Naresuan University Journal
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Treatment mechanism in the MRC preschool autism communication trial:implications for study design and parent-focussed therapy for children
No full textBackground: The PACT randomised-controlled trial evaluated a parent-mediated communication-focused treatment for children with autism, intended to reduce symptom severity as measured by a modified Autism Diagnostic Observation Schedule-Generic (ADOS-G) algorithm score. The therapy targeted parental behaviour, with no direct interaction between therapist and child. While nonsignificant group differences were found on ADOS-G score, significant group differences were found for both parent and child intermediate outcomes. This study aimed to better understand the mechanism by which the PACT treatment influenced changes in child behaviour though the targeted parent behaviour. Methods: Mediation analysis was used to assess the direct and indirect effects of treatment via parent behaviour on child behaviour and via child behaviour on ADOS-G score. Alternative mediation was explored to study whether the treatment effect acted as hypothesised or via another plausible pathway. Mediation models typically assume no unobserved confounding between mediator and outcome and no measurement error in the mediator. We show how to better exploit the information often available within a trial to begin to address these issues, examining scope for instrumental variable and measurement error models. Results: Estimates of mediation changed substantially when account was taken of the confounder effects of the baseline value of the mediator and of measurement error. Our best estimates that accounted for both suggested that the treatment effect on the ADOS-G score was very substantially mediated by parent synchrony and child initiations. Conclusions: The results highlighted the value of repeated measurement of mediators during trials. The theoretical model underlying the PACT treatment was supported. However, the substantial fall-off in treatment effect highlighted both the need for additional data and for additional target behaviours for therapy. © 2014 Association for Child and Adolescent Mental Health
Remittances and chain migration: Longitudinal evidence from Bosnia and Herzegovina
No full textMost of the literature on remittances focuses on their implications for the welfare of family members in the country of origin and disregards their role as facilitator of chain migration. We address this issue with the use of longitudinal data from Bosnia and Herzegovina, one of the primary exporters of migrants and recipients of remittances in the world. We find that remittances have a significant positive impact on the migration prospects of their recipients. Better endowed people are most likely to migrate, which highlights a potential negative implication of migration and remittances
Assessment of the sensitivity of core/shell parameters derived using the single-particle soot photometer to density and refractive index
No full textBlack carbon (BC) is the dominant absorbing aerosol in the atmosphere, and plays an important role in climate and human health. The optical properties and cloud condensation nuclei (CCN) activity of soot depend on the amounts (both relative and absolute) of BC and non-refractory material in the particles. Mixing between these two components is often represented in models by a core / shell coated sphere. The single-particle soot photometer (SP2) is one of, if not the only, instrument capable of reporting distributions of both core size and coating thickness. Most studies combine the SP2's incandescence and 1064 nm scattering data to report coating properties, but to date there is no consistency in the assumed values of density and refractive index of the core that are used in these calculations, which can greatly affect the reported parameters such as coating thickness. Given that such data are providing an important constraint for model comparisons and comparison between large data sets, it is important that this lack of consistency is addressed. In this study we explore the sensitivity of the reported coatings to these parameters. An assessment of the coating properties of freshly emitted, thermodenuded ambient particles demonstrated that a core density of 1.8 g cm(3) and refractive index of (2.26-1.26i) were the most appropriate to use with ambient soot in the Los Angeles area. Using these parameters generated a distribution with median shell / core ratio of 1.02 +/- 0.11, corresponding to a median absolute coating thickness of 2 +/- 8 nm. The main source of statistical error in the single-particle data was random variation in the incandescence signals. Other than the sensitivity to core refractive index, the incandescence calibration was the main source of uncertainty when optically determining the average coatings. The refractive index of coatings was found to have only a minor influence. This work demonstrates that using this technique the SP2 can accurately determine the average mixing state (externally or internally mixed) of ambient soot within the precision of the instrument calibration. Ambient coatings were measured up to a median shell / core ratio of 1.50 +/- 0.11, meaning that this technique is able to resolve absolute changes in mixing state. However, when different core parameters were used, the core = shell ratio and the coating thickness were shown to be offset by amounts that could be larger than the atmospheric variability in these parameters, though the results have a similar precision. For comparison, using the core parameters that resulted in the thickest coatings, on the same thermodenuded fresh particles as before, generated a median shell = core ratio of 1.39 +/- 0.11, corresponding to a median absolute coating thickness of 30 +/- 8 nm. These results must be taken into account when comparing BC coatings measured using this technique, or if using these data for optical or CCN calculations. We have determined the most appropriate values of BC density and refractive index to use to measure mixing state at 1064 nm where particle morphology has only a minor effect, but appropriate values to use for optical calculations of non-spherical particles at visible wavelengths will also be subject to similar, significant uncertainties. Without similar constraints as those provided here, constraining the behaviour of BC particles in models using field data will be subject to large systematic measurement uncertainties
Exploring the limitations of age-based models for health care planning
No full textHealth care decision makers are required to make planning decisions over a medium to long term planning horizon. Whilst population ageing is an important consideration for planners, age-stratified demographic models may produce misleading estimates of future resource requirements if the actual relationship between age and health is not fixed. We present a methodology which tests whether the assumption of a fixed age-health relationship is valid and estimate the magnitude of planning errors using a long time-series of measures of chronic health and service utilisation (N=2,419) taken from the Great British General Household Survey (1980-2008). We find that age-only models contain significant omitted variable bias, and that the relationship between age and health varies significantly across birth cohorts. Chronic sickness has fallen across birth cohorts born between 1890 and 2008, particularly before birth year 1930. Generational health improvements have mitigated the effects of population ageing, meaning that the population rate of sickness fell between 1980 and 2008. Planning based only on age leads to overestimation of the population level of health care need if successive cohorts are becoming healthier. Many alternative approaches exist which allow planners to relax the assumption of a fixed relationship between age and health
Developmentally appropriate healthcare for young people: a scoping study.
No full textBACKGROUND: There is increasing recognition of the importance of providing quality healthcare to meet the biopsychosocial needs of young people. 'Developmentally appropriate healthcare' (DAH) for young people is one term used to explain what these services consist of. However, this term remains ill defined. AIMS: (i) To analyse the use of the term DAH in the scientific literature and (ii) to identify and explore the range of meanings attributed to the term in relation to young people. METHODS: A scoping review was conducted to map the presence of the term DAH in the literature. To analyse the use and meanings attributed to the DAH terminology, data underwent qualitative content analysis using a summative approach. RESULTS: 62 papers were selected and subjected to content analysis. An explicit definition of DAH was provided in only 1 of the 85 uses of the term DAH within the data set and in none of the 58 uses of the prefix 'developmentally appropriate'. A link between the use of the term DAH and the domains of adolescent medicine, young people, chronic conditions and transitional care was identified; as were the core ideas underpinning the use of DAH. CONCLUSIONS: There is a need for consistency in the use of the term DAH for young people, the related stage-of-life terminology and age range criteria. Consensus is now needed as to the content and range of a formal conceptual and operational definition
An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.
No full textChronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes
Annuity choices and income drawdown: Evidence from the decumulation phase of defined contribution pensions in England
No full textWe provide new empirical evidence on the importance of defined contribution pension wealth in England, and the nature of annuitization decisions taken by older adults who retire with such sources of wealth. Other things equal, financial literacy, and numeracy in particular, are important factors governing individuals' choices over whether to shop around for an annuity as opposed to taking the "path of least resistance" option and purchasing from their original pension fund provider. This has important policy and welfare implications given that buying an annuity on the open market has significant financial benefits for most people. In the context of the increasing reliance on private provision for retirement, the importance of individuals having the financial literacy to successfully navigate complex financial decisions late in life should not be underestimated
Respiratory allergenic potential of plant-derived proteins: Understanding the relationship between exposure and potency for risk assessments.
No full textBotanical ingredients (ingredients derived from plants) are finding increasing application in personal care products and the public perceives these ingredients to be safe. However, some proteins in botanicals have the potential to cause immediate-type (IgE-mediated) respiratory allergic reactions. Although reports of such reactions are uncommon, when they do occur, they can be severe. Experience with soap containing wheat proteins illustrated that under certain specific conditions, consumers may be affected. Establishing safe exposure levels for botanical proteins has been challenging. Industrial enzymes provide a rich reference dataset based on their historical association with allergic reactions among workers, which includes robust dose-response information. In the absence of similar data on the potency of plant proteins, a conservative default approach has historically been applied based on information derived from allergenic enzymes. In this article we review the historical default approach and dataset for setting limits for plant proteins in botanical ingredients based on analogy to industrial enzymes followed by a synthesis of literature data on allergic reactions following inhalation exposure to plant-derived proteins. The aim is to share relevant background information and display the relationship between exposure and potency as a first step in the development of a strategy for the development of an improved approach to support the risk assessment of plant-derived proteins
Solution-processed nanocomposite dielectrics for low voltage operated OFETs
No full textA novel, solution processed high-k nanocomposite/low-k polymer bilayer gate dielectric that enables the fabrication of organic field-effect transistors (OFETs) that operate effectively at 1 V in high yields is reported. Barium strontium titanate (BST) and barium zirconate (BZ) nanoparticles are dispersed in a poly (vinylidene fluoride-co-hexafluoropropylene) P(VDF-HFP) polymer matrix to form a high-k nanocomposite layer. This is capped with a thin layer (ca 30 nm) of cross-linked poly(vinyl phenol) (PVP) to improve the surface roughness and dielectric–semiconductor interface and reduces the leakage current by at least one order of magnitude. OFETs were fabricated using solution-processed semiconductors, poly(3,6-di(2-thien-5-yl)-2,5-di(2-octyldodecyl)-pyrrolo[3,4-c]pyrrole-1,4-dione)thieno[3,2-b]thiophene) and a blend of 6,13-bis (triisopropylsilylethynyl) pentacene and poly (α-methylstyrene), in high yield (>90%) with negligible hysteresis and low leakage current density (10−9 A cm−2 at ±1 V)
Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions
No full textNeuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal calcium sensor family of EF-hand Ca(2+)-binding proteins. It interacts with both the G-protein-coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalization and surface expression, and the cognate kinases GRK1 and GRK2. Determination of the crystal structures of Ca(2+)/NCS-1 alone and in complex with peptides derived from D2R and GRK1 reveals that the differential recognition is facilitated by the conformational flexibility of the C-lobe-binding site. We find that two copies of the D2R peptide bind within the hydrophobic crevice on Ca(2+)/NCS-1, but only one copy of the GRK1 peptide binds. The different binding modes are made possible by the C-lobe-binding site of NCS-1, which adopts alternative conformations in each complex. C-terminal residues Ser-178-Val-190 act in concert with the flexible EF3/EF4 loop region to effectively form different peptide-binding sites. In the Ca(2+)/NCS-1·D2R peptide complex, the C-terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide complex it forms an α-helix. Removal of Ser-178-Val-190 generated a C-terminal truncation mutant that formed a dimer, indicating that the NCS-1 C-terminal region prevents NCS-1 oligomerization. We propose that the flexible nature of the C-terminal region is essential to allow it to modulate its protein-binding sites and adapt its conformation to accommodate both ligands. This appears to be driven by the variability of the conformation of the C-lobe-binding site, which has ramifications for the target specificity and diversity of NCS-1.</p