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

Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep

A study was carried out to investigate the frequencies of abortion and congenital Toxoplasma gondii infection within 27 families (765 individuals) of a pedigree Charollais sheep flock maintained on a working farm in Worcestershire, UK, since 1992. Pedigree lambing records were analysed to establish the frequency of abortion for each family. The frequency of congenital infection was determined for each family by PCR analysis of tissue samples taken from newborn lambs. Atotal of 155 lambs were tested for congenital T. gondii infection, which were all born during the study period 2000–2003. Significant differences in the frequency of abortion between sheep families within this flock were observed with frequencies ranging between 0% and 48% (P<0.01). Significantly different infection frequencies with T. gondii were also observed for different families and ranged between 0% and 100% (P<0.01). Although the actual cause of each abortion was not verified, a highly significant positive correlation was found to exist between the frequency of abortion and the frequency of T. gondii infection in the same families (P<0.01). The data presented here raise further questions regarding the significance of congenital transmission of T. gondii within sheep populations, the possible successive vertical transmission of T. gondii within families of sheep, and the potential role of inherited genetic susceptibility to abortion with respect to T. gondii infection. This work invites further study into the epidemiology of ovine toxoplasmosis and may have implications for sheep husbandry methods in the future. Key words: Toxoplasma gondii, ovine, toxoplasmosis, congenital, transmission, pedigree, sheep

High levels of congenital transmission of toxoplasma gondii in longitudinal and cross-sectional studies on sheep farms provides evidence of vertical transmission in ovine hosts

Recent research suggests that vertical transmission may play an important role in sustaining Toxoplasma gondii infection in some species. We report here that congenital transmission occurs at consistently high levels in pedigree Charollais and outbred sheep flocks sampled over a 3-year period. Overall rates of transmission per pregnancy determined by PCR based diagnosis, were consistent over time in a commercial sheep flock (69%) and in sympatric (60%) and allopatric (41%) populations of Charollais sheep. The result of this was that 53·7% of lambs were acquiring an infection prior to birth: 46·4% of live lambs and 90·0% of dead lambs (in agreement with the association made between T. gondii and abortion). No significant differences were observed between lamb sexes. Although we cannot distinguish between congenital transmission occurring due to primary infection at pregnancy or reactivation of chronic infection during pregnancy, our observations of consistently high levels of congenital transmission over successive lambings favour the latter

Detection of high levels of congenital transmission of toxoplasma gondii in natural urban populations of mus domesticus

The relative importance of different transmission routes of Toxoplasma gondii has been a matter for debate. This ubiquitous parasite is generally thought to be transmitted by infective oocysts excreted by the definitive host, the cat. Ingestion of undercooked meat has also been considered an important route of transmission in many mammals while congenital transmission has generally been considered relatively rare. Experimental studies demonstrate the ability of T. gondii to be transmitted congenitally, but few studies have investigated the frequency of this transmission route in natural populations. We use PCR amplification of the SAG1 gene to investigate the frequency of congenital transmission in a wild population of mice (Mus domesticus) and show that congenital transmission is occurring in 75% of pregnancies in this population. Furthermore, for infected pregnant mice, transmission occurs to at least one foetus in 100% of cases while variable penetrance of congenital infection is observed. These high levels of congenital transmission in this wild population of mice, taken together with other recent data on congenital transmission in sheep, suggests that this phenomenon might be more widespread than previously thought

The prevalence of Neospora caninum and co-infection with Toxoplasma gondii by PCR analysis in naturally occurring mammal populations

Neospora caninum and Toxoplasma gondii are closely related intracellular protozoan parasites associated with bovine and ovine abortion respectively. Little is known about the extent of Neospora/Toxoplasma co-infection in naturally infected populations of animals. Using nested PCR techniques, based on primers from the Nc5 region of N. caninum and SAG1 for T. gondii, the prevalence of N. caninum and its co-infection with T. gondii were investigated in populations of Mus domesticus, Rattus norvegicus and aborted lambs (Ovis aries). A low frequency of infection with N. caninum was detected in the Mus domesticus (3%) and Rattus norvegicus (4·4%) populations. A relatively high frequency of infection with N. caninum was detected in the brains of aborted lambs (18·9%). There was no significant relationship between N. caninum and T. gondii co-infection. Investigation of the tissue distribution of Neospora, in aborted lambs, showed that Neospora could not be detected in tissues other than brain and this was in contrast to Toxoplasma where the parasite could be frequently detected in a range of tissues

Tunable cavity coupling of the zero phonon line of a nitrogen-vacancy defect in diamond

We demonstrate the tunable enhancement of the zero phonon line of a single nitrogen-vacancy color center in diamond at cryogenic temperature. An open cavity fabricated using focused ion beam milling provides mode volumes as small as 1.24 $\mu$m$^3$. In-situ tuning of the cavity resonance is achieved with piezoelectric actuators. At optimal coupling of the full open cavity the signal from individual zero phonon line transitions is enhanced by about a factor of 10 and the overall emission rate of the NV$^-$ center is increased by 40% compared with that measured from the same center in the absence of cavity field confinement. This result is important for the realization of efficient spin-photon interfaces and scalable quantum computing using optically addressable solid state spin qubits.Comment: 11 pages Main Article + 4 pages Supplementary Info Typos fixed from v

Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This systematic review and meta-analysis focused on randomized controlled trials (RCT) of multinutrients consisting of at least four vitamins and/or minerals as interventions for participants with psychiatric symptoms. A systematic search identified 16 RCTs that fit the inclusion criteria (n = 1719 participants) in six psychiatric categories: depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, and autism. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the evidence base. Significant clinical benefit was assessed using minimal clinically important differences (MIDs). Due to heterogeneity in participants, multinutrient formulas, outcome measures, and absence of complete data, only the Attention-Deficit/Hyperactivity Disorder (ADHD) category was eligible for meta-analyses. In ADHD populations, statistically and clinically significant improvements were found in global functioning, Mean Difference (MD) −3.3, p = 0.001, MID −3.26; Standardized Mean Difference (SMD) −0.49 p = 0.001 MD −0.5), clinician ratings of global improvement (MD −0.58, p = 0.001, MID −0.5) and ADHD improvement (MD −0.54, p = 0.002, MID −0.5), and clinician (but not observer) measures of ADHD inattentive symptoms (MD −1.53, p = 0.05, MID −0.5). Narrative synthesis also revealed a pattern of benefit for global measures of improvement, for example: in autism, and in participants with behavioral deficits in dementia. Post-natural disaster anxiety and the number of violent incidents in prison populations also improved. Broad-spectrum formulas (vitamins + minerals) demonstrated more robust effects than formulas with fewer ingredients. This review highlights the need for robust methodology-RCTs that report full data, including means and standard deviations for all outcomes-in order to further elucidate the effects of multinutrients for psychiatric symptoms

Airway smooth muscle CXCR3 ligand production: Regulation by JAK-STAT1 and intracellular Ca²⁺

In asthma, airway smooth muscle (ASM) chemokine (C-X-C motif) receptor 3 (CXCR3) ligand production may attract mast cells or T lymphocytes to the ASM, where they can modulate ASM functions. In ASM cells (ASMCs) from people with or without asthma, we aimed to investigate JAK-STAT1, JNK, and Ca2+ involvement in chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11 production stimulated by interferon-γ, IL-1β, and TNF-α combined (cytomix). Confluent, growth-arrested ASMC were treated with inhibitors for pan-JAK (pyridone-6), JAK2 (AG-490), JNK (SP-600125), or the sarco(endo)plasmic reticulum Ca2+ATPase (SERCA) pump (thapsigargin), Ca2+ chelator (BAPTA-AM), or vehicle before and during cytomix stimulation for up to 24 h. Signaling protein activation as well as CXCL10/CXCL11 mRNA and protein production were examined using immunoblot analysis, real-time PCR, and ELISA, respectively. Cytomix-induced STAT1 activation was lower and CXCR3 ligand mRNA production was more sensitive to pyridone-6 and AG-490 in asthmatic than nonasthmatic ASMCs, but CXCL10/CXCL11 release was inhibited by the same proportion. Neither agent caused additional inhibition of release when used in combination with the JNK inhibitor SP-600125. Conversely, p65 NF-κB activation was higher in asthmatic than nonasthmatic ASMCs. BAPTA-AM abolished early CXCL10/CXCL11 mRNA production, whereas thapsigargin reduced it in asthmatic cells and inhibited CXCL10/CXCL11 release by both ASMC types. Despite these inhibitory effects, neither Ca2+ agent affected early activation of STAT1, JNK, or p65 NF-κB. In conclusion, intracellular Ca2+ regulated CXCL10/CXCL11 production but not early activation of the signaling molecules involved. In asthma, reduced ASM STAT1-JNK activation, increased NF-κB activation, and altered Ca2+ handling may contribute to rapid CXCR3 ligand production and enhanced inflammatory cell recruitment. © 2013 the American Physiological Society