bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Dynamic Response for Floating Foundation of Offshore Wind Turbine
Authors: Tang Yougang , Hu Jun , Liu Liqin
Published: November 2011

The wind resources for ocean power generation are mostly distributed in sea areas with the distance of 5–50km from coastline, whose water depth are generally over 20m. To improve ocean power output and economic benefit of offshore wind farm, it is necessary to choose floating foundation for offshore wind turbine. According to the basic data of a 600kW wind turbine with a horizontal shaft, the tower, semi-submersible foundation and mooring system are designed in the 60-meter-deep sea area. Precise finite element models of the floating wind turbine system are established, including mooring lines, floating foundation, tower and wind turbine. Dynamic responses for the floating foundation of offshore wind turbine are investigated under wave load in frequency domain.
Probabilistic Risk Assessment for FPSO Topside Structures Under Drop Impact: An Application to Pipeline Protections
Authors: Heo YeongAe , Kim ByungWoo , Eom Jae-Kwang
Published: November 2011

In offshore structural design, it is necessary to evaluate probabilistic risk so that the topside structure has sufficient capacity to resist the effects of accidental loads such as drop impact, helicopter impact, vessel collision, fire, and explosion. Most engineers in the offshore industry, however, have difficulties in estimating a reliable risk value because there are still too many uncertainties in computing the probability of exceeding a target structural damage where the guideline for hazard analysis, which provides design load, is quite well described. Therefore, a framework to compute reasonable probability of structural failure is proposed in this paper. 88 impact scenarios were applied to a pipeline protection system on a topside module of Nexus genetic FPSO in order to perform regression analysis for structural damage. For risk calculation, the hazard analysis in this study is based on the detail engineering report worked by Ramboll Oil & Gas.
Determination of Viscous Damping for Low Frequency Motions of Floating Structures
Authors: Huang Z. J. , O’Donnell B. J. , Yung T. W. , Slocum S. T.
Published: November 2011

ExxonMobil Upstream Research Company developed an advanced model test method to determine reliable damping values for predicting low frequency motions of an FLNG barge and an LNG carrier [1]. An inertial compensation system was introduced in the test to confidently isolate the relatively very small viscous damping force from the total measured forces in the forced oscillation tests. In the system, the spring stiffness in the restoring mechanism was tuned such that the test was done near resonance. This method has been successfully applied to ExxonMobil forced oscillation tests to measure damping of deeply submerged, double body models. Three types of motions were generated in the tests: sinusoidal motions, decay motions and motions with multiple frequencies. In this paper, the authors attempt to correlate the damping obtained from decay tests and from tests with motions of multiple frequency components. Findings from this work help determine damping for predictions of full scale motion in irregular waves.
Epstein-Barr Virus: An Important Vaccine Target for Cancer Prevention
Authors: Cohen Jeffrey I. , Fauci Anthony S. , Varmus Harold , Nabel Gary J.
Published: November 2011

Clinical studies should focus on prevention of Epstein-Barr virus–associated cancers and infectious mononucleosis, facilitated by identification of disease-predictive surrogate markers.
Roaming Cancers Are Cooked
Authors: Tridandapani Srini
Published: November 2011

Microwaves can ablate tumors that have metastasized to lungs and improve survival in patients.
Palliative care in amyotrophic lateral sclerosis: a review of current international guidelines and initiatives: Table 1
Authors: Bede Peter , Oliver David , Stodart James , van den Berg Leonard , Simmons Zachary , Brannagáin Doiminic Ó , Borasio Gian Domenico , Hardiman Orla
Published: November 2011

Background

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative condition. Optimal management requires a palliative approach from diagnosis with emphasis on patient autonomy, dignity and quality of life.

Objective

To conduct a systematic analysis of the type, level and timing of specialist palliative care intervention in ALS.

Results

Despite an international consensus that ALS management should adopt a multidisciplinary approach, integration of palliative care into ALS management varies considerably across health care systems. Late referral to palliative services in ALS is not uncommon and may impact negatively on the quality of life of ALS patients and their caregivers. However, common themes and principles of engagement can be identified across different jurisdictions, and measurement systems have been established that can assess the impact of palliative care intervention.

Conclusions

There is considerable evidence that palliative care intervention improves quality of life in patients and carers. International consensus guidelines would assist in the development of a framework for active palliative care engagement in ALS and other neurodegenerative diseases.
Mortality in parents following the death of a child: a nationwide follow-up study from Sweden
Authors: Rostila Mikael , Saarela Jan , Kawachi Ichiro
Published: November 2011

Background

The death of a young child is so devastating that it can increase the risk of mortality in the grieving parent. Little is known about the impact of an adult child's death on the health of parents.

Methods

The authors conducted a follow-up study between 1980 and 2002 based on a linked-registers database that contains the total Swedish population. The authors examined mortality from all causes, natural causes and unnatural causes among parents following the death of children aged 10–49 years.

Results

An increased mortality risk (RR 1.31, 95% CI 1.02 to 1.68) in mothers following the death of a minor child (10–17 years) was found and especially following unnatural deaths (primarily accidents and suicides). Mothers also experienced elevated mortality following the death of an adult child aged 18–25 years (RR 1.15, 95% CI 1.03 to 1.29). Bereavement effects among fathers were more attenuated and chiefly found after >8 years of follow-up. From a short-term perspective (1–3 years), the death of an adult child (>25 years) was somewhat protective for parents. However, over longer follow-up periods, it approached (4–8 years) and exceeded (>8 years) the death risk of the general population.

Conclusions

These findings corroborate and extend earlier findings suggesting elevated mortality risks also following the death of an adult child.
SCHEDULING PROPORTIONALLY DETERIORATING JOBS IN TWO-MACHINE OPEN SHOP WITH A NON-BOTTLENECK MACHINE
Authors: LI SHISHENG
Published: November 2011

We address the problem of scheduling proportionally deteriorating jobs in two-machine open shop in which one of the machines is non-bottleneck. The objective is to minimize the makespan. We show that the decision version of the problem is [Formula: see text]-complete in the ordinary sense, and present for it a fully polynomial-time approximation scheme.
COORDINATION OF A BUYER-VENDOR SUPPLY CHAIN FOR A PERISHABLE PRODUCT UNDER SYMMETRIC AND ASYMMETRIC INFORMATION
Authors: ZHANG QIN-HONG , LUO JIAN-WEN
Published: November 2011

We consider a two-level supply chain for a perishable product with stock dependent demand, and study the supply chain coordination issues with quantity discount contract under both symmetric and asymmetric information. We design an optimal quantity discount contract for the vendor, and show that the quantity discount contract can coordinate the supply chain under symmetric information. However, the vendor is not able to realize supply chain coordination with only quantity discount contract if the buyer's holding cost is private information since the buyer may keep this information private for bargaining a higher price discount. Nevertheless, quantity discount contract is still beneficial to the vendor as compared to the case without quantity discount. Numerical experiments are conducted to demonstrate the theoretical results.
ULTRASONIC WAVE PROPAGATION IN SEMI-METALLIC SINGLE CRYSTALS
Authors: SINGH DEVRAJ , TRIPATHI SUDHANSHU , PANDEY DHARMENDRA KUMAR , GUPTA ALOK KUMAR , SINGH DHARMENDRA KUMAR , KUMAR JITENDRA
Published: November 2011

In this paper, ultrasonic attenuation due phonon–phonon interaction and thermoelastic loss mechanisms has been computed for longitudinal and shear waves along 〈100〉, 〈110〉 and 〈111〉 crystallographic directions in the temperature range 100 K to 300 K using modified Mason's approach in gadolinium monopnictides GdX ( X : P , As , Sb and Bi ). For the evaluation of ultrasonic attenuation with allied factors, the second and third order elastic constants were also evaluated using Coulomb and Born–Mayer type potential considering interaction up to second nearest neighborhood. The thermoelastic loss is not so important in present case due to lesser free electrons than metallic material. GdP is found to be ductile, more perfect, flawless in comparison to GdAs , GdSb and GdBi in this temperature regime and the direction 〈111〉 is more suitable for wave propagation in these B1structured materials due to low value of attenuation. The mechanical properties of GdP are better than other monochalcogenides because of higher valued elastic constants. The thermal conductivity is the leading factor to study ultrasonic attenuation in these monopnictides. The characteristic features are discussed in correlation with other physical properties like thermal conductivity, specific heat etc.
EXPERIMENTAL AND THEORETICAL INVESTIGATIONS OF MEMBRANE-BASED ENERGY RECOVERY VENTILATOR PERFORMANCE
Authors: MIN J. C. , SU M. , WANG L. N.
Published: November 2011

Experimental and theoretical studies were conducted to investigate the performance of a membrane-based energy recovery ventilator, which is an air-to-air heat exchanger with a water vapor permeable core. Tests were done on a commercially available membrane-based energy recovery ventilator, during which the supply and exhaust air states were recorded continuously over a long period of time. The test results show that as time passes the sensible effectiveness decreases very slightly from 56% to 55%, while the latent effectiveness increases appreciably from 28% to 39%. As a resultant of sensible and latent effectiveness, the enthalpy effectiveness provides an intermediate value between them and increases from 39% to 43%. The reason that the effectiveness changes with time is that the air relative humidity changes with time, which alters the moisture content at the membrane surface. Calculations were then implemented to predict the performance of the membrane-based energy recovery ventilator based on the model we developed previously and the calculation results were compared with the experimental data. The comparison suggests that the calculated effectiveness agrees well with the measured one, supporting the reasonability of the model. Calculations were also made to investigate the effects of various membrane parameters on latent and enthalpy effectiveness and latent-to-sensible heat ratio.
Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat
Authors: Delghingaro-Augusto Viviane , Décary Simon , Peyot Marie-Line , Latour Martin G. , Lamontagne Julien , Paradis-Isler Nicolas , Lacharité-Lemieux Marianne , Akakpo Huguette , Birot Olivier , Nolan Christopher J. , Prentki Marc , Bergeron Raynald
Published: November 2011

Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.
Strain-specific modifier genes ofCecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes
Authors: Kooistra Megan K. , Leduc Renee Y. M. , Dawe Christine E. , Fairbridge Nicholas A. , Rasmussen Jay , Man Julie H. Y. , Bujold Mattea , Juriloff Diana , King-Jones Kirst , McDermid Heather E.
Published: November 2011

Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain-specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because a large portion of this region is syntenic to human chromosome 10q25, the site of a human susceptibility locus.
High-Yield Synthesis of Zinc Oxide Nanoparticles from Bicontinuous Microemulsions
Authors: López-Cuenca S. , Pérez Carrillo L. A. , Rabelero Velasco M. , Díaz de León R. , Saade H. , López R. G. , Mendizábal E. , Puig J. E.
Published: November 2011

The high-yield synthesis of zinc oxide (ZnO) primary nanoparticles with high purity and with diameters between 6 and 22 nm using bicontinuous microemulsions is reported in this work. The ZnO nanoparticles were made by hydrolysis of Zn(NO3)2with NaOH aqueous solution and precipitation, followed by calcination of the precipitate. Higher yields and productivities of ZnO nanoparticles were obtained compared to values produced with w/o micremulsions reported in the literature. Particles were characterized by transmission electronic microscopy (TEM), X-ray diffraction, and atomic absorption spectroscopy.
Persistence of Overseeded Cool-Season Grasses in Bermudagrass Turf
Authors: Serensits Thomas , Cutulle Matthew , Derr Jeffrey F.
Published: November 2011

Cool-season grass species are commonly overseeded into bermudagrass turf for winter color. When the overseeded grass persists beyond the spring; however, it becomes a weed. The ability of perennial ryegrass, Italian (annual) ryegrass, intermediate ryegrass, and hybrid bluegrass to persist in bermudagrass one year after seeding was determined. Perennial ryegrass, intermediate ryegrass, and Italian ryegrass produced acceptable ground cover in the spring after fall seeding. Hybrid bluegrass did not establish well, resulting in unacceptable cover. Perennial ryegrass generally persisted the most one year after seeding, either because of summer survival of plants or because of new germination the following fall. Plant counts one year after seeding were greater in the higher seeding rate treatment compared to the lower seeding treatment rate of perennial ryegrass, suggesting new germination had occurred. Plant counts one year after seeding plots with intermediate ryegrass or Italian ryegrass were attributed primarily to latent germination and not summer survival. Applications of foramsulfuron generally did not prevent overseeded species stand one year after seeding, supporting the conclusion of new germination. Although quality is less with intermediate ryegrass compared to perennial ryegrass, it transitions out easier than perennial ryegrass, resulting in fewer surviving plants one year later.
Dynamic Analysis of Partially Embedded Structures Considering Soil‐Structure Interaction in Time Domain
Authors: Mahmoudpour Sanaz , Attarnejad Reza , Behnia Cambyse
Published: November 2011

Analysis and design of structures subjected to arbitrary dynamic loadings especially earthquakes have been studied during past decades. In practice, the effects of soil‐structure interaction on the dynamic response of structures are usually neglected. In this study, the effect of soil‐structure interaction on the dynamic response of structures has been examined. The substructure method using dynamic stiffness of soil is used to analyze soil‐structure system. A coupled model based on finite element method and scaled boundary finite element method is applied. Finite element method is used to analyze the structure, and scaled boundary finite element method is applied in the analysis of unbounded soil region. Due to analytical solution in the radial direction, the radiation condition is satisfied exactly. The material behavior of soil and structure is assumed to be linear. The soil region is considered as a homogeneous half‐space. The analysis is performed in time domain. A computer program is prepared to analyze the soil‐structure system. Comparing the results with those in literature shows the exactness and competency of the proposed method.
Lymphoepithelioma-Like Carcinoma of the Salivary Gland: Is Radiotherapy Alone Adequate?
Authors: Kaidar-Person Orit , Kuten Abraham , Billan Salem
Published: November 2011

Introduction. Lymphoepithelioma-like carcinoma (LELC) of the salivary gland is a rare tumor. Currently, surgery with or without radiotherapy is the recommended treatment for all salivary gland carcinomas. However, in contrast to other high-grade salivary gland carcinomas, LELCs are considered radiosensitive. There are only a few published reports of radiotherapy alone for the treatment of salivary gland LELC.Case. We present two cases of LELC of the salivary gland. One was treated with surgery and postoperative radiotherapy, and the other was given a single cycle of chemotherapy and then radiotherapy. Currently, both patients have no evidence of disease.Conclusion. Radiotherapy as a single modality should be reevaluated. The role of systemic chemotherapy to gain systemic control should be addressed due to noteworthy metastatic disease.
Mapping Irrigated Area Fragments for Crop Water Use Assessment Using Handheld Spectroradiometer
Authors: Sovoe S.
Published: November 2011

As climatic change and land use are altering the hydrographic regime, most catchments are progressively becoming drier and farmers are shifting from rainfed agriculture to irrigation practices to enable them to carry out income-generating activities throughout the year. The Ghanaian government has recently been promoting irrigation agricultural practices as the population keeps increasing and the demand for food keeps soaring. In order to keep pace with high demand for food coupled with increasing aridity of the subregion, some farmers resort to informal irrigation practices. In this study, hyperspectral reflectance data of the irrigated crops under informal practices were collected to assess their efficiency of water use. Photochemical reflectance index (PRI), soil-specific nitrogen index (SSN), and water band index (WBI) were computed. ThePRIandWBIwere significantly correlated, while there was no significant correlation betweenPRIandSSN. The map showing the probability of water stress indicated that informal irrigation practices are not an efficient water management approaches.
Selective Estrogen Receptor Modulators Regulate Dendritic Spine Plasticity in the Hippocampus of Male Rats
Authors: González-Burgos Ignacio , Rivera-Cervantes Martha C. , Velázquez-Zamora Dulce A. , Feria-Velasco Alfredo , Garcia-Segura Luis Miguel
Published: November 2011

Some selective estrogen receptor modulators, such as raloxifene and tamoxifen, are neuroprotective and reduce brain inflammation in several experimental models of neurodegeneration. In addition, raloxifene and tamoxifen counteract cognitive deficits caused by gonadal hormone deprivation in male rats. In this study, we have explored whether raloxifene and tamoxifen may regulate the number and geometry of dendritic spines in CA1 pyramidal neurons of the rat hippocampus. Young adult male rats were injected with raloxifene (1 mg/kg), tamoxifen (1 mg/kg), or vehicle and killed 24 h after the injection. Animals treated with raloxifene or tamoxifen showed an increased numerical density of dendritic spines in CA1 pyramidal neurons compared to animals treated with vehicle. Raloxifene and tamoxifen had also specific effects in the morphology of spines. These findings suggest that raloxifene and tamoxifen may influence the processing of information by hippocampal pyramidal neurons by affecting the number and shape of dendritic spines.
Photocatalytic Ethanol Oxidative Dehydrogenation over Pt/TiO2: Effect of the Addition of Blue Phosphors
Authors: Murcia J. J. , Hidalgo M. C. , Navío J. A. , Vaiano V. , Ciambelli P. , Sannino D.
Published: November 2011

Ethanol oxidative dehydrogenation over Pt/TiO2photocatalyst, in the presence and absence of blue phosphors, was performed. The catalyst was prepared by photodeposition of Pt on sulphated TiO2. This material was tested in a gas-solid photocatalytic fluidized bed reactor at high illumination efficiency. The effect of the addition of blue phosphors into the fluidized bed has been evaluated. The synthesized catalysts were extensively characterized by different techniques. Pt/TiO2with a loading of 0.5 wt% of Pt appeared to be an active photocatalyst in the selective partial oxidation of ethanol to acetaldehyde improving its activity and selectivity compared to pure TiO2. In the same way, a notable enhancement of ethanol conversion in the presence of the blue phosphors has been obtained. The blue phosphors produced an increase in the level of ethanol conversion over the Pt/TiO2catalyst, keeping at the same time the high selectivity to acetaldehyde.
Bleeding risk assessment and management in atrial fibrillation patients
Authors: Fauchier Laurent , Hylek Elaine , Knight Eve , Lane Deirdre , Levi Marcel , Marin Francisco , Palareti Gualtiero , Collet J.-P. , Rubboli A. , Poli D. , Camm A. J. , Lip Gregory , Andreotti Felicita , Huber Kurt , Kirchhof Paulus
Published: November 2011

In this executive summary of a Consensus Document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in atrial fibrillation (AF) patients. The main aim of the document was to summarise ‘best practice’ in dealing with bleeding risk in AF patients when approaching antithrombotic therapy, by addressing the epidemiology and size of the problem, and review established bleeding risk factors. We also summarise definitions of bleeding in the published literature. Patient values and preferences balancing the risk of bleeding against thromboembolism as well as the prognostic implications of bleeding are reviewed. We also provide an overview of published bleeding risk stratification and bleeding risk schema. Brief discussion of special situations (e.g. periablation, peri-devices such as implantable cardioverter defibrillators [ICD] or pacemakers, presentation with acute coronary syndromes and/or requiring percutanous coronary interventions/stents and bridging therapy) is made, as well as a discussion of the prevention of bleeds and managing bleeding complications. Finally, this document puts forwards consensus statements that may help to define evidence gaps and assist in everyday clinical practice.
Effect of
CYP2C19*2
and
*3
Loss-of-Function Alleles on Platelet Reactivity and Adverse Clinical Events in East Asian Acute Myocardial Infarction Survivors Treated With Clopidogrel and Aspirin
Authors: Jeong Young-Hoon , Tantry Udaya S. , Kim In-Suk , Koh Jin-Sin , Kwon Tae Jung , Park Yongwhi , Hwang Seok-Jae , Bliden Kevin P. , Kwak Choong Hwan , Hwang Jin-Yong , Gurbel Paul A.
Published: November 2011

Background—

As compared with whites, East Asians more often carry the cytochrome P450 (
CYP
)
2C19
loss-of-function (LOF) allele with the
CYP2C19*3
variant. The influence of the
CYP2C19
LOF alleles (
*2
and
*3
) on clopidogrel response and clinical outcomes in East Asians with acute myocardial infarction (AMI) has not been reported. We sought to evaluate the effect of the
CYP2C19
variants on clopidogrel pharmacodynamics and long-term prognosis in these patients.

Methods and Results—

Patients who survived an AMI (n=266) were enrolled in a single-center registry. Predischarge platelet reactivity was assessed with light transmittance aggregometry and the VerifyNow P2Y12 assay; the
CYP2C19*2, *3, *17
and
ABCB1 3435C>T
variants were determined. The primary clinical end point was the composite of cardiovascular death, nonfatal MI, and ischemic stroke. The median exposure to clopidogrel was 21 months (interquartile range, 13–29). The
ABCB1
3435C>T was not related to clopidogrel response or cardiovascular events. Carriage of the
CYP2C19
LOF variant allele was relatively high (60.9%, n=162; *2/*17=2, *3/*17=1, *1/*2=96, *1/*3=29, *2/*2=20, and *2/*3=14). Platelet reactivity increased proportionally according to the number of the
CYP2C19
LOF alleles. In a multivariate regression analysis, the risk of high on-treatment platelet reactivity (HPR) increased depending on the number of
CYP2C19
LOF allele [1 LOF allele; odds ratio (OR), 1.8; 95% confidence interval (CI), 0.8 to 4.2,
P
=0.152; and 2 LOF alleles; OR, 2.8; 95% CI, 1.2 to 6.5;
P
=0.016]; platelet reactivity and the rate of HPR did not differ between the
CYP2C19*2
versus
*3
allele carriage. In addition, cardiovascular event occurrence increased according to the number of the
CYP2C19
LOF allele; compared with noncarriers, carriers of 1 [hazard ratio (HR), 3.1; 95% CI, 0.8 to 11.6;
P
=0.089] and 2
CYP2C19
LOF allele(s) (HR, 10.1; 95% CI, 1.8–58.8;
P
=0.008) were associated with clinical end point. The clinical impact of the
CYP2C19*2
versus
*3
allele carriage also did not differ.

Conclusions—

Among East Asian patients who survived an AMI, the
CYP2C19
LOF allele carriage appears to affect clopidogrel pharmacodynamics and cardiovascular events according to the number of the
CYP2C19
LOF allele; the influence of the
CYP2C19*2
and
*3
alleles on clopidogrel response and long-term outcomes does not differ.
Pharmacokinetic‐Pharmacodynamic Assessment of the Interrelationships Between Tesaglitazar Exposure and Renal Function in Patients With Type 2 Diabetes Mellitus
Authors: Hamrén Bengt , Öhman K. Peter , Svensson Maria K. , Karlsson Mats O.
Published: November 2011

The effects of tesaglitazar on renal function (assessed as urinary clearance of 125I‐sodium iothalamate or estimated by the modification of diet in renal disease formula) were studied in a 24‐week open‐label trial in type 2 diabetes mellitus patients randomized to daily doses of either tesaglitazar 2 mg or pioglitazone 45 mg. The aim of the analysis was to develop a population pharmacokinetic‐pharmacodynamic model that could simultaneously describe the interrelationship between tesaglitazar exposure and reduction in renal function over time in patients with type 2 diabetes mellitus. The pharmacokinetic‐pharmacodynamic model could adequately describe the interplay between tesaglitazar and glomerular filtration rate. A one‐compartment model in which the apparent clearance was influenced by glomerular filtration rate characterized the pharmacokinetics of tesaglitazar. An indirect‐response model was used for the slow time course of change in glomerular filtration rate, which decreased from 100 to 78 mL/min/1.73m2 after 12 weeks of treatment. All tesaglitazar‐treated patients had a reduction in glomerular filtration rate, and available demographic variables could not explain differences in response. Patients treated with an angiotensin converting enzyme inhibitor were more sensitive to tesaglitazar and had larger glomerular filtration rate decrease compared to nontreated patients. Approximately 8 weeks after discontinuing treatment, mean glomerular filtration rate had returned towards baseline. The model and data give valuable insights into the dynamic changes in glomerular filtration rate over time.
Enhanced Sensitivity to Drug‐Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction
Authors: Tisdale James E. , Overholser Brian R. , Wroblewski Heather A. , Sowinski Kevin M. , Amankwa Kwadwo , Borzak Steven , Kingery Joanna R. , Coram Rita , Zipes Douglas P. , Flockhart David A. , Kovacs Richard J.
Published: November 2011

Patients with heart failure (HF) are at increased risk for drug‐induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug‐induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12‐lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia‐corrected QT (QTF) intervals (EC50) were determined, and areas under the effect (QTF interval vs time) curves (AUECs) were calculated. Ibutilide concentration—QTF relationships were best described by a sigmoidal Emax model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86–1.93] vs 1.82 [1.81–1.84] s·h; P = .04). Median EC50 was lower in the HF group (0.48 [0.46–0.49] vs 1.85 [1.10–3.23] μg/L; P = .008). Sensitivity to drug‐induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug‐induced TdP.
Assessing quality of care for the dying: The development and initial validation of a postal self-completion questionnaire for bereaved relatives
Authors: Mayland Catriona R , Williams Evelyn MI , Ellershaw John E
Published: November 2011

Background:

Evaluating ‘quality of care for the dying’ from the patients’ perspective has practical and ethical difficulties: an alternative is to use bereaved relatives’ views as ‘proxy’ measures. Currently, within the United Kingdom, there is no validated instrument which specifically examines quality of care in the last days of life or the impact of the Liverpool Care Pathway (LCP) for the Dying Patient.

Aim:

To develop and validate a questionnaire for use with bereaved relatives assessing the quality of care for patients and families in the last days of life and the immediate period after the bereavement.

Design:

The instrument, ‘Evaluating Care and Health Outcomes – for the Dying’ (ECHO-D), was developed in four distinct phases: 1. Question formulation, 2. Expert panel review ( n = 6), 3. Wider audience review ( n = 25), 4. Pilot, including cognitive pre-testing interviews and preliminary test–retest reliability assessment with bereaved relatives ( n = 80)

Setting:

The study was conducted within a hospice and an acute hospital involving healthcare professionals, lay members and bereaved relatives.

Results:

The systematic and robust process of questionnaire development generated evidence for ECHO-D’s face and content validity. Response rate for the pilot stage with bereaved relatives, however, was comparatively low (23.4%). Test–retest analysis from the pilot showed moderate or good stability for 13 out of 17 key questions, although small sample numbers limited the interpretation.

Conclusions:

ECHO-D is the first instrument specifically to assess ‘quality of care for the dying’, focussing on the last days of life, and has direct links with the use of the LCP Programme.
Influence of flavonoid extracts from celery on oxidative stress induced by dichlorvos in rats
Authors: Cao J , Zhang X , Wang Q , Jia L , Zhang Y , Zhao X
Published: November 2011

The present work was to investigate the effects of flavonoid extracts from celery on oxidative stress induced by dichlorvos (DIC) in male Wistar rats maintained on a normal diet. The rats were given DIC through intragastric administration by the dose of 7.2 mg/kg·body weight (bw)/day and additionally added 5% flavonoid extracts to the diet for 4 weeks continuously. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione- S-transferase (GST) and the content of malondialdehyde (MDA) in livers of rats were measured at the end of the experiment. Under the influence of DIC, there were significant decrease in the activities of SOD, CAT and GST and significant increase in GPx activity and MDA content. The results also showed that the activities of SOD, GST and CAT in the DIC-treated group declined significantly when compared with the flavonoid extracts group and the DIC + flavonoid extracts group, respectively. With regard to GPx activity and MDA content, significant increase were showed in the DIC-treated group in comparison to those in the flavonoid extracts group and the DIC + flavonoid extracts group, respectively. The observations presented lead us to conclude the harmful effects of DIC during the exposure and the protective role of flavonoids in minimizing these effects.
Successful therapy with hemoperfusion and plasma exchange in acute 1,2,3-trichloropropane poisoning
Authors: Liu P , Liang Y-G , Meng Q-Y , Zhang C-G , Wang H-C , Zhang X-G , Li G , Liu Z-Y , He Y-Z
Published: November 2011

1,2,3-trichloropropane (1,2,3-TCP) is commonly used as an intermediate in pesticide and an industrial specialty solvent. Acute 1,2,3-TCP poisoning is rare but a medical emergency. Sporadic cases of toxic hepatic injury from 1,2,3-TCP in humans have been reported. Liver is a target organ for 1,2,3-TCP toxicity, which may ensue in a short period after ingestion. A specific antidote against 1,2,3-TCP is not available. So it is important to distinguish that a patient with 1,2,3-TCP poisoning constitutes a medical emergency. In this case study, the poisoned patient’s clinical condition and laboratory values improved gradually after she received hemoperfusion (HP) and plasma exchange, which indicated that the therapy with HP and plasma exchange were helpful in the treatment of 1,2,3-TCP poisoning.
Experimental Evidence That Positive Moods Cause Sociability
Authors: Whelan Deanna C. , Zelenski John M.
Published: November 2011

Although intuitive and predicted by the broaden-and-build theory of positive emotions, previous research has not seriously tested the idea that positive moods can cause sociability. The authors developed a new measure to assess preferences for social (vs. nonsocial) situations, carefully controlling for the fact that social situations are, on average, also more pleasant. Across two additional experiments (combined n = 237), the authors induced positive, negative, and neutral moods with film clips (between-subjects) and found that participants in the positive conditions felt more social (adjective ratings) and indicated stronger preferences for social situations (on the new measure), compared to those in both negative and neutral conditions. Beyond filling an important gap in the empirical record, the authors also explore the implications of this finding for broaden-and-build theory and a large literature linking trait extraversion with happiness.
Biofilm and planktonic pneumococci demonstrate disparate immunoreactivity to human convalescent sera
Authors: Sanchez Carlos J , Hurtgen Brady J , Lizcano Anel , Shivshankar Pooja , Cole Garry T , Orihuela Carlos J
Published: November 2011

Background

Streptococcus pneumoniae (the pneumococcus) is the leading cause of otitis media, community-acquired pneumonia (CAP), sepsis, and meningitis. It is now evident that S. pneumoniae forms biofilms during nasopharyngeal colonization; the former which facilitates persistence, the latter, a prerequisite for subsequent development of invasive disease. Proteomic evaluation of S. pneumoniae suggests the antigen profile available for host-recognition is altered as a consequence of biofilm growth. This has potentially meaningful implications in regards to adaptive immunity and protection from disseminated disease. We therefore examined the antigen profile of biofilm and planktonic pneumococcal cell lysates, tested their reactivity with human convalescent sera and that generated against biofilm pneumococci, and examined whether immunization with biofilm pneumococci protected mice against infectious challenge.

Results

Biofilm pneumococci have dramatically altered protein profiles versus their planktonic counterparts. During invasive disease the humoral immune response is skewed towards the planktonic protein profile. Immunization with biofilm bacteria does not elicit a strong-cross-reactive humoral response against planktonic bacteria nor confer resistance against challenge with a virulent isolate from another serotype. We identified numerous proteins, including Pneumococcal serine-rich repeat protein (PsrP), which may serve as a protective antigens against both colonization and invasive disease.

Conclusion

Differential protein production by planktonic and biofilm pneumococci provides a potential explanation for why individuals remain susceptible to invasive disease despite previous colonization events. These findings also strongly suggest that differential protein production during colonization and disease be considered during the selection of antigens for any future protein vaccine.
DPO multiplex PCR as an alternative to culture and susceptibility testing to detect Helicobacter pylori and its resistance to clarithromycin
Authors: Lehours Philippe , Siffré Elodie , Mégraud Francis
Published: November 2011

Background

Macrolide resistance in Helicobacter pylori is the major risk factor for treatment failure when using a proton pump inhibitor-clarithromycin containing therapy. Macrolide resistance is due to a few mutations on the 23S ribomosal subunit encoded by the 23S rRNA gene. The present study aimed at investigating the performance of the dual priming oligonucleotide (DPO)-PCR kit named Seeplex® ClaR-H. pylori ACE detection designed to detect H. pylori and two types of point mutations causing clarithromycin resistance in H. pylori.

Methods

The performance of Seeplex® ClaR-H. pylori ACE detection was evaluated on 127 gastric biopsies in comparison to conventional bacterial culture followed by the determination of susceptibility to clarithromycin by E-test, as well as by an in-house real-time PCR using a fluorescence resonance energy transfer (FRET) technology.

Results

Considering culture as the reference test, the sensitivity of DPO-PCR and real-time FRET-PCR was 97.7% and 100% while specificity was 83.1% and 80.7%, respectively. However, both PCR were concordant in detecting 14 H. pylori positive cases which were negative by culture. Globally, E-test and DPO-PCR were concordant with regard to clarithromycin susceptibility in 95.3% of the cases (41/43), while real-time FRET-PCR and DPO-PCR were concordant in 95% (57/60).

Conclusion

The DPO-PCR is an interesting tool to detect H. pylori on gastric biopsies and to study its susceptibility to clarithromycin in laboratories that cannot perform real-time PCR assays.
High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology
Authors: Crawford Robin , Grignon Anne-Laure , Kitson Sarah , Winder David M , Ball Siolian LR , Vaughan Katie , Stanley Margaret A , Sterling Jane C , Goon Peter KC
Published: November 2011

Background

Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro-pharyngeal sites are from studies of higher-risk populations. There is a paucity of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+ women and this study was designed to provide initial pilot data on a population of women recalled for colposcopy as part of the UK cervical screening programme.

Methods

100 non-HIV+ women with abnormal cervical cytology, attending clinic for colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and cervical sites were taken and DNA extracted. HPV detection and genotyping were performed using a standardised, commercially available PCR-line blot assay, which is used to genotype 37 HPV subtypes known to infect the ano-genital and oro-pharyngeal areas. Strict sampling and laboratory precautions were taken to prevent cross-contamination.

Results

There was a very high prevalence of HPV infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro-pharynx, respectively. Multiple HPV subtype infections were dominant at all 3 mucosal sites. At least one or more HR genotype was present at both the cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56 (85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16 infection was highly dominant across all mucosal sites, with over a 2-fold increase over the next most prevalent subtype (HPV 31).

Conclusions

Women with abnormal smears have widespread infection with high-risk HPV at the cervical, anal and oro-pharyngeal mucosal sites and may represent a higher risk population for HPV disease in the future.
Stretch and Inflammatory Cytokines Drive Myometrial Chemokine Expression Via NF-κB Activation
Authors: Hua Renyi , Pease James E. , Sooranna Suren R. , Viney Jonathan M. , Nelson Scott M. , Myatt Les , Bennett Philip R. , Johnson Mark R.
Published: November 2011

Both human preterm labor (PTL) and term labor are consistently associated with a chemokine-induced inflammatory infiltration of the myometrium. However, what regulates myometrial chemokine expression and whether the increase in expression precedes the onset of labor, and so may have a role in its causation, or occurs after, and is simply a consequence of labor, is uncertain. Therefore, we assessed 1) chemokine expression in nonlaboring and laboring myometrial samples obtained at and before term and 2) the factors that regulate myometrial chemokine expression. We found that term labor was characterized by an increase in CXCL8 and CCL2 in both upper and lower segments, whereas PTL was associated with a distinct pattern of chemokine expression, with increases in CCL5, CXCL5, and CCL20 in the lower segment myometrium only. Further, we found that chemokine expression in myometrial cell cultures was increased by stretch and inflammatory cytokines and reduced by prostglandins and oxytocin and that the primary mediator of stretch and cytokine effects was nuclear factor κB (NF-κB) and to a lesser extent MAPK. These data show that PTL appears to be associated with a distinct pattern of chemokine expression, that stretch and cytokines both drive myometrial chemokine expression primarily via activation of NF-κB. These data suggest that the modulation of NF-κB activity may be of potential benefit in the management of PTL.
Prevnar 13, the New 13-Valent Pneumococcal Conjugate Vaccine
Authors: Sucher Allana J , Chahine Elias B , Nelson Michael , Sucher Brandon J
Published: November 2011

Objective:

To review the immurtogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients.

Data Sources:

A MEDLINE search (2000-September 2011) was conducted using the key words Streptococcus pneumoniae and pneumococcal conjugate vaccine for clinical trials, limited to studies conducted in humans and published in English.

Studv Selection And Data Extraction:

Randomized, controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of PCV13, Literature on the epidemiology and pathology of pneumococcal Infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed.

Data Synthesis:

PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2,4,6, and 12–15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications. PCV13 has comparable immunogenicity to the serotypes common with PCV7 and also provides protection against 6 additional pneumococcal serotypes. PCV13 has also been shown to have a comparable adverse reaction profile to PCV7.

Conclusions:

Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies.
Age-Related Alterations in Neurons of the Mouse Retina
Authors: Samuel Melanie A. , Zhang Yifeng , Meister Markus , Sanes Joshua R.
Published: November 2011

The behavioral consequences of age-related alterations in neural function are well documented, but less is known about their cellular bases. To characterize such changes, we analyzed 14 molecularly identified subsets of mouse retinal projection neurons (retinal ganglion cells or RGCs) and interneurons (amacrine, bipolar, and horizontal cells). The retina thinned but expanded with age, maintaining its volume. There was minimal decline in the number of RGCs, interneurons, or photoreceptors, but the diameter of RGC dendritic arbors decreased with age. Together, the increased retinal area and the decreased dendritic area may lead to gaps in RGC coverage of the visual field. Axonal arbors of RGCs in the superior colliculus also atrophied with age, suggesting that the relay of visual information to central targets may decline over time. On the other hand, the laminar restriction of RGC dendrites and the interneuronal processes that synapse on them were not detectably disturbed, and RGC subtypes exhibited distinct electrophysiological responses to complex visual stimuli. Other neuronal types aged in different ways: amacrine cell arbors did not remodel detectably, whereas horizontal cell processes sprouted into the photoreceptor layer. Bipolar cells showed arbor-specific alterations: their dendrites sprouted but their axons remained stable. In summary, retinal neurons exhibited numerous age-related quantitative alterations (decreased areas of dendritic and axonal arbors and decreased density of cells and synapses), whereas their qualitative features (molecular identity, laminar specificity, and feature detection) were largely preserved. Together, these data reveal selective age-related alterations in neural circuitry, some of which could underlie declines in visual acuity.