Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

Safe and effective prescribing with dyslexia

Background: The term ‘dyslexia’ refers to a condition that impacts upon reading and writing abilities whilst not altering intelligence. Individuals with dyslexia may have difficulties with the speed and accuracy and their reading and writing, amongst other issues. Dyslexia is not automatically considered a disability but is a protected characteristic under the UK Equality Act (2010), and therefore employers and educational institutions are required to provide ‘reasonable adjustments’ in order to allow individuals to reach their full potential. There is a lack of research on this issue, but what little there is suggests that doctors feel as though any support they received ended when they graduated from medical school. Main body: A core distinction between medical school and medical practice is the requirement to prescribe medicines as registered medical practitioners. Junior doctors have to master this complex and potentially hazardous skill “on the job”, with a perceived lack of support. Here, we open up a debate about the potential impact of dyslexia on prescribing, and the need to find supports that may be effective in enabling doctors with dyslexia prescribe medicines safely and effectively – and thus reach their full potential as medical practitioners and promote patient safety. Conclusion: We argue that medical schools and hospitals could immediately provide dyslexia awareness training in both undergraduate and postgraduate settings. We discuss electronic prescribing systems, and conclude that research is required to identify effective supports for junior doctors with dyslexia

The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity

Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants’ stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control

Eye Tracking as a Measure of Receptive Vocabulary in Children with Autism Spectrum Disorders

This study examined the utility of eye tracking research technology to measure speech comprehension in 14 young boys with autism spectrum disorders (ASD) and 15 developmentally matched boys with typical development. Using eye tracking research technology, children were tested on individualized sets of known and unknown words, identified based on their performance on the Peabody Picture Vocabulary Test. Children in both groups spent a significantly longer amount of time looking at the target picture when previous testing indicated the word was known (known condition). Children with ASD spent similar amounts of time looking at the target and non-target pictures when previous testing indicated the word was unknown (unknown condition). However, children with typical development looked longer at the target pictures in the unknown condition as well, potentially suggesting emergent vocabulary knowledge

Opportunities and conditions to learn (OCL): A conceptual framework

“Opportunity to learn” has evolved into an umbrella phrase for describing a large range of settings, resources, structures, and processes. The aim of this study is to develop a conceptual framework that can accommodate a wide range of opportunities to learn, not just those provided by teachers in classrooms. An inclusive framework can bring together diverse studies about opportunity to learn, increasing synergies and uncovering interconnections, and making more visible marginalized forms of learning. It can also be used as a framework for holding governments, education authorities, and policy makers accountable for providing equitable opportunities and conditions to learn. This article presents a three-dimensional conceptual framework of opportunities and conditions to learn (OCL) that captures (a) notions of what opportunities exist and where those opportunities exist and opportunities offered by whom, as well as (b) a spate of conditions that can shape those opportunities

Exploring the Quality of Life of People in North Eastern and Southern Thailand.

The assumption that development brings not only material prosperity but also a better overall quality of life lies at the heart of the development project. Against this, critics assert that development can undermine social cohesion and threaten cultural integrity. Rarely, however, is the impact of development on wellbeing rigourously analysed using empirical data. This is what the Wellbeing in Developing Countries Group at the University of Bath aims to do drawing on fieldwork carried out in four developing countries, which addresses the themes of resources, needs, agency and structure, and subjective Quality of life (QoL). The first phase of the QoL research in Thailand aimed to explore the categories and components of quality of life for people from different backgrounds and locations with the aim of developing methods for QoL assessment in the third phase of the WeD QoL research. The study presents data obtained from rural and peri-urban sites in Southern and Northeastern Thailand (two villages in Songkhla and three in Khon Kaen, Mukdaharn, and Roi-et). Participants were divided into six groups by gender and age, and were divided again by religion (Buddhist and Muslim) and wealth status in the South. Data collection was conducted between October and December 2004 using focus group discussions, semi-structured interviews, and the Person Generated Index. Content analysis was used for data analysis. The use of a qualitative approach enabled the gathering of empirical data that reflects the sources of difficulty and happiness in the lives of participants. Respondents identified 26 aspects to their quality of life, including family relations, health and longevity, income and having money, jobs, housing, education, debt, and so on. The results reveal clear similarities and differences in the role of traditions, religious beliefs, and values in the lives of people living in remote rural or peri-urban areas in Northeastern and Southern Thailand. These results, together with the findings from Peru, Ethiopia, and Bangladesh, will inform the rest of the WeD research and be used to develop measures to assess the quality of life of people living in developing countries

Enhancements in Cloud Condensation Nuclei Activity From Turbulent Fluctuations in Supersaturation

The effect of aerosols on the properties of clouds is a large source of uncertainty in predictions of weather and climate. These aerosol-cloud interactions depend critically on the ability of aerosol particles to form cloud droplets. A challenge in modeling aerosol-cloud interactions is the representation of interactions between turbulence and cloud microphysics. Turbulent mixing leads to small-scale fluctuations in water vapor and temperature that are unresolved in large-scale atmospheric models. To quantify the impact of turbulent fluctuations on cloud condensation nuclei (CCN) activation, we used a high-resolution Large Eddy Simulation of a convective cloud chamber to drive particle-based cloud microphysics simulations. We show small-scale fluctuations strongly impact CCN activity. Once activated, the relatively long timescales of evaporation compared to fluctuations causes droplets to persist in subsaturated regions, which further increases droplet concentrations

The Acinetobacter baumannii two-component system aders regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner

The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR), causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in an ex vivo porcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example, A. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery. IMPORTANCE Acinetobacter baumannii is a nosocomial pathogen and is an increasing problem in hospitals worldwide. This organism is often multidrug resistant, can persist in the environment, and forms a biofilm on environmental surfaces and wounds. Overproduction of efflux pumps can allow specific toxic compounds to be pumped out of the cell and can lead to multidrug resistance. This study demonstrates the role of the A. baumannii efflux pump AdeB, and its regulator AdeRS, in multidrug resistance, epithelial cell killing, and biofilm formation. Deletion of the genes encoding these systems led to increased susceptibility to antibiotics, decreased biofilm formation on biotic and abiotic surfaces, and decreased virulence. Our data suggest that inhibition of AdeB could prevent biofilm formation or colonization in patients by A. baumannii and provides a good target for drug discovery