Using a hypothetical scenario to assess public preferences for colorectal surveillance following screening-detected, intermediate-risk adenomas: annual home-based stool test vs. triennial colonoscopy

Background To assess public preferences for colorectal cancer (CRC) surveillance tests for intermediate-risk adenomas, using a hypothetical scenario. Methods Adults aged 45–54 years without CRC were identified from three General Practices in England (two in Cumbria, one in London). A postal survey was carried out during a separate study on preferences for different first-line CRC screening modalities (non- or full-laxative computed tomographic colonography, flexible sigmoidoscopy, or colonoscopy). Individuals were allocated at random to receive a pack containing information on one first-line test, and a paragraph describing CRC surveillance recommendations for people who are diagnosed with intermediate-risk adenomas during screening. All participants received a description of two surveillance options: annual single-sample, home-based stool testing (consistent with Faecal Immunochemical Tests; FIT) or triennial colonoscopy. Invitees were asked to imagine they had been diagnosed with intermediate-risk adenomas, and then complete a questionnaire on their surveillance preferences. Results 22.1 % (686/3,100) questionnaires were returned. 491 (15.8 %) were eligible for analysis. The majority of participants stated a surveillance preference for the stool test over colonoscopy (60.8 % vs 31.0 %; no preference: 8.1 %; no surveillance: 0.2 %). Women were more likely to prefer the stool test than men (66.7 % vs. 53.6 %; p = .011). The primary reason for preferring the stool test was that it would be done more frequently. The main reason to prefer colonoscopy was its superiority at finding polyps. Conclusions A majority of participants stated a preference for a surveillance test resembling FIT over colonoscopy. Future research should test whether this translates to greater adherence in a real surveillance setting

Versatile Wideband Balanced Detector for Quantum Optical Homodyne Tomography

We present a comprehensive theory and an easy to follow method for the design and construction of a wideband homodyne detector for time-domain quantum measurements. We show how one can evaluate the performance of a detector in a specific time-domain experiment based on electronic spectral characteristic of that detector. We then present and characterize a high-performance detector constructed using inexpensive, commercially available components such as low-noise high-speed operational amplifiers and high-bandwidth photodiodes. Our detector shows linear behavior up to a level of over 13 dB clearance between shot noise and electronic noise, in the range from DC to 100 MHz. The detector can be used for measuring quantum optical field quadratures both in the continuous-wave and pulsed regimes with pulse repetition rates up to about 250 MHz.Comment: 11 pages, 8 figures, 1 tabl

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Structural insights into RNA processing by the human RISC-loading complex.

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2

(4-Hydr­oxy-3-nitro­benz­yl)methyl­ammonium chloride

The title compound, C8H11N2O3 +·Cl−, was synthesized as an inter­mediate in the development of a new sugar sensor. The structure displays N—H⋯Cl and O—H⋯O hydrogen bonding, as well as weak O—H⋯Cl inter­actions and π–π stacking (3.298 Å). There are two formula units in the asymmetric unit

8-(Naphthalen-1-yl)quinoline

In the title mol­ecule, C19H13N, the angle between the mean planes of the naphthalene and quinoline ring systems is 68.59 (2)°. The compound is of inter­est with respect to its potential for spontaneous resolution. In the crystal structure, the R and S isomers are arranged in alternating homochiral layers. The mol­ecules of a given layer are oriented with their major axes (i.e. the axis perpendicular to the interannular bond) in the same direction and their naphthalene and quinoline ring systems are arranged parallel. Like the configurations, this orientation alternates in adjacent layers

Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification

The fundamental process of endochondral ossification is under tight regulation in the healthy individual so as to prevent disturbed development and/or longitudinal bone growth. As such, it is imperative that we further our understanding of the underpinning molecular mechanisms involved in such disorders so as to provide advances towards human and animal patient benefit. The mouse metatarsal organ explant culture is a highly physiological ex vivo model for studying endochondral ossification and bone growth as the growth rate of the bones in culture mimic that observed in vivo. Uniquely, the metatarsal organ culture allows the examination of chondrocytes in different phases of chondrogenesis and maintains cell-cell and cell-matrix interactions, therefore providing conditions closer to the in vivo situation than cells in monolayer or 3D culture. This protocol describes in detail the intricate dissection of embryonic metatarsals from the hind limb of E15 murine embryos and the subsequent analyses that can be performed in order to examine endochondral ossification and longitudinal bone growth

2-Bromo-2-methyl-N-(4-nitro­phen­yl)propanamide

The title compound, C10H11BrN2O3, exhibits a small twist between the amide residue and benzene ring [the C—N—C—C torsion angle = 12.7 (4)°]. The crystal structure is stabilized by weak N—H⋯O, C—H⋯Br and C—H⋯O inter­actions. These lead to supra­molecular layers in the bc plane

8-(Biphenyl-4-yl)-8-hydroxy­penta­cyclo­[5.4.0.02,6.03,10.05,9]undecan-11-one ethyl­ene ketal

The title compound, C25H24O3, synthesized as a potential chiral catalyst, exhibits a range of C—C bond lengths in the penta­cyclo­undecane cage between 1.5144 (18) and 1.5856 (16) Å. The two benzene rings are not planar with respect to each other, but rather are twisted at a torsion angle of 34.67 (17)°. The mol­ecule has an intra­molecular O—H⋯O inter­action and participates in two C—H⋯O inter­molecular inter­actions to form a one-dimensional chain