Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

Improved luminosity determination in pp collisions at root s=7 TeV using the ATLAS detector at the LHC

Abstract: The luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented. Evaluation of the luminosity scale is performed using several luminosity-sensitive detectors, and comparisons are made of the long-term stability and accuracy of this calibration applied to the pp collisions at root s = 7 TeV. A luminosity uncertainty of delta L/L = +/- 3.5 % is obtained for the 47 pb(-1) of data delivered to ATLAS in 2010, and an uncertainty of delta L/L = +/- 1.8 % is obtained for the 5.5 fb(-1) delivered in 2011.

Active efflux mechanisms for antimicrobial resistance.

Abstract: Bacteria have inventive and versatile ways to resist antibiotics and other toxic elements (6). The earliest characterized mechanisms were those which inactivated the drug or altered its target in the cell. When decreased drug uptake accompanied resistance, decreased permeability or decreased binding was the initially proposed explanation (31, 40, 61). Active efflux as a mechanism to explain decreased accumulation came later. The early studies of transport in bacteria focused on how substances, particularly nutrients, get into the cells (75). In the 1970s, investigations widened to identify how certain substances came out of cells. Initially, those studies of efflux dealt with simple cations (Na+, K+, Ca2+) which were extruded by an energy-dependent process linked to the proton motive force (PMF) or ATP (2, 4, 5, 27, 37, 101). This transport occurred via cation-specific export proteins which were characterized by a number of laboratories (2, 4, 5, 27, 37, 79). Later, resistance to an organic compound, the antibiotic tetracycline, was linked to the energy-dependent efflux of tetracyclines in gram-negative bacteria (52). Today, active efflux systems, which are responsible for resistance to a variety of structurally unrelated antibiotics and toxic compounds, are being recognized more frequently in increasing numbers of environmental and clinical isolates (Table 1).

Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration

Abstract: We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10−75), ARMS2 (P < 10−59), C2/CFB (P < 10−20), C3 (P < 10−9), and CFI (P < 10−6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10−11), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10−7; CETP, P = 7.4 × 10−7) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL (P = 3.0 × 10−3) and ABCA1 (P = 5.6 × 10−4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Three-dimensional mapping of cortical thickness using Laplace's equation.

Abstract: We present a novel, computerized method of examining cerebral cortical thickness. The normal cortex varies in thickness from 2 to 4 mm, reflecting the morphology of neuronal sublayers. Cortical pathologies often manifest abnormal variations in thickness, with examples of Alzheimer's disease and cortical dysplasia as thin and thick cortex, respectively. Radiologically, images are 2-D slices through a highly convoluted 3-D object. Depending on the relative orientation of the slices with respect to the object, it is impossible to deduce abnormal cortical thickness without additional information from neighboring slices. We approach the problem by applying Laplace's Equation (∇2ψ = 0) from mathematical physics. The volume of the cortex is represented as the domain for the solution of the differential equation, with separate boundary conditions at the gray-white junction and the gray-CSF junction. Normalized gradients of ψ form a vector field, representing tangent vectors along field lines connecting both boundaries. We define the cortical thickness at any point in the cortex to be the pathlength along such lines. Key advantages of this method are that it is fully three-dimensional, and the thickness is uniquely defined for any point in the cortex. We present graphical results that map cortical thickness everywhere in a normal brain. Results show global variations in cortical thickness consistent with known neuroanatomy. The application of this technique to visualization of cortical thickness in brains with known pathology has broad clinical implications. Hum. Brain Mapping 11:12–32, 2000. © 2000 Wiley-Liss, Inc.

Effects of the antifungal agents on oxidative drug metabolism: clinical relevance.

Abstract: This article reviews the metabolic pharmacokinetic drug-drug interactions with the systemic antifungal agents: the azoles ketoconazole, miconazole, itraconazole and fluconazole, the allylamine terbinafine and the sulfonamide sulfamethoxazole. The majority of these interactions are metabolic and are caused by inhibition of cytochrome P450 (CYP)-mediated hepatic and/or small intestinal metabolism of coadministered drugs. Human liver microsomal studies in vitro, clinical case reports and controlled pharmacokinetic interaction studies in patients or healthy volunteers are reviewed. A brief overview of the CYP system and the contrasting effects of the antifungal agents on the different human drug-metabolising CYP isoforms is followed by discussion of the role of P-glycoprotein in presystemic extraction and the modulation of its function by the antifungal agents. Methods used for in vitro drug interaction studies and in vitro—in vivo scaling are then discussed, with specific emphasis on the azole antifungals. Ketoconazole and itraconazole are potent inhibitors of the major drugmetabolising CYP isoform in humans, CYP3A4. Coadministration of these drugs with CYP3A substrates such as cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine or astemizole can result in clinically significant drug interactions, some of which can be life-threatening. The interactions of ketoconazole with cyclosporin and tacrolimus have been applied for therapeutic purposes to allow a lower dosage and cost of the immunosuppressant and a reduced risk of fungal infections. The potency of fluconazole as a CYP3A4 inhibitor is much lower. Thus, clinical interactions of CYP3A substrates with this azole derivative are of lesser magnitude, and are generally observed only with fluconazole dosages of ≥200 mg/day. Fluconazole, miconazole and sulfamethoxazole are potent inhibitors of CYP2C9. Coadministration of phenytoin, warfarin, sulfamethoxazole and losartan with fluconazole results in clinically significant drug interactions. Fluconazole is a potent inhibitor of CYP2C19 in vitro, although the clinical significance of this has not been investigated. No clinically significant drug interactions have been predicted or documented between the azoles and drugs that are primarily metabolised by CYP 1A2, 2D6 or 2E1. Terbinafine is a potent inhibitor of CYP2D6 and may cause clinically significant interactions with coadministered substrates of this isoform, such as nortriptyline, desipramine, perphenazine, metoprolol, encainide and propafenone. On the basis of the existing in vitro and in vivo data, drug interactions of terbinafine with substrates of other CYP isoforms are unlikely.