bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir‐boosted saquinavir. The CIVSA Study*
Authors: Mallolas J , Blanco JL , Labarga P , Vergara A , Ocampo A , Sarasa M , Arnedo M , López‐Púa Y , García J , Juega J , Guelar A , Terrón A , Dalmau D , García I , Zárraga M , Martínez E , Carné X , Pumarola T , Escayola R , Gatell JM 
Published: April 2007

BackgroundThe addition of a low dose of ritonavir to protease inhibitors (PIs) has become a widespread strategy to improve PI pharmacokinetics. As resistance is a major barrier to long‐term suppression, in salvage therapy genotype and/or phenotype scoring is currently used to predict the response. We evaluated the relationship between the saquinavir (SQV) inhibitory quotient (IQ) (virtual and genotypic) and virological response.MethodsEligible patients were on a PI‐containing highly active antiretroviral therapy (HAART) regimen excluding SQV and had a viral load >5000 HIV‐1 RNA copies/mL. The PI was switched to SQV/ritonavir (RTV) 1000/100 mg twice a day (bid) and the same two backbone nucleoside reverse transcriptase inhibitors (NRTIs) were maintained at least until week 4, when the resistance test results became available. Genotype and virtual phenotype were determined at baseline, while the SQV trough plasma concentration was determined at week 4.ResultsFifty‐three patients were included in the study. Mean baseline viral load and CD4 count were 137 693 copies/mL and 263 cells/μL, respectively, the mean number of previous PIs was 2.3 and the mean number of protease gene mutations (PGMs) was 4.1. Using an on‐treatment analysis, at week 16 the mean increase in CD4 count was 70.9 cells/μL, viral load was <200 copies/mL in 17 out of 37 patients (45.9%), and 30 out of 45 patients (66.7%) were considered virological responders (VRs) (viral load <200 copies/mL or viral load declined ≥1 log10 at week 16). Median virtual phenotype was 1.3 (0.6–6.9). Baseline differences were detected between VR and non‐VR populations: the mean numbers of PGMs were 3.2 and 5.8 (P<0.05), the mean numbers of SQV‐associated mutations were 2 and 3.8 (P<0.05), and the mean CD4 counts were 365.9 and 184.3 cells/μL (P<0.05), respectively. Mean SQV trough concentrations at week 4 were 1.1 and 1.0 μg/mL (not significant), and mean virtual IQs were 0.7 and 0.1 (P<0.01), respectively. Multivariate analysis showed that baseline PGMs >5 or SQV‐associated mutations>5, virtual phenotype, baseline viral load >50 000 copies/mL, and virtual IQ <0.5, but not genotypic IQ, were the variables independently associated with non‐VR.ConclusionIn heavily pretreated patients, the use of SQV virtual IQ or alternatively virtual phenotype, as well as PGMs, is a useful tool for the prediction of virological response.
Prediction of clinical benefits of ritonavir‐boosted TMC114 from treatment effects on CD4 counts and HIV RNA
Authors: Hill A , Montaner J , Smith C 
Published: April 2007

ObjectiveThe aim of the study was to predict reductions in progression to AIDS/death associated with the treatment benefit of antiretrovirals on CD4 counts and HIV RNA in the era of highly active antiretroviral therapy (HAART).DesignThe study design was a pooled analysis of two trials (POWER 1 and POWER 2) of optimized background treatment plus either TMC114/ritonavir (TMC114/r) or control protease inhibitor (CPI).MethodsAcross the two randomized trials (mean baseline CD4 count 114 cells/μL and HIV RNA 4.6 log10 HIV‐1 RNA copies/mL), CD4 counts rose by a mean of 98 cells/μL for TMC114/r 600/100 mg twice a day (bid) vs. 17 cells/μL for CPI at week 24; HIV RNA fell by a median of 1.90 and 0.49 log10 copies/mL in the two groups, respectively. For the CD4 categorization method, cohort data on rates of progression to AIDS/death during HAART within preset CD4 ranges were used to predict rates of progression during TMC114/r and CPI treatment. For the regression method, data from clinical endpoint trials were used to correlate historical treatment effects on HIV RNA and CD4 with clinical benefits.ResultsThe CD4 categorization method predicted a 48% reduction in clinical progression to AIDS/death for TMC114/r vs. CPI. The regression method predicted a 55% reduction [95% confidence interval (CI) 45–66%] in the hazard of progression to AIDS/death based on CD4 counts, with a 47% reduction (95% CI 38–53%) predicted from effects on HIV RNA.ConclusionsIndependent methods generated similar predictions of a 47–55% reduction in progression to AIDS/death for TMC114/r vs. CPI treatment, based on the changes in CD4 counts and HIV RNA from the POWER 1 and POWER 2 trials. These methods could be used to estimate clinical benefits of other antiretrovirals.
A double‐blind, parallel‐group, placebo‐controlled, multicentre study of acetyl l‐carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV‐1 infection
Authors: Youle M , Osio M ,   on behalf of the ALCAR Study Group
Published: April 2007

BackgroundNucleoside reverse transcriptase inhibitors (NRTIs) disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl‐l‐carnitine (ALCAR) enhances neurotrophic support of sensory neurones, potentially providing symptom relief and nerve regeneration.ObjectiveThe objective of the study was to assess the safety and efficacy compared to placebo of intramuscular ALCAR in HIV‐positive patients with symptomatic distal symmetrical polyneuropathy.MethodsNinety patients were enrolled and randomized to receive ALCAR [500 mg twice a day (bid); n=43] or placebo (n=47) intramuscularly twice daily for 14 days followed by 42 days of oral ALCAR 1000 mg bid. Assessment of pain was obtained using the Visual Analogue Scale (VAS), Total Symptom Score (TSS), Clinical Global Impression of Change, McGill Pain Questionnaire (MPQ), and the need for rescue analgesics.ResultsThere was no statistically significant difference in changes in VAS over 14 days between groups for the intent‐to‐treat (ITT) population, but for the efficacy‐evaluable (EE) population ALCAR treatment produced a significantly greater reduction in pain compared with placebo (P=0.022). The proportion of patients with an improvement in TSS over 14 days was greater in the ALCAR group compared with the placebo group, but the differences were not statistically significant. During the open‐label phase, patients experienced an improvement in pain, as measured by the VAS, TSS and McGill Pain Questionnaire.ConclusionALCAR, administered twice a day intramuscularly to HIV‐1‐infected patients with symptomatic ATN, significantly reduced weekly mean pain ratings on the VAS compared with placebo. Treatment with oral ALCAR improved symptoms for the patient group as a whole. Intramuscular and oral ALCAR was generally safe and well tolerated.
Untangling syntactic and sensory processing: An ERP study of music perception
Authors: Koelsch Stefan , Jentschke Sebastian , Sammler Daniela , Mietchen Daniel 
Published: April 2007

AbstractThe present study investigated music‐syntactic processing with chord sequences that ended on either regular or irregular chord functions. Sequences were composed such that perceived differences in the cognitive processing between syntactically regular and irregular chords could not be due to the sensory processing of acoustic factors like pitch repetition, pitch commonality (the major component of “sensory dissonance”), or roughness. Three experiments with independent groups of subjects were conducted: a behavioral experiment and two experiments using electroencephalography. Irregular chords elicited an early right anterior negativity (ERAN) in the event‐related brain potentials (ERPs) under both task‐relevant and task‐irrelevant conditions. Behaviorally, participants detected around 75% of the irregular chords, indicating that these chords were only moderately salient. Nevertheless, the irregular chords reliably elicited clear ERP effects. Amateur musicians were slightly more sensitive to musical irregularities than nonmusicians, supporting previous studies demonstrating effects of musical training on music‐syntactic processing. The findings indicate that the ERAN is an index of music‐syntactic processing and that the ERAN can be elicited even when irregular chords are not detectable based on acoustical factors such as pitch repetition, sensory dissonance, or roughness.
Psychomotor speed in hypertension: Effects of reaction time components, stimulus modality, and phase of the cardiac cycle
Authors: Edwards Louisa , Ring Christopher , McIntyre David , Carroll Douglas , Martin Una 
Published: April 2007

AbstractHypertension is characterized by cognitive deficits. As evidence for impaired psychomotor speed, including slower reaction times, is mixed, we aimed to provide a detailed investigation of simple reaction time in hypertension. Pre‐motor and motor reaction times were measured across the cardiac cycle in 30 hypertensives and 29 normotensives to determine the effects of phasic and tonic blood pressure on performance. Auditory, visual, and tactile simple reaction time tasks were completed with stimuli presented 0, 300, and 600 ms after the R‐wave of the electrocardiogram. Reaction times did not differ between hypertensives and normotensives. Although pre‐motor reaction times were faster during the late phase than the early phase of the cardiac cycle whereas motor reaction times were unchanged, this effect was similar for hypertensives and normotensives. No sensory‐motor deficits were evident in these hypertensives regardless of baroreceptor activity.
Dynamics of water use in Scotland
Authors: Moran Dominic , MacLeod Michael , McVittie Alistair , Lago Manuel , Oglethorpe David 
Published: April 2007

AbstractThis paper uses a variety of data sources and methodologies to construct business as usual (BAU) water‐use scenarios for the Water Framework Directive (WFD) characterisation report, a key preliminary benchmarking requirement for member states. The paper addresses the most significant water‐use sectors in Scotland over the period 2001–2015. In terms of volumetric use, our figures are dominated by the demands of electricity generation. The next highest demands come from fish farming/aquaculture, which is mostly direct abstraction. Various industrial uses are estimated to be associated with significant volumetric uses (specifically electrical and engineering, fibres and food and drink). Because of structural changes in farm support, agriculture is the only sector showing a decline. Household demand is also a highly significant use and we are able to specify the public/private breakdown of demand.
Three Concepts of Causation
Authors: Hitchcock Christopher 
Published: April 2007

AbstractI distinguish three different concepts of causation: Thescientificconcept, or causal structure, is the subject of recent work in causal modeling. Thefolk attributiveconcept has been studied by philosophers of law and social psychologists. Themetaphysicalconcept is the one that metaphysicians have attempted to analyze. I explore the relationships between these three concepts, and suggest that the metaphysical concept is an untenable and dispensable mixture of the other two.
Reduced tear production in three canine endocrinopathies*
Authors: Williams D. L. , Pierce V. , Mellor P. , Heath M. F. 
Published: April 2007

Objectives:Previous reports have suggested that hypothyroid and diabetic patients can be predisposed to keratoconjunctivitis sicca. This study aimed to measure tear production in dogs with diabetes, hypothyroidism and hyperadrenocorticism using the Schirmer tear test and to compare these results with Schirmer tear test values for a group of normal dogs.Methods:Schirmer tear tests were performed on 16 dogs with hyperadrenocorticism, 18 with diabetes and 12 with hypothyroidism together with 100 control dogs. Corneal sensitivity was also measured in 12 of the 18 diabetic dogs with a Cochet Bonnet aesthesiometer and compared with age‐ and breed‐matched normal dogs.Results:Schirmer tear test values in dogs with hypothyroidism, hyperadrenocorticism and diabetes were 12·3±3·2, 14·0±4·0 and 12·3±5·3 mm/minutes, respectively. Schirmer tear test values were significantly lower than that for the control group (19·6±4·2 mm/minutes) in all dogs with an endocrinopathy. Only in two hypothyroid dogs and three diabetics, this was manifested as profound keratoconjunctivitis sicca with Schirmer tear test value lower than 5 mm/minutes. Diabetic dogs had significantly reduced corneal sensitivity compared with a matched set of control dogs.ClinicalSignificance:This study shows a significant reduction in tear production in animals with diabetes mellitus, hypothyroidism and hyperadrenocorticism. Further research is needed to elucidate the mechanisms by which this reduction in tear production occurs. Assessment of tear production should be undertaken in animals diagnosed with these endocrinopathies, as these animals may progress to clinical keratoconjunctivitis sicca.
Turbulent
Heat Transfer in Ribbed Coolant Passages of Different Aspect Ratios: Parametric
Effects
Authors: Saha Arun
K. , Acharya Sumanta 
Published: April 2007

Abstract
Turbulent flow and heat transfer in rotating ribbed ducts of different aspect ratios (AR) are studied numerically using an unsteady Reynolds averaged Navier–Stokes procedure. Results for three ARs (1:1, 1:4, and 4:1) and staggered ribs with constant pitch (P∕e=10) in the periodically developed region are presented and compared. To achieve periodic flow behavior in successive inter-rib modules calculations are performed in a computational domain that extends to two or three inter-rib modules. The computations are carried out for an extended parameter set with a Reynolds number range of 25,000–150,000, density ratio range of 0–0.5, and rotation number range of 0–0.50. Under rotational conditions, the highest heat transfer along the leading and side walls are obtained with the 4:1 AR, while the 1:4 AR has the highest trailing wall Nu ratio and the lowest leading wall Nu ratio. The 1:4 AR duct shows flow reversal near the leading wall (leading to low Nu) at high rotation numbers and density ratios. For certain critical parameter values (low Re, high Ro, and/or DR), the leading wall flow is expected to become nearly stagnant, due to the action of centrifugal buoyancy, leading to conduction-limited heat transfer. The 4:1 AR duct shows evidence of multiple rolls in the secondary flow that direct the core flow to both the leading and trailing surfaces which reduces the difference between the leading and trailing wall heat transfer relative to the other two AR ducts.
An
Explicit Algebraic Model for Turbulent Heat Transfer in Wall-Bounded Flow With Streamline
Curvature
Authors: Younis B.
A. , Weigand B. , Spring S. 
Published: April 2007

Abstract
Fourier’s law, which forms the basis of most engineering prediction methods for the turbulent heat fluxes, is known to fail badly in capturing the effects of streamline curvature on the rate of heat transfer in turbulent shear flows. In this paper, an alternative model, which is both algebraic and explicit in the turbulent heat fluxes and which has been formulated from tensor-representation theory, is presented, and its applicability is extended by incorporating the effects of a wall on the turbulent heat transfer processes in its vicinity. The model’s equations for flows with curvature in the plane of the mean shear are derived and calculations are performed for a heated turbulent boundary layer, which develops over a flat plate before encountering a short region of high convex curvature. The results show that the new model accurately predicts the significant reduction in the wall heat transfer rates wrought by the stabilizing-curvature effects, in sharp contrast to the conventional model predictions, which are shown to seriously underestimate the same effects. Comparisons are also made with results from a complete heat-flux transport model, which involves the solution of differential transport equations for each component of the heat-flux tensor. Downstream of the bend, where the perturbed boundary layer recovers on a flat wall, the comparisons show that the algebraic model yields indistinguishable predictions from those obtained with the differential model in regions where the mean-strain field is in rapid evolution and the turbulence processes are far removed from local equilibrium.
Multiple-Dose Escalation Study of the Safety, Pharmacokinetics, and Biologic Activity of Oral AMD070, a Selective CXCR4 Receptor Inhibitor, in Human Subjects
Authors: Stone Nimalie D. , Dunaway Shelia B. , Flexner Charles , Tierney Camlin , Calandra Gary B. , Becker Stephen , Cao Ying-Jun , Wiggins Ilene P. , Conley Jeanne , MacFarland Ron T. , Park Jeong-Gun , Lalama Christina , Snyder Sally , Kallungal Beatrice , Klingman Karin L. , Hendrix Craig W. 
Published: April 2007

ABSTRACT

AMD070 is an oral CXCR4 antagonist with in vitro activity against X4-tropic human immunodeficiency virus type 1. Thirty fasting healthy male volunteers received oral doses of AMD070 ranging from a single 50-mg dose to seven 400-mg doses given every 12 h (q12h). Nine subjects received a 200-mg dose during fasting and prior to a meal. Subjects were monitored for safety and pharmacokinetics. AMD070 was well tolerated, without serious adverse events. Transient headaches (13 subjects) and neurocognitive (8 subjects) and gastrointestinal (7 subjects) symptoms were the most common complaints. Seven subjects had sinus tachycardia, and two were symptomatic. AMD070 plasma concentrations peaked 1 to 2 h after patient dosing. The estimated terminal half-life ranged from 11.2 to 15.9 h among cohorts. Dose proportionality was not demonstrated. Less than 1% of the drug appeared unchanged in the urine. Food reduced the maximum concentration of drug in serum and the area under the concentration-time curve from 0 to 24 h by 70% and 56%, respectively (
P
≤ 0.01). A dose-dependent elevation of white blood cells (WBC) demonstrated a maximum twofold increase over baseline (95% confidence interval, 2.0- to 2.1-fold) in an
E
max
model. In healthy volunteers, AMD070 was well tolerated and demonstrated mixed-order pharmacokinetics, and food reduced drug exposure. AMD070 induced a dose-related elevation of WBC which was attributed to CXCR4 blockade. Using leukocytosis as a surrogate marker for CXCR4 inhibition, this dose-response relationship suggests that the doses used in this study were active in vivo, though not maximal, throughout the dosing interval. Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro 90% effective concentration of AMD070.
Defining Limits of Treatment with Humanized Neutralizing Monoclonal Antibody for West Nile Virus Neurological Infection in a Hamster Model
Authors: Morrey John D. , Siddharthan Venkatraman , Olsen Aaron L. , Wang Hong , Julander Justin G. , Hall Jeffery O. , Li Hua , Nordstrom Jeffrey L. , Koenig Scott , Johnson Syd , Diamond Michael S. 
Published: April 2007

ABSTRACT
A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperitoneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for the treatment of WNV infection in hamsters by comparing single-dose peripheral (i.p.) therapy with direct administration into the pons through a convection-enhanced delivery (CED) system. At day 5 after infection, treatments with hE16 by the peripheral and the CED routes were equally effective at reducing morbidity and mortality. In contrast, at day 6 only the treatment by the CED route protected the hamsters from lethal infection. These experiments suggest that hE16 can directly control WNV infection in the central nervous system. In support of this, hE16 administered i.p. was detected in a time-dependent manner in the serum, cerebrospinal fluid (CSF), cerebral cortex, brain stem, and spinal cord in CSF. A linear relationship between the hE16 dose and the concentration in serum was observed, and maximal therapeutic activity occurred at doses of 0.32 mg/kg of body weight or higher, which produced serum hE16 concentrations of 1.3 μg/ml or higher. Overall, these data suggest that in hamsters hE16 can ameliorate neurological disease after significant viral replication has occurred, although there is a time window that limits therapeutic efficacy.
AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN
Authors: Serrano-Gómez Diego , Martínez-Nuñez Rocío T. , Sierra-Filardi Elena , Izquierdo Nuria , Colmenares María , Pla Jesús , Rivas Luis , Martinez-Picado Javier , Jimenez-Barbero Jesús , Alonso-Lebrero José Luis , González Salvador , Corbí Angel L. 
Published: April 2007

ABSTRACT

AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of
Candida
,
Aspergillus
, and
Leishmania
to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV
trans
-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and
1
D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.