Eliciting preferences for continuing medication among adult patients and parents of children with attention‐deficit hyperactivity disorder

Background: Adherence to medication for attention‐deficit hyperactivity disorder (ADHD) is less than optimal. Previous studies have primarily focused on qualitative assessment of factors that influence medication adherence. Objective: This study aimed to quantify the factors that influence patient and parent preferences for continuing ADHD medication. Method: A discrete‐choice experiment was conducted to investigate preferences. Adults, and parents of children, with ADHD were presented with eight hypothetical choice tasks of three options (Medication A, Medication B, No Medication) described by six attributes related to medication outcomes. Preferences were estimated using a mixed multinomial logit model. Results: Overall, respondents' preferences (n = 216) for continuing medication were negative (mean [β] = −1.426, p < .001); however, a significant heterogeneity in preferences was observed amongst respondents (standard deviation = 0.805, p < .001). Improvements in education, aggressive behaviour, social behaviour and family functioning, and side effects and stigma, influenced respondents' decision to continue taking medication. The respondents were willing to continue medication if they experienced positive effects, but side effects (even moderate) were the strongest concern for not continuing medication. While side effects were the most important factor for both adult patients and parents of children with ADHD, improvement in education was relatively more important for adults and improvement in aggressive behaviour, social behaviour and family functioning was relatively more important for parents of children with ADHD. Parents were more likely to not continue a medication with severe side effects even at the highest level of improvement in education. Conclusions: Side effects are the most important factor that influenced preferences for continuing medication for both adults with ADHD, as well as parents of children with ADHD. While overall the respondents preferred not to take/give medication, discrete‐choice experiment showed that the relative importance of factors that influenced continuation of medications was different for the two groups. Patient and Public Involvement: Adults, and parents of children, with ADHD participated in this study by completing the online questionnaire. The questionnaire was based on findings of research in the literature, as well as earlier focus groups conducted with adults, and parents of children, with ADHD. The face validity of the questionnaire was determined by asking parents of children, and adults, with ADHD (n = 3) to complete the survey and participate in a short discussion on their understanding of the questions and their recommendations on improving the clarity of the survey

Assessing Multivariate Constraints to Evolution across Ten Long-Term Avian Studies

Background In a rapidly changing world, it is of fundamental importance to understand processes constraining or facilitating adaptation through microevolution. As different traits of an organism covary, genetic correlations are expected to affect evolutionary trajectories. However, only limited empirical data are available. Methodology/Principal Findings We investigate the extent to which multivariate constraints affect the rate of adaptation, focusing on four morphological traits often shown to harbour large amounts of genetic variance and considered to be subject to limited evolutionary constraints. Our data set includes unique long-term data for seven bird species and a total of 10 populations. We estimate population-specific matrices of genetic correlations and multivariate selection coefficients to predict evolutionary responses to selection. Using Bayesian methods that facilitate the propagation of errors in estimates, we compare (1) the rate of adaptation based on predicted response to selection when including genetic correlations with predictions from models where these genetic correlations were set to zero and (2) the multivariate evolvability in the direction of current selection to the average evolvability in random directions of the phenotypic space. We show that genetic correlations on average decrease the predicted rate of adaptation by 28%. Multivariate evolvability in the direction of current selection was systematically lower than average evolvability in random directions of space. These significant reductions in the rate of adaptation and reduced evolvability were due to a general nonalignment of selection and genetic variance, notably orthogonality of directional selection with the size axis along which most (60%) of the genetic variance is found. Conclusions These results suggest that genetic correlations can impose significant constraints on the evolution of avian morphology in wild populations. This could have important impacts on evolutionary dynamics and hence population persistence in the face of rapid environmental change

A Novel Criticality Analysis Method for Assessing Obesity Treatment Efficacy

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: In accordance with the General Data Protection Regulation (GDPR) guidelines, the database utilised in this study is maintained in a confidential and secure manner within the purview of the Faculty of Health and Life Sciences at Oxford Brookes University. Owing to privacy considerations, access to the dataset is restricted to authorised personnel only.Human gait is a significant indicator of overall health and well-being due to its dependence on metabolic requirements. Abnormalities in gait can indicate the presence of metabolic dysfunction, such as diabetes or obesity. However, detecting these can be challenging using classical methods, which often involve subjective clinical assessments or invasive procedures. In this work, a novel methodology known as Criticality Analysis (CA) was applied to the monitoring of the gait of teenagers with varying amounts of metabolic stress who are taking part in an clinical intervention to increase their activity and reduce overall weight. The CA approach analysed gait using inertial measurement units (IMU) by mapping the dynamic gait pattern into a nonlinear representation space. The resulting dynamic paths were then classified using a Support Vector Machine (SVM) algorithm, which is well-suited for this task due to its ability to handle nonlinear and dynamic data. The combination of the CA approach and the SVM algorithm demonstrated high accuracy and non-invasive detection of metabolic stress. It resulted in an average accuracy within the range of 78.2% to 90%. Additionally, at the group level, it was observed to improve fitness and health during the period of the intervention. Therefore, this methodology showed a great potential to be a valuable tool for healthcare professionals in detecting and monitoring metabolic stress, as well as other associated disorders.Newton Fun

The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica)

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51kya, into the Americas, from where a relatively recent (&lt;20kya) back migration to Asia took place. The exception to the haplogroup subspecies specificity is represented by the sedentary Levantine H. r.Transitiva that extensively shares haplogroup A with the migratory European H. r. rustica and, to a lesser extent, haplogroup B with the Egyptian H. r. savignii. Our data indicate that rustica and transitiva most likely derive from a sedentary Levantine population source that split at the end of the Younger Dryas (YD) (11.7kya). Since then, however, transitiva received genetic inputs from and admixed with both the closely related rustica and the adjacent savignii. Demographic analyses confirm this species' strong link with climate fluctuations and human activities making it an excellent indicator for monitoring and assessing the impact of current global changes on wildlife

Crosstalk between Virulence Loci: Regulation of Salmonella enterica Pathogenicity Island 1 (SPI-1) by Products of the std Fimbrial Operon

Invasion of intestinal epithelial cells is a critical step in Salmonella infection and requires the expression of genes located in Salmonella pathogenicity island 1 (SPI-1). A key factor for SPI-1 expression is DNA adenine (Dam) methylation, which activates synthesis of the SPI-1 transcriptional activator HilD. Dam-dependent regulation of hilD is postranscriptional (and therefore indirect), indicating the involvement of unknown cell functions under Dam methylation control. A genetic screen has identified the std fimbrial operon as the missing link between Dam methylation and SPI-1. We show that all genes in the std operon are part of a single transcriptional unit, and describe three previously uncharacterized ORFs (renamed stdD, stdE, and stdF). We present evidence that two such loci (stdE and stdF) are involved in Dam-dependent control of Salmonella SPI-1: in a Dam− background, deletion of stdE or stdF suppresses SPI-1 repression; in a Dam+ background, constitutive expression of StdE and/or StdF represses SPI-1. Repression of SPI-1 by products of std operon explains the invasion defect of Salmonella Dam− mutants, which constitutively express the std operon. Dam-dependent repression of std in the ileum may be required to permit invasion, as indicated by two observations: constitutive expression of StdE and StdF reduces invasion of epithelial cells in vitro (1,000 fold) and attenuates Salmonella virulence in the mouse model (>60 fold). In turn, crosstalk between std and SPI-1 may play a role in intestinal infections by preventing expression of SPI-1 in the caecum, an intestinal compartment in which the std operon is known to be expressed

Cartography of Methicillin-Resistant S. aureus Transcripts: Detection, Orientation and Temporal Expression during Growth Phase and Stress Conditions

BACKGROUND: Staphylococcus aureus is a versatile bacterial opportunist responsible for a wide spectrum of infections. The severity of these infections is highly variable and depends on multiple parameters including the genome content of the bacterium as well as the condition of the infected host. Clinically and epidemiologically, S. aureus shows a particular capacity to survive and adapt to drastic environmental changes including the presence of numerous antimicrobial agents. Mechanisms triggering this adaptation remain largely unknown despite important research efforts. Most studies evaluating gene content have so far neglected to analyze the so-called intergenic regions as well as potential antisense RNA molecules. PRINCIPAL FINDINGS: Using high-throughput sequencing technology, we performed an inventory of the whole transcriptome of S. aureus strain N315. In addition to the annotated transcription units, we identified more than 195 small transcribed regions, in the chromosome and the plasmid of S. aureus strain N315. The coding strand of each transcript was identified and structural analysis enabled classification of all discovered transcripts. RNA purified at four time-points during the growth phase of the bacterium allowed us to define the temporal expression of such transcripts. A selection of 26 transcripts of interest dispersed along the intergenic regions was assessed for expression changes in the presence of various stress conditions including pH, temperature, oxidative shocks and growth in a stringent medium. Most of these transcripts showed expression patterns specific for the defined stress conditions that we tested. CONCLUSIONS: These RNA molecules potentially represent important effectors of S. aureus adaptation and more generally could support some of the epidemiological characteristics of the bacterium

Low but contrasting neutral genetic differentiation shaped by winter temperature in European great tits

Gene flow is usually thought to reduce genetic divergence and impede local adaptation by homogenising gene pools between populations. However, evidence for local adaptation and phenotypic differentiation in highly mobile species, experiencing high levels of gene flow, is emerging. Assessing population genetic structure at different spatial scales is thus a crucial step towards understanding mechanisms underlying intraspecific differentiation and diversification. Here, we studied the population genetic structure of a highly mobile species – the great tit Parus major – at different spatial scales. We analysed 884 individuals from 30 sites across Europe including 10 close-by sites (< 50 km), using 22 microsatellite markers. Overall we found a low but significant genetic differentiation among sites (FST = 0.008). Genetic differentiation was higher, and genetic diversity lower, in south-western Europe. These regional differences were statistically best explained by winter temperature. Overall, our results suggest that great tits form a single patchy metapopulation across Europe, in which genetic differentiation is independent of geographical distance and gene flow may be regulated by environmental factors via movements related to winter severity. This might have important implications for the evolutionary trajectories of sub-populations, especially in the context of climate change, and calls for future investigations of local differences in costs and benefits of philopatry at large scales

Adaptive responses of animals to climate change are most likely insufficient

Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species. © 2019, The Author(s)