Overcoming barriers to effective early parenting interventions for attention-deficit hyperactivity disorder (ADHD): parent and practitioner views

BackgroundThe importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low take-up' and high drop-out' rates compromise the effectiveness of such programmes within the community. MethodsThis qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. Results and conclusionsMany of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented

Dissolution and drug release profiles of phosphate glasses doped with high valency oxides

This paper investigates phosphate glasses incorporating vanadium and molybdenum oxides for effective management of dissolution and drug release. These glass formulations are found to reduce the rate of dissolution from the glass surfaces. The drug functional groups of vancomycin molecules loaded by immersion showed stronger hydrogen bonding with Vanadium doped glasses and consequently lower rate of drug release over 2 weeks indicating better surface attachment with the drug molecules and slow drug release profiles. This can be explained by the strong adherence of drug molecules to glass surfaces compared with the molybdenum containing glasses (PM5 and PM10). The strong attachment relates to hydrogen bonding between the amino-functional groups of vancomycin and the hydrated P-O-H groups in the glass network. In conclusion, the rate of dissolution of doped glasses and the rate of drug release can be administered to deliver the drug molecules over weeks

P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors

Activation of visceral nociceptors by inflammatory mediators contributes to visceral hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine and pyrimidine nucleotides (e.g., ATP and UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation of the gut, and from immune cells during inflammation. Actions of ATP are mediated through both ionotropic P2X receptors and metabotropic P2Y receptors. P2X receptor activation causes excitation of visceral afferents; however, the impact of P2Y receptor activation on visceral afferents innervating the gut is unclear. Here we investigate the effects of stimulating P2Y receptors in isolated mouse colonic sensory neurons, and visceral nociceptor fibers in mouse and human nerve-gut preparations. Additionally, we investigate the role of Na(v)1.9 in mediating murine responses. The application of UTP (P2Y(2) and P2Y(4) agonist) sensitized colonic sensory neurons by increasing action potential firing to current injection and depolarizing the membrane potential. The application of ADP (P2Y(1), P2Y(12), and P2Y(13) agonist) also increased action potential firing, an effect blocked by the selective P2Y(1) receptor antagonist MRS2500. UTP or ADP stimulated afferents, including mouse and human visceral nociceptors, in nerve-gut preparations. P2Y(1) and P2Y(2) transcripts were detected in 80% and 56% of retrogradely labeled colonic neurons, respectively. Na(v)1.9 transcripts colocalized in 86% of P2Y(1)-positive and 100% of P2Y(2)-positive colonic neurons, consistent with reduced afferent fiber responses to UTP and ADP in Na(v)1.9(−/−) mice. These data demonstrate that P2Y receptor activation stimulates mouse and human visceral nociceptors, highlighting P2Y-dependent mechanisms in the generation of visceral pain during gastrointestinal disease. SIGNIFICANCE STATEMENT Chronic visceral pain is a debilitating symptom of many gastrointestinal disorders. The activation of pain-sensing nerves located in the bowel wall and their sensitization to physiological stimuli, including bowel movements, underpins the development of such pain, and is associated with mediators released during disease. This work addresses the unstudied role of purine and pyrimidine nucleotides in modulating colonic nociceptors via P2Y receptors using a combination of electrophysiological recordings from human ex vivo samples and a detailed functional study in the mouse. This is the first report to identify colonic purinergic signaling as a function of P2Y receptor activation, in addition to established P2X receptor activity, and the results contribute to our understanding of the development of visceral pain during gastrointestinal disease

Learners Self-directing Learning in FutureLearn MOOCs: A Learner-Centered Study

This qualitative research study focuses on how experienced online learners self-direct their learning while engaging in a MOOC delivered on the FutureLearn platform. Self-directed learning is an important concept within informal learning and online learning. This study distinguishes itself from previous MOOC learner studies, by reporting the self-directed learning using a bottom-up approach. By looking at self-reported learning logs and interview transcripts an in-depth analysis of the self-directed learning is achieved. The data analysis used constructed grounded theory, which aligns with the bottom-up approach where the learner data is coded and investigated in an open, yet evidence-based way, leaving room for insights to emerge from the learner data. The data corpus is based on 56 participants following three FutureLearn MOOCs, providing 147 learning logs and 19 semi-structured one-on-one interviews with a selection of participants. The results show five specific areas in which learners react with either the material or other learners to self-direct their learning: context, individual or social learning, technology and media provided in the MOOCs, learner characteristics and organising learning. This study also indicates how intrinsic motivation and personal learning goals are the main inhibitors or enablers of self-directed learning

Electrically Tunable Scattering from Devitrite–Liquid Crystal Hybrid Devices

Devitrite is normally an unwanted crystalline impurity in the soda-lime-silica glass making process. Thin needles formed by heterogeneous nucleation of devitrite on the glass surface provide unique birefringence properties for potential applications in tunable optical devices. Here, devitrite and a liquid crystal are combined to create an electrically variable optical diffuser. The magnitude and scattering angle of the transmitted light propagating through the diffuser are tuned by varying the voltage between the graphene and indium tin oxide electrodes on either side of the liquid crystal. The threshold voltage to switch the transmitted light from a predominantly horizontal diffusion to a random order is 3.5 V. Angle-resolved measurements show broad diffusion angles of transmitted light with a maximum deflection of ±60°. The dynamically tunable devitrite-liquid crystal hybrid devices may advance the development of currently less viable technologies including beam shaping and automatic light transmission control.Leverhulme Trust, Royal Society, Engineering and Physical Sciences Research Council (IAA Follow on Fund

Electrically Tunable Scattering from Devitrite–Liquid Crystal Hybrid Devices

Devitrite is normally an unwanted crystalline impurity in the soda-lime-silica glass making process. Thin needles formed by heterogeneous nucleation of devitrite on the glass surface provide unique birefringence properties for potential applications in tunable optical devices. Here, devitrite and a liquid crystal are combined to create an electrically variable optical diffuser. The magnitude and scattering angle of the transmitted light propagating through the diffuser are tuned by varying the voltage between the graphene and indium tin oxide electrodes on either side of the liquid crystal. The threshold voltage to switch the transmitted light from a predominantly horizontal diffusion to a random order is 3.5 V. Angle-resolved measurements show broad diffusion angles of transmitted light with a maximum deflection of ±60°. The dynamically tunable devitrite-liquid crystal hybrid devices may advance the development of currently less viable technologies including beam shaping and automatic light transmission control.Leverhulme Trust, Royal Society, Engineering and Physical Sciences Research Council (IAA Follow on Fund

Predominant constitutive CFTR conductance in small airways

BACKGROUND: The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. METHODS: We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. RESULTS: In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25), but when gluconate replaced luminal Cl(-), the bionic Cl(- )diffusion potentials (-58 ± 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl(- )permeability was at least 5 times greater than Na(+ )permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5–50 μM), and CFTR(Inh)-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. CONCLUSION: These results indicate that the small airway of the pig is characterized by a constitutively active Cl(- )conductance that is most likely due to CFTR

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

Self-assembled amyloid fibrils with controllable conformational heterogeneity

Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite recent findings concerning the pathological role of their conformational diversity, the way in which the heterogeneous conformations of amyloid fibrils can be formed has remained elusive. Here, we show that microwave-assisted chemistry affects the self-assembly process of amyloid fibril formation, which results in their conformational heterogeneity. In particular, microwave-assisted chemistry allows for delicate control of the thermodynamics of the self-assembly process, which enabled us to tune the molecular structure of ??-lactoglobulin amyloid fibrils. The heterogeneous conformations of amyloid fibrils, which can be tuned with microwave-assisted chemistry, are attributed to the microwave-driven thermal energy affecting the electrostatic interaction during the self-assembly process. Our study demonstrates how microwave-assisted chemistry can be used to gain insight into the origin of conformational heterogeneity of amyloid fibrils as well as the design principles showing how the molecular structures of amyloid fibrils can be controlledopen0

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm