bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of drug resistance and importance of viral load measurements in Honduran HIV‐infected patients failing antiretroviral treatment
Authors: Murillo W , De Rivera IL , Parham L , Jovel E , Palou E , Karlsson AC , Albert J 
Published: August 2009

ObjectiveThe Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV‐1‐infected individuals.MethodsWe collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV‐1 pol sequences were obtained using an in‐house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)‐USA list and predicted susceptibility to cART was scored using the anrs algorithm.ResultsResistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple‐, dual‐ and single‐class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030–0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063–0.22)], route of transmission (OR=42.8; 95% CI 3.73–491), and years on therapy (OR=1.81; 95% CI 1.11–2.93).ConclusionThe prevalence of antiretroviral resistance was high in Honduran HIV‐infected patients with signs of treatment failure. A majority of study subjects showed dual‐ or triple‐class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.
Legal and Economic Issues in Completing the EU Internal Market for Services: An Interdisciplinary Perspective*
Authors: BADINGER HARALD , MAYDELL NIKLAS 
Published: August 2009

AbstractWe investigate, from an interdisciplinary perspective, the legal and economic consequences of the EU Services Directive, which was adopted in a revised version on 12 December 2006. Studies on the effect of its original version point to moderate macroeconomic effects. Compared with its initial version, the directive has undergone substantial changes, which have eliminated many core elements that would have triggered additional liberalization in services markets. As a result, the Services Directive has moved away from its economic motivation and is likely to miss its aim of completing the EU internal market for services.
The Application of Neofunctionalism to the Enlargement Process: The Case of Turkey
Authors: MACMILLAN CATHERINE 
Published: August 2009

AbstractThis article examines Turkey's EU accession process from a neofunctionalist viewpoint in an attempt to understand why it has proceeded so far despite considerable opposition from some of the Member States. It argues that, although neofunctionalist spillover can account for this, the eventual outcome is still far from certain.
Apatite grain boundary morphology and its response to low‐temperature fluid infiltration in crystalline basement
Authors: LAWTHER S. E. M. , DEMPSTER T. J. 
Published: August 2009

AbstractApatite grain boundaries on fractured rock surfaces have been examined in an amphibolite facies regional metamorphic granite gneiss from the central Swiss Alps. The morphology of apatite has been characterized using a scanning electron microscope and matched to surface textures in adjoining silicates. Apatites show a wide variety of different surface features ranging from planar crystal faces, to small‐scale ridges and dimples, to extensive irregular pitting. Many of these features form in response to the periodic infiltration of fluids along open grain boundaries during the cooling history of the gneiss. Apatite shows evidence of both dissolution and re‐precipitation that is controlled by the nature of the grain boundary, the structure of the adjoining silicate phase and the alteration of the host rock. Fracturing occurs in a range of retrograde conditions and is common both within the apatite and along grain boundaries. This coupled to the evidence of fluid interaction with mineral surfaces suggests that extensive permeable networks may be typical of cooling crystalline basement rocks. Grain boundary textures have the potential to reveal a unique record of fluid infiltration in the crust that would be very difficult to decipher using traditional petrographic methods.
Response of Alum Rock springs to the October 30, 2007 Alum Rock earthquake and implications for the origin of increased discharge after earthquakes
Authors: MANGA MICHAEL , ROWLAND JOEL C. 
Published: August 2009

AbstractThe origins of increased stream flow and spring discharge following earthquakes have been the subject of controversy, in large part because there are many models to explain observations and few measurements suitable for distinguishing between hypotheses. On October 30, 2007 a magnitude 5.5 earthquake occurred near the Alum Rock springs, California, USA. Within a day we documented a several‐fold increase in discharge. Over the following year, we have monitored a gradual return towards pre‐earthquake properties, but for the largest springs there appears to be a permanent increase in discharge. The Alum Rock springs discharge waters that are a mixture between modern (shallow) meteoric water and old (deep) connate waters expelled by regional transpression. After the earthquake, there was a small and temporary decrease in the fraction of connate water in the largest springs. Accompanying this geochemical change was a small (1–2°C) temperature decrease. Combined with the rapid response, this implies that the increased discharge has a shallow origin. Increased discharge at these springs occurs both for earthquakes that cause static volumetric expansion and for those that cause contraction, supporting models in which dynamic strains are responsible for the subsurface changes that cause flow to increase. We make a quantitative comparison between the observed changes and model predictions for three types of models: (i) a permanent increase in permeability; (ii) an increase in permeability followed by a gradual decrease to its pre‐earthquake value; and (iii) an increase of hydraulic head in the groundwater system discharging at the springs. We show that models in which the permeability of the fracture system feeding the springs increases after the earthquake are in general consistent with the changes in discharge. The postseismic decrease in discharge could either reflect the groundwater system adjusting to the new, higher permeability or a gradual return of permeability to pre‐earthquake values; the available data do not allow us to distinguish between these two scenarios. However, the response of these springs to another earthquake will provide critical constraints on the changes that occur in the subsurface and should permit a test of all three types of models.
Spring temperatures in the Sagehen Basin, Sierra Nevada, CA: implications for heat flow and groundwater circulation
Authors: BRUMM MARIA , WANG CHI‐YUEN , MANGA MICHAEL 
Published: August 2009

AbstractHeat flow in the Sierra Nevada, CA, is low despite its young geologic age. We investigate the possibility that advective heat transport by groundwater flow leads to an underestimate of heat flow in the Sierras based purely on borehole measurements. Using temperature and discharge measurements at springs in Sagehen Basin, we find that groundwater removes the equivalent of approximately 20–40 mW m−2 of geothermal heat from the basin. This is comparable with other heat flow measurements in the region and indicates that, in this basin, at least, groundwater does transport a significant amount of geothermal heat within the basin. Additionally, we use estimates of the mean residence time of water discharged at the springs along with hourly temperature records in springs to provide constraints on groundwater flow depths within the basin. An analytical model based on these constraints indicates that the heat removed by groundwater may represent 20% to >90% of the total heat flow in the basin. Without better constraints on the regional hydrogeology and the depth of circulation, we cannot determine whether the heat discharged at the springs represents a change in the mode of heat transfer, i.e. from conduction to advection at shallow depths (<100 m) or whether this is a component of heat transfer that should be added to measured conductive values. If the latter is true, and Sagehen Basin is representative of the Sierras, basal heat flow in the Sierra Nevada may be higher than previously thought.
Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: therapeutic implications
Authors: Gaspar Pablo A. , Bustamante M. Leonor , Silva Hernán , Aboitiz Francisco 
Published: August 2009

AbstractEarly models for the etiology of schizophrenia focused on dopamine neurotransmission because of the powerful anti‐psychotic action of dopamine antagonists. Nevertheless, recent evidence increasingly supports a primarily glutamatergic dysfunction in this condition, where dopaminergic disbalance is a secondary effect. A current model for the pathophysiology of schizophrenia involves a dysfunctional mechanism by which the NMDA receptor (NMDAR) hypofunction leads to a dysregulation of GABA fast‐ spiking interneurons, consequently disinhibiting pyramidal glutamatergic output and disturbing the signal‐to‐noise ratio. This mechanism might explain better than other models some cognitive deficits observed in this disease, as well as the dopaminergic alterations and therapeutic effect of anti‐psychotics. Although the modulation of glutamate activity has, in principle, great therapeutic potential, a side effect of NMDAR overactivation is neurotoxicity, which accelerates neuropathological alterations in this illness. We propose that metabotropic glutamate receptors can have a modulatory effect over the NMDAR and regulate excitotoxity mechanisms. Therefore, in our view metabotropic glutamate receptors constitute a highly promising target for future drug treatment in this disease.
Stress‐induced responses of human skin fibroblasts in vitro reflect human longevity
Authors: Dekker Pim , Maier Andrea B. , Van Heemst Diana , De Koning‐Treurniet Corine , Blom Joke , Dirks Roeland W. , Tanke Hans J. , Westendorp Rudi G.J. 
Published: August 2009

SummaryUnlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence‐associated β‐galactosidase (SA‐β‐gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin‐V/PI assay and cell‐cycle analysis (Sub‐G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA‐β‐gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress‐induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub‐G1: P = 0.014) and lower stress‐induced increases (Sub‐G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA‐β‐gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress‐induced increases were lower for SA‐β‐gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI− cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone‐induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity.
Randomised controlled trial of the effects of two rigid gas permeable (RGP) contact lens materials and two surface cleaners on straylight values
Authors: Fortuin Marten F. , Schilperoort John , Evans Bruce J. W. , Edgar David F. , Van Den Berg Tom J. T. P. , Kiers Henri 
Published: August 2009

AbstractPurpose:  In a double‐masked randomized controlled crossover study we investigated both the retinal responses to straylight, and the effects of lens cleaners on straylight values, in two different RGP contact lens materials.Methods:  Thirty patients (20–59 years) wearing RGP lenses were refitted with new lenses made of Boston XO material in one eye and made of Comfort O2 (ONSI‐56) material in the other eye. Reported wetting angles for the Boston XO material (103°) and for the ONSI‐56 material (7.2°) were obtained by sessile drop measurements. After refitting, the study comprised three 5‐week trial periods. In Period 1 half of the participants (Group A) wore Boston XO lenses in their right eye and Comfort O2 (ONSI‐56) lenses in their left eye, and the other half (Group B) vice versa. In Period 2 Group A wore Comfort O2 (ONSI‐56) lenses in their right eye and Boston XO lenses in their left, and Group B vice versa. All participants used Miraflow cleaner during periods 1 and 2. In Period 3, during which all participants used Boston cleaner, Group A wore Boston XO lenses in their right eye and Comfort O2 (ONSI‐56) lenses in their left eye and Group B vice versa. Straylight data (log S) were obtained with and without contact lenses using the Oculus C‐Quant straylight meter in all three periods. Central corneal thickness (CCT) was measured in the second and third periods.Results:  When not wearing lenses (n = 60 eyes) at the end of the second 5 week trial period straylight was measured twice with averages of 1.07 log S, and the corrected CCT measurements averaged 546 μm. Straylight values with Comfort O2 (ONSI‐56) reached 1.15 log S at the end of both the second (n = 25 eyes) and third periods (n = 23 eyes). Straylight values with Boston XO were 1.17 log S (n = 26 eyes) at the end of the second period, and 1.16 log S (n = 25 eyes) at the end of the third period.Conclusions:  Existing RGP lens wearers refitted with new lenses with different contact angles, made of Boston XO and Comfort O2 (ONSI‐56) showed, over three 5 week periods, relatively small increases in straylight, which were functionally comparable, irrespective of the type of lens material or lens cleaner used. At every visit, straylight values and CCTs returned to baseline levels after RGP lens removal, confirming that the straylight fluctuations were mainly due to scattering from the RGP lenses; or tear film interaction; or a combination of both.
Analysis of optimized profiles for ‘aberration‐free’ refractive surgery
Authors: Arba‐Mosquera Samuel , De Ortueta Diego 
Published: August 2009

AbstractPurpose:  To provide a model of an aberration‐free profile and to clinically evaluate the impact of treatments based upon these theoretical profiles in the post‐operative cornea.Methods:  Aberration‐free profiles were deduced from the Zernike expansion of the difference between two corneal cartesian‐ovals. Compensation for the focus‐shift effects of removing corneal tissue were incorporated by preserving the location of the optical focus of the anterior corneal surface. Simulation of the surgical performance of the profile was performed by means of simulated ray‐tracing through a cornea described by its anterior surface and pachymetry. Clinical evaluation was retrospectively analysed in terms of visual outcomes, corneal wavefront aberration and asphericity changes at 3‐month follow‐up compared to the baseline on 100 eyes treated for compound myopic astigmatism.Results:  The proposed ‘aberration‐free’ profiles theoretically preserve aberrations, becoming more oblate asphericity after myopic treatments, and more prolate after hyperopic ones. In the clinical evaluation, 94% of eyes were within ±0.50 D of emmetropia. BSCVA improved significantly (p < 0.001). Induced corneal aberrations at 6‐mm were below clinically relevant levels: 0.123 ± 0.129 μm for HO‐RMS (p < 0.001), 0.065 ± 0.128 μm for spherical aberration (p < 0.001) and 0.058 ± 0.128 μm for coma (p < 0.01), whereas the rate of induced aberrations per achieved D of correction were −0.042, −0.031, and −0.030 μm D−1 for HO‐RMS, SphAb, and coma (all p < 0.001). Induction of positive asphericity correlated to achieved correction (p < 0.001) at a rate 3× theoretical prediction.Conclusions:  ‘Aberration‐free’ patterns for refractive surgery as defined here together with consideration of other sources of aberrations such as blending zones, eye‐tracking, and corneal biomechanics yielded results comparable to those of customisation approaches. Having close‐to‐ideal profiles should improve clinical outcomes decreasing the need for nomograms, and diminishing induced aberrations after surgery.
Renal Function in Older Hospital Patients Is More Accurately Estimated Using the Cockcroft‐Gault Formula Than the Modification Diet in Renal Disease Formula
Authors: Péquignot Renaud , Belmin Joël , Chauvelier Sophie , Gaubert Jean‐Yves , Konrat Cécile , Duron Emmanuelle , Hanon Olivier 
Published: August 2009

OBJECTIVES: To compare the accuracy of the two most popular creatinine clearance (CrCl) estimation formulae (Cockcroft‐Gault (CG) and Modification Diet in Renal Disease (MDRD)) in older hospitalized patients.DESIGN: Prospective, cross‐sectional, observational study.SETTING: Two hospital geriatric wards.PARTICIPANTS: Consecutive patients aged 70 and older with an indwelling urinary catheter for the purpose of care.MEASUREMENTS: CrCl was determined according to three methods: measured CrCl from plasma and urine creatinine and 24‐hour urine volume, CG (CG‐CrCl), and MDRD (MDRD‐CrCl). Results were expressed as median and interquartile range (IQR). Moderate and severe renal impairment were defined as a CrCl between 30.0 and 59.9 mL/min and less than 30.0 mL/min, respectively.RESULTS: One hundred twenty‐one patients were included (46% male). Mean age was 86.1±6.7 (range 72–100). Median measured CrCl was 43.8 mL/min (IQR 33.6–61.1 mL/min), CG‐CrCl was 40.9 mL/min (IQR 31.0–52.6 mL/min), and MDRD‐CrCl was 61.3 mL/min (IQR 49.4–77.0 mL/min). The biases of CG‐CrCl and MDRD were −3.5±22.5 and 20.1±28.2, respectively (P<.001). Misclassification of renal impairment (absent/moderate/severe) occurred in 33% of patients according to CG‐CrCl, and concordance was mild to moderate (kappa=0.50). Misclassification occurred in 50% of patients according to MDRD‐CrCl, and concordance was poor (kappa=0.33). Bias was significantly related to bed confinement for both formulae and to plasma creatinine for MDRD.CONCLUSION: In elderly hospitalized patients, CG slightly underestimates CrCl, and MDRD strongly overestimates it. CG gave a better prediction of measured CrCl than MDRD.
Understanding Advance Care Planning as a Process of Health Behavior Change
Authors: Fried Terri R. , Bullock Karen , Iannone Lynne , O'Leary John R. 
Published: August 2009

OBJECTIVES: To explore whether models of health behavior change can help to inform interventions for advance care planning (ACP).DESIGN: Qualitative cross‐sectional study.SETTING: Community.PARTICIPANTS: Sixty‐three community‐dwelling persons aged 65 and older and 30 caregivers with experience as surrogate decision‐makers.MEASUREMENTS: In focus groups conducted separately with older persons and caregivers, participants were asked to discuss ways they had planned for future declines in health and why they had or had not engaged in such planning. Transcripts were analyzed using grounded theory.RESULTS: Four themes illustrated the potential of applying models of health behavior change to improve ACP. (1) Participants demonstrated variable readiness to engage in ACP and could be in different stages of readiness for different components of ACP, including consideration of treatment goals, completion of advance directives, and communication with families and physicians. (2) Participants identified a wide range of benefits of and barriers to ACP. (3) Participants used a variety of processes of change to progress through stages of readiness, and ACP was only one of a broader set of behaviors that participants engaged in to prepare for declines in their health or for death. (4) Experience with healthcare decision‐making for loved ones was a strong influence on perceptions of susceptibility and engagement in ACP.DISCUSSION: The variability in participants' readiness, barriers and benefits, perceptions of susceptibility, and use of processes to increase readiness for participating in each component of ACP suggests the utility of customized, stage‐specific interventions based on individualized assessments to improve ACP.
IMMUNOHEMATOLOGY: Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment
Authors: Jackman Rachael P. , Heitman John W. , Marschner Susanne , Goodrich Raymond P. , Norris Philip J. 
Published: August 2009

BACKGROUND:Donor white blood cells (WBCs) present in transfusion products can lead to immune sequelae such as production of HLA antibodies or graft‐versus‐host disease in susceptible transfusion recipients. Eliminating the immunogenicity of blood products may prove to be of clinical benefit, particularly in patients requiring multiple transfusions in whom allosensitization is common. This study examines a method of pathogen reduction based on ultraviolet light illumination in the presence of riboflavin. In addition to pathogens, WBCs treated with this system are affected and fail to stimulate proliferation of allogeneic peripheral blood mononuclear cells (PBMNCs) in vitro.STUDY DESIGN AND METHODS:This study sought to determine the mechanisms regulating this loss of immunogenicity. Treated cells were examined for surface expression of a number of molecules involved in activation and adhesion, viability, cell‐cell conjugation, and ability to stimulate immune responses in allogeneic PBMNCs.RESULTS:Compared with untreated controls, ultraviolet (UV)‐irradiated antigen‐presenting cells showed slightly reduced surface expression of HLA Class II and costimulatory molecules and had more significant reductions in surface expression of a number of adhesion molecules. Furthermore, treated cells had a severe defect in cell‐cell conjugation. The observed loss of immunogenicity was nearly complete, with UV‐irradiated cells stimulating barely measurable interferon‐γ production and no detectable STAT‐3, STAT‐5, or CD3‐ε phosphorylation in allospecific primed T cells.CONCLUSION:These results suggest that defective cell‐cell adhesion prevents UV‐irradiated cells from inducing T‐cell activation.