Concealed concern: Fathers' experience of having a child with Juvenile Idiopathic Arthritis

Despite increased research into families of chronically ill children, more needs to be known about the father’s experience. We address this issue through asking: ‘What is it like to be the father of a child with juvenile idiopathic arthritis?’ (JIA). Four members of eight families with an adolescent diagnosed with JIA, including seven fathers, were interviewed and transcripts analyzed using grounded theory. This study suggests that fathers of children with JIA experience several severe losses which are exacerbated through comparisons they make between their own situation and that of fathers of healthy children. In addition, the fathers faced several constraints which reduced their opportunities to communicate with their ill child through shared activities. Fathers appeared to conceal their distress by adopting strategies of denial and distraction however their adjustment was facilitated, to some extent, by social support. They could also develop greater acceptance of their situation over time as the care of their ill child became assimilated into family life and constraints upon their life gradually reduced through the increased maturity of their son or daughter with JIA. These findings have implications for healthcare professionals and voluntary organizations

Harnessing Single Cell Sorting to Identify Cell Division Genes and Regulators in Bacteria

Cell division is an essential cellular process that requires an array of known and unknown proteins for its spatial and temporal regulation. Here we develop a novel, high-throughput screening method for the identification of bacterial cell division genes and regulators. The method combines the over-expression of a shotgun genomic expression library to perturb the cell division process with high-throughput flow cytometry sorting to screen many thousands of clones. Using this approach, we recovered clones with a filamentous morphology for the model bacterium, Escherichia coli. Genetic analysis revealed that our screen identified both known cell division genes, and genes that have not previously been identified to be involved in cell division. This novel screening strategy is applicable to a wide range of organisms, including pathogenic bacteria, where cell division genes and regulators are attractive drug targets for antibiotic development. © 2013 Burke et al

Expression of microRNAs and target proteins in skeletal muscle of rats selectively bred for high and low running capacity

Impairments in mitochondrial function and substrate metabolism are implicated in the etiology of obesity and Type 2 diabetes. MicroRNAs (miRNAs) can degrade mRNA or repress protein translation and have been implicated in the development of such disorders. We used a contrasting rat model system of selectively bred high- (HCR) or low- (LCR) intrinsic running capacity with established differences in metabolic health to investigate the molecular mechanisms through which miRNAs regulate target proteins mediating mitochondrial function and substrate oxidation processes. Quantification of select miRNAs using the rat miFinder miRNA PCR array revealed differential expression of 15 skeletal muscles (musculus tibialis anterior) miRNAs between HCR and LCR rats (14 with higher expression in LCR; P < 0.05). Ingenuity Pathway Analysis predicted these altered miRNAs to collectively target multiple proteins implicated in mitochondrial dysfunction and energy substrate metabolism. Total protein abundance of citrate synthase (CS; miR-19 target) and voltage-dependent anion channel 1 (miR-7a target) were higher in HCR compared with LCR cohorts (~57 and ~26%, respectively; P < 0.05). A negative correlation was observed for miR-19a-3p and CS (r = 0.32, P = 0.015) protein expression. To determine whether miR-19a-3p can regulate CS in vitro, we performed luciferase reporter and transfection assays in C2C12 myotubes. MiR-19a-3p binding to the CS untranslated region did not change luciferase reporter activity; however, miR-19a-3p transfection decreased CS protein expression (∼70%; P < 0.05). The differential miRNA expression targeting proteins implicated in mitochondrial dysfunction and energy substrate metabolism may contribute to the molecular basis, mediating the divergent metabolic health profiles of LCR and HCR rat

Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma

<p>Abstract</p> <p>Background</p> <p>This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.</p> <p>Methods</p> <p>Adult patients with mild persistent asthma (≥ 80% predicted FEV₁) receiving 200–500 μg of BDP or equivalent were randomised to receive either FP 100 μg or SFC 50/100 μg twice daily from a Diskus^®inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.</p> <p>Results</p> <p>A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 – 0.89, p < 0.001) at week 2 and 0.81 (0.71 – 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV₁was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 – 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 – 0.34, p = 0.060).</p> <p>Conclusion</p> <p>SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV₁values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry</p> <p>Trial registration number</p> <p>NCT00370591.</p

Mixing of Active and Sterile Neutrinos

We investigate mixing of neutrinos in the $\nu$MSM (neutrino Minimal Standard Model), which is the MSM extended by three right-handed neutrinos. Especially, we study elements of the mixing matrix $\Theta_{\alpha I}$ between three left-handed neutrinos $\nu_\alpha$ ($\alpha = e,\mu,\tau$) and two sterile neutrinos $N_I$ ($I=2,3$) which are responsible to the seesaw mechanism generating the suppressed masses of active neutrinos as well as the generation of the baryon asymmetry of the universe (BAU). It is shown that $\Theta_{eI}$ can be suppressed by many orders of magnitude compared with $\Theta_{\mu I}$ and $\Theta_{\tau I}$, when the Chooz angle $\theta_{13}$ is large in the normal hierarchy of active neutrino masses. We then discuss the neutrinoless double beta decay in this framework by taking into account the contributions not only from active neutrinos but also from all the three sterile neutrinos. It is shown that $N_2$ and $N_3$ give substantial, destructive contributions when their masses are smaller than a few 100 MeV, and as a results $\Theta_{e I}$ receive no stringent constraint from the current bounds on such decay. Finally, we discuss the impacts of the obtained results on the direct searches of $N_{2,3}$ in meson decays for the case when $N_{2,3}$ are lighter than pion mass. We show that there exists the allowed region for $N_{2,3}$ with such small masses in the normal hierarchy case even if the current bound on the lifetimes of $N_{2,3}$ from the big bang nucleosynthesis is imposed. It is also pointed out that the direct search by using $\pi^+ \to e^+ + N_{2,3}$ and $K^+ \to e^+ + N_{2,3}$ might miss such $N_{2,3}$ since the branching ratios can be extremely small due to the cancellation in $\Theta_{eI}$, but the search by $K^+ \to \mu^+ + N_{2,3}$ can cover the whole allowed region by improving the measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure

Socio-economic drivers of specialist anglers targeting the non-native European catfish (Silurus glanis) in the UK.

Information about the socioeconomic drivers of Silurus glanis anglers in the UK were collected using questionnaires from a cross section of mixed cyprinid fisheries to elucidate human dimensions in angling and non-native fisheries management. Respondents were predominantly male (95%), 30-40 years of age with £500 per annum. The proportion of time spent angling for S. glanis was significantly related to angler motivations; fish size, challenge in catch, tranquil natural surroundings, escape from daily stress and to be alone were considered important drivers of increased time spent angling. Overall, poor awareness of: the risks and adverse ecological impacts associated with introduced S. glanis, non-native fisheries legislation, problems in use of unlimited ground bait and high fish stocking rates in angling lakes were evident, possibly related to inadequate training and information provided by angling organisations to anglers, as many stated that they were insufficiently informed

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)

Oxygen uptake and denitrification in soil aggregates

A mathematical model of oxygen uptake by bacteria in agricultural soils is presented with the goal of predicting anaerobic regions in which denitrification occurs. In an environment with a plentiful supply of oxygen, microorganisms consume oxygen through normal respiration. When the local oxygen concentration falls below a threshold level, denitrification may take place leading to the release of nitrous oxide, a potent agent for global warming. A two-dimensional model is presented in which one or more circular soil aggregates are located at a distance below the ground-level at which the prevailing oxygen concentration is prescribed. The level of denitrification is estimated by computing the area of any anaerobic cores which may develop in the interior of the aggregates. The oxygen distribution throughout the model soil is calculated first for an aggregated soil for which the ratio of the oxygen diffusivities between an aggregate and its surround is small via an asymptotic analysis. Second, the case of a non-aggregated soil featuring one or more microbial hotspots, for which the diffusion ratio is arbitrary, is examined numerically using the boundary-element method. Calculations with multiple aggregates demonstrate a sheltering effect whereby some aggregates receive less oxygen than their neighbours. In the case of an infinite regular triangular network representing an aggregated soil, it is shown that there is an optimal inter-aggregate spacing which minimises the total anaerobic core area

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014