Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels

BACKGROUND: Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients' adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3). METHODS: We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients' adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3). RESULTS: Eight TDF domains were perceived to influence patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3). CONCLUSIONS: Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future

Treatment adherence and health outcomes in patients with bronchiectasis

BACKGROUND: We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. METHODS: Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. RESULTS: Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. CONCLUSIONS: Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies

Collapse of a Bose gas: kinetic approach

We have analytically explored temperature dependence of critical number of particles for the collapse of a harmonically trapped attractively interacting Bose gas below the condensation point by introducing a kinetic approach within the Hartree-Fock approximation. The temperature dependence obtained by this easy approach is consisted with that obtained from the scaling theory.Comment: Brief Report, 4 pages, 1 figure, Accepted in Pramana-Journal of Physic

Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

Microbial dynamics in a High Arctic glacier forefield: A combined field, laboratory, and modelling approach

Modelling the development of soils in glacier forefields is necessary in order to assess how microbial and geochemical processes interact and shape soil development in response to glacier retreat. Furthermore, such models can help us predict microbial growth and the fate of Arctic soils in an increasingly ice-free future. Here, for the first time, we combined field sampling with laboratory analyses and numerical modelling to investigate microbial community dynamics in oligotrophic proglacial soils in Svalbard. We measured low bacterial growth rates and growth efficiencies (relative to estimates from Alpine glacier forefields) and high sensitivity of bacterial growth rates to soil temperature (relative to temperate soils). We used these laboratory measurements to inform parameter values in a new numerical model and significantly refined predictions of microbial and biogeochemical dynamics of soil development over a period of roughly 120 years. The model predicted the observed accumulation of autotrophic and heterotrophic biomass. Genomic data indicated that initial microbial communities were dominated by bacteria derived from the glacial environment, whereas older soils hosted a mixed community of autotrophic and heterotrophic bacteria. This finding was simulated by the numerical model, which showed that active microbial communities play key roles in fixing and recycling carbon and nutrients. We also demonstrated the role of allochthonous carbon and microbial necromass in sustaining a pool of organic material, despite high heterotrophic activity in older soils. This combined field, laboratory, and modelling approach demonstrates the value of integrated model-data studies to understand and quantify the functioning of the microbial community in an emerging High Arctic soil ecosystem

Football-induced fatigue in hypoxia impairs repeated sprint ability and perceptual-cognitive skills

The present study investigated the effects of football-induced fatigue during hypoxia on RS and perceptual-cognitive skills. Ten male semi-professional football players underwent four sessions; a control session (0-m) to quantify RS in a non-fatigued state; and three further sessions at hypoxia (0-m;1500-m;3000-m) examining RS and perceptual-cognitive skill responses for a given physical workload. Anticipation and decision-making accuracy were obtained at the 30-min mark of each half. The mean number of trials (%) in which the player made the correct response was used for analysis. HR, TC, RPE and % saturation of O2 were measured during the warm-up, football-induced fatigue and RS test. It was found that HR, RPE and % saturation of O2 were different between conditions (P<0.05; ES=0.44-6.13). Further, RS were affected by football-induced fatigue for DC (4.8%; P=0.019; ES=0.68) and AV (5.5%; P=0.006; ES=0.79). In hypoxia, it was observed that football-induced fatigue decreased by 6.5% in DC, 6.3% in AV and 3.1% in PV at 1500-m compared to 0-m (P<0.05). Further significant changes were found at 3000-m compared to 0-m decreasing 12.8% in DC, 12.8% in AV and 6.2% in PV (P<0.0005). More pronounced declines in perceptual-cognitive skills were found as altitude increased (5.0-12.5 %; P<0.05; ES=1.17-2.41) and between both halves (5.3-6.7 %; P<0.05). The data demonstrates that the RS test was highly sensitive to fatigue and hypoxia for a given physical load. Simulated matches in hypoxia revealed larger decreases, when compared to normoxia in RS and perceptual-cognitive skills, highlighting the need for optimal acclimatisation strategies, including physical and technical preparation, prior to playing a

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency