A follow-up study of characteristics of young people that dropout and continue psychotherapy: service implications for a clinic in the community

Background: The paper reports the findings from a follow-up study of the factors that contribute to whether young people dropout or continue once-weekly psychotherapy at a voluntary sector psychotherapy service for young people aged 12 to 21 years. Method: The study uses data from an ongoing audit of the psychotherapy service that started in 1993; 882 young people were included in the study. Premature termination of treatment was defined as dropping out before the 21st session. Continuation in treatment was defined as remaining in therapy after 20 sessions. Measures and areas of interest used in the study include diagnostic measures, the Youth Self Report Form and Young Adult Self Report Form, demographic characteristics and treatment related information. Results: Young people who continued in treatment were more likely to be older, have anxieties about sexual and relationship issues and have higher scores on self-reported anxiety-depression. Young people who dropped out of treatment were more likely to be younger, have higher self-reported delinquency scores, have a diagnosis of hyperactivity-conduct disorder and be homeless. Conclusions: The study of treatment termination has demonstrated the value of service audit and has led to a significant change in clinical practice.

Persistent, symptomless, systemic, and seed-borne infection of lettuce by Botrytis cinerea

Experiments are presented which show that Botrytis cinerea, the cause of gray mould disease, is often present in symptomless lettuce plants as a systemic, endophytic, infection which may arise from seed. The fungus was isolated on selective media from surface sterilized sections of roots, stem pieces and leaf discs from symptomless plants grown in a conventional glasshouse and in a spore-free air-flow provided by an isolation propagator. The presence of B. cinerea was confirmed by immuno-labelling the tissues with the Botrytis-specific monoclonal antibody BC-12.CA4. As plants grew, infection spread from the roots to stems and leaves. Surface sterilization of seeds reduced the number of infected symptomless plants. Artificial infection of seedlings with dry conidia increased the rate of infection in some experiments. Selected isolates were genetically finger-printed using microsatellite loci. This confirmed systemic spread of the inoculating isolates but showed that other isolates were also present and that single plants hosted multiple isolates. This shows that B. cinerea commonly grows in lettuce plants as an endophyte, as has already been shown for Primula. If true for other hosts, the endophytic phase may be as important a component of the species population as the aggressive necrotrophic phase.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.

Considering the normative, systemic and procedural dimensions in indicator-based sustainability assessments in agriculture

This paper develops a framework for evaluating sustainability assessment methods by separately analyzing their normative, systemic and procedural dimensions as suggested by Wiek and Binder [Wiek, A, Binder, C. Solution spaces for decision-making – a sustainability assessment tool for city-regions. Environ Impact Asses Rev 2005, 25: 589-608.]. The framework is then used to characterize indicator-based sustainability assessment methods in agriculture. For a long time, sustainability assessment in agriculture has focused mostly on environmental and technical issues, thus neglecting the economic and, above all, the social aspects of sustainability, the multifunctionality of agriculture and the applicability of the results. In response to these shortcomings, several integrative sustainability assessment methods have been developed for the agricultural sector. This paper reviews seven of these that represent the diversity of tools developed in this area. The reviewed assessment methods can be categorized into three types: (i) top-down farm assessment methods; (ii) top-down regional assessment methods with some stakeholder participation; (iii) bottom-up, integrated participatory or transdisciplinary methods with stakeholder participation throughout the process. The results readily show the trade-offs encountered when selecting an assessment method. A clear, standardized, top-down procedure allows for potentially benchmarking and comparing results across regions and sites. However, this comes at the cost of system specificity. As the top-down methods often have low stakeholder involvement, the application and implementation of the results might be difficult. Our analysis suggests that to include the aspects mentioned above in agricultural sustainability assessment, the bottomup, integrated participatory or transdisciplinary methods are the most suitable ones.

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.

Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations.

Effects of psychotherapy for anxiety in children and adolescents: a meta-analytic review

This paper provides a comprehensive quantitative review of high quality randomized controlled trials of psychological therapies for anxiety disorders in children and young people. Using a systematic search for randomized controlled trials which included a control condition and reported data suitable for meta-analysis, 55 studies were included. Eligible studies were rated for methodological quality and outcome data were extracted and analyzed using standard methods. Trial quality was variable, many studies were underpowered and adverse effects were rarely assessed; however, quality ratings were higher for more recently published studies. Most trials evaluated cognitive behavior therapy or behavior therapy and most recruited both children and adolescents. Psychological therapy for anxiety in children and young people was moderately effective overall, but effect sizes were small to medium when psychological therapy was compared to an active control condition. The effect size for non-CBT interventions was not significant. Parental involvement in therapy was not associated with differential effectiveness. Treatment targeted at specific anxiety disorders, individual psychotherapy, and psychotherapy with older children and adolescents had effect sizes which were larger than effect sizes for treatments targeting a range of anxiety disorders, group psychotherapy, and psychotherapy with younger children. Few studies included an effective follow-up. Future studies should follow CONSORT reporting standards, be adequately powered, and assess follow-up. Research trials are unlikely to address all important clinical questions around treatment delivery. Thus, careful assessment and formulation will remain an essential part of successful psychological treatment for anxiety in children and young people.

Adeno-associated virus-8-Mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle

Myostatin is a member of the transformating growth factor-_ (TGF-_) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a ‘double muscling’ phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own propeptide; therefore, we assessed the impact of adeno associated virus-8 (AAV8) myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted a significant systemic increase in muscle mass in both slow and fast muscle phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm ratio in all myofiber types was significantly reduced. An increase in muscle mass in slow (soleus) muscle led to an increase in force output; however, an increase in fast (extensor digitorum longus [EDL]) muscle mass did not increase force output. These results suggest that the use of gene therapeutic regimens of myostatin inhibition for age-related or disease-related muscle loss may have muscle-specific effects.

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.

International office investment in global cities: the production of financial space and systemic risk

The paper explores the relationships between UK commercial real estate and regional economic development as a foundation for the analysis of the role of real estate investment in local economic development. Linkages between economic growth, development, real estate performance and investment allocations are documented. Long-run regional property performance is not the product of long-run economic growth, and weakly related to indicators of long-run supply and demand. Changes in regional portfolio weights seem driven by neither market performance nor underlying fundamentals. In the short run, regional investment shifts show no clear leads or lags with market performance.