Multiple strategies to prevent premature termination in psychotherapy

A Review of Premature Termination in Psychotherapy: Strategies for Engaging Clients and Improving Outcomes by Joshua K. Swift and Roger P. Greenberg Washington, DC: American Psychological Association. 2015. 212 pp, ISBN 978-1-4338-1801- 1. $69.95 http://dx.doi.org/10.1037/a0038612 Premature Termination in Psychotherapy: Strategies for Engaging Clients and Improving Outcomes is one of the very best examples of the new generation of psychotherapy development. Based on rigorous research findings and a deep look into the preexisting literature, this book presents practical guidelines to understand premature termination and provides evidence-based strategies for how to engage patients in treatment. It will especially be a highlight for practitioners who are interested in a broad insight of the overall empirical literature. For graduate students in clinical and counseling psychology, this book might be an excellent prototype for how to bring rigorous quantitative research and convenient practice examples together.

Preclinical testing of strategies for therapeutic targeting of human T-cell trafficking in vivo

Naive T cells are migratory cells that continuously recirculate between blood and lymphoid tissues. Antigen-specific stimulation of T cells within the lymph nodes reprograms the trafficking properties of T cells by inducing a specific set of adhesion molecules and chemokine receptors on their surface which allow these activated and effector T cells to effectively and specifically home to extralymphoid organs. The observations of organ-specific homing of T cells initiated the development of therapeutic strategies targeting adhesion receptors for organ-specific inhibition of chronic inflammation. As most adhesion receptors have additional immune functions besides mediating leukocyte trafficking, these drugs may have additional immunomodulatory effects. Therapeutic targeting of T-cell trafficking to the central nervous system is the underlying concept of a novel treatment of relapsing remitting multiple sclerosis with the humanized anti-alpha-4-integrin antibody natalizumab. In this chapter, we describe a possible preclinical in vivo approach to directly visualize the therapeutic efficacy of a given drug in inhibiting T-cell homing to a certain organ at the example of the potential of natalizumab to inhibit the trafficking of human T cells to the inflamed central nervous system in an animal model of multiple sclerosis.

Genetic diversity in an indigenous horse breed: implications for mating strategies and the control of future inbreeding

The Franches-Montagnes is an indigenous Swiss horse breed, with approximately 2500 foalings per year. The stud book is closed, and no introgression from other horse breeds was conducted since 1998. Since 2006, breeding values for 43 different traits (conformation, performance and coat colour) are estimated with a best linear unbiased prediction (BLUP) multiple trait animal model. In this study, we evaluated the genetic diversity for the breeding population, considering the years from 2003 to 2008. Only horses with at least one progeny during that time span were included. Results were obtained based on pedigree information as well as from molecular markers. A series of software packages were screened to combine best the best linear unbiased prediction (BLUP) methodology with optimal genetic contribution theory. We looked for stallions with highest breeding values and lowest average relationship to the dam population. Breeding with such stallions is expected to lead to a selection gain, while lowering the future increase in inbreeding within the breed.

Copper and human health: biochemistry, genetics, and strategies for modeling dose-response relationships

Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Antigen Processing and Presentation in Multiple Sclerosis

CD4(+) T cells play a central role in the pathogenesis of multiple sclerosis (MS). Generation, activation and effector function of these cells crucially depends on their interaction with MHC II-peptide complexes displayed by antigen presenting cells (APC). Processing and presentation of self antigens by different APC therefore influences the disease course at all stages. Selection by thymic APC leads to the generation of autoreactive T cells, which can be activated by peripheral APC. Reactivation by central nervous system APC leads to the initiation of the inflammatory response resulting in demyelination. In this review we will focus on how MHC class II antigenic epitopes are created by different APC from the thymus, the periphery and from the brain, and will discuss the relevance of the balance between creation and destruction of such epitopes in the context of MS. A solid understanding of these processes offers the possibility for designing future therapeutic strategies.

Carbon sequestration in community forests: trade-offs, multiple outcomes and institutional diversity in the Bolivian Amazon

Carbon sequestration in community forests presents a major challenge for the Reducing Emissions from Deforestation and Forest Degradation (REDD+) programme. This article uses a comparative analysis of the agricultural and forestry practices of indigenous peoples and settlers in the Bolivian Amazon to show how community-level institutions regulate the trade-offs between community livelihoods, forest species diversity, and carbon sequestration. The authors argue that REDD+ implementation in such areas runs the risk of: 1) reinforcing economic inequalities based on previous and potential land use impacts on ecosystems (baseline), depending on the socio-cultural groups targeted; 2) increasing pressure on land used for food production, possibly reducing food security and redirecting labour towards scarce off-farm income opportunities; 3) increasing dependence on external funding and carbon market fluctuations instead of local production strategies; and 4) further incentivising the privatization and commodification of land to avoid transaction costs associated with collective property rights. The article also advises against taking a strictly economic, market-based approach to carbon sequestration, arguing that such an approach could endanger fragile socio-ecological systems. REDD+ schemes should directly support existing efforts towards forest sustainability rather than simply compensating local land users for avoiding deforestation and forest degradation

Assessing the impact of multiple stressors on aquatic biota: the receptor's side matters.

Aquatic ecosystems are confronted with multiple stress factors. Current approaches to assess the risk of anthropogenic stressors to aquatic ecosystems are developed for single stressors and determine stressor effects primarily as a function of stressor properties. The cumulative impact of several stressors, however, may differ markedly from the impact of the single stressors and can result in nonlinear effects and ecological surprises. To meet the challenge of diagnosing and predicting multiple stressor impacts, assessment strategies should focus on properties of the biological receptors rather than on stressor properties. This change of paradigm is required because (i) multiple stressors affect multiple biological targets at multiple organizational levels, (ii) biological receptors differ in their sensitivities, vulnerabilities, and response dynamics to the individual stressors, and (iii) biological receptors function as networks, so that actions of stressors at disparate sites within the network can lead via indirect or cascading effects, to unexpected outcomes.

Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair

Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.

Decision strategies for policy decisions under uncertainties: The case of mitigation measures addressing methane emissions from ruminants

Decision strategies aim at enabling reasonable decisions in cases of uncertain policy decision problems which do not meet the conditions for applying standard decision theory. This paper focuses on decision strategies that account for uncertainties by deciding whether a proposed list of policy options should be accepted or revised (scope strategies) and whether to decide now or later (timing strategies). They can be used in participatory approaches to structure the decision process. As a basis, we propose to classify the broad range of uncertainties affecting policy decision problems along two dimensions, source of uncertainty (incomplete information, inherent indeterminacy and unreliable information) and location of uncertainty (information about policy options, outcomes and values). Decision strategies encompass multiple and vague criteria to be deliberated in application. As an example, we discuss which decision strategies may account for the uncertainties related to nutritive technologies that aim at reducing methane (CH4) emissions from ruminants as a means of mitigating climate change, limiting our discussion to published scientific information. These considerations not only speak in favour of revising rather than accepting the discussed list of options, but also in favour of active postponement or semi-closure of decision-making rather than closure or passive postponement.

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.