bluuebunny/crossref_metadata_2025 huggingface dataset:
RANKL Inhibition With Denosumab Does Not Influence 3-Year Progression of Aortic Calcification or Incidence of Adverse Cardiovascular Events in Postmenopausal Women With Osteoporosis and High Cardiovascular Risk
Authors: Samelson Elizabeth J , Miller Paul D , Christiansen Claus , Daizadeh Nadia S , Grazette Luanda , Anthony Mary S , Egbuna Ogo , Wang Andrea , Siddhanti Suresh R , Cheung Angela M , Franchimont Nathalie , Kiel Douglas P
Published: July 2013

Atherosclerosis and osteoporosis are chronic diseases that progress with age, and studies suggest aortic calcification, an indicator of atherosclerosis, is inversely associated with bone mineral density (BMD). The osteoprotegerin (OPG)/receptor activator of NF-κB (RANK)/RANK ligand (RANKL) system has been proposed as a shared regulatory system for bone and vasculature. Denosumab (DMAb), a monoclonal antibody against RANKL, improved BMD and reduced fracture risk in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. We evaluated whether or not treatment with DMAb influenced progression of aortic calcification (AC) and incidence of cardiovascular (CV) adverse events. We included 2363 postmenopausal women with osteoporosis (1142 placebo, 1221 DMAb), selected from 7808 participants in the FREEDOM trial (3906 placebo, 3902 DMAb), at high risk of CV events according to modified Raloxifene Use for the Heart (RUTH) criteria. CV adverse events were reported by participants. AC scores were assessed using a semiquantitative method from lateral spine X-rays. Change in AC score from baseline to 12 (n = 1377), 24 (n = 1231), and 36 months (n = 1045) was calculated as AC score at follow-up minus AC score at baseline. AC progression was defined as change in AC score >0. Baseline characteristics, CV risk factors, and AC scores were similar between treatment groups. Mean age of participants was 74 years (range, 60–90), 88% were white, and 77% had AC score >0 at baseline. Frequency of AC progression over 3 years did not differ between women in placebo (22%) and DMAb (22%) groups (p = 0.98). AC progression did not differ between treatment groups when analyzed by baseline estimated glomerular filtration rate or by baseline AC scores. Frequency of CV adverse events did not differ between placebo (40%) and DMAb (38%) groups (p = 0.26). In conclusion, DMAb treatment had no effect on progression of AC or incidence of CV adverse events compared to placebo. © 2014 American Society for Bone and Mineral Research.
The Sclerostin-Independent Bone Anabolic Activity of Intermittent PTH Treatment Is Mediated by T-Cell–Produced Wnt10b
Authors: Li Jau-Yi , Walker Lindsey D , Tyagi Abdul Malik , Adams Jonathan , Weitzmann M Neale , Pacifici Roberto
Published: July 2013

Both blunted osteocytic production of the Wnt inhibitor sclerostin (Scl) and increased T-cell production of the Wnt ligand Wnt10b contribute to the bone anabolic activity of intermittent parathyroid hormone (iPTH) treatment. However, the relative contribution of these mechanisms is unknown. In this study, we modeled the repressive effects of iPTH on Scl production in mice by treatment with a neutralizing anti-Scl antibody (Scl-Ab) to determine the contribution of T-cell–produced Wnt10b to the Scl-independent modalities of action of iPTH. We report that combined treatment with Scl-Ab and iPTH was more potent than either iPTH or Scl-Ab alone in increasing stromal cell production of OPG, osteoblastogenesis, osteoblast life span, bone turnover, bone mineral density, and trabecular bone volume and structure in mice with T cells capable of producing Wnt10b. In T-cell–null mice and mice lacking T-cell production of Wnt10b, combined treatment increased bone turnover significantly more than iPTH or Scl-Ab alone. However, in these mice, combined treatment with Scl-Ab and iPTH was equally effective as Scl-Ab alone in increasing the osteoblastic pool, bone volume, density, and structure. These findings demonstrate that the Scl-independent activity of iPTH on osteoblasts and bone mass is mediated by T-cell–produced Wnt10b. The data provide a proof of concept of a more potent therapeutic effect of combined treatment with iPTH and Scl-Ab than either alone. © 2014 American Society for Bone and Mineral Research.
Trabecular Bone Score (TBS) Predicts Vertebral Fractures in Japanese Women Over 10 Years Independently of Bone Density and Prevalent Vertebral Deformity: The Japanese Population-Based Osteoporosis (JPOS) Cohort Study
Authors: Iki Masayuki , Tamaki Junko , Kadowaki Eiko , Sato Yuho , Dongmei Namiraa , Winzenrieth Renaud , Kagamimori Sadanobu , Kagawa Yoshiko , Yoneshima Hideo
Published: July 2013

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow-up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual-energy X-ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey-Kanis criteria or Genant's grade 2 fracture at follow-up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/103 person-years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings. © 2014 American Society for Bone and Mineral Research.
Mortality After Lower Extremity Fractures in Men With Spinal Cord Injury
Authors: Carbone Laura D , Chin Amy S , Burns Stephen P , Svircev Jelena N , Hoenig Helen , Heggeness Michael , Bailey Lauren , Weaver Frances
Published: July 2013

In the United States, there are over 200,000 men with spinal cord injuries (SCIs) who are at risk for lower limb fractures. The risk of mortality after fractures in SCI is unknown. This was a population-based, cohort study of all male veterans (mean age 54.1; range, 20.3–100.5 years) with a traumatic SCI of at least 2 years' duration enrolled in the Veterans Affairs (VA) Spinal Cord Dysfunction Registry from FY2002 to FY2010 to determine the association between lower extremity fractures and mortality. Mortality for up to 5 years was determined. The lower extremity fracture rate was 2.14 per 100 patient-years at risk for at least one fracture. In unadjusted models and in models adjusted for demographic, SCI-related factors, healthcare use, and comorbidities, there was a significant association between incident lower extremity fracture and increased mortality (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17–1.63; HR, 1.36; 95% CI, 1.15–1.61, respectively). In complete SCI, the hazard of death after lower extremity fracture was also increased (unadjusted model: HR, 1.46; 95% CI, 1.13–1.89; adjusted model: HR, 1.32; 95% CI, 1.02–1.71). In fully-adjusted models, the association of incident lower extremity fracture with increased mortality was substantially greater in older men (age ≥50 years) for the entire cohort (HR, 3.42; 95% CI, 2.75–4.25) and for those with complete SCI (HR, 3.13; 95% CI, 2.19–4.45), compared to younger men (age <50 years) (entire cohort: HR, 1.42; 95% CI, 0.94–2.14; complete SCI: HR, 1.71; 95% CI, 0.98–3.01). Every additional point in the Charlson comorbidity index was associated with a 10% increase in the hazard of death in models involving the entire cohort (HR, 1.11; 95% CI, 1.09–1.13) and also in models limited to men with complete SCI (HR, 1.10; 95% CI, 1.06–1.15). These data support the concept that both the fracture itself and underlying comorbidities are drivers of death in men with SCI. © 2014 American Society for Bone and Mineral Research.
Relationship of Weight, Height, and Body Mass Index With Fracture Risk at Different Sites in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women (GLOW)
Authors: Compston Juliet E , Flahive Julie , Hosmer David W , Watts Nelson B , Siris Ethel S , Silverman Stuart , Saag Kenneth G , Roux Christian , Rossini Maurizio , Pfeilschifter Johannes , Nieves Jeri W , Netelenbos J Coen , March Lyn , LaCroix Andrea Z , Hooven Frederick H , Greenspan Susan L , Gehlbach Stephen H , Díez-Pérez Adolfo , Cooper Cyrus , Chapurlat Roland D , Boonen Steven , Anderson Frederick A , Adami Silvano , Adachi Jonathan D ,   for the GLOW Investigators
Published: July 2013

Low body mass index (BMI) is a well-established risk factor for fracture in postmenopausal women. Height and obesity have also been associated with increased fracture risk at some sites. We investigated the relationships of weight, BMI, and height with incident clinical fracture in a practice-based cohort of postmenopausal women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3 years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle, lower leg, and upper leg fractures, we modeled the time to incident self-reported fracture over a 3-year period using the Cox proportional hazards model and fitted the best linear or nonlinear models containing height, weight, and BMI. Of 52,939 women, 3628 (6.9%) reported an incident clinical fracture during the 3-year follow-up period. Linear BMI showed a significant inverse association with hip, clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) per increase of 5 kg/m2 were 0.80 (0.71–0.90), 0.83 (0.76–0.92), and 0.88 (0.83–0.94), respectively (all p < 0.001). For ankle fractures, linear weight showed a significant positive association: adjusted HR per 5-kg increase 1.05 (1.02–1.07) (p < 0.001). For upper arm/shoulder and clavicle fractures, only linear height was significantly associated: adjusted HRs per 10-cm increase were 0.85 (0.75–0.97) (p = 0.02) and 0.73 (0.57–0.92) (p = 0.009), respectively. For pelvic and rib fractures, the best models were for nonlinear BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low BMI/body weight and positive associations at high values. These data demonstrate that the relationships between fracture and weight, BMI, and height are site-specific. The different associations may be mediated, at least in part, by effects on bone mineral density, bone structure and geometry, and patterns of falling. © 2014 American Society for Bone and Mineral Research.
Dietary Acid Load Is Associated With Lower Bone Mineral Density in Men With Low Intake of Dietary Calcium
Authors: Mangano Kelsey M , Walsh Stephen J , Kenny Anne M , Insogna Karl L , Kerstetter Jane E
Published: July 2013

High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38–0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake. © 2014 American Society for Bone and Mineral Research.
Evaluation of Antimicrobial Activity of Some Newly Synthesized 4‐Thiazolidinones
Authors: Abdul‐kader Saleh Nabil , El‐abd Saltani Hussein , Abbas Al‐Issa Fadhil , Gomaa Melad Al‐Sadek
Published: July 2013

The antimicrobial activity of thirteen newly synthesized 4‐thiazolidinones (TZONs) and four dithiolane derivatives was assessed against susceptible and resistant bacteria, including MRSA, as well as Candida albicans. The structure‐activity relationships revealed that 4‐Thiazolidinone derivatives harboring p‐chlorophenyl and dicarboxyethyl at the 2‐ethenyl and 5‐arylidine positions of the thiazolidinone ring display considerable antibacterial properties. No antifungal activity was recorded by all tested compounds against Candida albicans. The possible potentiative (synergistic) effect of the most active compounds to a few commercial antibiotics was also investigated.
Evaluation of Antifungal and Antioxidant Activity of Newly Synthesized 4‐Thiazolidinones
Authors: Abdul‐Kader Saleh Nabil , El‐Abd Saltani Hussein , Abbas Al‐Issa Fadhil , Abul‐kasem Errabie Ahmad , Gomaa Melad Al‐Sadek
Published: July 2013

The antifungal and antioxidant activities of thirty newly synthesized 4‐thiazolidinone (TZON) derivatives were assessed against some fungal species including Candida albicans and Aspergillus niger. The introduction of different arylidene moieties at 5‐positions of the thiazolidinone ring successfully enhanced its biological activity. The structure–activity relationships revealed that 4‐thiazolidinone derivatives harboring dicarboxyethyl (at the 2‐ethenyl) and p‐nitrophenylhydrazyl arm (at the 5‐arylidine positions of the thiazolidinone ring) display considerable antifungal and antioxidant properties.
An Environmental Friendly Approach for the Synthesis of Spiro[indoline‐3′,2‐quinazoline]2′,4(3H)‐dione Using 1‐Methylimidazolium Hydrogen Sulfate, as Reusable Catalyst
Authors: Kefayati Hassan , Vazifeh Masoumeh , Kazemi‐Rad Reyhaneh
Published: July 2013

A facile and environmentally benign procedure for the synthesis of 3‐aryl‐1H‐spiro[indoline‐3′,2‐quin‐azoline]2′,4(3H)‐dione from isatoic anhydride, aromatic amines and isatin derivatives in Brønsted acidic ionic liquid, 1‐methylimidazolium hydrogen sulfate, was reported. The ability to reuse the ionic liquid, the high yield, short reaction time and ease of purification are the important features of this process.
Automated Sequential‐injection Chemiluminescence Determination of Glucosamine Sulphate via Luminol‐Hydrogen Peroxide System
Authors: Alarfaj Nawal A. , El‐Tohamy Maha F.
Published: July 2013

A highly sensitive automated sequential‐injection chemiluminescence (SIA‐CL) method for determination of glucosamine sulphate (GLS) was developed. The goal of the present work is the evaluation of the enhancement effect of the investigated drug glucosamine sulphate on the chemiluminescence reaction between luminol and H2O2 in alkaline medium of 1.0 × 10−2 mol L−1 sodium hydroxide at pH 11. The experimental conditions affecting the CL reaction such as the sequence of the reagents, concentrations, flow rate and aspirated volumes of reactants were systematically investigated and optimized. Under optimum conditions 50 μL of 1.0 × 10−3 mol L−1 luminol, 30 μL of a GLS test solution and 50 μL of 1.0 × 10−2 mol L−1 H2O2 were used and the luminescing zone was pushed into the detector at a flow rate 100 μL s−1. The proposed method recorded high sensitivity, accuracy and simplicity that could be clarified as linear concentration range 1.0‐2000 ng mL−1 with rectilinear part (r = 0.9992, n = 9) and limit of detection 0.3 ng mL−1, along with relative standard deviation 1.3%. It was found that the developed method can be used directly to determine the investigated drug GLS in its pharmaceutical dosage forms and in spiked serum and urine by diluting the samples for a 1000 fold. The obtained results were statistically analyzed and compared with those obtained by the reported method.
THE RELATIONSHIP OF CUMULATIVE STRESSORS, CHRONIC ILLNESS AND ABUSE TO THE SELF‐REPORTED SUICIDE RISK OF BLACK AND HISPANIC SEXUAL MINORITY YOUTH
Authors: Craig Shelley L. , McInroy Lauren
Published: July 2013

Sexual minority youth [SMY] are a population who experience considerable stress related to their sexual identities. Previous investigations have identified individual risk factors that contribute to suicide among SMY, yet little research has focused on cumulative stressors that may exacerbate negative outcomes for multiethnic sexual minority youth [MSMY]. This study used hierarchical logistic regression to explore the relationship between cumulative risks and their relationship to self‐reported suicide risk for MSMY. The community‐based clinical sample (n = 137) reported high co‐occurrence of risks, with an average of 9. Overall, MSMY with a higher number of cumulative risk factors were twice as likely to express self‐reported suicide risk. Specifically, experiencing chronic illness and physical or sexual abuse resulted in threefold higher odds of self‐reported suicide risk among MSMY. These findings address a gap in the literature about the relationship of cumulative and specific stressors to the self‐reported suicide risk for an understudied, vulnerable population.
USING GIS TO DESCRIBE RISK AND NEIGHBORHOOD‐LEVEL FACTORS ASSOCIATED WITH SUBSTANCE ABUSE TREATMENT OUTCOMES
Authors: Mendoza Natasha S. , Conrow Lindsey , Baldwin Adrienne , Booth Jaime
Published: July 2013

Neighborhood‐level geographic factors may put individuals at risk of developing substance abuse problems. The purpose of this descriptive study was to assess the spatial distribution of risk in Buffalo, New York. The study serves as an example of how neighborhood geographical markers can be used to determine areas with elevated risk that may lead providers to better target and address substance use disorder prevalence in communities. Results showed highest risk for negative treatment outcomes in areas with either high socioeconomic or physical environmental risk; maximum total risk was largely located on the Lower West Side, West Side, and East Sides of Buffalo, while maximum socioeconomic and physical environmental risks were dispersed throughout the city. This landscape model and risk assessment delineates the distribution of risk factors associated with negative treatment outcomes and is therefore a useful tool for treatment providers who wish to better target interventions.
MOTIVATIONAL INTERVIEWING TO IMPROVE MIDDLE SCHOOL STUDENTS’ ACADEMIC PERFORMANCE: A REPLICATION STUDY
Authors: Terry John , Smith Bradley , Strait Gill , McQuillin Sam
Published: July 2013

Motivational interviewing (MI) is brief therapy originally designed to motivate adults to change risky or dysfunctional behavior. There is a push to use MI with middle and high school students; however, current research focuses on MI with families or teachers or to support program fidelity. In one of the few randomized studies, Strait et al. (2012) found one MI session produced statistically significant changes in middle school students’ math grades and self‐reported positive academic behavior. This study replicates Strait et al.'s study by using the exact MI protocol and similar data collection methods. In this study, 49 students were randomly assigned to either an MI (n = 25) or control (n = 24) group. As with the original MI study, there was a positive main effect on math grades. Effect sizes on academic behavioral outcomes were also similar. Independent replication, mechanisms of action research, and better understanding of why the effects are concentrated on math grades are needed.
Pretreatment of Miscanthus×giganteus using aqueous ammonia with hydrogen peroxide to increase enzymatic hydrolysis to sugars
Authors: Yu Guangren , Afzal Waheed , Yang Fuxin , Padmanabhan Sasisanker , Liu Zhongguo , Xie Hongxue , Shafy Mahmoud Abdel , Bell Alexis T. , Prausnitz John M.
Published: July 2013

BACKGROUND

Miscanthus×giganteus (M.×giganteus) is a potential source for bioethanol or other useful products. Pretreatment of lignocellulosic biomass is an essential step prior to enzymatic hydrolysis to sugars and fermentation to bioethanol.

RESULTS

In this work, a one‐step process uses aqueous ammonia with or without hydrogen peroxide; a proposed two‐step process uses aqueous ammonia in the first step and hydrogen peroxide in the second step. In the two‐step process, overall 89.5% lignin is removed. The pretreated biomass is followed by using cellulase and β‐glucosidase to convert cellulose and hemicellulose from the recovered solid to fermentable sugars. The conversion of cellulose to glucose is 90.2% and to xylose is 73.4%. Characterization data are obtained for the recovered solid using scanning electron microscopy (SEM), attenuated total reflection‐infrared spectroscopy (ATR‐IR), and X‐ray diffraction (XRD) for better understanding of the two‐step process.

CONCLUSION

Results from the two‐step process using aqueous ammonia and hydrogen peroxide separately are much better than those from the one‐step process for removing lignin and for enhancing conversion to sugars by enzymatic hydrolysis. © 2013 Society of Chemical Industry
Mechanisms of field‐aligned current formation in magnetic reconnection
Authors: Ma Xuanye , Otto Antonius
Published: July 2013

Satellite observations provide strong evidence for the generation of significant field‐aligned currents (FACs) during magnetic reconnection. Reconnection of antiparallel magnetic field does not generate FACs in magnetohydrodynamics (MHD) due to coplanarity in MHD shocks. However, a guide magnetic field and a sheared velocity component are almost always present at the magnetopause and their absence is a singular case. It is illustrated that the presence of these noncoplanar fields requires FACs. Contrary to intuition, such currents are generated more efficiently for a small guide field and are more likely to be a result of the redistribution of already present FACs for large guide fields. It is demonstrated that moderate values of shear flow can generate significant ionospheric FACs. Similar to shear flow, the presence of Hall physics leads to significant FACs and we examine the scaling of these current with the ion inertia length.
Bathymetry correction using an adjoint component of a coupled nearshore wave‐circulation model: Tests with synthetic velocity data
Authors: Kurapov Alexander L. , Özkan‐Haller H. Tuba
Published: July 2013

The impact of assimilation of wave‐averaged flow velocities on the bathymetric correction is studied in tests with synthetic (model‐generated) data using tangent‐linear and adjoint components of a one‐way coupled nearshore wave‐circulation model. Weakly and strongly nonlinear regimes are considered, featuring energetic unsteady along‐beach flows responding to time‐independent wave‐averaged forcing due to breaking waves. It is found that assimilation of time‐averaged velocities on a regular grid (mimicking an array of remotely sensed data) provides sensible corrections to bathymetry. Even though the wave data are not assimilated, flow velocity assimilation utilizes adjoint components of both the circulation and wave models. The representer formalism allows separating contributions of these two components to the bathymetric correction. In a test case considered, involving a beach with an alongshore varying bar, the adjoint wave model contribution was mainly to determine the cross‐shore position of the bar crest. The adjoint circulation model provided an additional contribution, mostly adding to alongshore variability in the shape of the bar. The array mode analysis reveals that there are very few modes that can be effectively corrected, given the assumed data error level. Bathymetry perturbations associated with these modes are a mixture of near‐coast intensified modes as well as modes extending their influence to deep water (along the background wave characteristics). Additional tests show the utility of different observational arrays in providing the bathymetric correction.
Mapping the radio sky with an interferometric network of low‐frequency radio receivers
Authors: Mezentsev Andrew , Füllekrug Martin
Published: July 2013

The structure of the 100 kHz radio sky is determined with two interferometric networks of 10 radio receivers which are distributed over local areas of ∼1 × 1 km2 and ∼10 × 10 km2. The radio waves arrive at individual receiver pairs with small time differences which are used to determine the arrival direction of the electromagnetic waves including both the bearing and the elevation angle. The results show that the major part of the 100 kHz radio wave energy comes from the horizon at bearings which are consistent with known locations of Long Range Navigation (LORAN) transmitters. Some part of the radio wave energy arrives from the sky at elevation angles which are consistent with the first and second sky hop waves of LORAN transmissions. A minor part of the 100 kHz radio wave energy comes from lightning discharges at distances up to ∼1000 km with bearings which are consistent with lightning locations reported by the arrival time difference (ATD) lightning detection network of the UK Met Office. The angular resolution for mapping the radio sky depends on the network geometry, the instrumental timing accuracy, and on the signal‐to‐noise ratio of the radio waves. The resulting angular resolution of the interferometric networks used in this study is ∼1° in bearing at zero elevation and several degrees in elevation.
Influence of boundary layer dynamics and isoprene chemistry on the organic aerosol budget in a tropical forest
Authors: Janssen R. H. H. , Vilà‐Guerau de Arellano J. , Jimenez J. L. , Ganzeveld L. N. , Robinson N. H. , Allan J. D. , Coe H. , Pugh T. A. M.
Published: July 2013

We study the organic aerosol (OA) budget in a tropical forest by analyzing a case that is representative for the OP3 campaign at Borneo. A model is designed that combines the essential dynamical and chemical processes that drive the diurnal evolution of reactants in the atmospheric boundary layer (BL). In this way, the model simultaneously represents the effects and interactions of various dynamical and chemical factors on the OA budget. The model is able to reproduce the observed diurnal dynamics of the BL, including the evolution of most chemical species involved in secondary organic aerosol (SOA) formation. A budget analysis of the contributions of the dynamic and chemical processes reveals the significance of the entrainment process in the diurnal evolution of SOA. Further, we perform a series of sensitivity analyses to determine the effect of meteorological forcings and isoprene chemical pathways on the OA budget. Subsidence and advection of cool air have opposing effects on the OA concentration, although both suppress BL growth. Recycling of the OH radical in the oxidation of isoprene may affect the amount of SOA that is formed, but must be understood better before its impact can be definitely determined. SOA formation from isoprene is calculated for both the low‐ and high‐NOx pathway, with the latter dominating the isoprene peroxy radical chemistry. Finally, we study the significance of SOA formation through the reactive uptake of isoprene epoxydiols on acidic sulfate aerosol. Despite the incorporation of these new pathways, the OA concentration is systematically underestimated by about a factor of 2.
THE EAST‐CENTRAL EUROPEAN NEW DONORS: MAPPING CAPACITY BUILDING AND REMAINING CHALLENGES
Authors: Szent‐Iványi Balázs , Tétényi András
Published: July 2013

In the past decade, the East‐Central European countries were provided significant external capacity building assistance to help their emergence as donors of foreign aid. This paper aims to map these capacity development programmes and identify where they have helped and what challenges remain for the new donors. The main conclusion is that although capacity building has been instrumental in building organisational structures, working procedures and training staff, deeper underlying problems such as low levels of financing, lacking political will, the need for visibility and low staff numbers continue to hinder the new international development policies. Copyright © 2013 John Wiley & Sons, Ltd.
CHALLENGES OF PROMOTING MULTIPLE ACCOUNTABILITIES IN FRAGILE CONTEXTS: EXPERIENCES OF A SWISS INTERNATIONAL NON‐GOVERNMENTAL ORGANISATION
Authors: Krösschell Celestine
Published: July 2013

The findings of an applied research project on ‘Accountability in Fragile Contexts’ in Nepal, Bangladesh and Mozambique show that accountability lines are complex, blurred and multilinear. Particular challenges in promoting accountability are weak legislation, distrust and patron‐client relationships. Yet, especially in fragile contexts, transparency, accountability and inclusion of all stakeholders, they appear to be essential. Practising downward accountability can be an ‘incubator’ for social accountability, but international non‐governmental organisations must pay particular attention to the inclusion of marginalised women and men. Copyright © 2013 John Wiley & Sons, Ltd.
Hyperbaric oxygen therapy suppresses osteoclast formation and bone resorption
Authors: Hadi Hadil Al , Smerdon Gary R. , Fox Simon W.
Published: July 2013

The cellular and molecular mechanism through which hyperbaric oxygen therapy (HBO) improves osteonecrosis (ON) is unclear. The present study therefore examined the effect of HBO, pressure and hyperoxia on RANKL‐induced osteoclast formation in RAW 264.7 cells and human peripheral blood monocytes (PBMC). Daily exposure to HBO (2.4 ATA, 97% O2, 90 min), hyperbaric pressure (2.4 ATA, 8.8% O2, 90 min) or normobaric hyperoxia (1 ATA, 95% O2, 90 min) significantly decreased RANKL‐induced osteoclast formation and bone resorption in normoxic conditions. HBO had a more pronounced anti‐osteoclastic effect than hyperoxia or pressure alone and also directly inhibited osteoclast formation and resorption in hypoxic conditions a hallmark of many osteolytic skeletal disorders. The suppressive action of HBO was at least in part mediated through a reduction in RANK, NFATc1, and Dc‐STAMP expression and inhibition of hypoxia‐induced HIF‐1α mRNA and protein expression. This data provides mechanistic evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation and bone loss associated with low oxygen partial pressure. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1839–1844, 2013
Implant‐associated localized osteitis in murine femur fracture by biofilm forming Staphylococcus aureus: A novel experimental model
Authors: Windolf Ceylan D. , Meng Wei , Lögters Tim T. , MacKenzie Colin R. , Windolf Joachim , Flohé Sascha
Published: July 2013

Staphylococcus aureus (SA) is the most common causative agent for implant‐associated osteitis. The present study characterizes a novel model of a low grade acute SA osteitis with bone defect in the femur which is stabilized by a titanium locking plate. Wild‐type Balb/c mice were osteotomized, fixed by a locking plate and infected with SA. Mice underwent debridement 7 and 14 days later and were sacrificed at Day 28. At Days 7, 14, and 28 after inoculation local and systemic cell populations and IL‐6 were analyzed. Fracture healing was quantified by radiography. The control group underwent the same procedure without infection. The bacterial load of implant‐associated osteitis with biofilm formation was quantified by counting CFU and real‐time PCR. Fracture healing determined by radiography was delayed in infected compared to non‐infected mice. Throughout the investigation period CFU and leukocyte counts, as well as IL‐6 levels were found to be significantly elevated in infected mice at the infection site but not systemically. Our murine model allows the detailed investigation of implant associated localized osteitis with biofilm producing SA and its influence on fracture healing. The model provides a tool to analyze therapeutic or prophylactic approaches to the problem of biofilm‐associated osteitis. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:2013–2020, 2013
Connexin 43 is a potential regulator in fluid shear stress‐induced signal transduction in osteocytes
Authors: Li Xiaoting , Liu Chenglin , Li Ping , Li Shengnan , Zhao Zhihe , Chen Yangxi , Huo Bo , Zhang Ding
Published: July 2013

Connexin 43 (Cx43), a gap junctional protein, regulates osteocyte viability, and modulates mechanical stimulation‐induced bone remodeling. However, the underlying mechanisms of its action remain unclear. In the current study, osteocyte‐like MLO‐Y4 cells were exposed to fluid shear stress (FSS) of 16 (physiological) or 30 (high) dyne/cm2 for the indicated time points. Cx43 gene (Gja1) was silenced using siRNA or the protein was blocked chemically. The signaling molecules related to osteocyte apoptosis, osteogenesis, or osteoclastogenesis were detected at mRNA or protein levels. The results showed that physiological FSS significantly upregulated Cx43, which further inhibited apoptosis pathways (e.g., caspase‐3) and osteoclastogenesis signaling (e.g., RANKL), but activated osteogenesis signaling (Sost/sclerostin). Suppressing Cx43 gene (Gja1) by siRNA or chemically blocking gap junction communication enhanced caspase‐3, RANKL, and Sost/sclerostin, which could be restored with physiological FSS over 8 h. In addition, high FSS decreased Cx43 expression and adversely affected signaling molecules compared with physiological FSS. The findings indicate the involvement of Cx43 in mechanotransduction of FSS and in the modulation of mechanical loading‐related apoptosis, osteogenesis, and osteoclastogenesis of osteocytes. This may provide a cellular and molecular basis for interpreting the biomechanical mechanism of bone absorption and remodeling. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1959–1965, 2013
Efficient excitation of Raman coherence by a gradient force
Authors: Ma Dongxia , Rostovtsev Yuri V.
Published: July 2013

The vibrational molecular excitation by strong laser fields have been studied. Starting with the molecular Hamiltonian, we derive the vibrational excitation rate due to a gradient of laser field and show that the rate can be two to three orders of magnitude larger than the regular Raman rates. The developed theory contributes to understanding of interaction of powerful laser pulses with molecular systems, and it might be used in developing quantitative coherent Raman spectroscopy. Copyright © 2013 John Wiley & Sons, Ltd.
Pump power dependence in resonance femtosecond stimulated Raman spectroscopy
Authors: Lee Joohyun , Challa J. Reddy , McCamant David W.
Published: July 2013

Femtosecond stimulated Raman spectroscopy (FSRS) has emerged as a powerful new technique that is capable of obtaining resonance Raman spectra of fluorescent species and transient photochemical intermediates. Unlike related transient infrared absorption techniques, the FSRS signal is quite sensitive to the laser power utilized in the vibrational probing event. In particular, FSRS spectra are highly sensitive to the intensity of the picosecond Raman‐pump pulse. We have measured the power dependence of the FSRS signal using pulse energies from ~10−9 to ~10−5 J and molecules with a range of molar absorptivities at the Raman‐pump wavelength of 400 nm, including β‐carotene (ε400 = 58 300 M−1 cm−1), para‐nitroaniline (17 800 M−1 cm−1), nitronaphthalene (247 M−1 cm−1) and ferrocene (57 M−1 cm−1). We show that for strongly absorbing molecular systems, such as β‐carotene and para‐nitroaniline, the ground‐state (GS) FSRS signal actually decreases with increasing pump power at pump fluences above ~10−2 J cm−2, due to depletion of the GS population. However, for weakly absorbing species like nitronaphthalene and ferrocene, the signal increases linearly with increasing pump fluence until ~0.5 J cm−2, at which point two‐photon absorption by the solute induces nonlinear absorption of the pump pulse and attenuation of the FSRS signal. The data are quantitatively simulated with a photophysical kinetic model, and the results are analyzed to provide simple guidelines for acceptable Raman‐pump powers in resonance FSRS experiments. The acceptable Raman‐pump power is proportional to the focused beam area and depends inversely on the sample's molar absorptivity. Copyright © 2013 John Wiley & Sons, Ltd.
Determinants of resident competence in mastoidectomy: Role of interest and deliberate practice
Authors: Malik Mohammad U. , Diaz Voss Varela David A. , Park EunMi , Masood Hamid , Laeeq Kulsoom , Bhatti Nasir I. , Francis Howard W.
Published: July 2013

Objectives/Hypothesis

This study explores the influence of selected factors on achievement of competency in mastoid surgery.

Study Design

A prospective study of surgical performance and a retrospective survey of learner and training factors.

Methods

The longitudinal performance of 15 residents was evaluated using the mastoidectomy task‐based checklist (TBC). The influence of surgical experience, resident interest, and training factors (course attendance, voluntary use of simulation laboratory) was also examined and compared for the acquisition of distinct levels of technical skill difficulty (cortical mastoidectomy vs. facial recess).

Results

Ninety‐six observations made during the first otology rotation were analyzed. Cortical mastoidectomy tasks showed positive associations with cumulated case numbers (OR 1.13, CI 1.04–1.23,P = .003) and interest in otology (OR 3.86, CI 1.21–12.27,P = .022). Facial recess tasks showed a larger positive association with interest in otology (OR 10.38, CI 2.25–47.94,P = .003), and negative association with extra time spent in laboratory practice (OR .05, CI 0.011–0.23,P = .000).

Conclusions

Learning trajectory for cortical mastoidectomy and facial recess may be influenced by different factors. Interest in otology, in particular, may have a moderating effect on the acquisition of more complex skills in mastoid surgery. A negative association between self‐directed laboratory simulation and performance may reflect the impact of assessment‐guided feedback in promoting deliberate practice. Further investigations are suggested to explore the interactions between individual trainee differences, educational models, and learning outcomes.

Level of Evidence

N/A.Laryngoscope, 123:3162–3167, 2013
Chemical Composition Separation of EP Copolymers by CEF and HT‐SGIC: Crystallization versus Adsorption
Authors: Cheruthazhekatt Sadiqali , Mayo Nuria , Monrabal Benjamin , Pasch Harald
Published: July 2013

Preparative temperature rising elution fractionation (prep TREF) suffers from co‐crystallization effects and, therefore, cannot provide reliable chemical composition distribution (CCD) information. This limitation can be overcome when prep TREF is combined with further fractionation methods such as crystallization elution fractionation (CEF) or high‐temperature solvent‐gradient‐interaction chromatography (HT‐SGIC) as a new approach. By CEF, significant amounts of (co‐crystallizing) amorphous ethylene‐propylene (EP) copolymer are identified in semicrystalline TREF fractions of a heterophasic ethylene/propylene copolymer (HEPC). Complete compositional fractionation with no influence of crystallization effects is accomplished by HT‐SGIC. Prep TREF–HT‐SGIC is found to be the most selective and suitable method for the fast and complete CCD analysis of such complex EP copolymers with CEF providing complementary information.

image
Group Purchasing Organizations, Monopsony, and Antitrust Policy
Authors: Blair Roger D. , Durrance Christine Piette
Published: July 2013

Group purchasing organizations (GPOs) consolidate the purchasing power of their members and negotiate contracts with input suppliers on their behalf. GPOs have received attention from the Department of Justice and Federal Trade Commission because of concerns over monopsony power and standardization of hospital production costs. GPOs have been criticized in the literature for their contracting practices, which may appear to be exclusionary, and their funding mechanism, which may lead to incentive incompatibility. We analyze these competitive concerns in turn. We find GPOs to be procompetitive and suggest an antitrust policy that preserves the benefits of GPO operations while protecting consumers from any competitive shortcomings. Copyright © 2013 John Wiley & Sons, Ltd.
Boundedness of fractional integrals on weighted Orlicz–Hardy spaces
Authors: Cao Jun , Chang Der‐Chen , Yang Dachun , Yang Sibei
Published: July 2013

Let Iα be the fractional integral on the Euclidean space , where α ∈ (0, n). Assume that Φ and Ψ are two Orlicz functions satisfying i(Φ), i(Ψ) ∈ (0, 1], and for all t ∈ (0, ∞ ), where i(Φ) and i(Ψ) are, respectively, the critical lower type indices of Φ and Ψ, and Φ − 1 and Ψ − 1 their inverses. In this paper, the authors prove that Iα is bounded from the weighted Orlicz–Hardy space to the weighted Orlicz–Hardy space , whenever there exist 1 < p1 < q1 < ∞ , satisfying , such that belongs to the weight. To this end, the authors first establish the atomic and the molecular characterizations of these weighted Orlicz–Hardy spaces, which are defined via the nontangential grand maximal function. Thus, as a byproduct, the authors establish the nontangential grand maximal function and molecular characterizations of the weighted atomic Orlicz–Hardy space introduced by Harboure, Salinas, and Viviani. Copyright © 2013 John Wiley & Sons, Ltd.
Quantitative 31P HR‐MAS MR spectroscopy for detection of response to PI3K/mTOR inhibition in breast cancer xenografts
Authors: Esmaeili Morteza , Bathen Tone F. , Engebråten Olav , Mælandsmo Gunhild M. , Gribbestad Ingrid S. , Moestue Siver A.
Published: July 2013

Purpose

Phospholipid metabolites are of importance in cancer studies, and have been suggested as candidate metabolic biomarkers for response to targeted anticancer drugs. The purpose of this study was to develop a phosphorus (31P) high resolution magic angle spinning magnetic resonance spectroscopy protocol for quantification of phosphorylated metabolites in intact cancer tissue.

Methods

31P spectra were acquired on a 14.1 T spectrometer with a triplet 1H/13C/31P MAS probe. Quantification of metabolites was performed using the PULCON principle. Basal‐like and luminal‐like breast cancer xenografts were treated with the dual PI3K/mTOR inhibitor BEZ235, and the impact of treatment on the concentration of phosphocholine, glycerophosphocholine, phosphoethanolamine and glycerophosphoethanolamine was evaluated.

Results

In basal‐like xenografts, BEZ235 treatment induced a significant decrease in phosphoethanolamine (−25.6%, P = 0.01) whilst phosphocholine (16.5%, P = 0.02) and glycerophosphocholine (37.3%, P < 0.001) were significantly increased. The metabolic changes could partially be explained by increased levels of phospholipase A2 group 4A (PLA2G4A).

Conclusion

31P high resolution magic angle spinning magnetic resonance spectroscopy is a useful method for quantitative assessment of metabolic responses to PI3K inhibition. Using the PULCON principle for quantification, the levels of phosphocholine, glycerophosphocholine, phosphoethanolamine, and glycerophosphoethanolamine could be evaluated with high precision and accuracy. Magn Reson Med 71:1973–1981, 2014. © 2013 Wiley Periodicals, Inc.
Dynamic metabolic imaging of hyperpolarized [2‐13C]pyruvate using spiral chemical shift imaging with alternating spectral band excitation
Authors: Josan Sonal , Hurd Ralph , Park Jae Mo , Yen Yi‐Fen , Watkins Ron , Pfefferbaum Adolf , Spielman Daniel , Mayer Dirk
Published: July 2013

Purpose

In contrast to [1‐13C]pyruvate, hyperpolarized [2‐13C]pyruvate permits the ability to follow the 13C label beyond flux through pyruvate dehydrogenase complex and investigate the incorporation of acetyl‐coenzyme A into different metabolic pathways. However, chemical shift imaging (CSI) with [2‐13C]pyruvate is challenging owing to the large spectral dispersion of the resonances, which also leads to severe chemical shift displacement artifacts for slice‐selective acquisitions.

Methods

This study introduces a sequence for three‐dimensional CSI of [2‐13C]pyruvate using spectrally selective excitation of limited frequency bands containing a subset of metabolites. Dynamic CSI data were acquired alternately from multiple frequency bands in phantoms for sequence testing and in vivo in rat heart.

Results

Phantom experiments verified the radiofrequency pulse design and demonstrated that the signal behavior of each group of resonances was unaffected by excitation of the other frequency bands. Dynamic three‐dimensional 13C CSI data demonstrated the sequence capability to image pyruvate, lactate, acetylcarnitine, glutamate, and acetoacetate, enabling the analysis of organ‐specific spectra and metabolite time courses.

Conclusions

The presented method allows CSI of widely separated resonances without chemical shift displacement artifact, acquiring multiple frequency bands alternately to obtain dynamic time‐course information. This approach enables robust imaging of downstream metabolic products of acetyl‐coenzyme A with hyperpolarized [2‐13C]pyruvate. Magn Reson Med 71:2051–2058, 2014. © 2013 Wiley Periodicals, Inc.