where within each sub-period banks may contiguously fail due to links to either i) assets or ii) other banks, controlled by two parameters, probability of internal failure p and threshold T-h ("solvency" parameter). The systemic risk decreases with the average network degree faster when all assets are equally distributed across banks than if assets are randomly distributed. The more inactive banks each bank can sustain (smaller T-h), the smaller the systemic risk -for some Th values in I we report a discontinuity in systemic risk. When contiguous spreading becomes stochastic ii) controlled by probability p(2) -a condition for the bank to be solvent (active) is stochasticthe- systemic risk decreases with decreasing p(2). We analyse the asset allocation for the U.S. banks. Copyright (C) EPLA, 2014

The relationship between inflammation, dyslipidemia and physical exercise: from the epidemiological to molecular approach

Dyslipidemia and inflammation are frequently found in some diseases, such as obesity, type 2 diabetes mellitus, and cancer cachexia. Recent literature has identified that lipids have a pivotal role in the activation of inflammatory pathways, increasing the production of inflammatory cytokines, mainly tumor necrosis factor alpha, interleukin 6 and 1β. On the other hand, cytokines can promote disruption of lipid metabolism, in special cholesterol reverse transport, which is linked to development of atherosclerosis. With this in mind, acute and chronic exercise trainings have been pointed as important tools to counteract both dyslipidemia symptoms and systemic inflammation. Moreover, physical activity has been recommended in the prevention/treatment of the above mentioned outcomes by important health organizations around the world, mainly because it costs less and generates fewer side effects than isolated medicine. Despite the well-documented capacity of acute and chronic exercise training to counteract sustained disease-related immunometabolism, we have chosen to take a look from a current perspective in molecular pathways and in the field of epidemiology. The aim of the present review was therefore to discuss the results of dyslipidemia and inflammatory conditions with acute and chronic exercise training, which underlies the field of molecular pathways and epidemiology. The mechanisms underlying the response to the treatment are considered.

Anatrophic Nephrotomy as Nephron-Sparing Approach for Complete Removal of Intraparenchymal Renal Tumors

Objective: Partial nephrectomy for small kidney tumors has increased in the last decades, and the approach to non-palpable endophytic tumors became a challenge, with larger chances of positive margins or complications. The aim of this study is to describe an alternative nephron-sparing approach for small endophytic kidney tumors through anatrophic nephrotomy. Patients and Methods: A retrospective analysis of patients undergoing partial nephrectomy at our institution was performed and the subjects with endophytic tumors treated with anatrophic nephrotomy were identified. Patient demographics, perioperative outcomes and oncological results were evaluated. Results: Among the partial nephrectomies performed for intraparenchymal tumors between 06/2006 and 06/2010, ten patients were submitted to anatrophic nephrotomy. The mean patient age was 42 yrs, and the mean tumor size was 2.3 cm. Mean warm ischemia time was 22.4 min and the histopathological analysis showed 80% of clear cell carcinomas. At a mean follow-up of 36 months, no significant creatinine changes or local or systemic recurrences were observed. Conclusion: The operative technique described is a safe and effective nephron-sparing option for complete removal of endophytic renal tumors.

Reconstruction and analysis of the NF-kB pathway interactome: a systems biology approach

Background. One of the phenomena observed in human aging is the progressive increase of a systemic inflammatory state, a condition referred to as “inflammaging”, negatively correlated with longevity. A prominent mediator of inflammation is the transcription factor NF-kB, that acts as key transcriptional regulator of many genes coding for pro-inflammatory cytokines. Many different signaling pathways activated by very diverse stimuli converge on NF-kB, resulting in a regulatory network characterized by high complexity. NF-kB signaling has been proposed to be responsible of inflammaging. Scope of this analysis is to provide a wider, systemic picture of such intricate signaling and interaction network: the NF-kB pathway interactome. Methods. The study has been carried out following a workflow for gathering information from literature as well as from several pathway and protein interactions databases, and for integrating and analyzing existing data and the relative reconstructed representations by using the available computational tools. Strong manual intervention has been necessarily used to integrate data from multiple sources into mathematically analyzable networks. The reconstruction of the NF-kB interactome pursued with this approach provides a starting point for a general view of the architecture and for a deeper analysis and understanding of this complex regulatory system. Results. A “core” and a “wider” NF-kB pathway interactome, consisting of 140 and 3146 proteins respectively, were reconstructed and analyzed through a mathematical, graph-theoretical approach. Among other interesting features, the topological characterization of the interactomes shows that a relevant number of interacting proteins are in turn products of genes that are controlled and regulated in their expression exactly by NF-kB transcription factors. These “feedback loops”, not always well-known, deserve deeper investigation since they may have a role in tuning the response and the output consequent to NF-kB pathway initiation, in regulating the intensity of the response, or its homeostasis and balance in order to make the functioning of such critical system more robust and reliable. This integrated view allows to shed light on the functional structure and on some of the crucial nodes of thet NF-kB transcription factors interactome. Conclusion. Framing structure and dynamics of the NF-kB interactome into a wider, systemic picture would be a significant step toward a better understanding of how NF-kB globally regulates diverse gene programs and phenotypes. This study represents a step towards a more complete and integrated view of the NF-kB signaling system.

Data management and data analysis in the large European projects GEHA (GEnetics of Healthy Aging) and NU-AGE (NUtrition and AGEing): a bioinformatic approach

The aging process is characterized by the progressive fitness decline experienced at all the levels of physiological organization, from single molecules up to the whole organism. Studies confirmed inflammaging, a chronic low-level inflammation, as a deeply intertwined partner of the aging process, which may provide the “common soil” upon which age-related diseases develop and flourish. Thus, albeit inflammation per se represents a physiological process, it can rapidly become detrimental if it goes out of control causing an excess of local and systemic inflammatory response, a striking risk factor for the elderly population. Developing interventions to counteract the establishment of this state is thus a top priority. Diet, among other factors, represents a good candidate to regulate inflammation. Building on top of this consideration, the EU project NU-AGE is now trying to assess if a Mediterranean diet, fortified for the elderly population needs, may help in modulating inflammaging. To do so, NU-AGE enrolled a total of 1250 subjects, half of which followed a 1-year long diet, and characterized them by mean of the most advanced –omics and non –omics analyses. The aim of this thesis was the development of a solid data management pipeline able to efficiently cope with the results of these assays, which are now flowing inside a centralized database, ready to be used to test the most disparate scientific hypotheses. At the same time, the work hereby described encompasses the data analysis of the GEHA project, which was focused on identifying the genetic determinants of longevity, with a particular focus on developing and applying a method for detecting epistatic interactions in human mtDNA. Eventually, in an effort to propel the adoption of NGS technologies in everyday pipeline, we developed a NGS variant calling pipeline devoted to solve all the sequencing-related issues of the mtDNA.