Barriers and Facilitators to Use of a Clinical Evidence Technology in the Management of Skin Problems in Primary Care: Insights from Mixed Methods

Objective: Few studies have examined the impact of a single clinical evidence technology (CET) on provider practice or patient outcomes from the provider’s perspective. A previous cluster-randomized controlled trial with patient-reported data tested the effectiveness of a CET (i.e., VisualDx) in improving skin problem outcomes but found no significant effect. The objectives of this follow-up study were to identify barriers and facilitators to the use of the CET from the perspective of primary care providers (PCPs) and to identify reasons why the CET did not affect outcomes in the trial. Methods: Using a convergent mixed methods design, PCPs completed a post-trial survey and participated in interviews about using the CET for the management of patients’ skin problems. Data from both methods were integrated. Results: PCPs found the CET somewhat easy to use but only occasionally useful. Less experienced PCPs used the CET more frequently. Data from interviews revealed barriers and facilitators at four steps of evidence-based practice: clinical question recognition, information acquisition, appraisal of relevance, and application with patients. Facilitators included uncertainty in dermatology, intention for use, convenience of access, diagnosis and treatment support, and patient communication. Barriers included confidence in dermatology, preference for other sources, interface difficulties, presence of irrelevant information, and lack of decision impact. Conclusion: PCPs found the CET useful for diagnosis, treatment support, and patient communication. However, the barriers of interface difficulties, irrelevant search results, and preferred use of other sources limited its positive impact on patient skin problem management

Structure and function of gene regulatory networks associated with worker sterility in honeybees.

A characteristic of eusocial bees is a reproductive division of labor in which one or a few queens monopolize reproduction, while her worker daughters take on reproductively altruistic roles within the colony. The evolution of worker reproductive altruism involves indirect selection for the coordinated expression of genes that regulate personal reproduction, but evidence for this type of selection remains elusive. In this study, we tested whether genes coexpressed under queen-induced worker sterility show evidence of adaptive organization within a model brain transcriptional regulatory network (TRN). If so, this structured pattern would imply that indirect selection on nonreproductive workers has influenced the functional organization of genes within the network, specifically to regulate the expression of sterility. We found that literature-curated sets of candidate genes for sterility, ranging in size from 18 to 267, show strong evidence of clustering within the three-dimensional space of the TRN. This finding suggests that our candidate sets of genes for sterility form functional modules within the living bee brain\u27s TRN. Moreover, these same gene sets colocate to a single, albeit large, region of the TRN\u27s topology. This spatially organized and convergent pattern contrasts with a null expectation for functionally unrelated genes to be haphazardly distributed throughout the network. Our meta-genomic analysis therefore provides first evidence for a truly social transcriptome that may regulate the conditional expression of honeybee worker sterility

Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma

Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibrations (LIV), a component of mechanical signaling, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 85% less trabecular bone volume (BV) fraction in MM versus AC, yet only a 21% decrease in LIV as compared to as compared to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in L5 of LIV-treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9× higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of marrow in the tibia while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed systemic myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs

Chemical abundances in the protoplanetary disk LV2 (Orion): clues to the causes of the abundance anomaly in HII regions

Optical integral field spectroscopy of the archetype protoplanetary disk LV2 in the Orion Nebula is presented, taken with the VLT FLAMES/Argus fibre array. The detection of recombination lines of CII and OII from this class of objects is reported, and the lines are utilized as abundance diagnostics. The study is complemented with the analysis of HST Faint Object Spectrograph ultraviolet and optical spectra of the target contained within the Argus field of view. By subtracting the local nebula background the intrinsic spectrum of the proplyd is obtained and its elemental composition is derived for the first time. The proplyd is found to be overabundant in carbon, oxygen and neon compared to the Orion Nebula and the sun. The simultaneous coverage over LV2 of the CIII] 1908-A and [OIII] 5007-A collisionally excited lines (CELs) and CII and OII recombination lines (RLs) has enabled us to measure the abundances of C++ and O++ for LV2 with both sets of lines. The two methods yield consistent results for the intrinsic proplyd spectrum, but not for the proplyd spectrum contaminated by the generic nebula spectrum, thus providing one example where the long-standing abundance anomaly plaguing metallicity studies of HII regions has been resolved. These results would indicate that the standard forbidden-line methods used in the derivation of light metal abundances in HII regions in our own and other galaxies underestimate the true gas metallicity.Comment: Accepted by MNRAS November 8; 16 pages, 9 figs; typos corrected, error in FWHMs in table 4 corrected in this versio

Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura

BACKGROUND: The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. RESULTS: We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. CONCLUSIONS: Measuring conservation of sequence features closely linked to function - such as binding-site clustering - makes better use of comparative sequence data than commonly used methods that examine only sequence identity

PPAK Integral Field Spectroscopy survey of the Orion Nebula: Data Release

We present a low-resolution spectroscopic survey of the Orion nebula which data we release for public use. In this article, we intend to show the possible applications of this dataset analyzing some of the main properties of the nebula. We perform an integral field spectroscopy mosaic of an area of ~5' X 6' centered on the Trapezium region of the nebula, including the ionization front to the south-east. The analysis of the line fluxes and line ratios of both the individual and integrated spectra allowed us to determine the main characteristics of the ionization throughtout the nebula.The final dataset comprises 8182 individual spectra, which sample each one a circular area of \~2.7" diameter. The data can be downloaded as a single row-stacked spectra fits file plus a position table or as an interpolated datacube with a final sampling of 1.5"/pixel. The integrated spectrum across the field-of-view was used to obtain the main integrated properties of the nebula, including the electron density and temperature, the dust extinction, the Halpha integrated flux (after correcting for dust reddening), and the main diagnostic line ratios. The individual spectra were used to obtain line intensity maps of the different detected lines. These maps were used to study the distribution of the ionized hydrogen, the dust extinction, the electron density and temperature, and the helium and oxygen abundance...Comment: 13 pages, 8 figures, accepted for publishing in Astronomy & Astrophysic

Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis

BACKGROUND: Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. DESIGN: BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. RESULTS: Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. CONCLUSIONS: Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis

Infrared study of the Southern Galactic star forming region associated with IRAS 14416-5937

Aims: We have carried out an infrared study of the southern Galactic massive star forming region associated with IRAS 14416-5937. Methods: This star forming region has been mapped simultaneously in two far infrared bands at ~ 150 & 210 micron using the TIFR 1-m balloon borne telescope with ~ 1' angular resolution. We have used 2MASS JHK$_s$ as well as Spitzer-GLIMPSE data of this region to study the stellar populations of the embedded young cluster. This region comprises of two sources, designated as A & B and separated by ~ 2 pc. The spectrum of a region located close to the source A obtained using the Long Wavelength Spectrometer (LWS) on-board the Infrared Space Observatory (ISO), is presented. Emission from warm dust and from Unidentified Infrared Bands (UIBs) is estimated using the mid-infrared data of the MSX survey. Results: The spatial distributions of (1) the temperature of cool dust and (2) optical depth at 200 micron have been obtained taking advantage of the similar beams in both the TIFR bands. A number of atomic fine structure lines have been detected in the ISO-LWS spectrum, which have been used to estimate the electron density and the effective temperature of the ionising radiation in this region. From the near and mid infrared images, we identify a dust lane due north-west of source A. The dust lane is populated by Class I type sources. Class II type sources are found further along the dust lane as well as below it. Self consistent radiative transfer models of the two sources (A and B) are in good agreement with the observed spectral energy distributions. Conclusions: The spatial distribution of young stellar objects in and around the dust lane suggests that active star formation is taking place along the dust lane and is possibly triggered by the expanding HII regions of A and B.Comment: Accepted by the Astronomy and Astrophysics (21 pages, 7 tables and 13 figures

Three-dimensional chemically homogeneous and bi-abundance photoionization models of the "super-metal-rich" planetary nebula NGC 6153

Deep spectroscopy of the planetary nebula (PN) NGC\,6153 shows that its heavy element abundances derived from optical recombination lines (ORLs) are ten times higher than those derived from collisionally excited lines (CELs), and points to the existence of H-deficient inclusions embedded in the diffuse nebula. In this study, we have constructed chemically homogeneous and bi-abundance three-dimensional photoionization models, using the Monte Carlo photoionization code {\sc mocassin}. We attempt to reproduce the multi-waveband spectroscopic and imaging observations of NGC\,6153, and investigate the nature and origin of the postulated H-deficient inclusions, as well as their impacts on the empirical nebular analyses assuming a uniform chemical composition. Our results show that chemically homogeneous models yield small electron temperature fluctuations and fail to reproduce the strengths of ORLs from C, N, O and Ne ions. In contrast, bi-abundance models incorporating a small amount of metal-rich inclusions ($\sim 1.3$ per cent of the total nebular mass) are able to match all the observations within the measurement uncertainties. The metal-rich clumps, cooled down to a very low temperature ($\sim 800$~K) by ionic infrared fine-structure lines, dominate the emission of heavy element ORLs, but contribute almost nil to the emission of most CELs. We find that the abundances of C, N, O and Ne derived empirically from CELs, assuming a uniform chemical composition, are about 30 per cent lower than the corresponding average values of the whole nebula, including the contribution from the H-deficient inclusions. Ironically, in the presence of H-deficient inclusions, the traditional standard analysis of the optical helium recombination lines, assuming a chemically homogeneous nebula, overestimates the helium abundance by 40 per cent.Comment: 19 pages, 18 figures, accepted for publication in MNRA