Unsedated transnasal endoscopy:a safe, well-tolerated and accurate alternative to standard diagnostic peroral endoscopy

Diagnostic unsedated transnasal endoscopy (uTNE) has been proven to be a safe and well-tolerated procedure. Although its utilization in the United Kingdom (UK) is increasing, it is currently available in only a few centers. Through consideration of recent studies, we aimed to perform an updated review of the technological advances in uTNE, consider their impact on diagnostic accuracy, and to determine the role of uTNE in the COVID-19 era. Current literature has shown that the diagnostic accuracy of uTNE for identification of esophageal pathology is equivalent to conventional esophagogastroduodenoscopy (cEGD). Concerns regarding suction and biopsy size have been addressed by the introduction of TNE scopes with working channels of 2.4 mm. Advances in imaging have improved detection of early gastric cancers. The procedure is associated with less cardiac stress and reduced aerosol production; when combined with no need for sedation and improved rates of patient turnover, uTNE is an efficient and safe alternative to cEGD in the COVID-19 era. We conclude that advances in technology have improved the diagnostic accuracy of uTNE to the point where it could be considered the first line diagnostic endoscopic investigation in the majority of patients. It could also play a central role in the recovery of diagnostic endoscopic services during the COVID-19 pandemic

Photophysics of Organic Semiconductors: From Ensemble to the Single-Molecule Level

We present photophysical properties of functionalized anthradithiophene (ADT) and pentacene (Pn) derivatives, as well as charge and energy transfer properties of donor-acceptor (D/A) pairs of these derivatives. All molecules studied were fluorescent and photostable enough to be imaged on the single-molecule level in a variety of polymeric and in a functionalized benzothiophene (BTBTB) crystalline host using room-temperature wide- field epifluorescence microscopy. Flexibility of functionalization of both guest (ADT, Pn) and host (BTBTB or polymer) molecules can be used for systematic studies of nanoscale morphology and photophysics of D/A organic semiconductor bulk heterojunctions, as well as in applications relying on FRET, using single-molecule fluorescence microscopy

Tumor-immune metaphenotypes orchestrate an evolutionary bottleneck that promotes metabolic transformation

Introduction: Metabolism plays a complex role in the evolution of cancerous tumors, including inducing a multifaceted effect on the immune system to aid immune escape. Immune escape is, by definition, a collective phenomenon by requiring the presence of two cell types interacting in close proximity: tumor and immune. The microenvironmental context of these interactions is influenced by the dynamic process of blood vessel growth and remodelling, creating heterogeneous patches of well-vascularized tumor or acidic niches. Methods: Here, we present a multiscale mathematical model that captures the phenotypic, vascular, microenvironmental, and spatial heterogeneity which shapes acid-mediated invasion and immune escape over a biologically-realistic time scale. The model explores several immune escape mechanisms such as i) acid inactivation of immune cells, ii) competition for glucose, and iii) inhibitory immune checkpoint receptor expression (PD-L1). We also explore the efficacy of anti-PD-L1 and sodium bicarbonate buffer agents for treatment. To aid in understanding immune escape as a collective cellular phenomenon, we define immune escape in the context of six collective phenotypes (termed “meta-phenotypes”): Self-Acidify, Mooch Acid, PD-L1 Attack, Mooch PD-L1, Proliferate Fast, and Starve Glucose. Results: Fomenting a stronger immune response leads to initial benefits (additional cytotoxicity), but this advantage is offset by increased cell turnover that leads to accelerated evolution and the emergence of aggressive phenotypes. This creates a bimodal therapy landscape: either the immune system should be maximized for complete cure, or kept in check to avoid rapid evolution of invasive cells. These constraints are dependent on heterogeneity in vascular context, microenvironmental acidification, and the strength of immune response. Discussion: This model helps to untangle the key constraints on evolutionary costs and benefits of three key phenotypic axes on tumor invasion and treatment: acid-resistance, glycolysis, and PD-L1 expression. The benefits of concomitant anti-PD-L1 and buffer treatments is a promising treatment strategy to limit the adverse effects of immune escape

New Constraints on Cosmic Reionization from the 2012 Hubble Ultra Deep Field Campaign

Understanding cosmic reionization requires the identification and characterization of early sources of hydrogen-ionizing photons. The 2012 Hubble Ultra Deep Field (UDF12) campaign has acquired the deepest infrared images with the Wide Field Camera 3 aboard Hubble Space Telescope and, for the first time, systematically explored the galaxy population deep into the era when cosmic microwave background (CMB) data indicates reionization was underway. The UDF12 campaign thus provides the best constraints to date on the abundance, luminosity distribution, and spectral properties of early star-forming galaxies. We synthesize the new UDF12 results with the most recent constraints from CMB observations to infer redshift-dependent ultraviolet (UV) luminosity densities, reionization histories, and electron scattering optical depth evolution consistent with the available data. Under reasonable assumptions about the escape fraction of hydrogen ionizing photons and the intergalactic medium clumping factor, we find that to fully reionize the universe by redshift z~6 the population of star-forming galaxies at redshifts z~7-9 likely must extend in luminosity below the UDF12 limits to absolute UV magnitudes of M_UV\sim -13 or fainter. Moreover, low levels of star formation extending to redshifts z~15-25, as suggested by the normal UV colors of z\simeq7-8 galaxies and the smooth decline in abundance with redshift observed by UDF12 to z\simeq10, are additionally likely required to reproduce the optical depth to electron scattering inferred from CMB observations.Comment: Version accepted by ApJ (originally submitted Jan 5, 2013). The UDF12 website can be found at http://udf12.arizona.ed

Ciprofloxacin Poly(β-amino ester) Conjugates Enhance Antibiofilm Activity and Slow the Development of Resistance

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial biofilms are a particular concern in this context as they are responsible for over 80% of bacterial infections and are inherently more recalcitrant toward antimicrobial treatments. The high tolerance of biofilms to conventional antibiotics has been attributed to several factors, including reduced drug diffusion through the dense exopolymeric matrix and the upregulation of antimicrobial resistance machinery with successful biofilm eradication requiring prolonged high doses of multidrug treatments. A promising approach to tackle bacterial infections involves the use of polymer drug conjugates, shown to improve upon free drug toxicity and bioavailability, enhance drug penetration through the thick biofilm matrix, and evade common resistance mechanisms. In the following study, we conjugated the antibiotic ciprofloxacin (CIP) to a small library of biodegradable and biocompatible poly(β-amino ester) (PBAE) polymers with varying central amine functionality. The suitability of the polymers as antibiotic conjugates was then verified in a series of assays including testing of efficacy and resistance response in planktonic Gram-positive and Gram-negative bacteria and the reduction of viability in mono- and multispecies biofilm models. The most active polymer within the prepared PBAE-CIP library was shown to achieve an over 2-fold increase in the reduction of biofilm viability in a Pseudomonas aeruginosa monospecies biofilm and superior elimination of all the species present within the multispecies biofilm model. Hence, we demonstrate that CIP conjugation to PBAEs can be employed to achieve improved antibiotic efficacy against clinically relevant biofilm models

Weak Interaction Studies with 6He

The 6He nucleus is an ideal candidate to study the weak interaction. To this end we have built a high-intensity source of 6He delivering ~10^10 atoms/s to experiments. Taking full advantage of that available intensity we have performed a high-precision measurement of the 6He half-life that directly probes the axial part of the nuclear Hamiltonian. Currently, we are preparing a measurement of the beta-neutrino angular correlation in 6He beta decay that will allow to search for new physics beyond the Standard Model in the form of tensor currents.Comment: 5 pages, 4 figures, proceedings for the Eleventh Conference on the Intersections of Particle and Nuclear Physics (CIPANP 2012

A massive proto-cluster of galaxies at a redshift of z {\approx} 5.3

Massive clusters of galaxies have been found as early as 3.9 Billion years (z=1.62) after the Big Bang containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter paradigm predict these systems should descend from "proto-clusters" - early over-densities of massive galaxies that merge hierarchically to form a cluster. These proto-cluster regions themselves are built-up hierarchically and so are expected to contain extremely massive galaxies which can be observed as luminous quasars and starbursts. However, observational evidence for this scenario is sparse due to the fact that high-redshift proto-clusters are rare and difficult to observe. Here we report a proto-cluster region 1 billion years (z=5.3) after the Big Bang. This cluster of massive galaxies extends over >13 Mega-parsecs, contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of >4x10^11 solar masses of dark and luminous matter in this region consistent with that expected from cosmological simulations for the earliest galaxy clusters.Comment: Accepted to Nature, 16 Pages, 6 figure