Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.Martin Donnelley, Kaye S. Morgan, Karen K. W. Siu, Nigel R. Farrow, Charlene S. Stahr, Richard C. Boucher, Andreas Fouras & David W. Parson

Outline of a Genome Navigation System Based on the Properties of GA-Sequences and Their Flanks

Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. (1) Poly(A) binding proteins interact with the upstream poly(A)-segments and arrange adjacent GA-sequences side-by-side (‘GA-ribbon’), while folding the intervening DNA sequences between them into loops (‘associated DNA-loops’). (2) Genome navigation uses the GA-ribbon as a search path for specific target genes that is up to 730-fold shorter than the full-length chromosome. (3) As to the specificity of the search, each molecule of a target protein is assumed to catalyze the formation of specific oligomers from a set of transcription factors that recognize tetra-GA-motifs. Their specific combinations of tetra-GA motifs are assumed to be present in the particular GA-sequence whose associated loop contains the gene for the target protein. As long as the target protein is abundant in the cell it produces sufficient numbers of such oligomers which bind to their specific GA-sequences and, thereby, inhibit locally the transcription of the target protein in the associated loop. However, if the amount of target protein drops below a certain threshold, the resultant reduction of specific oligomers leaves the corresponding GA-sequence ‘denuded’. In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Underlying Dimensions of DSM-5 Posttraumatic Stress Disorder and Major Depressive Disorder Symptoms

This study examined the relationship between the underlying latent factors of major depression symptoms and DSM-5 posttraumatic stress disorder (PTSD) symptoms (American Psychiatric Association, 2013). A nonclinical sample of 266 participants with a trauma history participated in the study. Confirmatory factor analyses were conducted to evaluate the fit of the DSM-5 PTSD model and dysphoria model, as well as a depression model comprised of somatic and nonsomatic factors. The DSM-5 PTSD model demonstrated somewhat better fit over the dysphoria model. Wald tests indicated that PTSD's negative alterations in cognitions and mood factor was more strongly related to depression's nonsomatic factor than its somatic factor. This study furthers a nascent line of research examining the relationship between PTSD and depression factors in order to better understand the nature of the high comorbidity rates between the two disorders. Moreover, this study provides an initial analysis of the new DSM-5 diagnostic criteria for PTSD

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Ubx Regulates Differential Enlargement and Diversification of Insect Hind Legs

Differential enlargement of hind (T3) legs represents one of the hallmarks of insect evolution. However, the actual mechanism(s) responsible are yet to be determined. To address this issue, we have now studied the molecular basis of T3 leg enlargement in Oncopeltus fasciatus (milkweed bug) and Acheta domesticus (house cricket). In Oncopeltus, the T3 tibia displays a moderate increase in size, whereas in Acheta, the T3 femur, tibia, and tarsus are all greatly enlarged. Here, we show that the hox gene Ultrabithorax (Ubx) is expressed in the enlarged segments of hind legs. Furthermore, we demonstrate that depletion of Ubx during embryogenesis has a primary effect in T3 legs and causes shortening of leg segments that are enlarged in a wild type. This result shows that Ubx is regulating the differential growth and enlargement of T3 legs in both Oncopeltus and Acheta. The emerging view suggests that Ubx was co-opted for a novel role in regulating leg growth and that the transcriptional modification of its expression may be a universal mechanism for the evolutionary diversification of insect hind legs

Disturbances in Body Ownership in Schizophrenia: Evidence from the Rubber Hand Illusion and Case Study of a Spontaneous Out-of-Body Experience

A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature.The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire.Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self-reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences.The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity

Tackling health literacy: adaptation of public hypertension educational materials for an Indo-Asian population in Canada

<p>Abstract</p> <p>Background</p> <p>Indo-Asians in Canada are at increased risk for cardiovascular diseases. There is a need for cultural and language specific educational materials relating to this risk. During this project we developed and field tested the acceptability of a hypertension public education pamphlet tailored to fit the needs of an at risk local Indo-Asian population, in Calgary, Alberta, Canada.</p> <p>Methods</p> <p>A community health board representing Calgary's Indo-Asian communities identified the culturally specific educational needs and language preferences of the local population. An adaptation of an existing English language Canadian Public Hypertension Recommendations pamphlet was created considering the literacy and translation challenges. The adapted pamphlet was translated into four Indo-Asian languages. The adapted pamphlets were disseminated as part of the initial educational component of a community-based culturally and language-sensitive cardiovascular risk factor screening and management program. Field testing of the materials was undertaken when participants returned for program follow-up seven to 12 months later.</p> <p>Results</p> <p>Fifty-nine English-speaking participants evaluated and confirmed the concept validity of the English adapted version. 28 non-English speaking participants evaluated the Gujarati (N = 13) and Punjabi (N = 15) translated versions of the adapted pamphlets. All participants found the pamphlets acceptable and felt they had improved their understanding of hypertension.</p> <p>Conclusions</p> <p>Involving the target community to identify health issues as well as help to create culturally, language and literacy sensitive health education materials ensures resources are highly acceptable to that community. Minor changes to the materials will be needed prior to formal testing of hypertension knowledge and health decision-making on a larger scale within this at risk community.</p

A participatory action research approach to strengthening health managers’ capacity at district level in Eastern Uganda

BACKGROUND: Many approaches to improving health managers’ capacity in poor countries, particularly those pursued by external agencies, employ non-participatory approaches and often seek to circumvent (rather than strengthen) weak public management structures. This limits opportunities for strengthening local health managers’ capacity, improving resource utilisation and enhancing service delivery. This study explored the contribution of a participatory action research approach to strengthening health managers’ capacity in Eastern Uganda. METHODS: This was a qualitative study that used open-ended key informant interviews, combined with review of meeting minutes and observations to collect data. Both inductive and deductive thematic analysis was undertaken. The Competing Values Framework of organisational management functions guided the deductive process of analysis and the interpretation of the findings. The framework builds on four earlier models of management and regards them as complementary rather than conflicting, and identifies four managers’ capacities (collaborate, create, compete and control) by categorising them along two axes, one contrasting flexibility versus control and the other internal versus external organisational focus. RESULTS: The findings indicate that the participatory action research approach enhanced health managers’ capacity to collaborate with others, be creative, attain goals and review progress. The enablers included expanded interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability. Tension and conflict across different management functions was apparent; for example, while there was a need to collaborate, maintaining control over processes was also needed. These tensions meant that managers needed to learn to simultaneously draw upon and use different capacities as reflected by the Competing Values Framework in order to maximise their effectiveness. CONCLUSIONS: Improved health manager capacity is essential if sustained improvements in health outcomes in lowincome countries are to be attained. The expansion of interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability were the key means by which participatory action research strengthened health managers’ capacity. The participatory approach to implementation therefore created opportunities to strengthen health managers’ capacity