Independent Research Teams Research Articles

Brown Adipose Tissue: A New Target for Antiobesity Therapy

BACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure.CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated.SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therapy

The role and importance of brown adipose tissue in energy homeostasis

Children and adults have two major types of adipocytes, which represent the predominant cells in white adipose tissue, which is involved in energy storage, and brown adipose tissue (BAT), which is responsible for thermogenesis and energy expenditure. This review discusses BAT physiology and evaluates the recent discoveries regarding its development, identification, and function. Last year, multiple independent research teams using combined PET and computed tomography imaging, immunohistochemistry, and gene and protein expression have proven conclusively that adult humans have functional BAT. In parallel, basic studies defined BAT origins, its transcriptional regulation, and the role of hormones in BAT growth and activation. These methods have begun to be applied to children to understand pediatric BAT anatomy and physiology. Adult humans have functional BAT, which plays a role in energy balance. BAT is more prevalent in children, suggesting an even greater physiological role than that seen in adults. Future studies will identify safe ways to quantify BAT mass and activity and which interventions might be used to increase BAT mass, thermogenesis, or both to treat obesity.

Lightning talk: PyPop - a software pipeline for large-scale multilocus population genomics

AbstractPyPop (Python for Population Genomics) is an open-source framework for performing large-scale population genetic analyses on multilocus genotype and allele frequency data. It computes tests and measures of Hardy-Weinberg equilibrium (locus-level and individual genotype-level), linkage disequilibrum, and selection, and estimates multi-locus haplotypes. PyPop supplements and extends existing population genetic software incorporating them as modules, modified to accommodate highly polymorphic data, rather than reimplementing them from scratch. It facilitates evolutionary analyses by integrating population genetic statistics within and across populations.Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It was the primary platform for evolutionary analysis of data collected for a major NIH-funded collaborative grant that included over 30 laboratories and 200 populations (Lancaster et al., 2007a,b). PyPop has also been successfully used in studies by our group, with collaborators, and in publications by many independent research teams in over 70 peer reviewed papers.PyPop deploys a standard Extensible Markup Language (XML) output format and integrates the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of larger analysis pipelines. It also features an Application Programming Interface (API) allowing functionality to be incorporated into other programs. This lightning talk will focus on recent features of PyPop which include the prefiltering of the input genotype data and the ability to translate arbitrary allele names into full amino acid or nucleotide sequences.All code is made available under the terms of the GNU General Public License (GNU GPL):Homepage: http://www.pypop.org/

Short-beaked common dolphin ( Delphinus delphis) occurrence in the Moray Firth, north-east Scotland

The short-beaked common dolphin (Delphinus delphis) is regarded as notably rare or absent from the northern North Sea, but recent evidence suggests a rising frequency of the species in these waters with increasing regional sea temperatures. The following paper documents the presence of D. delphis in the Moray Firth in north-east Scotland and provides the first evidence for the sustained occurrence of these delphinids in this region during the warmer summer months at least. Sightings were collated during systematic surveys of the outer Moray Firth between 2001 and 2009 by independent research teams from the CRRU and WDCS. A total of 13 encounters (with group sizes ranging from 2 to 450+ animals) were recorded with the species across this period, the first of which was in June 2006, with annual encounters being logged thereafter between the months of May and August from 2007 to 2009 inclusive. The animals were recorded in water depths of 51 to 209 m (mean depth: 88.6±42.2 m) and at a distance from shore of 5 to 32 km (mean distance: 16.6±8.0 km). New born calves were observed in June and July, and photographic recaptures of identifiable ‘marked’ adults were determined in 2009. The consistent presence of common dolphins in the outer firth post 2005 and the recapture of recognizable individuals suggest a comparatively recent colonization of these waters by the species over a relatively short period of time. The impacts resulting from such a range expansion upon the existing cetacean community and the subsequent implications for management are discussed.

Brown fat as a therapy for obesity and diabetes

Human fat consists of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. This review evaluates the recent discoveries regarding the identification of functional BAT in adult humans and its potential as a therapy for obesity and diabetes. Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry, and gene and protein expression assays to prove conclusively that adult humans have functional BAT. This has occurred against a backdrop of basic studies defining the origins of BAT, new components of its transcriptional regulation, and the role of hormones in stimulation of BAT growth and differentiation. Adult humans have functional BAT, a new target for antiobesity and antidiabetes therapies focusing on increasing energy expenditure. Future studies will refine the methodologies used to measure BAT mass and activity, expand our knowledge of critical-control points in BAT regulation, and focus on testing pharmacological agents that increase BAT thermogenesis and help achieve long-lasting weight loss and an improved metabolic profile.

Clinical implications of design characteristics, flow rates, and suction pressure attributes in commercially available training cups

Transitioning from a bottle to open cup drinking can be a lengthy process in typical development. Children are often introduced to training cups during this period. Due to a lack of standardization in commercially available training cups, differences in design and performance characteristics may potentially create medical complications in developmentally delayed individuals. Our purpose is to report commercially available training cup design characteristics, residual fluid, flow rates, and suction pressures and discuss the potential clinical implications. A testing apparatus was developed to determine suction pressure and flow rate. Nine commercially available training cups were tested by two independent research teams. Experimental data were filtered and then fit with a linear approximation determined by a least squares method. Commercially available cups exhibited extensive variability in design parameters, suction pressure, rate of flow, and residual fluid. The extensive variability of design and function within current commercially available cups has clinical implications for children with development delays such as the ingestion of air and aspiration. Studying the variability of existing training cup performance identifies characteristics that impact cup function which can influence future cup design.

Maximising engagement, motivation and long term change in a Structured Intensive Education Programme in Diabetes for children, young people and their families: Child and Adolescent Structured Competencies Approach to Diabetes Education (CASCADE)

BackgroundThis trial aims to evaluate effective delivery and cost effectiveness of an innovative structured psycho-educational programme (CASCADE) for young people and their families living with diabetes. The increase in numbers of people being diagnosed with diabetes is posing a challenge for both the UK and the rest of the world. The peak age for diagnosis is between 10 and 14 years of age. There is clear evidence that improved diabetes control from diagnosis in childhood can reduce the incidence and progression of long-term complications. However, despite the development of improved insulin regimens and delivery methods, the overall metabolic control in children and adolescents has improved little in the UK in the past decade. Therefore there is a need for novel interventions and health delivery mechanisms aimed at young people and their families to help improve control and reduce complications, illness burden and costs to the NHS.Methods/DesignThe CASCADE trial is a multi-centre randomised control trial with 26 clinics randomised to control or intervention groups, with 572 children and young people involved in the study. The intervention will be delivered in 4 group sessions, over a 4 month period. A developmentally appropriate curriculum will be delivered to groups of 3 - 4 families, focusing on achievement of increasing competency in self-management of diabetes. The control group will receive standard care from their clinical team, usually consisting of regular 3-monthly clinic visits and telephone contact as required with the clinical nurse specialist and consultant. The primary outcomes of the trial will be change in HbA1c between baseline and 12 months and 24 months post recruitment. Secondary outcomes will include measures related to the economic evaluation, psychosocial outcomes, outcomes related to management of diabetes outcomes, and adherence to the intervention.DiscussionThe trial will be run by independent research and service delivery teams and supervised by a trial steering committee. A data monitoring and ethics committee has been put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The trial will be conducted according to the principles of MRC Good Clinical Practice (GCP) Guidelines and CTRU Phase III Trial Standard Operating procedures.Trial RegistrationCurrent Controlled Trials ISRCTN52537669

Comparison of two new short-term wind-power forecasting systems

This paper presents a comparison of two new advanced statistical short-term wind-power forecasting systems developed by two independent research teams. The input variables used in both systems were the same: forecasted meteorological variable values obtained from a numerical weather prediction model; and electric power-generation registers from the SCADA system of the wind farm. Both systems are described in detail and the forecasting results compared, revealing great similarities, although the proposed structures of the two systems are different. The forecast horizon for both systems is 72 h, allowing the use of the forecasted values in electric market operations, as diary and intra-diary power generation bid offers, and in wind-farm maintenance planning.

PARTICIPATION IN RESEARCH: Reference, or advisory, groups involving disabled people: reflections from three contrasting research projects

Increasingly in recent years, the involvement of disabled people as co‐researchers has been regarded as ‘good practice’. This has been informed by growing participatory and emancipatory research paradigms as well as user‐focused policy imperatives. The benefits of these shifts apply to the research itself (improved definition, direction, applicability and impact), to non‐disabled researchers (personal growth and enhanced understanding of the reflexive research process), to people with disabilities involved as researchers or collaborators (personal growth and enhanced opportunities), and (if externally funded) to the funder whose ways of operating are likely to be challenged profoundly. In this paper, Ann Lewis, Sarah Parsons and Christopher Robertson (based at the University of Birmingham), Anthony Feiler, Beth Tarleton and Debby Watson (based at the University of Bristol) and Richard Byers, Jill Davies, Ann Fergusson and Claire Marvin (based at the University of Cambridge) discuss the work of three independent research teams carrying out concurrent projects. The authors share their experiences of trying to take seriously the participation of disabled people in research. All three projects were informed, to a significant degree, by their respective reference groups of disabled people. The work of these groups in each of the three projects is outlined and then discussed in relation to five common themes: formal contracts with members of reference groups; considerations concerning drawing on an established reference group; planning for reference group involvement; style of reference group involvement; and building on good practice.

Transdiagnostic approaches to the treatment of anxiety disorders: A quantitative review.

Transdiagnostic cognitive-behavioral group treatments for anxiety, treatments that are designed to be applicable to diagnostically mixed groups of anxiety disorder clients, have been garnering interest in recent years. At least 7 independent research teams have developed transdiagnostic anxiety treatment protocols and reported preliminary outcomes data. In this review, we outline the basic theoretical rationale underlying transdiagnostic models of anxiety and review each of the treatment protocols that have been reported to date. Finally, the efficacy of these treatments is examined using meta-analytic methods. Results indicated that overall, transdiagnostic treatments are associated with a very large pre- to posttreatment effect size, and stable maintenance of gains through follow-up. Recommendations for transdiagnostic treatment implementation are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

PyPop update – a software pipeline for large‐scale multilocus population genomics

Population genetic statistics from multilocus genotype data inform our understanding of the patterns of genetic variation and their implications for evolutionary studies, generally, and human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation from Hardy-Weinberg equilibrium, test for balancing or directional selection, and investigate patterns of linkage disequilibrium. Existing software packages are oriented primarily toward the computation of such statistics on a population-by-population basis, not on comparisons among populations and across different statistics. We developed PyPop (Python for Population Genomics) to facilitate the analyses of population genetic statistics across populations and the relationships among different statistics within and across populations. PyPop is an open-source framework for performing large-scale population genetic analyses on multilocus genotype data. It computes the statistics described above, among others. PyPop deploys a standard Extensible Markup Language (XML) output format and can integrate the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of a larger analysis pipeline. Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It is the primary analysis platform for analyzing data collected for the Anthropological component of the 13th and 14th International Histocompatibility Workshops. PyPop has also been successfully used in studies by our group, with collaborators, and in publications by several independent research teams.

Building comparable global change vulnerability assessments: The vulnerability scoping diagram

Advancing vulnerability science depends in part on identifying common themes from multiple, independent vulnerability assessments. Such insights are difficult to produce when the assessments use dissimilar, often qualitative, measures. The Vulnerability Scoping Diagram is presented to facilitate the comparison of assessments with dissimilar measures. The diagram is illustrated with recent research on drought vulnerabilities, showing that common insights into vulnerability may emerge if independent research teams use a common structure for organizing information about exposure, sensitivity and adaptive capacity—even if the underlying measures differ between assessments. Broadly adopting this technique, which is grounded in the “Eight Steps” methodological protocol [Schröter, D., Polsky, C., Patt, A., 2005. Assessing vulnerabilities to the effects of global change: an eight step approach. Mitigation and Adaptation Strategies for Global Change 10(4), 573–595], will enable a vulnerability meta-analysis, the lessons from which may permit places to identify helpful adaptation or mitigation options without first having to conduct their own vulnerability assessments.

UV treatment of fresh fruits and vegetables for improved quality: a status report

Purpose of review: Over the past 20 years, ultraviolet (UV) hormesis has been evaluated as a postharvest treatment for fresh fruits and vegetables. Results from several independent research teams highlight the potential of this new technology. The objectives of this review are to present an overview of UV hormesis in postharvest crops and to characterise their responses to this physical stressor. Considerations related to future directions for the application of UV treatment are also discussed. Findings: UV treatment applied to fresh fruits and vegetables at defined low effective doses, termed hormic or hormetic, results in a beneficial response in treated plant organs. UV-treated horticultural crops show improved resistance to disease development that is primarily related to the induced synthesis and accumulation of phytoalexins, as well as other defence mechanisms. UV treatment also favourably affects the evolution of several quality parameters in treated commodities. For model commodities such as grape, citrus and strawberry, results have been presented on the UV enhancement of bioactive compounds known to be beneficial to human health and well-being. Directions for future research: UV treatment is likely ready for commercial application. However, any attempt to develop an online apparatus must address crop specificity and the range of factors that affect hormetic responses. Future multidisciplinary research should support the development of effective technological designs applicable to particular postharvest systems.

Cellules dendritiques et gliomes : un espoir en immunothérapie ?

Immunotherapy has been explored for several decades to try to improve the prognosis of gliomas, but until recently no therapeutic benefit has been achieved. The discovery of dendritic cells, the most potent professional antigen presenting cells to initiate specific immune response, and the possibility of producing them ex vivo gave rise to new protocols of active immunotherapy. In oncology, promising experimental and clinical therapeutic results were obtained using these dendritic cells loaded with tumor antigen. Patients bearing gliomas have deficit antigen presentation making this approach rational. In several experimental glioma models, independent research teams have showed specific antitumor responses using these dendritic cells. Phase I/II clinical trials have demonstrated the feasibility and the tolerance of this immunotherapeutic approach. In neuro-oncology, the efficiency of such an approach remains to be established, similarly in oncology where positive phase III studies are missing. Nevertheless, dendritic cells comprise a complex network which is only partially understood and capable of generating either immunotolerance or immune response. Numerous parameters remain to be explored before any definitive conclusion about their utility as an anticancer weapon can be drawn. It seems however logical that immunotherapy with dendritic cells could prevent or delay tumor recurrence in patients with minor active disease. A review on glioma and dendritic cells is presented.

Script-like attachment representations and behavior in families and across cultures: Studies of parental secure base narratives

The articles included in this Special Issue of Attachment and Human Development were originally presented as contributions to symposia at the Society for Research in Child Development (Atlanta, Georgia, April 2005) and at the European Developmental Psychology Conference (Laguna, Canary Islands, August 2005). The articles represent efforts of independent research teams studying the emergence, maintenance, and implications of attachment representations. In each study, a central measure of attachment representation was a recently described measure of the secure base script (Waters & Rodrigues-Doolabh, 2004). This measure assesses the “scriptedness” of secure base content in stories told in response to a set of word-prompts. Each paper included in this special issue addresses a specific issue relevant to the reliability, validity, or broader utility of the attachment script representation measure as an indicator of the respondent's awareness of and access to a secure base script. The first paper provides a précis of the measure itself, including its conceptual underpinnings and the notion of “scriptedness” as it relates to the secure base construct. In the second article, the cross-time stability of the scriptedness scores is tested. The third and fourth articles present relations between the scriptedness score from the new measure and indices of state of mind about attachment from the Adult Attachment Interview (one sample of Italian mothers, the other in a sample of adolescents). The fifth article describes relations between the attachment script representation score and mother – child interaction during a memory reminiscence task. The final article in this set is a report on associations between the maternal attachment script representations and child attachment security for a sample of adopting mothers and adopted children. Taken together, these studies provide broad support for this new procedure and scoring system to capture important aspects of secure base knowledge for adults and also provide evidence for the relevance of secure base scripts in the socialization of child secure base behavior.

Bats and human emerging diseases

Recently, two independent research teams reported evidence of infection with SARS-like coronaviruses in insectivorous horseshoe bats (genus Rhinolophus) in China [1, 2]. SARS emerged in China in 2002, and eventually infected over 8000 people around the world, killing about 10% of them. Early epidemiological studies suggested that the human disease may have originated in Chinese live-animal food markets, and the hunt for a source of the virus quickly identified apparently healthy Himalayan palm civets (Paguma larvata) as prime suspects [3]. Other studies, however, failed to find any evidence of widespread infection in civets [4] or a variety of other animals traditionally used as food in China. Rather, palm civets, like human beings, seem to be only accidental hosts of the virus, becoming infected, again like people, when mixed with other species in markets. More structured hunts for the reservoir continued, although not before thousands of palm civets had been slaughtered.

Reaction Time Distribution Analysis of Neuropsychological Performance in an ADHD Sample

Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners’ Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials. The MTA is a cooperative treatment study performed by six independent research teams in collaboration with the staff of the Division of Clinical and Treatment Research of the National Institute of Mental Health (NIMH), Rockville, Maryland and the Office of Special Education Programs (OSEP) of the U.S. Department of Education (DOE). The NIMH Principal Collaborators are Peter S. Jensen, M.D., L. Eugene Arnold, M.Ed., M.D., John E. Richters, Ph.D., Joanne B. Severe, M.S., Donald Vereen, M.D., and Benedetto Vitiello, M.D. Principal Investigators and coinvestigators from the six sites are as follows: University of California at Berkeley/San Francisco (UO1 MH50461): Stephen P. Hinshaw, Ph.D., Glen R. Elliott, M.D., Ph.D.; Duke University (UO1 MH50447): C. Keith Conners, Ph.D., Karen C. Wells, Ph.D., John S. March, M.D., M.P.H.; University of California at Irvine/Los Angeles (UO1 MH50440): James M. Swanson, Ph.D.; Dennis P. Cantwell, M.D.; Timothy Wigal, Ph.D.; Long Island Jewish Medical Center/Montreal Children's Hospital (UO1 MH50453): Howard B. Abikoff, Ph.D., Lily Hechtman, M.D.; New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center (UO1 MH50454): Laurence L. Greenhill, M.D., Jeffrey H. Newcorn, M.D.; University of Pittsburgh (UO1 MH50467): William E. Pelham, Ph.D., Betsy Hoza, Ph.D. Helena C. Kraemer, Ph.D. (Stanford University) is statistical and design consultant. The OSEP/DOE Principal Collaborator is Thomas Hanley, Ed.D. Aaron Hervey, Ph.D. was supported on this project by a midcareer development award to the second author (K24 MH64478).

Mechanisms of change in dialectical behavior therapy: Theoretical and empirical observations

Dialectical behavior therapy (DBT) can be considered a well-established treatment for borderline personality disorder (BPD) as evidenced by seven well-controlled randomized clinical trials across four independent research teams. The primary purpose of this article is to address a variety of potential mechanisms of change that may be associated with those aspects of DBT that are unique to the treatment and its theoretical underpinnings. Based on the biosocial theory of BPD, many of these mechanisms can be distilled down to the following process: the reduction of ineffective action tendencies linked with dysregulated emotions. Specifically we address the following interventions and associated mechanisms of change: mindfulness, validation, targeting and chain analysis, and dialectics. Patient change in BPD is conceptualized primarily as helping the patient to engage in functional, life-enhancing behavior, even when intense emotions are present. Ultimately, our goal was to provide guidance for theoretically and empirically grounded research on the mechanisms of change in DBT.

New Light on the Earliest Hominid Occupation in East Asia

New Light on the Earliest Hominid Occupation in East Asia

Use of the Questionnaire on Resources and Stress (QRS-F) with parents of young children with autism

The Questionnaire on Resources and Stress (Friedrich, short form: QRS-F) has been used widely with parents of children with disabilities. However, its psychometric properties in parents of young children with autism have not been established. Here, 174 mothers and 43 fathers of children under 6 years with autism spectrum disorder were studied by two independent research teams. Each parent completed a 31-item version of the QRS-F. Factor analysis of the mothers' scores on these items failed to identify an expected two- or three-factor structure. Thus, the properties of a total stress score were explored. Analyses revealed evidence of good reliability, and expected associations with social support, coping and autism severity. These analyses lend preliminary support to the convergent validity of the scale. Overall, the data support the use of a total stress score from the 31-item version of the QRS-F in research with parents of young children with autism.