Landscape of the Raritan River Basin: A technical report for the Raritan Basin Watershed Management Project

This technical report focuses on the landscape of the Raritan River Basin and includes detailed descriptions of historical, current and future land uses, soils, vegetation and wildlife resources of the Basin. It also provides a general summary of the existing regulations and plans that aid in the protection of these natural resources.This report relies heavily upon the State Development and Redevelopment Plan (SDRP) Policy Map for comparisons of current and future land uses with planning area designations. In addition, 1995 land use/land cover (LU/LC) data obtained from the NJDEP was compared to existing and approved sewer service areas for the Basin as well as to New Jersey Department of Transportation (NJDOT) Road Network geographic information systems (GIS) data to assess existing land uses.August 200

Birdshot Retinochoroidopathy: Prognostic Factors of Long-Term Visual Outcome.

International audienc

Discovery of Efficacious Pseudomonas aeruginosa-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-Mechanistic PK/PD Model

In order to identify new agents for the treatment of Pseudomonas aeruginosa infections to address the serious threat to society posed by the evolution of multi-drug resistant P. aeruginosa, we focused on the well established family of Beta-lactams antibiotics. There is evidence they are effective against the target pathogen and their resistance profiles and pharmacology are well established. To address the major resistance mechanisms to other Beta-lactam antibiotics we studied siderophore-conjugated monocarbams. This class of monocyclic Beta-lactams is stable to metallo Beta-lactamases and they have excellent P. aeruginosa activities due to their ability to exploit the iron uptake machinery of the Gram-negative bacteria. Our medicinal chemistry plan focused on identifying a molecule with optimal potency and physical properties and activity for in vivo efficacy. We examined modifications to the monocarbam linker, the siderophore, and the oxime portion of the molecules. Through these efforts we identified a series of pyrrolidinone-based monocarbams which have good P. aeruginosa cellular activity (P. aeruginosa MIC90 = 2 g/ml), excellent free fraction levels (> 20 % free) and good hydrolytic stability (t1/2 ≥ 100 h). In order to differentiate our compounds and enable prioritization for future in vivo studies, we developed a robust mechanistic PK/PD model which enables prediction of in vivo efficacy from in vitro data

Sci Rep

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.10(6)) was lower in Provence-Cote d'Azur with a Mediterranean diet (1.9/1.10(6)), and higher in regions with intensive farming or industrialized activities (5 to 20/1.10(6)). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina

Discovery of Efficacious Pseudomonas aeruginosa-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-mechanistic Pharmacokinetic/Pharmacodynamic Model

To identify new agents for the treatment of multi-drug-resistant Pseudomonas aeruginosa, we focused on siderophore-conjugated monocarbams. This class of monocyclic β-lactams are stable to metallo-β-lactamases and have excellent P. aeruginosa activities due to their ability to exploit the iron uptake machinery of Gram-negative bacteria. Our medicinal chemistry plan focused on identifying a molecule with optimal potency and physical properties and activity for in vivo efficacy. Modifications to the monocarbam linker, siderophore, and oxime portion of the molecules were examined. Through these efforts, a series of pyrrolidinone-based monocarbams with good P. aeruginosa cellular activity (P. aeruginosa MIC₉₀ = 2 μg/mL), free fraction levels (>20% free), and hydrolytic stability (<i>t</i>_1/2 ≥ 100 h) were identified. To differentiate the lead compounds and enable prioritization for in vivo studies, we applied a semi-mechanistic pharmacokinetic/pharmacodynamic model to enable prediction of in vivo efficacy from in vitro data