Ambient air pollution exposure estimation for the Global Burden of Disease 2013 (Publications)
World Health Organization Air Quality Guideline of 10 mug/m(3) PM2.5 (annual average). Between 1990 and 2013, global population-weighted PM2.5 increased by 20.4% driven by trends in South Asia, Southeast Asia [...] measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1 degrees x 0.1 degrees spatial resolution for five-year intervals from [...] Asia, and China. Decreases in population-weighted mean...
Meta-analysis identifies seven susceptibility loci involved in the atopic march (Publications)
12q21.3 (OR 1.58; P=5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21)
Discovery of inhibitors of<em> Trypanosoma brucei</em> by phenotypic screening of a focused protein kinase library (Publications)
compounds, which showed > 50 % inhibition at 5 muM. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)-one scaffold that showed [...] showed sub-micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and [...] brucei growth assay, which could differentiate static and cidal action....
Long-term outcome in elderly patients with chronic angina managed invasively versus by optimized medical therapy: four-year follow-up of the... (Publications)
years (range, 1.1 to 5.9 years). At baseline, patients were 80+/-4 years old, 42% were women, and they were designated as being in angina class 3.2+/-0.7, despite their taking 2.5+/-0.7 antiischemic drugs [...] (n=148) strategy. Survival of invasive-strategy versus medical-strategy patients was 91.5% versus 95.9% after 6 months, 89.5% versus 93.9% after 1 year, and 70.6% versus 73.0% after 4.1 years (P=NS). Mortality
Treatment strategies to control blood pressure in people with hypertension in Tanzania and Lesotho: a randomized clinical trial (Publications)
hydrochlorothiazide if needed), 2-pill strategy (amlodipine, 5 mg; losartan, 25 mg), or 3-pill strategy (amlodipine, 2.5 mg; losartan, 12.5 mg; hydrochlorothiazide, 6.25 mg). Drugs were up titrated monthly [...] starting low-dose 3 pills vs monotherapy allowing for monthly up titration. Recruitment lasted from March 5, 2020, to March 30, 2022. The setting was 2 hospitals in rural Lesotho and Tanzania. Participants included
Development of land use regression models for particle composition in twenty study areas in Europe (Publications)
for V and S in the PM10 and PM2.5 fractions and Si, Ni, and K in the PM10 fraction performed moderately with R(2) ranging from 50 to 61%. Si, NI, and K models for PM2.5 performed poorest with R(2) under [...] composition. As part of the ESCAPE project, we measured the elemental composition in both the PM10 and PM2.5 fraction sizes at 20 sites in each of 20 study areas across Europe. LUR models for eight a priori selected [...] (Zn)) were developed. Good models were developed for Cu, Fe, and Zn...
Meta-analysis identifies seven susceptibility loci involved in the atopic march (Publications)
12q21.3 (OR 1.58; P=5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21)
Discovery of inhibitors of<em> Trypanosoma brucei</em> by phenotypic screening of a focused protein kinase library (Publications)
compounds, which showed > 50 % inhibition at 5 muM. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)-one scaffold that showed [...] showed sub-micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and [...] brucei growth assay, which could differentiate static and cidal action....
Ambient air pollution exposure estimation for the Global Burden of Disease 2013 (Publications)
World Health Organization Air Quality Guideline of 10 mug/m(3) PM2.5 (annual average). Between 1990 and 2013, global population-weighted PM2.5 increased by 20.4% driven by trends in South Asia, Southeast Asia [...] measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1 degrees x 0.1 degrees spatial resolution for five-year intervals from [...] Asia, and China. Decreases in population-weighted mean...
Design of proteasome inhibitors with oral efficacy <em>in vivo</em> against<em> Plasmodium falciparum</em> and selectivity over the human proteasome (Publications)
Exemplar compounds, MPI-5 and MPI-13, show potent activity against P. falciparum infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly [...] boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) beta5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth [...] Comparison of the cryo-electron microscopy (EM) structures of Pf20S and Hs20Sc in...