Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

This Letter was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Scottish Universities Life Sciences Alliance (SULSA) in 2011Peer reviewedPostprin

Shear wave generation using a spiral electromagnetic acoustic transducer

A spiral electromagnetic acoustic transducer (EMAT) is efficient in eddy current generation and has been used for surface defect inspection using Rayleigh waves or thickness gauging based on plane waves in echo mode. Measured and calculated particle velocities and directivities are presented. It is found that the shear wave is not predominantly a plane wave. It has zero amplitude on the axis of the generation EMAT and has maximum amplitude at the critical angle. The shear wave could be used in the steel industry for both internal and surface defect inspections together with Rayleigh wave

The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators (PAMs)

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jmedchem.9b00252. Experimental procedures, characterization of all intermediates and target compounds, and copies of NMR spectra of compounds 1, 39-57. Molecular formula strings of target compounds are available. ACKNOWLEDGEMENTS. We gratefully thank Signal Pharma and the Canadian Institutes of Health Research Proof of Principle grants PPP-125784 and PP2-139101 for financial support and fellowship (C.C.T), NIH grants R01DA039942, P30DA033934 and VCU School of Pharmacy start-up funds (A.H.L.). We thank the EPSRC National Crystallography Service (University of Southampton) for the X-ray data collection. We are grateful to Dr Monica Sani (CNR-ICRM, Milan, Italy) and Mr Massimo Frigerio (Politecnico di Milano, Italy) for the synthesis of two tetrazole-substituted indoles (Het-1 and Het-2)Peer reviewedPostprin

A Cannabinoid CB 1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects

Peer reviewedPostprin

Using imaging to combat a pandemic:rationale for developing the UK National COVID-19 Chest Imaging Database

No abstract available

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.

OBJECTIVE: To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19). DESIGN: Prospective observational cohort study. SETTING: International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: 35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). CONCLUSIONS: An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations. STUDY REGISTRATION: ISRCTN66726260

The climate sensitivity of Norway spruce [Picea abies (L.) Karst.] in the southeastern European Alps

Tree ring chronologies were developed from trees growing at two sites in Slovenia which differed in their ecological and climatological characteristics. Ring width, maximum latewood density, annual height increment and latewood cellulose carbon isotope composition were developed at both sites and time-series verified against instrumental climate data over the period (AD 1960–AD 2002). Ring width sensitivity to summer temperature is site-dependent, with contrasting responses at alpine and lowland sites. Maximum density responds to September temperatures, suggesting lignification after cell division has ended for the season. Stable carbon isotopes have great potential, responding to summer temperature at oth alpine and lowland stands. Height increment appears relatively insensitive to climate, and is likely to be dominated by local stand dynamics