Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

© 2018 SPIE. Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of-care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The experience of providing young people attending general practice with an online risk assessment tool to assess their own sexual health risk

<p>Abstract</p> <p>Background</p> <p>Targeted chlamydia screening has been advocated to reduce chlamydia associated reproductive sequelae. General practitioners are well positioned to play a major role in chlamydia control. The primary aim of this pilot study was to measure the effect of offering an online sexual health assessment tool, <it>Youth Check Your Risk</it>, on chlamydia testing rates among young people attending general practices. The secondary aim was to test the acceptability of the tool among general practitioners and young people.</p> <p>Methods</p> <p>General practitioners at three practices in Melbourne, Australia, referred patients aged 16 to 24 years to <it>Youth Check Your Risk </it><url>http://www.checkyourrisk.org.au</url> for use post-consultation between March to October 2007. The proportion of young people tested for chlamydia before and during the implementation of the tool was compared. Acceptability was assessed through a structured interviewer-administered questionnaire with general practitioners, and anonymous online data provided by <it>Youth Check Your Risk </it>users.</p> <p>Results</p> <p>The intervention did not result in any significant increases in the proportion of 16 to 24 year old males (2.7% to 3.0%) or females (6.3% to 6.4%) tested for chlamydia. A small increase in the proportion of 16 to 19 year old females tested was seen (4.1% to 7.2%). Of the 2997 patients seen during the intervention phase, 871 (29.1%) were referred to <it>Youth Check Your Risk </it>and 120 used it (13.8%). Major reasons for low referral rates reported by practitioners included lack of time, discomfort with raising the issue of testing, and difficulty in remembering to refer patients.</p> <p>Conclusion</p> <p>Offering an online sexual risk assessment tool in general practice did not significantly increase the proportion of young people tested for chlamydia, with GPs identifying a number of barriers to referring young people to <it>Youth Check Your Risk</it>. Future interventions aimed at increasing chlamydia screening in general practice with the aid of an online risk assessment tool need to identify and overcome barriers to testing.</p

Genome-Wide Analysis of Natural Selection on Human Cis-Elements

Background: It has been speculated that the polymorphisms in the non-coding portion of the human genome underlie much of the phenotypic variability among humans and between humans and other primates. If so, these genomic regions may be undergoing rapid evolutionary change, due in part to natural selection. However, the non-coding region is a heterogeneous mix of functional and non-functional regions. Furthermore, the functional regions are comprised of a variety of different types of elements, each under potentially different selection regimes. Findings and Conclusions: Using the HapMap and Perlegen polymorphism data that map to a stringent set of putative binding sites in human proximal promoters, we apply the Derived Allele Frequency distribution test of neutrality to provide evidence that many human-specific and primate-specific binding sites are likely evolving under positive selection. We also discuss inherent limitations of publicly available human SNP datasets that complicate the inference of selection pressures. Finally, we show that the genes whose proximal binding sites contain high frequency derived alleles are enriched for positive regulation of protein metabolism and developmental processes. Thus our genome-scale investigation provide

Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice

BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical role in the regulation of cell apoptosis, inflammation and production of reactive oxygen species (ROS), which may contribute to heart failure. However, the role of Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant-negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5 days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1 transgenic mice (TG) showed decreased cardiac function and increased apoptosis, autophagy and oxidative stress as compared with wild-type (WT) mice (P<0.01). Survival rate was significantly lower in Nrdp1 TG mice than in WT mice 10 days after DOX injection (P<0.01). CONCLUSIONS/SIGNIFICANCE: These results were associated with decreased activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Nrdp1 may be a key mediator in the development of cardiac dysfunction after DOX treatment and associated with inhibition of Akt, ERK1/2 and STAT3. Nrdp1 may be a new therapeutic target in protecting against the cardiotoxic effects of DOX

Genetic variation and linkage disequilibrium in Bacillus anthracis

We performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 Bacillus anthracis strains. We used an efficient algorithm contained within a custom software program, UniqueMER, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. We discovered a total of 240 single nucleotide variants (SNVs) and showed that B. anthracis strains have an average of 2.25 differences per 10,000 bases in the region we resequenced. Common SNVs in this region are found to be in complete linkage disequilibrium. These patterns of variation suggest there has been little if any historical recombination among B. anthracis strains since the origin of the pathogen. This pattern of common genetic variation suggests a framework for recognizing new or genetically engineered strains

Solution Structure of Tensin2 SH2 Domain and Its Phosphotyrosine-Independent Interaction with DLC-1

Background: Src homology 2 (SH2) domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1) via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode. Principal Findings: Tensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five b-strands flanked by two a-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1) as well as phosphorylated ligand. Conclusions: We determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner

Diagnostically Challenging Epithelial Odontogenic Tumors: A Selective Review of 7 Jawbone Lesions

Considerable variation in the clinicopathologic presentation of epithelial odontogenic tumors can sometimes be confusing and increase the chance of misdiagnosis. Seven diagnostically challenging jawbone lesions are described. There were 2 cases of mistaken identity in our ameloblastoma file. One unicystic type, initially diagnosed and treated as a lateral periodontal cyst, showed destructive recurrence 6 years postoperatively. The other globulomaxillary lesion was managed under the erroneous diagnosis of adenomatoid odontogenic tumor and recurred 4 times over an 11-year period. This tumor was found in retrospect to be consistent with an adenoid ameloblastoma with dentinoid. The diagnosis of cystic squamous odontogenic tumor (SOT) occurring as a radicular lesion of an impacted lower third molar was one of exclusion. Of two unsuspected keratocystic odontogenic tumors, one depicted deceptive features of pericoronitis, while the other case has long been in our files with the diagnosis of globulomaxillary SOT. Two cases of primary intraosseous squamous cell carcinoma appeared benign clinically and exhibited unexpected findings; an impacted third molar began to erupt in association with the growth of carcinoma and another periradicular carcinoma showed dentinoid formation. Cases selectively reviewed in this article present challenging problems which require clinical and radiographic correlation to avoid potential diagnostic pitfalls

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