Mucosal dye spraying (chromoendoscopy CE) has been shown in controlled studies to enhance lesion detection in colitis surveillance. Narrow band imaging (NBI) potentially offers a more convenient mode ...of highlighting mucosal lesions. The primary objectives of this study were to compare CE and NBI in colitis surveillance with respect to lesion detection. A secondary objective was to assess the accuracy of the mucosal pit pattern (Kudo classification) with NBI in predicting mucosal histology.
Patients with colitis of 8 years or greater disease duration underwent screening colonoscopy with NBI, followed immediately by CE by 2 endoscopists blinded to each other's results. All lesions were biopsied to confirm histology. Diagnostic yield of each modality for dysplastic lesions. Accuracy of Kudo classification by NBI for neoplasia.
Forty-four participants were enrolled. One hundred forty-four colonic lesions were identified in total. Overall, CE identified more lesions than NBI (131 versus 102, P < 0.001); however, most were nondysplastic. CE detected 23 neoplastic (dysplastic or indefinite for dysplasia) lesions in 11 patients and NBI 20 lesions in 10 patients, P = 0.180. Kudo assessment by NBI had low sensitivity for dysplasia (42%) and modest accuracy (74%) for dysplasia.
NBI detected fewer lesions than CE in chronic colitis; however, most were not dysplastic. There was a nonsignificant trend in favor of CE for detection of dysplasia. At present, NBI cannot be recommended as an alternative to CE for dysplasia surveillance in colitis.
Fire is both a widespread natural disturbance that affects the distribution of species and a tool that can be used to manage habitats for species. Knowledge of temporal changes in the occurrence of ...species after fire is essential for conservation management in fire-prone environments. Two key issues are: whether postfire responses of species are idiosyncratic or if multiple species show a limited number of similar responses; and whether such responses to time since fire can predict the occurrence of species across broad spatial scales. We examined the response of bird species to time since fire in semiarid shrubland in southeastern Australia using data from surveys at 499 sites representing a 100-year chronosequence. We used nonlinear regression to model the probability of occurrence of 30 species with time since fire in two vegetation types, and compared species' responses with generalized response shapes from the literature. The occurrence of 16 species was significantly influenced by time since fire: they displayed six main responses consistent with generalized response shapes. Of these 16 species, 15 occurred more frequently in mid- or later-successional vegetation (>20 years since fire), and only one species occurred more often in early succession (<5 years since fire). The models had reasonable predictive ability for eight species, some predictive ability for seven species, and were little better than random for one species. Bird species displayed a limited range of responses to time since fire; thus a small set of fire ages should allow the provision of habitat for most species. Postfire successional changes extend for decades and management of the age class distribution of vegetation will need to reflect this timescale. Response curves revealed important seral stages for species and highlighted the importance of mid- to late-successional vegetation (>20 years). Although time since fire clearly influences the distribution of numerous bird species, predictive models of the spatial distribution of species in fire-prone landscapes need to incorporate other factors in addition to time since fire.
Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates ...composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation.
Localized and controlled delivery systems for the sustained release of drugs are essential. Many strategies have been developed for this purpose, but most rely on degradation (and loss of material properties) for delivery. Here, we developed a bilayer delivery system (BiLDS) that decouples the physical properties of a scaffold from its delivery kinetics. For this, biodegradable PLGA microspheres were sequestered within a central pocket of a slowly degrading nanofibrous bilayer. Using this device, we show enhanced cell activity with FGF delivery from the BiLDS both in vitro and in vivo. These data support that BiLDS can localize sustained protein and biofactor delivery to a surgical site while also serving as a mechanical scaffold for tissue repair and regeneration.
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To examine use of CT colonography (CTC) in the English Bowel Cancer Screening Programme (BCSP) and investigate detection rates.
Retrospective analysis of routinely coded BCSP data. Guaiac faecal ...occult blood test (gFOBt)-positive screenees undergoing CTC from June 2006 to July 2012 as their first-line colonic investigation were included. Abnormalities found at CTC, subsequent polyp, adenoma and cancer detection and positive predictive value (PPV) were calculated. Detection rates were compared with those observed in gFOBt-positive screenees investigated by colonoscopy. Multilevel logistic regression was used to examine factors associated with variable detection.
2731 screenees underwent CTC. Colorectal cancer (CRC) or polyps were suspected in 1027 individuals (37.6%; 95% CI 33.8% to 41.4%); 911 of these underwent confirmatory testing. 124 screenees had CRC (4.5%) and 533 had polyps (19.5%), 468 adenomatous (17.1%). Overall detection was 24.1% (95% CI 21.5% to 26.6%) for CRC or polyps and 21.7% (95% CI 19.2% to 24.1%) for CRC or adenoma. Advanced neoplasia was detected in 504 screenees (18.5%; 95% CI 16.1% to 20.8%). PPV for CRC or polyp was 72.1% (95% CI 66.6% to 77.6%). By comparison, 9.0% of 72 817 screenees undergoing colonoscopy had cancer and 50.6% had polyps; advanced neoplasia was detected in 32.7%. CTC detection rates and PPV were higher at centres with experienced radiologists (>1000 examinations) and at high-volume centres (>175 cases/radiologist/annum). Centres using three-dimensional interpretation detected more neoplasia.
In the BCSP, detection rates after positive gFOBt are lower for CTC than colonoscopy, although populations undergoing the two tests are different. Centres with more experienced radiologists have higher detection and accuracy. Rigorous quality assurance of BCSP radiology is needed.
Insufficient pancreatic β-cell mass or function results in diabetes mellitus. While significant progress has been made in regulating insulin secretion from β-cells in diabetic patients, no ...pharmacological agents have been described that increase β-cell replication in humans. Here we report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B. Aminopyrazine-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of these compounds in diabetic mice induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Biochemical, genetic and cell biology data point to Dyrk1a as the key molecular target. This study supports the feasibility of treating diabetes with an oral therapy to restore β-cell mass, and highlights a tractable pathway for future drug discovery efforts.
Aim: A common strategy for conserving biodiversity in fire-prone environments is to maintain a diversity of post-fire age classes at the landscape scale, under the assumption that 'pyrodiversity ...begets biodiversity'. Another strategy is to maintain extensive areas of a particular seral state regarded as vital for the persistence of threatened species, under the assumption that this will also cater for the habitat needs of other species. We investigated the likely effects of these strategies on bird assemblages in tree mallee vegetation, characterized by multistemmed Eucalyptus species, where both strategies are currently employed. Location: The semi-arid Murray Mallee region of south-eastern Australia. Methods: We systematically surveyed birds in 26 landscapes (each 4-km diameter), selected to represent gradients in the diversity of fire age classes and the proportion of older vegetation (> 35 years since fire). Additional variables were measured to represent underlying vegetation- or fire-mediated properties of the landscape, as well as its biogeographic context. We used an informationtheoretic approach to investigate the relationships between these predictor variables and the species richness of birds (total species, threatened species and rare species). Results: Species richness of birds was not strongly associated with fire-mediated heterogeneity. Species richness was associated with increasing amounts of older vegetation in landscapes, but not with the proportion of recently burned vegetation in landscapes. Main conclusions: The preference of many mallee birds for older vegetation highlights the risk of a blanket application of the 'pyrodiversity begets biodiversity' paradigm. If application of this paradigm involved converting large areas from long unburned to recently burned vegetation to increase fire-mediated heterogeneity in tree mallee landscapes, our findings suggest that this could threaten birds. This research highlights the value of adopting a landscape-scale perspective when evaluating the utility of fire-management strategies intended to benefit biodiversity.
Abstract
BACKGROUND
Though it is well known that normal pressure hydrocephalus (NPH) patients can cognitively improve after ventriculoperitoneal shunting (VPS), one of the major dilemmas in NPH is ...the ability to prospectively predict which patients will improve.
OBJECTIVE
To prospectively assess preoperative predictors of postshunt cognitive improvement.
METHODS
This was a prospective observational cohort including 52 consecutive patients with approximately 1-yr follow-up. Patients underwent neuropsychological testing at baseline, postlumbar drainage, and postshunt. Cerebrospinal fluid (CSF) biomarkers and cortical biopsies were also collected to examine their relationship with postshunt cognitive improvement.
RESULTS
Rey Auditory Verbal Learning Test-L (RAVLT-L) was the only neuropsychological test to demonstrate statistically significant improvement both postlumbar drain and postshunt. Improvement on the RAVLT-L postlumbar drain predicted improvement on the RAVLT-L postshunt. Patients with biopsies demonstrating Aβ+ Tau+ had lower ventricular CSF Aβ42 and higher lumbar CSF pTau compared to Aβ– Tau– patients. A receiver operating curve analysis using lumbar pTau predicted Aβ+ Tau+ biopsy status but was not related to neuropsychological test outcome.
CONCLUSION
The RAVLT can be a useful preoperative predictor of postoperative cognitive improvement, and thus, we recommend using the RAVLT to evaluate NPH patients. CSF biomarkers could not be related to neuropsychological test outcome. Future research in a larger patient sample will help determine the prospective utility of CSF biomarkers in the evaluation of NPH patients.
Genetic bottlenecks can limit the success of populations colonizing new ranges. However, successful colonizations can occur despite bottlenecks, a phenomenon known as the genetic paradox of invasion. ...Eusocial Hymenoptera such as bumblebees (
spp.) should be particularly vulnerable to genetic bottlenecks, since homozygosity at the sex-determining locus leads to costly diploid male production (DMP). The Tree Bumblebee (
) has rapidly colonized the UK since 2001 and has been highlighted as exemplifying the genetic paradox of invasion. Using microsatellite genotyping, combined with the first genetic estimates of DMP in UK
, we tested two alternative genetic hypotheses ('bottleneck' and 'gene flow' hypotheses) for
's colonization of the UK. We found that the UK population has not undergone a recent severe genetic bottleneck and exhibits levels of genetic diversity falling between those of widespread and range-restricted
species. Diploid males occurred in 15.4% of reared colonies, leading to an estimate of 21.5 alleles at the sex-determining locus. Overall, the findings show that this population is not bottlenecked, instead suggesting that it is experiencing continued gene flow from the continental European source population with only moderate loss of genetic diversity, and does not exemplify the genetic paradox of invasion.
Highlights • First to study the prognostic significance of non-HPV16 genotypes with p16 status. • HPV16-positve oropharynx tumors have better survival than non-HPV16-positive genotypes. • The ...survival benefit for HPV16-positve genotypes holds for tumors positive for p16, but not for p16-negative tumors.
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