bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilised Biosensing Using Needle‐Based Recess Electrodes
Authors: Anastasova Salzitsa , Spehar‐Délèze Anna‐Maria , Bickham Dale , Uebel Patrick , Schmidt Markus , Russell Philip , Vadgama Pankaj
Published: December 2011

A recess disk electrode for amperometric monitoring of oxygen and glucose is reported. The basic design of sensor is a needle structure for easy implantation, embodying a gold filled silica capillary with a 80 µm inner diameter working electrode. Recess and inlaid disc electrodes, placed inside stainless steel tubes which served as a counter/reference electrode, were compared. The working electrode surface was modified with different treatments and barrier membranes to achieve selectivity for the analytes of interest. The basic needle format is ideal for in vivo use, and the format is easily extendable to other analyte targets. The sensors show linear working range for oxygen up to 160 mmHg partial pressure of oxygen, and for glucose from 1 to 10 mM. Bio‐fouling, as assessed by exposure to bovine serum albumin, was significantly reduced. Response times for the recess construct was increased but remained within the acceptable range for physiological monitoring. The operational stability of the sensors is demonstrated as well as the interference‐free detection of peroxide in the presence of physiologically relevant levels of ascorbic acid, uric acid, acetaminophen, and catechol. Preliminary in vivo tests showed excellent response towards glucose.
Electrochemistry of Zirconium Tetrachloride in the Ionic Liquid N‐Butyl‐N‐methylpyrrolidinium Bis(trifluoromethylsulfonyl)imide: Formation of Zr(III) and Exploitation of ZrCl4 as a Facile Ionic Liquid Drying Agent
Authors: Fu Chaopeng , Aldous Leigh , Manan Ninie S. A. , Compton Richard G.
Published: December 2011

The electrochemistry of zirconium tetrachloride in the ionic liquid N‐butyl‐N‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide has been studied, and the one electron reduction is proved by chronoamperometry. Furthermore, we report the application of ZrCl4 as a facile and general ionic liquid drying agent for use in voltammetry.
Story‐by‐story estimation of the stiffness parameters of laterally‐torsionally coupled buildings using forced or ambient vibration data: I. Formulation and verification
Authors: Omrani Roshanak , Hudson Ralph E. , Taciroglu Ertugrul
Published: December 2011

A new parameter estimation algorithm is described for identifying the stiffness properties of torsionally coupled shear buildings from their linear response due to ambient excitations or during low‐amplitude forced‐vibration tests. The algorithm is based on the time‐domain equations of motion, and yields estimates of the stiffness properties using a measure of the equilibrium of forces acting on each floor over a time interval. The banded structure of the stiffness matrix — a property intrinsic to torsion‐shear buildings — is exploited to decompose the initial inverse problem into several problems of reduced size. This decomposition allows the identification of lateral and torsional stiffnesses of individual stories, independent of the others. The algorithm utilizes vibration data where input excitation is known/measured, which is typical for forced‐vibration tests and earthquakes. If the ambient vibrations of the structure are adequately uncorrelated to the (unknown) external forces that induce such vibrations, then the algorithm can also be modified for output‐only system identification. The proposed algorithm is verified — and its various attributes are investigated — using simulation data from the ‘Analytical Phase I’ of the IASC (International Association for Structural Control)‐ASCE (American Society of Civil Engineers) benchmark studies. The companion article is devoted to the algorithm's application to experimental data, using data from the ‘Experimental Phase’ of the same benchmark studies. Copyright © 2011 John Wiley & Sons, Ltd.
Story‐by‐story estimation of the stiffness parameters of laterally‐torsionally coupled buildings using forced or ambient vibration data: II. Application to experimental data
Authors: Omrani Roshanak , Hudson Ralph E. , Taciroglu Ertugrul
Published: December 2011

Herein, an attempt is made to apply the method developed and verified in the companion paper (Part I) to physical data. To this end, stiffness parameters of the IASC‐ASCE test structure are identified using data from the experimental phase of the benchmark studies. The physical specimen is a quarter‐scale, four‐story, braced‐frame, steel structure. Ambient vibration and free vibration data induced by hammer strikes from various configurations of the structure are used to identify stiffness parameters of individual stories. These configurations had been created by removing various members from the test structure in an effort to mimic damage. Results indicate that the proposed method is successful in identifying even the minor changes (damage) introduced to the structure. An additional study on the method's sensitivity to structure's assumed mass distribution reveals that it is fairly robust to mass uncertainties. Copyright © 2011 John Wiley & Sons, Ltd.
Retinoic acid receptor–related orphan receptor α–induced activation of adenosine monophosphate–activated protein kinase results in attenuation of hepatic steatosis
Authors: Kim Eun-Jin , Yoon Young-Sil , Hong Suckchang , Son Ho-Young , Na Tae-Young , Lee Min-Ho , Kang Hyun-Jin , Park Jinyoung , Cho Won-Jea , Kim Sang-Gun , Koo Seung-Hoi , Park Hyeung-geun , Lee Mi-Ock
Published: December 2011

There is increasing evidence that the retinoic acid receptor–related orphan receptor α (RORα) plays an important role in the regulation of metabolic pathways, particularly of fatty acid and cholesterol metabolism; however, the role of RORα in the regulation of hepatic lipogenesis has not been studied. Here, we report that RORα attenuates hepatic steatosis, probably via activation of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) and repression of the liver X receptor α (LXRα). First, RORα and its activator, cholesterol sulfate (CS), induced phosphorylation of AMPK, which was accompanied by the activation of serine–threonine kinase liver kinase B1 (LKB1). Second, the activation of RORα, either by transient transfection or CS treatment, decreased the TO901317-induced transcriptional expression of LXRα and its downstream target genes, such as the sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase. RORα interacted physically with LXRα and inhibited the LXRα response element in the promoter of LXRα, indicating that RORα interrupts the autoregulatory activation loop of LXRα. Third, infection with adenovirus encoding RORα suppressed the lipid accumulation that had been induced by a free-fatty–acid mixture in cultured cells. Furthermore, we observed that the level of expression of the RORα protein was decreased in the liver of mice that were fed a high-fat diet. Restoration of RORα via tail-vein injection of adenovirus (Ad)-RORα decreased the high-fat-diet–induced hepatic steatosis. Finally, we synthesized thiourea derivatives that activated RORα, thereby inducing activation of AMPK and repression of LXRα. These compounds decreased hepatic triglyceride levels and lipid droplets in the high-fat-diet–fed mice.

Conclusion :

We found that RORα induced activation of AMPK and inhibition of the lipogenic function of LXRα, which may be key phenomena that provide the beneficial effects of RORα against hepatic steatosis. (Hepatology 2012;)
Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: A prospective study
Authors: Fernández Javier , Acevedo Juan , Castro Miriam , Garcia Orlando , de Lope Carlos Rodríguez , Roca Daria , Pavesi Marco , Sola Elsa , Moreira Leticia , Silva Anibal , Seva-Pereira Tiago , Corradi Francesco , Mensa Jose , Ginès Pere , Arroyo Vicente
Published: December 2011

Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (

P

< 0.001). Extended-spectrum β-lactamase-producing

Enterobacteriaceae

(ESBL-
E

; n = 43) was the main multiresistant organism identified, followed by

Pseudomonas aeruginosa

(n = 17), methicillin-resistant

Staphylococcus aureus

(n = 14), and

Enterococcus faecium

(n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively;

P

< 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%;

P

< 0.0001) and mortality rate (25% versus 12%;

P

= 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of β-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series.

Conclusions :

Multiresistant bacteria, especially ESBL-producing

Enterobacteriaceae

, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis. (Hepatology 2012)
Hepatic endothelin-1 and endocannabinoids-dependent effects of hyperleptinemia in nonalcoholic steatohepatitis-cirrhotic rats
Authors: Yang Ying-Ying , Tsai Tung-Hu , Huang Yi-Tsau , Lee Tzung-Yan , Chan Che-Chang , Lee Kuei-Chuan , Lin Han-Chieh
Published: December 2011

Leptin, the

ob

gene product, is a protein released from adipocytes and has been detected in fibrotic and cirrhotic livers. Leptin in brain has an inhibitory effect on food intake. Nonalcoholic steatohepatitis (NASH) is characterized by hyperleptinemia. This study explores the possible mechanisms of hyperleptinemia in relation to increased intrahepatic resistance (IHR) and portal hypertension in NASH cirrhotic rats. NASH cirrhotic rats with hyperleptinemia were induced in Zucker (

fa/fa

) and lean rats by feeding the animals a high fat/methionine-choline-deficient (HF/MCD) diet with and without exogenous administration of recombinant leptin. Portal venous pressure (PVP), IHR, plasma and hepatic levels of various substances, histopathology of the liver, the hepatic hydroxyproline content, and the expression of various hepatic protein and messenger RNA (mRNA) were measured. Hepatic microcirculatory dysfunction and the vasoconstrictive response to endothelin-1 were also observed using a liver perfusion system and intravital microscopy. Finally, the effect of leptin on hepatic stellate cells (HSCs) was evaluated. Both in HF/MCD-Zucker and HF/MCD+leptin lean rats, significant hepatic fibrogenesis and cirrhosis, marked portal hypertension, microcirculatory dysfunction, an enhanced vasoconstrictive response to endothelin-1, and an increased IHR were found to be associated with higher levels of hepatic endothelin-1 and endocannabinoids, expression levels of the cannabinoid type 1 receptor, endothelin-1 type A receptor (ETAR), activator protein-1, transforming growth factor beta (TGF-β)1, osteopontin, tumor necrosis factor alpha (TNF-α), leptin, and the leptin receptor (OBRb). Interestingly, acute incubation of leptin directly increases the expression of ETAR, OBRb and activator protein-1 in HSCs.

Conclusion :

An HF/MCD diet and hyperleptinemia increase hepatic endocannabinoids production, promote hepatic fibrogenesis, enhance the hepatic vasoconstrictive response to endothelin-1, and aggravate hepatic microcirculatory dysfunction; these events subsequently increase IHR and portal hypertension in NASH cirrhotic rats. (Hepatology 2012)
Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease
Authors: Reddy Srinevas K. , Steel Jennifer L. , Chen Hui-Wei , DeMateo David J. , Cardinal Jon , Behari Jaideep , Humar Abhinav , Marsh Wallis J. , Geller David A. , Tsung Allan
Published: December 2011

Concomitant increasing incidences of hepatocellular carcinoma (HCC) and nonalcoholic steatohepatitis (NASH) suggest that a substantial proportion of HCC arises as a result of hepatocellular injury from NASH. The aim of this study was to determine differences in severity of liver dysfunction at HCC diagnosis and long-term survival outcomes between patients undergoing curative therapy for HCC in the background of NASH compared to hepatitis C virus (HCV) and/or alcoholic liver disease (ALD). Patient demographics and comorbidities, clinicopathologic data, and long-term outcomes among patients who underwent liver transplantation, hepatic resection, or radiofrequency ablation for HCC were reviewed. From 2000 to 2010, 303 patients underwent curative treatment of HCC; 52 (17.2%) and 162 (53.5%) patients had NASH and HCV and/or alcoholic liver disease. At HCC diagnosis, NASH patients were older (median age 65 versus 58 years), were more often female (48.1% versus 16.7%), more often had the metabolic syndrome (45.1% versus 14.8%), and had lower model for end-stage liver disease scores (median 9 versus 10) (all

P

< 0.05). NASH patients were less likely to have hepatic bridging fibrosis or cirrhosis (73.1% versus 93.8%;

P

< 0.001). After a median follow-up of 50 months after curative treatment, the most frequent cause of death was liver failure. Though there were no differences in recurrence-free survival after curative therapy (median, 60 versus 56 months;

P

= 0.303), NASH patients had longer overall survival (OS) (median not reached versus 52 months;

P

= 0.009) independent of other clinicopathologic factors and type of curative treatment.

Conclusion:

Patients with HCC in the setting of NASH have less severe liver dysfunction at HCC diagnosis and better OS after curative treatment compared to counterparts with HCV and/or alcoholic liver disease.
Local‐ and field‐scale infiltration into vertically non‐uniform soils with spatially‐variable surface hydraulic conductivities
Authors: Govindaraju Rao S. , Corradini C. , Morbidelli R.
Published: December 2011

We studied the problem of local‐ and field‐scale infiltration over a particular class of heterogeneous soils. At the local scale, the soils are described as being vertically non‐uniform, with the saturated hydraulic conductivity continuously decreasing with depth according to a power law function. Analogous to the Green–Ampt model, analytical expressions are first developed for local‐scale infiltration using a sharp front approximation, and model results are compared with numerical solutions of the Richards equation. These results show that saturation does not occur from below in soils with such vertical non‐uniformity, thereby allowing for the use of a sharp front approximation. Because of vertical non‐uniformity, ponding conditions are achieved locally even for rainfall rates less than the surface saturated hydraulic conductivity. Furthermore, infiltration rates asymptotically approach zero at long times. To determine field‐scale infiltration properties, the spatial variability in the surface saturated hydraulic conductivity is represented by a log‐normal random field. Using cumulative infiltration as the independent variable, expressions are developed for the ensemble mean of field‐scale infiltration and the expected time for a given depth of water to infiltrate over the field. Surface horizontal heterogeneity is found to control field‐scale infiltration at small times, whereas local vertical non‐uniformity exerts a strong control at long times. Copyright © 2011 John Wiley & Sons, Ltd.
PIG: a numerical index for dissemination of groundwater contamination zones
Authors: Subba Rao N.
Published: December 2011

A pollution index of groundwater (PIG) is proposed for quantification of water contamination. PIG quantifies the status of concentrations of water quality measures with respect to their drinking water quality standards. The validity of the proposed index is verified by choosing the data of groundwater quality of the Varaha River Basin (Visakhapatnam District, Andhra Pradesh, India) as a case study. The computed index from the study area varies from 0.83 to 2.55. The index disseminates the area into zones of insignificant (PIG <1.0), low (PIG: 1.0 to 1.5), moderate (PIG: 1.5 to 2.0), high (PIG 2.0 to 2.5) and very high (PIG >2.5) pollution. Insignificant pollution zone is observed from the upstream area, where the groundwater is dominated by , and very high pollution zone from the downstream area, where the groundwater is associated with Cl−. This indicates that the quality of groundwater in the study area is mainly influenced by the source of geogenic origin, but it is subsequently modified by the effects of anthropogenic and marine sources. Geochemical ratios (Na+ : Cl−,  : Cl−, Na+ : Ca2+ and Mg2+ : Ca2+) also form the quantitative basis of the index. The present study paves the way to implement appropriate management strategies at a specific site to circumvent the pollution. As the classification of the pollution zones with PIG depends upon the drinking water quality standards, it becomes a universal assessment tool for groundwater contamination at any test area. Copyright © 2011 John Wiley & Sons, Ltd.
Temporal trends and spatial characteristics of drought and rainfall in arid and semiarid regions of Iran
Authors: Tabari Hossein , Abghari Hirad , Hosseinzadeh Talaee P.
Published: December 2011

Drought, a normal recurrent event in arid and semiarid lands such as Iran, is typically of a temporary nature usually leaving little permanent aftermath. In the current study, the rainfall and drought severity time series were analyzed at 10 stations in the eastern half of Iran for the period 1966–2005. The drought severity was computed using the Standardized Precipitation Index (SPI) for a 12‐month timescale. The trend analyses of the data were also performed using the Kendall and Spearman tests. The results of this study showed that the rainfall and drought severity data had high variations to average values in the study period, and these variations increased with increasing aridity towards the south of the study area. The negative serial correlations found in the seasonal and annual rainfall time series were mostly insignificant. The trend tests detected a significant decreasing trend in the spring rainfall series of Birjand station at the rate of 8.56 mm per season per decade and a significant increasing trend in the summer rainfall series of Torbateheydarieh station at the rate of 0.14 mm per season per decade, whereas the rest of the trends were insignificant. Furthermore, the 12‐month values of the standardized precipitation index decreased at all the stations except Zabol during the past four decades. During the study period, all of the stations experienced at least one extreme drought which mainly occurred in the winter season. Copyright © 2011 John Wiley & Sons, Ltd.
EVALUATION OF THE TRANSFERABILITY OF A SVAT MODEL––RESULTS FROM FIELD AND GREENHOUSE APPLICATIONS
Authors: Walser Sabine , Schütze Niels , Marcus Guderle , Susanne Liske , Schmidhalter Urs
Published: December 2011

Soil–Vegetation–Atmosphere Transfer (SVAT) models are commonly used to describe crop‐seasonal dynamics including the prediction of crop yield and water balance. In the case of absent detailed information, a straightforward application of the model using given parameter sets may take place against rather different soil and/or climate conditions. The objective of this study was (i) to calibrate and validate a SVAT model utilizing data of two sites and two crops, (ii) to evaluate the model's ability to employ plant parameters determined on the basis of field data against greenhouse data, and (iii) to estimate optimal irrigation schedules for maximizing water productivity. Irrigation experiments were conducted on a field rain‐out shelter (wheat and barley) and in a container greenhouse experiment (barley). In the case of barley which was only grown in 2009, inverse calibration of plant data was carried out using field data, whereas the DAISY model was validated against independent greenhouse data. For validation, the specific condition in a container greenhouse experiment was taken into account. The study shows that DAISY performed well with simulating lightly drought‐stressed crop growth and water balance. For both crops and sits, optimal irrigation schedules were determined in a simulation‐optimization study which led to considerable irrigation water savings. Copyright © 2011 John Wiley & Sons, Ltd.
INTEGRATING SCIENCE AND POLICY FOR CREATING TOOLS FOR SAFER EUROPEAN COASTS IN A CHANGING CLIMATE
Authors: de Vries W. S. , Zanuttigh B. , Steendam G. J. , Kloosterboer H. , Van der Nat A. , Graaff H.
Published: December 2011

Densely populated areas along the coast face many problems, including erosion, increasing flood risk and habitat deterioration. As economies develop, the asset base at risk increases. Simultaneously, the effects of climate change result in more extreme events, thus more damage and habitat decline. Existing management and defence approaches are not well tuned to these challenges, as most assume static situations.

In the THESEUS1 project (2009–2013), 31 partners are working together in an interdisciplinary way to develop instruments for creating low‐risk coasts for human use and healthy habitats (INFRAM, 2011).

For this, eight study sites were identified across Europe in the most vulnerable coastal environments such as deltas, estuaries and wetlands. Many large cities and industrial areas are located in these areas.

The authors have assessed the coastal systems of these sites from the perspective of the risk assessment due from every Member State by 2011. A questionnaire was developed and interviews were input for a systems analysis, for which the coastal systems were divided into subsystems according to risk function (chance × consequences), physical elements (sea, foreshore, flood defence, protected area) and land use. Based on these analyses, a first impression of possible policy changes, organisational and/or mitigation measures was identified. Copyright © 2011 John Wiley & Sons, Ltd.
APPLICATION OF LANDSCAPE ECOLOGICAL DECISION AND EVALUATION SUPPORT SYSTEM ON FLOOD MITIGATION STRATEGIES
Authors: Yang Chun‐Yao , Wang Hsiao‐Wen , Kuo Pin‐Han
Published: December 2011

While flood mitigation measures are needed in flood‐prone areas, some may impact the environment, for example by causing habitat fragmentation. As flooding issues nowadays are more complicated and should be discussed taking multidisciplinary considerations into account, the purpose of this study was to evaluate the effects of land use changes on flooding, landscape pattern, and ecological resources as a whole, based on past environmental changes and trends in future development, using the concept of the Landscape Ecological Decision and Evaluation Support System Model (LEDESS).

Yunlin County, one of the demonstration sites of the Regulation Project of Flood‐Prone Areas, proposed by the Water Resource Agency of Taiwan in 2005, was studied. We designed three scenarios, i.e. Scenario A for the current situation, Scenario B for the government policy, and Scenario C as a sustainable policy integrating room for water. We used people, planet, and profit as the indicators to understand the consequences under different scenarios. The results indicated that lots of land will be abandonedin the near future due to flooding regardless of whether or not mitigation measures are adopted. That is to say, the coastal area will turn into a wetland area through natural processes. Hence, we need to reconsider land use strategy. Copyright © 2011 John Wiley & Sons, Ltd.
WATER MANAGEMENT AND MULTIPLE LAND USE: THE DUTCH APPROACH: COMPETING AND COMPLEMENTARY FUNCTIONS IN WATER MANAGEMENT
Authors: Zeeman Wim
Published: December 2011

Climate change, food crises and deterioration of the environment create immense challenges in water management. In the Netherlands land subsidence, high population density and intensity of land use aggravate these problems. Increased awareness of these problems and civil society's participation in the discussions complicate these challenges.

The Netherlands' Government Service for Land and Water Management (DLG), an organisation specialising in integrated land development, has tackled these problems at a regional/local scale.

Land use planning for various different functions within the same territorial area require a special approach to reach sustainable and economically feasible solutions. Different functions of land and water require different hydrological/hydraulic conditions. Therefore regional, physical and socio‐economic characteristics determine the conditions for land and water management strategies. Projects are implemented while different interests such as agriculture, nature and water have to be met according to a participatory, multi‐stakeholder and integrated approach.

Therefore the DLG developed special instruments, tested them in practice and applied them. Examples are ‘touch table’, ‘sketch match’ and ‘virtual reality’.

The projects that the DLG is involved in are increasingly implemented in cooperation with regional/local public institutions. These projects are directed by provincial governments, the regional authorities with overall responsibility for the implementation. Several examples will illustrate this. Copyright © 2011 John Wiley & Sons, Ltd.
Prediction of fracture risk in men: A cohort study
Authors: Byberg Liisa , Gedeborg Rolf , Cars Thomas , Sundström Johan , Berglund Lars , Kilander Lena , Melhus Håkan , Michaëlsson Karl
Published: December 2011

FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R2) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526) years. During the total follow-up period from age 50 years, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 years and 25.9/1000 person-years at risk from age 82 years. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25% to 45% of all fractures and 80% to 92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7% to 17% for all fractures and 41% to 60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40% and 53% for any fracture and between 40% and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, one-third of the men will have a fracture within 10 years after age 71 years and two-thirds after age 82 years. We conclude that the addition of comorbidity, medication, and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. © 2012 American Society for Bone and Mineral Research.
Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization
Authors: Bala Yohann , Depalle Baptiste , Farlay Delphine , Douillard Thierry , Meille Sylvain , Follet Helene , Chapurlat Roland , Chevalier Jérôme , Boivin Georges
Published: December 2011

In the treatment of postmenopausal osteoporosis (PMOP), the use of alendronate (ALN) leads to a decrease in the risk of vertebral and nonvertebral fractures. To explore the possible adverse effects of prolonged ALN therapy, we studied the effects of 8 ± 2 years (6–10 years) of ALN treatment on the iliac cortical bone mineral and collagen quality and micromechanical properties; by design, our study examined these parameters, independent of the degree of mineralization. From six ALN-treated and five age-matched untreated PMOP women, 153 bone structural units have been chosen according their degree of mineralization to obtain the same distribution in each group. In those bone structural units, Fourier transform infrared spectroscopy, quantitative microradiography, and nanoindentation were used to assess bone quality. Irrespective of the degree of mineralization, ALN treatment was associated with higher collagen maturity (+7%, p < 0.001, c.v. = 13% and 16% in treated and untreated women, respectively) and lower mineral crystallinity than that observed in the untreated PMOP group (−2%, p < 0.0001, c.v. = 3% in both groups). Bone matrix from ALN-treated women also had lower elastic modulus (−12%, p < 0.0001, c.v. = 14% in both groups) and, contact hardness (−6%, p < 0.05, c.v. = 14% in both groups) than that of untreated women. Crystallinity (which reflects the size and perfection of crystals) was associated with both elastic modulus and contact hardness in treated women exclusively (r = 0.43 and r = 0.54, p < 0.0001, respectively), even after adjustment for the amount of mineral. We infer that long-term ALN treatment compromises micromechanical properties of the bone matrix as assessed ex vivo. The strength deficits are in part related to difference in crystallinity, irrespective of the mineral amount and mineral maturity. These novel findings at local levels of bone structure will have to be taken into account in the study of the pathophysiology of bone fragilities associated with prolonged ALN treatment. © 2012 American Society for Bone and Mineral Research.
Central DXA utilization shifts from office-based to hospital-based settings among medicare beneficiaries in the wake of reimbursement changes
Authors: Zhang Jie , Delzell Elizabeth , Zhao Hong , Laster Andrew J , Saag Kenneth G , Kilgore Meredith L , Morrisey Michael A , Wright Nicole C , Yun Huifeng , Curtis Jeffrey R
Published: December 2011

In the United States, Medicare gradually reduced payments for central dual-energy X-ray absorptiometry (DXA) performed at physician offices (or other nonhospital settings) from an average of $139 in 2006 to about $82 in 2007 and 2008 and $72 in 2009. Reimbursement for hospital outpatient DXA service was unchanged. We investigated the utilization of hip and spine (central) DXA in the Medicare population before and after the reduction. We identified individuals from the national 5% random sample of Medicare beneficiaries who were ≥65 years of age and enrolled in Medicare Parts A and B but not in a Medicare Advantage plan from 2002 through 2009. For each calendar year, we calculated the proportion of beneficiaries who submitted claims for DXA, the proportions of DXAs performed in hospitals and in physician offices and the number of physician office-based practices that discontinued or started to provide DXA services. From 2002 to 2006, the proportion of beneficiaries who had at least one central DXA increased from 7.9% to 9.6% at an annual increase of 0.4% and from 2006 to 2009, the annual increase dropped to 0.1%. The number of DXAs performed in physician offices dropped from 1,643,720 (69% of 2,363,500 total DXAs) in 2006 to 1,534,240 (66% of 2,338,240) in 2009. This decline was offset by an increase in the number of DXAs performed in hospitals, which increased from 719,780 (31%) in 2006 to 804,000 (34%) in 2009. Among physician office-based practices, more practices initiated than discontinued DXA service each year from 2002 to 2006. However, the trend was reversed since 2007 such that in 2009, 1876 practices discontinued and only 1394 initiated DXA service. The reduction in DXA reimbursement was associated with a decrease in the number of DXAs performed in physician offices and fewer physician offices that provided DXA services. © 2012 American Society for Bone and Mineral Research.
Quantitative ultrashort echo time (UTE) MRI of human cortical bone: Correlation with porosity and biomechanical properties
Authors: Bae Won C , Chen Peter C , Chung Christine B , Masuda Koichi , D'Lima Darryl , Du Jiang
Published: December 2011

In this study we describe the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) to evaluate short and long T2* components as well as the water content of cortical bone. Fourteen human cadaveric distal femur and proximal tibia were sectioned to produce 44 rectangular slabs of cortical bone for quantitative UTE MR imaging, microcomputed tomography (µCT), and biomechanical testing. A two-dimensional (2D) UTE pulse sequence with a minimal nominal TE of 8 µseconds was used together with bicomponent analysis to quantify the bound and free water in cortical bone using a clinical 3T scanner. Total water concentration was measured using a 3D UTE sequence together with a reference water phantom. UTE MR measures of water content (total, free, and bound), T2* (short and long), and short and long T2* fractions were compared with porosity assessed with µCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation. Porosity significantly correlated positively with total (R2 = 0.23; p < 0.01) and free (R2 = 0.31; p < 0.001) water content as well as long T2* fraction (R2 = 0.25; p < 0.001), and negatively with short T2* fraction and short T2* (R2 = 0.24; p < 0.01). Failure strain significantly correlated positively with short T2* (R2 = 0.29; p < 0.001), ultimate stress significantly correlated negatively with total (R2 = 0.25; p < 0.001) and bound (R2 = 0.22; p < 0.01) water content, and failure energy significantly correlated positively with both short (R2 = 0 30; p < 0.001) and long (R2 = 0.17; p < 0.01) T2* values. These results suggest that UTE MR measures are sensitive to the structure and failure properties of human cortical bone, and may provide a novel way of evaluating cortical bone quality. © 2012 American Society for Bone and Mineral Research.
COL1A1 haplotypes and hip fracture
Authors: Urreizti Roser , Garcia-Giralt Natàlia , Riancho José A. , González-Macías Jesús , Civit Sergi , Güerri Roberto , Yoskovitz Guy , Sarrion Patricia , Mellivobsky Leonardo , Díez-Pérez Adolfo , Nogués Xavier , Balcells Susana , Grinberg Daniel
Published: December 2011

Fragility fractures resulting from low-trauma events such as a fall from standing height are associated with osteoporosis and are very common in older people, especially women. Three single nucleotide polymorphisms (SNPs) at the COL1A1 gene (rs1107946, rs11327935, and rs1800012) have been widely studied and previously associated with bone mineral density (BMD) and fracture. A rare haplotype (T-delT-T) of these three SNPs was found to be greatly overrepresented in fractured individuals compared with nonfractured controls, thus becoming a good candidate for predicting increased fracture risk. The aim of our study was to assess the association of this haplotype with fracture risk in Spanish individuals. We recruited two independent groups of ∼100 patients with hip fracture (a total of 203 individuals) and compared the genotype and haplotype distributions of the three SNPs in the fractured patients with those of 397 control individuals from the BARCOS Spanish cohort. We found no association with risk of fracture at the genotype level for any of the SNPs, and no differences in the SNP frequencies between the two groups. At the haplotype level, we found no association between the T-delT-T haplotype and fracture. However, we observed a small but significant (p = 0.03) association with another rare haplotype, G-insT-T, which was slightly overrepresented in the patient group. © 2012 American Society for Bone and Mineral Research.
Prediction of new clinical vertebral fractures in elderly men using finite element analysis of CT scans
Authors: Wang Xiang , Sanyal Arnav , Cawthon Peggy M , Palermo Lisa , Jekir Michael , Christensen John , Ensrud Kristine E , Cummings Steven R , Orwoll Eric , Black Dennis M ,   for the Osteoporotic Fractures in Men (MrOS) Research Group, Keaveny Tony M
Published: December 2011

Vertebral strength, as estimated by finite element analysis of computed tomography (CT) scans, has not yet been compared against areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) for prospectively assessing the risk of new clinical vertebral fractures. To do so, we conducted a case-cohort analysis of 306 men aged 65 years and older, which included 63 men who developed new clinically-identified vertebral fractures and 243 men who did not, all observed over an average of 6.5 years. Nonlinear finite element analysis was performed on the baseline CT scans, blinded to fracture status, to estimate L1 vertebral compressive strength and a load-to-strength ratio. Volumetric BMD by quantitative CT and areal BMD by DXA were also evaluated. We found that, for the risk of new clinical vertebral fracture, the age-adjusted hazard ratio per standard deviation change for areal BMD (3.2; 95% confidence interval [CI], 2.0–5.2) was significantly lower (p < 0.005) than for strength (7.2; 95% CI, 3.6–14.1), numerically lower than for volumetric BMD (5.7; 95% CI, 3.1–10.3), and similar for the load-to-strength ratio (3.0; 95% CI, 2.1–4.3). After also adjusting for race, body mass index (BMI), clinical center, and areal BMD, all these hazard ratios remained highly statistically significant, particularly those for strength (8.5; 95% CI, 3.6–20.1) and volumetric BMD (9.4; 95% CI, 4.1–21.6). The area-under-the-curve for areal BMD (AUC = 0.76) was significantly lower than for strength (AUC = 0.83, p = 0.02), volumetric BMD (AUC = 0.82, p = 0.05), and the load-to-strength ratio (AUC = 0.82, p = 0.05). We conclude that, compared to areal BMD by DXA, vertebral compressive strength and volumetric BMD consistently improved vertebral fracture risk assessment in this cohort of elderly men. © 2012 American Society for Bone and Mineral Research.
Structure and spectroscopy of water‐fluoride microclusters: A combined genetic algorithm and DFT‐based study
Authors: Neogi Soumya Ganguly , Chaudhury Pinaki
Published: December 2011

In this article, we explore the efficiency of using a coupled genetic algorithm (GA) and density functional theory (DFT) based strategy to evaluate probable structures of (H2O)nF− micro‐clusters, with n = 1 − 6. We use the stochastic optimization technique of GA to arrive at structures of the cluster systems and once the structures are obtained, do a DFT calculation with the optimized coordinates from the GA calculation as input to get the infra‐red spectrum of all the systems. The results of our work closely resembles the pure quantum chemical results obtained by Baik et al. (J Chem Phys 1999, 110, 9116–9127) © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
Facile synthesis of 5‐aryl‐1‐[(arylamino)methyl]‐ 1,3,5‐triazinane‐2‐thiones
Authors: Zhang Zhenfeng , Wang Siqian , Zhang Guisheng
Published: December 2011

A series of 5‐aryl‐1‐arylaminomethyl‐1,3,5‐triazinane‐2‐thiones has been prepared in a one‐step procedure from condensation of readily available aromatic amines with thiourea and formaldehyde. A mechanism is presented to account for the formation of the products. The overall sequence provides a simple and efficient route to prepare in good to excellent yields and in a short experimental time. J. Heterocyclic Chem., (2012).
1,3‐Di‐n‐butylimidazolium tribromide‐mediated chemoselective oxidative cyclization of benzothiazoyl carbaimides: A novel approach toward the synthesis of N‐bis‐benzothiazole derivatives
Authors: Kumbhare Ravindra M. , Dadmal Tulshiram , Kosurkar Umesh , Vijay Kumar K.
Published: December 2011

4‐(N,N‐Dimethylamino)pyridine is found to be an efficient catalyst for the synthesis of benzothiazoyl carbaimide derivatives using 2‐aminobenzothiazoles and phenylisothiocyanates, which on treatment with ionic liquid [bbim][Br3] at 70°C afforded exclusive formation of N‐bis‐benzothiazole derivatives in good yield. J. Heterocyclic Chem., (2012).
Expressions of hypoxic stress sensor proteins after transient cerebral ischemia in mice
Authors: Shang Jingwei , Liu Ning , Tanaka Nobuhito , Abe Koji
Published: December 2011

The role of hypoxia sensor proteins is important in responding and protecting cells against hypoxic/ischemic injury in brain. Seven in absentia homolog 1 (Siah1) regulates primarily the downstream sensor proteins factor inhibiting alpha subunit of hypoxia‐inducible factor‐1 (FIH) under normoxic conditions and prolyl hydroxylases domain 3 (PHD3) under hypoxic conditions. In the present study, we investigated the temporal and spatial changes of these hypoxia sensor proteins, Siah1, FIH, and PHD3, after 60 min of transient middle cerebral artery occlusion (tMCAO) up to 72 hr after reperfusion in ICR mice. Immunohistochemistry and Western blot analyses showed that Siah1 was quickly and strongly induced in neuronal cells of the ischemic penumbra, with a peak at 2 hr, and gradually returned toward the sham control (SC) level until 72 hr. In contrast, the expressions of FIH and PHD3 were strongly visualized in the SC brains, and significantly reduced in a time‐dependent manner with reperfusion until 72 hr. In the ischemic core region, Siah1, FIH, and PHD3 showed a similar change of strong and progressive decrease until 72 hr. Double‐immunofluorescence analyses showed a cytoplasmic localization of Siah1 and both cytoplasmic and nuclear localizations of FIH and PHD3 and that Siah1 plus FIH or PHD3 were well colocalized in same neuron at 2 hr after tMCAO. The present study suggests that hypoxia sensor proteins (Siah1, FIH, and PHD3) showed temporally and spatially different expressions after tMCAO, which could provide an effective neuroprotective reaction through their further downstream proteins after cerebral ischemia. © 2011 Wiley Periodicals, Inc.
Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction
Authors: Tokunaga Shinji , Araki Toshiyuki
Published: December 2011

Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wldS Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wldS mice are protected from, we exposed primary cultured neurons derived from wldS mice to various components of hypoxic stress. We found that wldS mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wldS mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that WldS protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. © 2011 Wiley Periodicals, Inc.
Localization of mature neprilysin in lipid rafts
Authors: Sato Kimihiko , Tanabe Chiaki , Yonemura Yoji , Watahiki Haruhiko , Zhao Yimeng , Yagishita Sosuke , Ebina Maiko , Suo Satoshi , Futai Eugene , Murata Masayuki , Ishiura Shoichi
Published: December 2011

Alzheimer's disease (AD) is characterized by senile plaques caused by amyloid‐β peptide (Aβ) accumulation. It has been reported that Aβ generation and accumulation occur in membrane microdomains, called lipid rafts, which are enriched in cholesterol and glycosphingolipids. Moreover, the ablation of cholesterol metabolism has been implicated in AD. Neprilysin (NEP), a neutral endopeptidase, is one of the major Aβ‐degrading enzymes in the brain. Activation of NEP is a possible therapeutic target. However, it remains unknown whether the activity of NEP is regulated by its association with lipid rafts. Here we show that only the mature form of NEP, which has been glycosylated in the Golgi, exists in lipid rafts, where it is directly associated with phosphatidylserine. Moreover, the localization of NEP in lipid rafts is enhanced by its dimerization, as shown using the NEP E403C homodimerization mutant. However, the protease activities of the mature form of NEP, as assessed by in vitro peptide hydrolysis, did not differ between lipid rafts and nonlipid rafts. We conclude that cholesterol and other lipids regulate the localization of mature NEP to lipid rafts, where the substrate Aβ accumulates but does not modulate the protease activity of NEP. © 2011 Wiley Periodicals, Inc.
Pituitary adenylate cyclase‐activating polypeptide counteracts the impaired adult neural stem cell viability induced by palmitate
Authors: Mansouri Shiva , Ortsäter Henrik , Pintor Gallego Otto , Darsalia Vladimer , Sjöholm Åke , Patrone Cesare
Published: December 2011

Diabetes and obesity are characterized by hyperlipidemia and represent risk factors for premature neurological disorders. Diabetic/obese animals have impaired adult neurogenesis. We hypothesize that lipotoxicity leading to neurogenesis impairment plays a role in the development of neurological complications. If so, normalizing neurogenesis in diabetes/obesity could be therapeutically useful in counteracting neurological dysfunction. The goal of this study was to determine the potential of pituitary adenylate cyclase‐activating polypeptide (PACAP) to protect adult neural stem cells (NSCs) from lipotoxicity and to study the expression of PACAP receptors in NSCs under lipotoxic conditions in vitro and in the subventricular zone in vivo. The viability of NSCs isolated from the adult mouse brain subventricular zone was assessed in the presence of a high‐fat milieu, as mimicked by palmitate, which characterizes diabetic lipotoxicity. Regulation studies of PACAP receptors were performed by quantitative PCR on NSCs in vitro or on subventricular tissues isolated from obese ob/ob mice and their lean littermates. We show that palmitate impairs NSC viability by promoting lipoapoptosis. We also show that PACAP counteracts lipotoxicity via PAC‐1 receptor activation. Studies on PACAP receptor expression revealed that PAC‐1 and VPAC‐2 are expressed by NSC in vitro and are upregulated by palmitate treatment and that PAC‐1, VPAC‐1, and VPAC‐2 are expressed in the subventricular zone/striatum in vivo and are upregulated in ob/ob mice. The present study reveals a previously uncharacterized role of PACAP to protect NSC from lipotoxicity and suggests a potential therapeutic role for PACAP receptor agonists in the treatment of neurological complications in obesity and diabetes. © 2011 Wiley Periodicals, Inc.