Local anaesthesia for pain control during outpatient hysteroscopy: systematic review and meta-analysis

Objective To compare the effects of different types of local anaesthetic for pain control during outpatient hysteroscopy

The impact of asking intention or self-prediction questions on subsequent behavior: a meta-analysis

The current meta-analysis estimated the magnitude of the impact of asking intention and self-prediction questions on rates of subsequent behavior, and examined mediators and moderators of this question–behavior effect (QBE). Random-effects meta-analysis on 116 published tests of the effect indicated that intention/prediction questions have a small positive effect on behavior (d+ = 0.24). Little support was observed for attitude accessibility, cognitive dissonance, behavioral simulation, or processing fluency explanations of the QBE. Multivariate analyses indicated significant effects of social desirability of behavior/behavior domain (larger effects for more desirable and less risky behaviors), difficulty of behavior (larger effects for easy-to-perform behaviors), and sample type (larger effects among student samples). Although this review controls for co-occurrence of moderators in multivariate analyses, future primary research should systematically vary moderators in fully factorial designs. Further primary research is also needed to unravel the mechanisms underlying different variants of the QBE

A practical drug discovery project at the undergraduate level

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. Forty-eight target compounds have been prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and 10-fold, respectively

Uncovering a Massive z~7.65 Galaxy Hosting a Heavily Obscured Radio-Loud QSO Candidate in COSMOS-Web

In this letter, we report the discovery of the highest redshift, heavily obscured, radio-loud QSO candidate selected using JWST NIRCam/MIRI, mid-IR, sub-mm, and radio imaging in the COSMOS-Web field. Using multi-frequency radio observations and mid-IR photometry, we identify a powerful, radio-loud (RL), growing supermassive black hole (SMBH) with significant spectral steepening of the radio SED ($f_{1.32 \mathrm{GHz}} \sim 2$ mJy, $q_{24\mu m} = -1.1$, $\alpha_{1.32-3\mathrm{GHz}}=-1.2$, $\Delta \alpha = -0.4$). In conjunction with ALMA, deep ground-based observations, ancillary space-based data, and the unprecedented resolution and sensitivity of JWST, we find no evidence of QSO contribution to the UV/optical/NIR data and thus infer heavy amounts of obscuration (N$_{\mathrm{H}} > 10^{23}$ cm$^{-2}$). Using the wealth of deep UV to sub-mm photometric data, we report a singular solution photo-z of $z_\mathrm{phot}$ = 7.65$^{+0.4}_{-0.3}$ and estimate an extremely massive host-galaxy ($\log M_{\star} = 11.92 \pm 0.06\,\mathrm{M}_{\odot}$). This source represents the furthest known obscured RL QSO candidate, and its level of obscuration aligns with the most representative but observationally scarce population of QSOs at these epochs.Comment: Submitted to ApJL, Comments welcom

A practical drug discovery project at the undergraduate level

Teaser'You make the compounds you design': this article describes a new way for chemistry undergraduates to learn about drug discovery. A practical drug discovery project at the undergraduate level In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kd) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. In total, 48 target compounds were prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and !tenfold, respectively. This article is an account of a 'hands-on' drug discovery course that has been running for the past 3 years at the University of Nottingham. The purpose is fivefold: (i) to teach students, who are in the third year of a 4-year MSci degree course, how new medicines are discovered; (ii) to give an appreciation of the role of the chemist in that process; (iii) to give students practice in compound design and data interpretation; (iv) to use industry-standard equipment and methods in the laboratory; and (v) to develop communication, team-working and interpersonal skills. Key aspects of the course included the participation of scientists from GlaxoSmithKline (GSK) as lecturers and workshop mentors and, above all, in the practical application of drug discovery principles in the laboratory

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

COSMOS-Web: Intrinsically Luminous z≳\gtrsim10 Galaxy Candidates Test Early Stellar Mass Assembly

We report the discovery of 15 exceptionally luminous $10\lesssim z\lesssim14$ candidate galaxies discovered in the first 0.28 deg$^2$ of JWST/NIRCam imaging from the COSMOS-Web Survey. These sources span rest-frame UV magnitudes of $-20.5>M_{\rm UV}>-22$, and thus constitute the most intrinsically luminous $z\gtrsim10$ candidates identified by JWST to-date. Selected via NIRCam imaging with Hubble ACS/F814W, deep ground-based observations corroborate their detection and help significantly constrain their photometric redshifts. We analyze their spectral energy distributions using multiple open-source codes and evaluate the probability of low-redshift solutions; we conclude that 12/15 (80%) are likely genuine $z\gtrsim10$ sources and 3/15 (20%) likely low-redshift contaminants. Three of our $z\sim12$ candidates push the limits of early stellar mass assembly: they have estimated stellar masses $\sim5\times10^{9}\,M_\odot$, implying an effective stellar baryon fraction of $\epsilon_{\star}\sim0.2-0.5$, where $\epsilon_{\star}\equiv M_{\star}/(f_{b}M_{halo})$. The assembly of such stellar reservoirs is made possible due to rapid, burst-driven star formation on timescales $<$100\,Myr where the star-formation rate may far outpace the growth of the underlying dark matter halos. This is supported by the similar volume densities inferred for $M_\star\sim10^{10}\,M_\odot$ galaxies relative to $M_\star\sim10^{9}\,M_\odot$ -- both about $10^{-6}$ Mpc$^{-3}$ -- implying they live in halos of comparable mass. At such high redshifts, the duty cycle for starbursts would be of order unity, which could cause the observed change in the shape of the UVLF from a double powerlaw to Schechter at $z\approx8$. Spectroscopic redshift confirmation and ensuing constraints of their masses will be critical to understanding how, and if, such early massive galaxies push the limits of galaxy formation in $\Lambda$CDM.Comment: 30 pages, 9 figures; ApJ submitte