bluuebunny/crossref_metadata_2025 huggingface dataset:
Fracturing and fluid flow in a sub-décollement sandstone; or, a leak in the basement
Authors: Hooker John N. , Larson Toti E. , Eakin Autumn , Laubach Stephen E. , Eichhubl Peter , Fall András , Marrett Randall
Published: May 2015

Crack-seal texture within fracture cements in the Triassic El Alamar Formation, NE Mexico, shows that the fractures opened during precipitation of quartz cements; later, overlapping calcite cements further occluded pore space. Previous workers defined four systematic fracture sets, A (oldest) to D (youngest), with relative timing constrained by crosscutting relationships. Quartz fluid inclusion homogenization temperatures are higher within Set B (148 ± 20°C) than in Set C (105 ± 12°C). These data and previous burial history modelling are consistent with Set C forming during exhumation. Fluid inclusions in Set C quartz have higher salinity than those in Set B (22.9 v. 14.2 wt% NaCl equivalent, respectively), and Set C quartz cement is more enriched in
18
O (20.2 v. 18.7‰ VSMOW). Under most assumptions about the true temperature during fracture opening, the burial duration, the amount of cement precipitated and fluid-flow patterns, it appears that the fracture fluid became depleted in
18
O and enriched in
13
C. This isotopic evolution, combined with increasing salinity, suggests that throughout fracture opening there was a gravity-driven influx of fluid from upsection Jurassic evaporites, which form a regional décollement. Fracture opening amid downward fluid motion suggests that fracturing was driven by external stresses such as tectonic stretching or unloading, rather than increases in fluid pressure.
Westgarth Forster’s Strata – a reappraisal of a geological pioneer
Authors: Forbes I.
Published: May 2015

In 1809, Westgarth Forster, an agent in the Northern Pennine lead mines, published his only book. Entitled ‘A Treatise on a Section of the Strata…etc.’, it is more usually known simply as his ‘Section of Strata’. Although some contemporaries doubted its originality, the reputation of this work has grown since its publication and Forster is now widely regarded as one of the pioneers of northern England geology. This paper gives an overview of Forster’s life and unsuccessful career before closely examining the text of his work. It shows how most of Forster’s text was copied without acknowledgement from earlier authors and was not drawn from observations made in the Northern Pennine Orefield. Reference is made to earlier sections of strata from mines in the north of England, and Forster’s ‘Strata’ is shown to be drawn mainly from these. Westgarth Forster should not be seen as a pioneer of the geology of northern England, but as an author who pieced together his book very largely from the work of others.
Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice
Authors: Puhl Sarah-Lena , Müller Andreas , Wagner Michael , Devaux Yvan , Böhm Michael , Wagner Daniel R. , Maack Christoph
Published: May 2015

Although exercise mediates beneficial effects in patients after myocardial infarction (MI), the underlying mechanisms as well as the question of whether an early start of exercise after MI is safe or even beneficial are incompletely resolved. The present study analyzed the effects of exercise before and reinitiated early after MI on cardiac remodeling and function. Male C57BL/6N mice were housed sedentary or with the opportunity to voluntarily exercise for 6 wk before MI induction (ligation of the left anterior descending coronary artery) or sham operation. After a 5-day exercise-free phase after MI, mice were allowed to reexercise for another 4 wk. Exercise before MI induced adaptive hypertrophy with moderate increases in heart weight, cardiomyocyte diameter, and left ventricular (LV) end-diastolic volume, but without fibrosis. In sedentary mice, MI induced eccentric LV hypertrophy with massive fibrosis but maintained systolic LV function. While in exercised mice gross LV end-diastolic volumes and systolic function did not differ from sedentary mice after MI, LV collagen content and thinning of the infarcted area were reduced. This was associated with ameliorated activation of inflammation, mediated by TNF-α, IL-1β, and IL-6, as well as reduced activation of matrix metalloproteinase 9. In contrast, no differences in the activation patterns of various MAPKs or adenosine receptor expressions were observed 5 wk after MI in sedentary or exercised mice. In conclusion, continuous exercise training before and with an early reonset after MI ameliorates adverse LV remodeling by attenuating inflammation, fibrosis, and scar thinning. Therefore, an early reonset of exercise after MI can be encouraged.
IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle
Authors: Robinson Mac B. , Deshpande Deepak A. , Chou Jeffery , Cui Wei , Smith Shelly , Langefeld Carl , Hastie Annette T. , Bleecker Eugene R. , Hawkins Gregory A.
Published: May 2015

Genetic data suggest that IL-6 trans-signaling may have a pathogenic role in the lung; however, the effects of IL-6 trans-signaling on lung effector cells have not been investigated. In this study, human airway smooth muscle (HASM) cells were treated with IL-6 (classical) or IL-6+sIL6R (trans-signaling) for 24 h and gene expression was measured by RNAseq. Intracellular signaling and transcription factor activation were assessed by Western blotting and luciferase assay, respectively. The functional effect of IL-6 trans-signaling was determined by proliferation assay. IL-6 trans-signaling had no effect on phosphoinositide-3 kinase and Erk MAP kinase pathways in HASM cells. Both classical and IL-6 trans-signaling in HASM involves activation of Stat3. However, the kinetics of Stat3 phosphorylation by IL-6 trans-signaling was different than classical IL-6 signaling. This was further reflected in the differential gene expression profile by IL-6 trans-signaling in HASM cells. Under IL-6 trans-signaling conditions 36 genes were upregulated, including PLA2G2A, IL13RA1, MUC1, and SOD2. Four genes, including CCL11, were downregulated at least twofold. The expression of 112 genes was divergent between IL-6 classical and trans-signaling, including the genes HILPDA, NNMT, DAB2, MUC1, WWC1, and VEGFA. Pathway analysis revealed that IL-6 trans-signaling induced expression of genes involved in regulation of airway remodeling, immune response, hypoxia, and glucose metabolism. Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis. These novel findings demonstrate differential effect of IL-6 trans-signaling on airway cells and identify IL-6 trans-signaling as a potential modifier of airway inflammation and remodeling.
The Role of TLR4 in Chemotherapy-Driven Metastasis
Authors: Ran Sophia
Published: May 2015

Tumor resistance to cytotoxic drugs is one of the main obstacles to successful cancer therapy. Emerging evidence suggests that chemoresistance is promoted by substances released from dead and damaged cells that activate the host repair program orchestrated by Toll-like receptor-4 (TLR4). TLR4 is often overexpressed in malignant and tumor-infiltrating immune cells. In addition to endogenous ligands released by therapy-induced tumor destruction, TLR4 is directly activated by paclitaxel, one of the most commonly used chemotherapeutic drugs against various human cancers. TLR4 activation promotes local and systemic inflammation, leading to induction of multiple circuits that create a regenerative environment favoring local recurrence and metastasis. Of particular importance is TLR4-mediated recruitment of endothelial progenitors derived from immature myeloid cells. These cells play a major role in rebuilding tumor-associated lymphatic and blood vessels, thereby promoting lymphatic and hematogenous metastasis. The latter is further enhanced by the premetastatic niche generated by mobilization of myeloid provascular cells to distant organs. This review summarizes the recent evidence demonstrating that paclitaxel and other clinically used anticancer drugs actively induce metastasis even while shrinking the primary tumor. Better understanding of the mechanisms underlying TLR4-dependent chemotherapy-driven metastasis might be the key to overcoming challenges of cancer eradication. Cancer Res; 75(12); 2405–10. ©2015 AACR.
Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma
Authors: Gustafson Michael P. , Lin Yi , Bleeker Jonathan S. , Warad Deepti , Tollefson Matthew K. , Crispen Paul L. , Bulur Peggy A. , Harrington Susan M. , Laborde Rebecca R. , Gastineau Dennis A. , Leibovich Bradley C. , Cheville John C. , Kwon Eugene D. , Dietz Allan B.
Published: May 2015

Purpose: Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development.

Experimental Design: Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients.

Results: We found that CD14+HLA-DRlo/neg monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14+HLA-DRlo/neg monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2.

Conclusions: Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 21(18); 4224–33. ©2015 AACR.
A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Benson Don M. , Cohen Adam D. , Jagannath Sundar , Munshi Nikhil C. , Spitzer Gary , Hofmeister Craig C. , Efebera Yvonne A. , Andre Pascale , Zerbib Robert , Caligiuri Michael A.
Published: May 2015

Purpose: Natural killer (NK) cells may play an important role in the immune response to multiple myeloma; however, multiple myeloma cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against multiple myeloma; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR antibody, has acceptable safety and tolerability in multiple myeloma as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for multiple myeloma.

Experimental Design: A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to 21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No corticosteroids were utilized. The primary endpoint was safety, and secondary endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD).

Results: The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single-agent IPH2101 trial. Five serious adverse events (SAE) were reported. Five objective responses occurred. No autoimmunity was seen.

Conclusions: These findings suggest that lenalidomide in combination with antiinhibitory KIR therapy warrants further investigation in multiple myeloma as a steroid-sparing, dual immune therapy. This trial was registered at www.clinicaltrials.gov (reference: NCT01217203). Clin Cancer Res; 21(18); 4055–61. ©2015 AACR.
Mathematical Modeling of Different Molecule Removal on On-Line Haemodiafiltration: Influence of Dialysis Duration and Infusion Flow
Authors: Maduell Francisco , Sanchez Juan , Net Marta , Gomez Miquel , Gonzalez Jose M. , Arias-Guillen Marta , Rodriguez Néstor , Rico Nayra , Campistol Josep M.
Published: May 2015

Background: In a previous study on a nocturnal, every-other-day online haemodiafiltration scheme, different removal patterns were observed for urea, creatinine, β2-​microglobulin, myoglobin and prolactin. The aim of this study was to evaluate the influence of dialysis duration and infusion flow (Qi) on the removal of different molecular weight (MW) solutes, and to quantify the effect of the different treatments on the kinetics of the solutes by using a classical two-compartment model. Methods: This prospective, in-center study was carried out in 10 patients on a nocturnal, every-other-day online post-dilution haemodiafiltration program. Each patient received four dialysis sessions with different conditions, two 4-h sessions (with infusion flows of 50 or 100 ml/min) and two 8-h sessions (with infusion flows of 50 or 100 ml/min). To analyze the solute kinetics, blood samples were obtained hourly during the dialysis treatments and in the first 3 h post-dialysis. Results: Removal patterns differed in the molecules studied, which were quantified by means of the two-compartment mathematical model. The main results show the impact of dialysis duration on the removal of low molecular weight molecules (urea and creatinine), while the impact of Qi is clearly shown for high molecular weight molecules (myoglobin and prolactin). For middle molecular weight solutes, such as β2-microglobulin, both factors (duration and Qi) enhance the removal efficiency of the dialyzer. Conclusions: Our study evaluates experimentally and mathematically how treatment time and infusion flow affect the filtration of solutes of different MW during post-dilution haemodiafiltration. The results provided by the present study should help physicians to select and individualise the most appropriate schedules to deliver an optimum diffusive and convective dialysis dose for each patient.
Incidence of Adverse Events during Continuous Renal Replacement Therapy
Authors: Akhoundi Abbasali , Singh Balwinder , Vela Myriam , Chaudhary Sanjay , Monaghan Myles , Wilson Gregory A. , Dillon John J. , Cartin-Ceba Rodrigo , Lieske John C. , Gajic Ognjen , Kashani Kianoush
Published: May 2015

Background/Aims: The incidence of adverse events (AEs) in adults who receive continuous renal replacement therapy (CRRT) is unknown. We report the incidence of mechanical, metabolic, and hemodynamic CRRT AEs. Methods: This is a retrospective study of all consecutive adult patients (≥18 years) who underwent CRRT from January 1, 2007 to December 31, 2009. Results: Out of 595 patients who underwent CRRT, 366 (62%) were male and 500 (84%) were Caucasian. Regional citrate anticoagulation was used in 98.6% of all patients. The most common clinically significant electrolyte derangements were ionized hypocalcemia (22%), ionized hypercalcemia (23%), and hyperphosphatemia (44%). Almost all (97%) patients had at least one additional AE including new onset hypotension (within the first hour after CRRT initiation) (43%), hypothermia (44%), new onset arrhythmias (29%), new onset anemia (31%) and thrombocytopenia (40%). Conclusions: ICU patients who require CRRT have a high incidence of AEs. Although the extent to which these complications are attributable to CRRT is not known, clinicians need to be cautious and aware of their high prevalence in this patient population.
Coagulation, Fibrinolysis and Inhibitors in Failing Filters during Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: Effect of Anticoagulation Modalities
Authors: Schilder Louise , Nurmohamed S. Azam , ter Wee Pieter M. , Paauw Nanne J. , Girbes Armand R.J. , Beishuizen Albertus , Beelen Robert H.J. , Groeneveld A.B. Johan
Published: May 2015

Introduction: The mechanisms of early filter failure and clotting with different anticoagulation modalities during continuous venovenous hemofiltration (CVVH) are largely unknown. Methods: Citrate, heparin and no anticoagulation were compared. Blood was drawn pre- and post filter up to 720 min. Concentrations of the thrombin-antithrombin (TAT), activated protein C-protein C inhibitor (APC-PCI), and type I plasminogen activator inhibitor (PAI-1) were determined. Results: In case of early filter failure (<24 h), inlet concentrations of TAT and APC-PCI were higher over time, irrespective of anticoagulation. There was more production of APC-PCI and platelet-derived PAI-1 in the filter after 10 min in the heparin group than in other groups. In clotting filters, production of APC-PCI and PAI was also higher with heparin than citrate. Conclusion: Coagulation activation in plasma and inhibition of anticoagulation in plasma and filter may partly determine early CVVH filter failure due to clotting, particularly when heparin is used. Regional anticoagulation by citrate circumvents the inhibition of anticoagulation and fibrinolysis by platelet activation following heparin.
Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells
Authors: Vicario Alba , Abellán Antonio , Medina Loreta
Published: May 2015

In a recent study, we tentatively identified different subdivisions of the central extended amygdala (EAce) in chicken based on the expression of region-specific transcription factors (including Pax6 and Islet1) and several phenotypic markers during embryonic development. Such a proposal was partially based on the suggestion that, similarly to the subdivisions of the EAce of mammals, the Pax6 and Islet1 neurons of the comparable chicken subdivisions derive from the dorsal (Std) or ventral striatal embryonic domains (Stv), respectively. To investigate whether this is true, in the present study, we carried out cell migration assays from chicken Std or Stv combined with immunofluorescence for Pax6 or Islet1. Our results showed that the cells of the proposed chicken EAce truly originate in either Std (expressing Pax6) or Stv (expressing Islet1). This includes lateral subdivisions previously compared to the intercalated amygdalar cells and the central amygdala of mammals, also rich in Std-derived Pax6 cells and/or Stv-derived Islet1 cells. In the medial region of the chicken EAce, the dorsal part of the lateral bed nucleus of the stria terminalis (BSTL) contains numerous cells expressing Nkx2.1 (mostly derived from the pallidal domain), but our migration assays showed that it also contains neuron subpopulations from the Stv (expressing Islet1) and Std (expressing Pax6), resembling the mouse BSTL. These findings, together with those previously published in different species of mammals, birds and reptiles, support the homology of the chicken EAce to that of other vertebrates, and reinforce the existence of several cell subcorridors inside the EAce. In addition, together with previously published data on neuropeptidergic cells, these results led us to propose the existence of at least seventeen neuron subtypes in the EAce in rodents and/or some birds (chicken and pigeon). The functional significance and the evolutionary origin of each subtype needs to be analyzed separately, and such studies are mandatory in order to understand the multifaceted modulation by the EAce of fear responses, ingestion, motivation and pain in different vertebrates.
Peritoneal Dialysis Catheter Placement Using an Ultrasound-Guided Transversus Abdominis Plane Block
Authors: Markić Dean , Vujičić Božidar , Ivanovski Mladen , Krpina Kristian , Gršković Antun , Živčić-Ćosić Stela , Župan Željko , Maričić Anton , Valenčić Maksim , Rački Sanjin
Published: May 2015

Background: Peritoneal dialysis (PD) catheter placement is usually performed using general or local anesthesia. We present our PD catheter placement experience using an ultrasound-guided transversus abdominis plane (TAP) block, which is a regional anesthesia technique. Methods: In this study, we analyzed 33 patients from our center with ESRD who underwent PD catheter placement using a TAP block between June 2011 and April 2014. Results: The TAP block was successful for 29/33 (87.9%) patients. Four patients (12.1%) had pain at the incision site and required general anesthesia. There were no anesthesia-, surgery- or catheter-related complications. Conclusion: ESRD patients have a substantial number of comorbidities that can be negatively influenced by general anesthesia. Because regional anesthesia has no systemic effect, this procedure could be recommended for this group of patients. A TAP block is an effective, safe method and can be used as the principal anesthesia technique for PD catheter placement.
Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors
Authors: Tao Xia , Thijssen Stephan , Levin Nathan , Kotanko Peter , Handelman Garry
Published: May 2015

Background: Indoxyl sulfate is a protein-bound uremic toxin and its dialytic clearance is comparatively low. We propose a method to increase indoxyl sulfate dialytic clearance. Methods: Human serum albumin, preloaded with indoxyl sulfate, was circulated on the blood side of an F40S dialyzer with single-pass counter-current dialysate flow. Tryptophan or docosahexaenoic acid (DHA), which are binding competitors to indoxyl sulfate, were infused into the blood-side circuit upstream of the dialyzer, and their abilities to increase the removal of indoxyl sulfate determined. Results: Baseline indoxyl sulfate removal was 10.2 ± 0.3%, which increased to 18.5 ± 0.4% with infusion of tryptophan (p < 0.001) and 27.7 ± 1.0% with infusion of DHA (p < 0.001). Conclusions: This study shows that tryptophan and DHA effectively increase indoxyl sulfate removal in an in vitro dialysis model. The concept of using binding competitors to enhance the clearance of protein-bound uremic toxins could be applied to current hemodialysis technology.
Plasma Pentraxin 3 Is Closely Associated with Peripheral Arterial Disease in Hemodialysis Patients and Predicts Clinical Outcome: A 6-Year Follow-Up
Authors: Zhou Yijun , Zhang Jiwei , Zhu Mingli , Lu Renhua , Wang Yongmei , Ni Zhaohui
Published: May 2015

Background: The aim of this study is to investigate the value of plasma PTX3 level for assessing peripheral artery disease (PAD) and clinical outcome in hemodialysis (HD) patients. Methods: The ankle-brachial index (ABI) was measured in HD patients. PTX3 levels in 116 HD patients were measured by ELISA. Results: Overall, 116 HD patients were enrolled; 21 (18%) patients had PAD. Using the ROC curve analysis for PAD, PTX3 (cut-off value 4.06 ng/ml, AUC 0.901, p < 0.0001) showed a significantly better positive predictive value than hsCRP (cut-off value 3.33 ng/ml, AUC 0.640, p < 0.05). During follow-up (mean 57 ± 26 months), 40 deaths (34%) occurred. Kaplan-Meier analysis found that those patients with elevated PTX3 had a significantly poor outcome (p < 0.0001), and Cox analysis further confirmed that PTX3 was an independent predictor of overall mortality (HR, 1.105, p = 0.03). For prediction of overall mortality, the AUC for PTX3 (cut-off value 3.22 ng/ml, AUC 0.690, p < 0.0001) was close to hsCRP (cut-off value 5.84 ng/ml, AUC 0.620, p < 0.001). Conclusions: For the prediction of PAD in HD patients, the diagnostic sensitivity and specificity of PTX3 were higher than those of hsCRP. Furthermore, PTX3 was also a predictor of all-cause mortality in HD patients. PTX3 may be considered a novel biomarker of inflammation in HD patients.
Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis
Authors: Carlsson Axel C. , Carrero Juan-Jesús , Stenvinkel Peter , Bottai Matteo , Barany Peter , Larsson Anders , Ärnlöv Johan
Published: May 2015

Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce. Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis. Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival. Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD.
Efficacy and Safety of Bisphosphonate Therapy in Children with Osteogenesis Imperfecta: A Systematic Review
Authors: Rijks Ester B.G. , Bongers Bart C. , Vlemmix Marloes J.G. , Boot Annemieke M. , van Dijk Atty T.H. , Sakkers Ralph J.B. , van Brussel Marco
Published: May 2015

Background/Aims: To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). Methods: PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for inclusion were (randomized) controlled trials assessing the effects of BPs in children with OI. Methodological quality was assessed independently by 4 reviewers using the Cochrane Collaboration's tool for risk of bias. Results: Ten studies (519 children) were included. Four studies (40%) showed a low risk of bias. All studies investigating lumbar spine areal bone mineral density indicated a significant increase as a result of BP treatment. Most studies observed a significant decrease in fracture incidence. The most frequently reported adverse events were gastrointestinal complaints, fever, and muscle soreness. A significant decrease in (bone) pain due to BP treatment was observed in more than half of the studies. Most studies measuring urinary markers of bone resorption reported a significant decrease. The majority of studies with intravenous treatment showed a significant increase in lumbar projection area, whereas studies with oral treatment did not. Conclusions: Treatment with oral or intravenous BPs in children with OI results in an increase in bone mineral density and seems to be safe and well tolerated.
Geriatric Nutritional Risk Index Is a Simple Predictor of Mortality in Chronic Hemodialysis Patients
Authors: Komatsu Mizuki , Okazaki Masayuki , Tsuchiya Ken , Kawaguchi Hiroshi , Nitta Kosaku
Published: May 2015

Background: Malnutrition is common in hemodialysis (HD) patients, and it is associated with increasing risk of mortality. The geriatric nutritional risk index (GNRI) has been developed as a tool to assess the nutritional risk. The aim of this study was to examine the reliability of the GNRI as a mortality predictor in a Japanese HD cohort. Methods: We prospectively examined the GNRI of 332 maintenance HD patients aged 65.4 ± 13.2, 213 males, and followed up on them for 36 months. The patients were divided into quartiles (Q) according to GNRI values (Q1: <91.6, Q2: 91.7-97.0, Q3: 97.1-102.2, Q4: >102.3). Predictors for all-cause mortality were examined using Kaplan-Meier and Cox proportional-hazards analyses. Results: The GNRI presented a normal distribution. During the follow-up period of 36 months, 76 patients died. The overall mortality at the end of the 3-year observational period was 22.3%. At the 3-year follow-up period, Kaplan-Meier survival rates for all-cause mortality were 72.3, 79.3, 84.9 and 92.6% in Q1, Q2, Q3, and Q4, respectively (p = 0.0067). Multivariate Cox proportional-hazards analysis demonstrated that the GNRI was a significant predictor of adjusted all-cause mortality (HR 0.958; 95% CI 0.929-0.989, p = 0.0073). Conclusions: The results of the present study demonstrate that the GNRI is a strong predictor of overall mortality in HD patients. However, cardiovascular mortality was not associated with GNRI values, and did not differ among the GNRI quartiles. The GNRI score can be considered a simple and reliable marker of predictor for mortality risk in Japanese HD patients.
PTK7
+
Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1
Authors: Chauhan Sunil K. , Lee Hyung Keun , Lee Hyun Soo , Park Eun Young , Jeong Eunae , Dana Reza
Published: May 2015

Objective—

In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood.

Approach and Results—

Here, we characterize the functional role of protein tyrosine kinase 7 (PTK7)–expressing CD11b
+
mononuclear cells in vitro and in vivo using a mouse model of angiogenesis. Although the frequencies of PTK7
+
CD11b
+
cells in the bone marrow remained similar after vascular endothelial growth factor-A–induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, vascular endothelial growth factor-A–induced chemotaxis of PTK7
+
cells was mediated by vascular endothelial growth factor receptor 2. In a coculture with endothelial cells, PTK7
+
CD11b
+
cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1. The enhanced vascular stability was abolished by knockdown of angiopoietin-1 in PTK7
+
CD11b
+
cells and could be restored by angiopoietin-1 treatment.

Conclusions—

We conclude that PTK7 expression in perivascular mononuclear cells induces vascular endothelial growth factor receptor 2 and angiopoietin-1 expression and thus contributes to vascular stabilization in angiogenesis.
Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice
Authors: Hajj Georges P. , Chu Yi , Lund Donald D. , Magida Jason A. , Funk Nathan D. , Brooks Robert M. , Baumbach Gary L. , Zimmerman Kathy A. , Davis Melissa K. , El Accaoui Ramzi N. , Hameed Tariq , Doshi Hardik , Chen BiYi , Leinwand Leslie A. , Song Long-Sheng , Heistad Donald D. , Weiss Robert M.
Published: May 2015

Objective—

We studied the mechanistic links between fibrocalcific changes in the aortic valve and aortic valve function in mice homozygous for a hypomorphic epidermal growth factor receptor mutation (Wave mice). We also studied myocardial responses to aortic valve dysfunction in Wave mice.

Approach and Results—

At 1.5 months of age, before development of valve fibrosis and calcification, aortic regurgitation, but not aortic stenosis, was common in Wave mice. Aortic valve fibrosis, profibrotic signaling, calcification, osteogenic markers, lipid deposition, and apoptosis increased dramatically by 6 and 12 months of age in Wave mice. Aortic regurgitation remained prevalent, however, and aortic stenosis was rare, at all ages. Proteoglycan content was abnormally increased in aortic valves of Wave mice at all ages. Treatment with pioglitazone prevented abnormal valve calcification, but did not protect valve function. There was significant left ventricular volume overload, hypertrophy, and fetal gene expression, at all ages in Wave mice with aortic regurgitation. Left ventricular systolic function was normal until 6 months of age in Wave mice, but became impaired by 12 months of age. Myocardial transverse tubules were normal in the presence of left ventricular hypertrophy at 1.5 and 3 months of age, but became disrupted by 12 months of age.

Conclusions—

We present the first comprehensive phenotypic and molecular characterization of spontaneous aortic regurgitation and volume-overload cardiomyopathy in an experimental model. In Wave mice, fibrocalcific changes are not linked to valve dysfunction and are epiphenomena arising from structurally incompetent myxomatous valves.
Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study
Authors: Gupta Deepak K. , Claggett Brian , Wells Quinn , Cheng Susan , Li Man , Maruthur Nisa , Selvin Elizabeth , Coresh Josef , Konety Suma , Butler Kenneth R. , Mosley Thomas , Boerwinkle Eric , Hoogeveen Ron , Ballantyne Christie M. , Solomon Scott D.
Published: May 2015

Background

Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (
HTN
) and cardiac hypertrophy, conditions more common among African Americans. Hospital‐based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community‐based cohorts are lacking.

Methods and Results

We examined plasma N‐terminal pro B‐type natriuretic peptide (
NT
pro
BNP
) levels according to race in 9137 Atherosclerosis Risk in Communities (
ARIC
) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to
NT
pro
BNP
levels in multivariable linear regression analysis.
NT
pro
BNP
levels were significantly lower in African Americans (median, 43 pg/
mL
; interquartile range [
IQR
], 18, 88) than Caucasians (median, 68 pg/
mL
;
IQR
, 36, 124;
P
<0.0001). In multivariable models, adjusted log
NT
pro
BNP
levels were 40% lower (95% confidence interval [
CI
], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender,
HTN
, diabetes, insulin resistance, and obesity. African‐American race was also significantly associated with having nondetectable
NT
pro
BNP
(adjusted
OR
, 5.74; 95%
CI
, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95%
CI
, 1, 13) increase in adjusted log
NT
proBNP.

Conclusions

African Americans have lower levels of plasma
NT
pro
BNP
than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for
HTN
and its sequalae in this population.
Catheter Ablation of Atrial Fibrillation in U.S. Community Practice—Results From Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF)
Authors: Holmqvist Fredrik , Simon DaJuanicia , Steinberg Benjamin A. , Hong Seok Jae , Kowey Peter R. , Reiffel James A. , Naccarelli Gerald V. , Chang Paul , Gersh Bernard J. , Peterson Eric D. , Piccini Jonathan P. ,   the ORBIT‐AF Investigators
Published: May 2015

Background

The characteristics of patients undergoing atrial fibrillation (
AF
) ablation and subsequent outcomes in community practice are not well described.

Methods and Results

Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (
ORBIT
‐
AF
), we investigated the prevalence and impact of catheter ablation of
AF
. Among 9935 patients enrolled, 5.3% had previous
AF
ablation. Patients with
AF
ablation were significantly younger, more frequently male, and had less anemia, chronic obstructive pulmonary disease, and previous myocardial infarction (P<0.05 for all analyses) than those without previous catheter ablation of
AF
. Ablated patients were more likely to have a family history of
AF
, obstructive sleep apnea, paroxysmal
AF
, and moderate‐to‐severe symptoms (P<0.0001 for all analyses). Patients with previous ablation were more often in sinus rhythm on entry into the registry (52% vs. 32%; P<0.0001). Despite previous ablation, 46% in the ablation group were still on antiarrhythmic therapy. Oral anticoagulation was prescribed in 75% of those with previous ablation versus 76% in those without previous ablation (P=0.5). The adjusted risk of death (hazard ratio [
HR
], 0.78; 95% confidence interval [
CI
], 0.52 to 1.18; P=0.2) and cardiovascular (
CV
) hospitalization (
HR
, 1.06; 95%
CI
, 0.90 to 1.26; P=0.5) were similar in both groups. Patients with incident
AF
ablation had higher risk of subsequent
CV
hospitalization than matched patients without incident ablation (
HR
, 1.67; 95%
CI
, 1.24 to 2.26; P=0.0008).

Conclusions

In U.S. clinical practice, a minority of patients with
AF
are managed with catheter ablation. Subsequent to ablation, there were no significant differences in oral anticoagulation use or outcomes, including stroke/non–central nervous system embolism/transient ischemic attack or death.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01165710.
Infratentorial Microbleeds
Authors: Arkink Enrico B. , Terwindt Gisela M. , de Craen Anton J.M. , Konishi Junya , van der Grond Jeroen , van Buchem Mark A. , Ferrari Michel D. , Kruit Mark C.
Published: May 2015

Background and Purpose—

Migraine is a risk factor for clinical stroke and for subclinical white matter hyperintensities and infratentorial infarcts. These subclinical lesions are linked to small-vessel pathology. Cerebral microbleeds (CMBs) are another biomarker of small-vessel disease but have not yet been studied in migraine.

Methods—

Identification of CMBs in 63 migraineurs (25 with aura/35 without aura/3 unknown aura status) and 359 controls (aged, 73–85 years) from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) magnetic resonance imaging study. We assessed the modifying role of migraine in the co-occurrence of CMBs, infarcts, and white matter hyperintensity-load.

Results—

Infratentorial microbleeds were more prevalent in migraine without aura patients than controls (14% versus 4%). Prevalence of other CMBs, infarcts, and white matter hyperintensities did not differ between groups. Migraineurs with CMBs had more often infarcts than controls with CMBs (65% versus 43%). In comparison with controls with infarcts, migraineurs with infarcts had more commonly CMBs (55% versus 30%).

Conclusions—

Migraine, notably without aura, is associated with infratentorial CMBs at older age. CMBs and infarcts co-occur more often in migraine than in controls. This supports the hypothesis of small-vessel involvement in migraine pathophysiology.
Accepting Regional Zero: Nuclear Weapon Free Zones, U.S. Nonproliferation Policy and Global Security, 1957–1968
Authors: Stocker James
Published: May 2015

Nuclear weapon free zones (NWFZs) were an important development in the history of nuclear nonproliferation efforts. From 1957 through 1968, when the Treaty of Tlatelolco was signed, the United States struggled to develop a policy toward NWFZs in response to efforts around the world to create these zones, including in Europe, Africa, Latin America, and the Middle East. Many within the U.S. government initially rejected the idea of NWFZs, viewing them as a threat to U.S. nuclear strategy. However, over time, a preponderance of officials came to see the zones as advantageous, at least in certain areas of the world, particularly Latin America. Still, U.S. policy pertaining to this issue remained conservative and reactive, reflecting the generally higher priority given to security policy than to nuclear nonproliferation.
The 1960 Coup in Turkey: A U.S. Intelligence Failure or a Successful Intervention?
Authors: Gunn Christopher
Published: May 2015

Coups d’état were a relatively common means of regime change during the Cold War. From 1945 through 1985, 357 attempted coups d’état occurred in the Third World, and 183 succeeded. The high frequency of coups during this period is unsurprising, especially considering the advantageous position of the military during the rapid and destabilizing pace of modernization and decolonization in Africa, Asia, Latin America, and the Middle East. Coups d’état were not exclusive to the Third World, however. They also occurred in members of the North Atlantic Treaty Organization (NATO). Surprisingly, however, few scholars have explored why these extra-constitutional regime changes were tolerated, or how they were even possible, within NATO. This article attempts to answer these questions within the context of the 1960 coup in Turkey by closely evaluating the notion that the United States had no knowledge or warning that a coup was about to unfold.
Faiths from the Archipelago
Authors: Majeri Mangunjaya Fachruddin , Tobing Imran S.L. , Binawan Andang , Pua Evangeline , Nurbawa Made
Published: May 2015

This paper explores the responses of faith-based movements in Indonesia to globalized environmental issues, including climate change. As a plural nation with six official religions, the leaders of the major recognized religions in Indonesia (i.e., Islam, Protestant and Roman Catholic Christianity, Hinduism, Buddhism and Confusianism) all offered statements in 2007 at COP 13, the international forum in response to the environmental challange and climate change in Bali. Each called for religious adherents to act in order to contribute to halting the problem of climate change. Faith is seen to be a key factor in motivating people to change their behavior towards the environment. The slogan, “Think globally, act locally,” is at the heart of this commitment, in hopes that environmental challenges including climate change, become a common issue among all the religions in Indonesia, and so that Indonesian responses may be collaborative and cooperative. This paper will document and analyze the development of such faith-based action with respect to environmental challenges in Indonesia, in light of global conditions.
Ammatoan Indigenous Religion and Forest Conservation
Authors: Maarif Samsul
Published: May 2015

This article is concerned with the indigenous religious-based forest conservation of the Ammatoans of Sulawesi in the eastern part of Indonesia. It explores the Ammatoans’ religious ideas of social actors that extend beyond human beings. Ammatoans understand that the cosmos is inhabited by not only human but also other non-human beings such as the land, forest, plants, animals, and so forth. Non-human beings do not only live together but also share the life with human beings in this world. Both human and non-human beings are equally perceived to be persons/subjects constitutive of intersubjective relationships. Such religious perception of intersubjective relations governs Ammatoans’ everyday behaviors and practices, including those of forest conservation. Ammatoans’ forest conservation practices include sets of regulations and punishments that are strictly enforced. Ammatoans’ religious ideas and practices of forest conservation illustrate what scholars have called “religious ecology.”
Against the Last Bastion of the West-centric Master Narrative
Authors: Mikhailova Yulia
Published: May 2015

This review discusses Reimagining Europe by Christian Raffensperger in the context of the evolution of academic history writing during the past few decades. It notes relations between the current political agendas and historical interpretations of the seemingly distant past exemplified by influence that modern perceptions of Russia and Ukraine exert on representations of their medieval “ancestor,” and it argues that marginal status of Rus’ in general medieval histories is the last survival of a discourse of Western European superiority. The review supports Raffensperger’s call to “reimagine” medieval Europe in such a way as to make Rus’ its integral part.
Notes of The Tale of the Rout of Mamai in the Context of the Collective Imagery Concerning the Battle of Kulikovo
Authors: Parppei Kati
Published: May 2015

Representations of military exploits are commonly used as “building material” in the post-Soviet reconstruction of collective identities. In the case of medieval battles, the scarcity of sources as well as temporal distance has allowed the production of relatively liberal representations, making them adjustable material for supporting contemporary ideas and power structures. The Battle of Kulikovo provides an illustrative case study. It took place in 1380 between troops commanded by Muscovite Grand Prince Dmitrii Ivanovich and Mongolian Emir Mamai. In Russian national historiography the battle has been considered as a major turning point. One of the most central sources used by national historians has been The Tale of the Rout of Mamai, presumably originally produced at the turn of the 16th century. In this article the text is examined as a reflection of certain contemporary religious-political developments. It can be claimed that the dualistic approach of the text, which emphasizes unified resistance against an external threat, has been applicable in strengthening ideas of internal cohesion in the Grand Duchy of Muscovy, the Russian empire and the Soviet Union, as well as post-Soviet Russia, creating an anachronistically toned basis for the collective imagery concerning the battle.
Preserving the Balance of Power in Muscovy
Authors: Pouncy Carolyn J.
Published: May 2015

In the late fifteenth and early sixteenth centuries, the successful reunification of Russia’s appanage principalities drained the pool of Orthodox princesses available to marry the grand princes (later tsars) of Muscovy. Foreign rulers often resisted Russian demands that brides convert to Orthodoxy, and the fiscal and cultural costs of finding wives abroad seemed to outweigh the benefits. But choosing a bride from one of the ruling boyar clans threatened to destabilize the balance of power at court. The Muscovite government’s solution to the problem of finding suitable wives for its rulers without undermining the existing political order was the bride-show. Martin argues that from 1505, when Grand Prince Vasilii III (1505–33) first sent messengers throughout his realm demanding that the middle service gentry produce its unmarried daughters for inspection, until Peter the Great (1682/89–1725) abandoned the practice in 1698 every Muscovite ruler and most male members of the dynasty in power chose their wives through a bride-show. In this way, the elite avoided having to deal with foreign cultural influences and largely prevented political conflict within the boyar clans, both outcomes considered potentially harmful to the state.
Doppler Radar Analysis of Triple Eyewalls in Typhoon Usagi (2013)
Authors: Zhao Kun , Lin Qing , Lee Wen-Chau , Qiang Sun Y. , Zhang Fuqing
Published: May 2015

Strong tropical cyclones often undergo eyewall replacement cycles that are accompanied by concentric eyewalls and/or rapid intensity changes while the secondary eyewall contracts radially inward and eventually replaces the inner eyewall. To the best of our knowledge, the only documented partial/incomplete tertiary eyewall has been mostly inferred from two-dimensional satellite images or one-dimensional aircraft flight-level measurements that can be regarded as indirect and tangential. This study presents the first high spatial and temporal resolution Doppler radar observations of a tertiary eyewall formation event in Typhoon Usagi (2013) over a 14-h time period before it makes landfall. The primary (tangential) and secondary (radial) circulations of Usagi deduced from the Ground-Based Velocity Track Display (GBVTD) methodology clearly portrayed three distinct axisymmetric maxima of radar reflectivity, tangential wind, vertical velocity, and vertical vorticity. Usagi’s central pressure steadily deepened during the contraction of the secondary and tertiary eyewalls until the tertiary eyewall hit the coast of southeast China, which erminated the intensification of the storm.