Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

<br>Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.</br> <br>Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.</br> <br>Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).</br><br>Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.</br&gt

Headwater Influences on Downstream Water Quality

We investigated the influence of riparian and whole watershed land use as a function of stream size on surface water chemistry and assessed regional variation in these relationships. Sixty-eight watersheds in four level III U.S. EPA ecoregions in eastern Kansas were selected as study sites. Riparian land cover and watershed land use were quantified for the entire watershed, and by Strahler order. Multiple regression analyses using riparian land cover classifications as independent variables explained among-site variation in water chemistry parameters, particularly total nitrogen (41%), nitrate (61%), and total phosphorus (63%) concentrations. Whole watershed land use explained slightly less variance, but riparian and whole watershed land use were so tightly correlated that it was difficult to separate their effects. Water chemistry parameters sampled in downstream reaches were most closely correlated with riparian land cover adjacent to the smallest (first-order) streams of watersheds or land use in the entire watershed, with riparian zones immediately upstream of sampling sites offering less explanatory power as stream size increased. Interestingly, headwater effects were evident even at times when these small streams were unlikely to be flowing. Relationships were similar among ecoregions, indicating that land use characteristics were most responsible for water quality variation among watersheds. These findings suggest that nonpoint pollution control strategies should consider the influence of small upland streams and protection of downstream riparian zones alone is not sufficient to protect water quality

Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

<p>Abstract</p> <p>Background</p> <p>Studies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.</p> <p>Methods</p> <p><it>Study Tool: </it>We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.</p> <p><it>Setting: </it>We recruited individuals from the outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.</p> <p><it>Analysis: </it>Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM₁= inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM₂= inaccurate appraisal of benefit obtained from the research study.</p> <p>Results</p> <p>Our findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM₁) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM₂). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.</p> <p>Conclusion</p> <p>The presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research.</p

Heterogeneity of human adipose blood flow

BACKGROUND: The long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics. METHODS: The heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al. RESULTS: The volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data. CONCLUSION: Human adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation

Defining features of the practice of global health research: an examination of 14 global health research teams

Objectives: This paper strives to develop a pragmatic view of the scope of practice and core characteristics of global health research (GHR) by examining the activities of 14 Canadian-funded global health teams that were in the process of implementing research programs. Methods: Information was collected by a reflective exploration of team proposals and progress reports, a content analysis of the outputs from an all-team meeting and review of the literature. Results: Teams adopted equity-centered, problem-focused, systems-based approaches intended to find upstream determinants that could make people more resilient to social and ecological factors impacting their health. Long-term visions and time frames were needed to develop and solidify fully functional interdisciplinary, multinational, multicultural partnerships. The implementation of research into practice was a motivating factor for all teams, but to do this, they recognized the need for evidence-based advice on how to best do this. Traditional measures of biomedical research excellence were necessary but not sufficient to encompass views of excellence of team-based interdisciplinary research, which includes features like originality, coherence and cumulative contributions to fields of study, acceptance by peers and success in translating research into gains in health status. An innovative and nuanced approached to GHR ethics was needed to deal with some unique ethical issues because the needs for GHR were not adequately addressed by institutional biomedical research ethics boards. Core competencies for GHR researchers were a blend of those needed for health promotion, population health, international development, sustainable development, and systems science. Discussion: Developing acceptable and meaningful ways to evaluate the short-term contributions for GHR and forecast its long-term impacts is a strategic priority needed to defend decisions being made in GHR development. Planning and investing to support the underlying GHR elements and competencies that allow for adaptive, innovative, and supportive research partnerships to achieve &#x2018;health for all&#x2019; are more likely to have long-term impacts than building research strategies around specific diseases of interest

Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is over-expressed in 70–75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.</p> <p>Methods</p> <p>CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).</p> <p>Results</p> <p>Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).</p> <p>Conclusion</p> <p>PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.</p

Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience

Item does not contain fulltextRATIONALE: We have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition. OBJECTIVES: We sought to examine the role of serotonin in punishment-induced inhibition. We also examined the impact of induced mood on this effect to assess whether effects of tryptophan depletion on affective inhibition are moderated by mood. METHODS: Healthy females consumed a balanced amino acid mixture with (N = 20) or without (N = 21) the serotonin precursor tryptophan. Each subject completed either negative or neutral mood induction. All subjects completed the reward and punishment reversal learning task adopted in the previous study. RESULTS: We demonstrate a punishment prediction impairment in individuals who consumed tryptophan which was absent in individuals who were depleted of tryptophan. This effect was impervious to mood state. CONCLUSIONS: Our results suggest that serotonin promotes the inhibition of responses to punishing outcomes. This may lead to reduced punishment prediction accuracy in the presence of tryptophan and may contribute to resilience to affective disorders. Reduction of serotonin via tryptophan depletion then removes this inhibition. As such, we highlight a mechanism by which reduced serotonin can contribute to disorders of impulsivity and compulsivity as well as disorders of emotion.1 januari 201

Interaction between non-executive and executive directors in English National Health Service trust boards: an observational study

Research funded by Burdett FoundationBackground National Health Service (NHS) trusts, which provide the majority of hospital and community health services to the English NHS, are increasingly adopting a ‘public firm’ model with a board consisting of executive directors who are trust employees and external non-executives chosen for their experience in a range of areas such as finance, health care and management. In this paper we compare the non-executive directors’ roles and interests in, and contributions to, NHS trust boards’ governance activities with those of executive directors; and examine non-executive directors’ approach to their role in board meetings. Methods Non-participant observations of three successive trust board meetings in eight NHS trusts (primary care trusts, foundation trusts and self-governing (non-foundation) trusts) in England in 2008–9. The observational data were analysed inductively to yield categories of behaviour reflecting the perlocutionary types of intervention which non-executive directors made in trust meetings. Results The observational data revealed six main perlocutionary types of questioning tactic used by non-executive directors to executive directors: supportive; lesson-seeking; diagnostic; options assessment; strategy seeking; and requesting further work. Non-executive board members’ behaviours in holding the executive team to account at board meetings were variable. Non-executive directors were likely to contribute to finance-related discussions which suggests that they did see financial challenge as a key component of their role. Conclusions The pattern of behaviours was more indicative of an active, strategic approach to governance than of passive monitoring or ‘rubber-stamping’. Nevertheless, additional means of maintaining public accountability of NHS trusts may also be required

Alpha thalassaemia-mental retardation, X linked

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s

Tracing Water Sources of Terrestrial Animal Populations with Stable Isotopes: Laboratory Tests with Crickets and Spiders

Fluxes of carbon, nitrogen, and water between ecosystem components and organisms have great impacts across levels of biological organization. Although much progress has been made in tracing carbon and nitrogen, difficulty remains in tracing water sources from the ecosystem to animals and among animals (the “water web”). Naturally occurring, non-radioactive isotopes of hydrogen and oxygen in water provide a potential method for tracing water sources. However, using this approach for terrestrial animals is complicated by a change in water isotopes within the body due to differences in activity of heavy and light isotopes during cuticular and transpiratory water losses. Here we present a technique to use stable water isotopes to estimate the mean mix of water sources in a population by sampling a group of sympatric animals over time. Strong correlations between H and O isotopes in the body water of animals collected over time provide linear patterns of enrichment that can be used to predict a mean mix of water sources useful in standard mixing models to determine relative source contribution. Multiple temperature and humidity treatment levels do not greatly alter these relationships, thus having little effect on our ability to estimate this population-level mix of water sources. We show evidence for the validity of using multiple samples of animal body water, collected across time, to estimate the isotopic mix of water sources in a population and more accurately trace water sources. The ability to use isotopes to document patterns of animal water use should be a great asset to biologists globally, especially those studying drylands, droughts, streamside areas, irrigated landscapes, and the effects of climate change