bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unified Software Framework for Empirical Gramians
Authors: Himpe Christian , Ohlberger Mario
Published: September 2013

A common approach in model reduction is balanced truncation, which is based on Gramian matrices classifying certain attributes of states or parameters of a given dynamic system. Initially restricted to linear systems, the empirical Gramians not only extended this concept to nonlinear systems but also provided a uniform computational method. This work introduces a unified software framework supplying routines for six types of empirical Gramians. The Gramian types will be discussed and applied in a model reduction framework for multiple-input multiple-output systems.
Imaging Comparison between18F-FDG-PET/CT and18F-Flouroethyl Choline PET/CT in Rare Case of Thymus Carcinoma Exhibiting a Positive Choline Uptake
Authors: Takesh Mustafa , Adams Stefan
Published: September 2013

It is of great value by using PET imaging in oncology to recognize any atypical uptake not related to the underlying disease. That helps in avoiding the false positive finding and may contribute in extending the application range of used radiopharmaceuticals in further disorders. It is well known that radiolabeled choline is an essential PET tracer used currently in prostate cancer. The physiological choline distribution was described. Nevertheless there is still a lack of studies, which describe this distribution in young patients; given that the radiolabeled choline is generally being used in the field of prostate cancer. Whether the thymus exhibits normally a positive choline uptake or not is still unknown. In particular, it is known that the lymphocytes express high affinity of choline transporter and enzymes involving its metabolism. Some cases of thymus carcinoma exhibiting a positive choline had been reported in the literature, however, mostly using11C-choline. We report a rare case of metastatic thymic carcinoma detected incidentally using18F-choline-PET in a 78-year-old male patient referred with elevation of prostate specific antigen. Moreover we present a comparison pattern with18F-FDG-PET modality, in which18F-choline-PET was turned out to be superior in tumor delineation.
Management of Synovial Osteochondromatosis of the Distal Radioulnar Joint with Imaging Features Consistent with Malignancy
Authors: McInnes Colin W. , Goetz Thomas J.
Published: September 2013

Synovial osteochondromatosis of the distal radioulnar joint is a rare entity with only 14 cases reported in the literature. Malignant transformation of synovial osteochondromatosis is the most worrisome complication of the disease. It has been described in joints such as the hip and knee but never for the distal radioulnar joint. We report a case of synovial osteochondromatosis of the distal radioulnar joint which presented with radiographic features which were worrisome for malignant transformation and required a comprehensive preoperative workup. Discussed are the preoperative management, surgical treatment, and a literature review of this rare disease.
Epithelioid Angiosarcoma of the Septum Pellucidum
Authors: Baldovini Chiara , Martinoni Matteo , Marucci Gianluca
Published: September 2013

Primary cerebral intra-axial epithelioid angiosarcoma is an extremely rare malignancy. To the best of our knowledge we describe the first case of epithelioid angiosarcoma arisen in the septum pellucidum of a 54-years-old man. Albeit extremely rare, this neoplasia is a potential source of misdiagnosis for other aggressive malignant tumors, and it should be taken into consideration.
Primary Biliary Cirrhosis-Specific Antimitochondrial Antibodies in Neonatal Haemochromatosis
Authors: Smyk Daniel S. , Mytilinaiou Maria G. , Grammatikopoulos Tassos , Knisely A. S. , Mieli-Vergani Giorgina , Bogdanos Dimitrios P. , Vergani Diego
Published: September 2013

Background and Aim. Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC).Material and Methods. To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months.Results. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child).Conclusion. The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.
The Preconditioned SOR Iterative Method for Positive Definite Matrices
Authors: Bai Yu-Qin , Xiao Yan-Ping , Ma Wei-Yuan
Published: September 2013

We present several iterations for preconditioners introduced by Tarazaga and Cuellar (2009), and study the convergence of the method for solving a linear system whose coefficient matrix is positive definite matrices, and we also find that they complete very well with the SOR iteration, which is shown through numerical examples.
Redox Mechanisms of AVS022, an Oriental Polyherbal Formula, and Its Component Herbs in Protection against Induction of Matrix Metalloproteinase-1 in UVA-Irradiated Keratinocyte HaCaT Cells
Authors: Pluemsamran Thanyawan , Tripatara Pinpat , Phadungrakwittaya Rattana , Akarasereenont Pravit , Laohapand Tawee , Panich Uraiwan
Published: September 2013

Ayurved Siriraj HaRak (AVS022) formula has been used for topical remedy of dermatologic disorders. Oxidative stress induced by ultraviolet (UV) A irradiation could be implicated in photoaged skin through triggering matrix metalloproteinase-1 (MMP-1). We, therefore, explored the antioxidant mechanisms by which AVS022 formulation and its individual components protected against UVA-dependent MMP-1 upregulation in keratinocyte HaCaT cells. TLC analysis revealed the presence of multiple phenolics including gallic acid (GA) in the AVS022 extracts. We demonstrated that pretreatment with the whole formula and individual herbal components exceptT. triandraprotected against increased MMP-1 activity in irradiated HaCaT cells. Moreover, all herbal extracts and GA, used as the reference compound, were able to reverse cytotoxicity, oxidant production, glutathione (GSH) loss, and inactivation of catalase and glutathione peroxidase (GPx).F. racemosawas observed to yield the strongest abilities to abolish UVA-mediated induction of MMP-1 and impairment of antioxidant defenses including GSH and catalase. Our observations suggest that upregulation of endogenous antioxidants could be the mechanisms by which AVS022 and its herbal components suppressed UVA-stimulated MMP-1 in HaCaT cells. In addition, pharmacological actions of AVS022 formula may be attributed to the antioxidant potential of its components, in particularF. racemosa, and several phenolics including GA.
Risk Management in Magnetic Resonance: Failure Mode, Effects, and Criticality Analysis
Authors: Petrillo Antonella , Fusco Roberta , Granata Vincenza , Filice Salvatore , Raiano Nicola , Amato Daniela Maria , Zirpoli Maria , di Finizio Alessandro , Sansone Mario , Russo Anna , Covelli Eugenio Maria , Pedicini Tonino , Triassi Maria
Published: September 2013

The aim of the study was to perform a risk management procedure in “Magnetic Resonance Examination” process in order to identify the critical phases and sources of radiological errors and to identify potential improvement projects including procedures, tests, and checks to reduce the error occurrence risk. In this study we used the proactive analysis “Failure Mode Effects Criticality Analysis,” a qualitative and quantitative risk management procedure; has calculated Priority Risk Index (PRI) for each activity of the process; have identified, on the PRI basis, the most critical activities and, for them, have defined improvement projects; and have recalculated the PRI after implementation of improvement projects for each activity. Time stop and audits are performed in order to control the new procedures. The results showed that the most critical tasks of “Magnetic Resonance Examination” process were the reception of the patient, the patient schedule drafting, the closing examination, and the organization of activities. Four improvement projects have been defined and executed. PRI evaluation after improvement projects implementation has shown that the risk decreased significantly following the implementation of procedures and controls defined in improvement projects, resulting in a reduction of the PRI between 43% and 100%.
Clinical Characteristics ofNocardiaInfection in Patients with Rheumatic Diseases
Authors: Yamagata Mieko , Hirose Koichi , Ikeda Kei , Nakajima Hiroshi
Published: September 2013

AlthoughNocardiosishas considerable recurrence and mortality rates, characteristics and risk factors ofNocardiainfection have not been assessed in patients with rheumatic diseases. Here, we examined the characteristics and risk factors ofNocardiainfection in rheumatic disease patients in our hospital. Ten rheumatic disease patients who developedNocardiainfection were identified by retrospectively reviewing the medical records. Possible predisposing factors forNocardiainfection were high-dose glucocorticoid treatment, concomitant use of immunosuppressants, preexisting pulmonary diseases, and diabetes mellitus. All patients had pulmonaryNocardiosis, and six of them had disseminatedNocardiosiswhen their pulmonary lesions were identified.
Enhanced Solar Photoelectrochemical Conversion Efficiency of ZnO:Cu Electrodes for Water-Splitting Application
Authors: Dom Rekha , Baby Lijin Rose , Kim Hyun Gyu , Borse Pramod H.
Published: September 2013

n-typeZnO:Cu photoanodes were fabricated by simple spray pyrolysis deposition technique. Influence of low concentration (range ~10−4–10−1%) of Cu doping in hexagonal ZnO lattice on its photoelectrochemical performance has been investigated. The doped photoanodes displayed 7-time enhanced conversion efficiencies with respect to their undoped counterpart, as estimated from the photocurrents generated under simulated solar radiation. This is the highest enhancement in the solar conversion efficiency reported so far for the Cu-doped ZnO. This performance is attributed to the red shift in the band gap of the Cu-doped films and is in accordance with the incident-photon-current-conversion efficiency (IPCE) measurements. Electrochemical studies reveal ann-typenature of these photoanodes. Thus, the study indicates a high potential of doped ZnO films for solar energy applications, in purview of the development of simple nanostructuring methodologies.
The Importance of Trichoscopy in Clinical Practice
Authors: Pedrosa Ana Filipa , Morais Paulo , Lisboa Carmen , Azevedo Filomena
Published: September 2013

Trichoscopy corresponds to scalp and hair dermoscopy and has been increasingly used as an aid in the diagnosis, follow-up, and prognosis of hair disorders. Herein, we report selected cases harbouring scalp or hair diseases, in whom trichoscopy proved to be a valuable tool in their management. A review of the recent literature on this hot topic was performed comparing the described patterns with our findings in clinically common conditions, as well as in rare hair shaft abnormalities, where trichoscopy may display pathognomonic features. In our view, trichoscopy represents a valuable link between clinical and histological diagnosis. We detailed some trichoscopic patterns, complemented with our original photographs and our insights into nondescribed patterns.
Adjuvants That Improve the Ratio of Antigen-Specific Effector to Regulatory T Cells Enhance Tumor Immunity
Authors: Perret Rachel , Sierro Sophie R. , Botelho Natalia K. , Corgnac Stéphanie , Donda Alena , Romero Pedro
Published: September 2013

Antitumor immunity is strongly influenced by the balance of tumor antigen-specific effector T cells (Teff) and regulatory T cells (Treg). However, the impact that vaccine adjuvants have in regulating the balance of antigen-specific T-cell populations is not well understood. We found that antigen-specific Tregs were induced following subcutaneous vaccination with either OVA or melanoma-derived peptides, with a restricted expansion of Teffs. Addition of the adjuvants CpG-ODN or Poly(I:C) preferentially amplified Teffs over Tregs, dramatically increasing the antigen-specific Teff:Treg ratios and inducing polyfunctional effector cells. In contrast, two other adjuvants, imiquimod and Quil A saponin, favored an expansion of antigen-specific Tregs and failed to increase Teff:Treg ratios. Following therapeutic vaccination of tumor-bearing mice, high ratios of tumor-specific Teffs:Tregs in draining lymph nodes were associated with enhanced CD8+ T-cell infiltration at the tumor site and a durable rejection of tumors. Vaccine formulations of peptide+CpG-ODN or Poly(I:C) induced selective production of proinflammatory type I cytokines early after vaccination. This environment promoted CD8+ and CD4+ Teff expansion over that of antigen-specific Tregs, tipping the Teff to Treg balance to favor effector cells. Our findings advance understanding of the influence of different adjuvants on T-cell populations, facilitating the rational design of more effective cancer vaccines. Cancer Res; 73(22); 6597–608. ©2013 AACR.
Risk of Colorectal Cancer in Patients with Acute Myocardial Infarction and Stroke: A Nationwide Cohort Study
Authors: Erichsen Rune , Sværke Claus , Sørensen Henrik T. , Sandler Robert S. , Baron John A.
Published: September 2013

Background: An association between colorectal cancer and acute myocardial infarction (AMI) and stroke has been suggested, but evidence is conflicting.

Method: We conducted a population-based cohort study (1978–2010) of the association between AMI/stroke and colorectal cancer by linking nationwide Danish registries. We calculated standardized incidence ratios (SIR) of colorectal cancer after AMI/stroke as the ratios of observed to expected incidence.

Results: A total of 297,523 patients with AMI (median age, 69.4 years; 64% men) were followed for a median of 3.1 years (range, 0–33 years) and 4,387 developed colorectal cancer [SIR, 1.08; 95% confidence interval (CI), 1.05–1.11; P < 0.001]. In the first year of follow-up, the SIR was 1.85 (95% CI, 1.73–1.98; P < 0.001), whereas it was 0.98 (95% CI, 0.95–1.02; P = 0.318) in the second and subsequent years. We followed 246,998 patients with stroke (median age, 72.4 years; 52% men) for a median of 2.9 years (range, 0–33 years) and 3,035 developed colorectal cancer (SIR, 1.04; 95% CI, 1.00–1.07; P = 0.053). In the first year of follow-up, the SIR was 1.42 (95% CI, 1.31–1.53; P < 0.001), whereas it was 0.96 (95% CI, 0.93–1.00; P = 0.072) thereafter. We found no difference between the SIRs for ischemic and hemorrhagic stroke. The increased one-year relative risks for AMI and stroke corresponded to a 0.3% absolute risk.

Conclusions: Our findings reflect detection of occult cancer at the time of the vascular event. The lack of increased risk after one year suggests that an association based on shared risk factors or chronic inflammation is unlikely.

Impact: In patients with AMI/stroke, the diagnostic workup including screening for colorectal cancer should follow that of the general population. Cancer Epidemiol Biomarkers Prev; 22(11); 1994–9. ©2013 AACR.
Monoclonal Antibody against Cell Surface GRP78 as a Novel Agent in Suppressing PI3K/AKT Signaling, Tumor Growth, and Metastasis
Authors: Liu Ren , Li Xiuqing , Gao Wenming , Zhou Yue , Wey Shiuan , Mitra Satyajit K. , Krasnoperov Valery , Dong Dezheng , Liu Shuanglong , Li Dan , Zhu Genyuan , Louie Stan , Conti Peter S. , Li Zibo , Lee Amy S. , Gill Parkash S.
Published: September 2013

Purpose: The ER chaperone GRP78 translocates to the surface of tumor cells and promotes survival, metastasis, and resistance to therapy. An oncogenic function of cell surface GRP78 has been attributed to the activation of the phosphoinositide 3-kinase (PI3K) pathway. We intend to use a novel anti-GRP78 monoclonal antibody (MAb159) to attenuate PI3K signaling and inhibit tumor growth and metastasis.

Experimental Design: MAb159 was characterized biochemically. Antitumor activity was tested in cancer cell culture, tumor xenograft models, tumor metastasis models, and spontaneous tumor models. Cancer cells and tumor tissues were analyzed for PI3K activity. MAb159 was humanized and validated for diagnostic and therapeutic application.

Results: MAb159 specifically recognized surface GRP78, triggered GRP78 endocytosis, and localized to tumors but not to normal organs in vivo. MAb159 inhibited tumor cell proliferation and enhanced tumor cell death both in vitro and in vivo. In MAb159-treated tumors, PI3K signaling was inhibited without compensatory MAPK pathway activation. Furthermore, MAb159 halted or reversed tumor progression in the spontaneous PTEN–loss-driven prostate and leukemia tumor models, and inhibited tumor growth and metastasis in xenograft models. Humanized MAb159, which retains high affinity, tumor specific localization, and the antitumor activity, was nontoxic in mice, and had desirable pharmacokinetics.

Conclusions: GRP78-specific antibody MAb159 modulates the PI3K pathway and inhibits tumor growth and metastasis. Humanized MAb159 will enter human trials shortly. Clin Cancer Res; 19(24); 6802–11. ©2013 AACR.
MTI-101 (Cyclized HYD1) Binds a CD44 Containing Complex and Induces Necrotic Cell Death in Multiple Myeloma
Authors: Gebhard Anthony W. , Jain Priyesh , Nair Rajesh R. , Emmons Michael F. , Argilagos Raul F. , Koomen John M. , McLaughlin Mark L. , Hazlehurst Lori A.
Published: September 2013

Our laboratory recently reported that treatment with the d-amino acid containing peptide HYD1 induces necrotic cell death in multiple myeloma cell lines. Because of the intriguing biological activity and promising in vivo activity of HYD1, we pursued strategies for increasing the therapeutic efficacy of the linear peptide. These efforts led to a cyclized peptidomimetic, MTI-101, with increased in vitro activity and robust in vivo activity as a single agent using two myeloma models that consider the bone marrow microenvironment. MTI-101 treatment similar to HYD1 induced reactive oxygen species, depleted ATP levels, and failed to activate caspase-3. Moreover, MTI-101 is cross-resistant in H929 cells selected for acquired resistance to HYD1. Here, we pursued an unbiased chemical biology approach using biotinylated peptide affinity purification and liquid chromatography/tandem mass spectrometry analysis to identify binding partners of MTI-101. Using this approach, CD44 was identified as a predominant binding partner. Reducing the expression of CD44 was sufficient to induce cell death in multiple myeloma cell lines, indicating that multiple myeloma cells require CD44 expression for survival. Ectopic expression of CD44s correlated with increased binding of the FAM-conjugated peptide. However, ectopic expression of CD44s was not sufficient to increase the sensitivity to MTI-101–induced cell death. Mechanistically, we show that MTI-101–induced cell death occurs via a Rip1-, Rip3-, or Drp1-dependent and -independent pathway. Finally, we show that MTI-101 has robust activity as a single agent in the SCID-Hu bone implant and 5TGM1 in vivo model of multiple myeloma. Mol Cancer Ther; 12(11); 2446–58. ©2013 AACR.
PHD4 Stimulates Tumor Angiogenesis in Osteosarcoma Cells via TGF-α
Authors: Klotzsche-von Ameln Anne , Prade Ina , Grosser Marianne , Kettelhake Antje , Rezaei Maryam , Chavakis Triantafyllos , Flamme Ingo , Wielockx Ben , Breier Georg
Published: September 2013

Solid tumor growth is intimately associated with angiogenesis, a process that is efficiently triggered by hypoxia. Therefore, oxygen-sensitive signaling pathways are thought to play a critical role in tumor angiogenesis and progression. Here, the function of prolyl hydroxylase-4 (PHD4), a relative of the prolyl hydroxylase domain proteins 1–3 that promote the degradation of hypoxia-inducible factors (HIF), was interrogated. To test the hypothesis that PHD4 might inhibit tumor angiogenesis, it was overexpressed in osteosarcoma cells, and unexpectedly, this manipulation led to increased tumor blood vessel density. However, the newly formed blood vessels were smaller than normal and appeared to be partially nonfunctional, as indicated by poor vessel perfusion. PHD4 overexpression in tumor cells stimulated the expression of TGF-α, which was necessary and sufficient to promote angiogenic sprouting of endothelial cells. On the other hand, PHD4 overexpression reduced HIF-2α protein levels, which in turn inhibited in vivo tumor growth. Combined, elevated PHD4 levels deregulate angiogenesis via increased TGF-α expression in vitro and in vivo. These data support the hypothesis that tumor growth can be uncoupled from vessel density and that the individual PHD family members exert distinct functions in tumors.

Implications: PHD4 influences tumor growth and vascularization through discrete mechanisms and molecular pathways that likely have therapeutic potential. Mol Cancer Res; 11(11); 1337–48. ©2013 AACR.
Physical Activity Is Associated with Reduced Risk of Gastric Cancer: A Systematic Review and Meta-analysis
Authors: Singh Siddharth , Varayil Jithinraj Edakkanambeth , Devanna Swapna , Murad Mohammad Hassan , Iyer Prasad G.
Published: September 2013

Physical activity may be associated with reduced risk of gastric cancer. We performed a systematic review and meta-analysis to evaluate the magnitude of the association and the quality of supporting evidence. After a comprehensive search of bibliographic databases and conference proceedings through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and gastric cancer risk, we identified 16 studies (seven cohort, nine case control) reporting 11,111 cases of gastric cancer among 1,606,760 patients. Summary adjusted-OR estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Meta-analysis demonstrated that the risk of gastric cancer was 21% lower among the most physically active people as compared with the least physically active people (OR = 0.79; 95% CI, 0.71–0.87) with moderate heterogeneity among studies (I2 = 55%). This protective effect was seen for gastric cancers in the cardia (four studies; OR = 0.80; 95% CI, 0.63–1.00) and distal stomach (five studies; OR = 0.63; 95% CI, 0.52–0.76). The effect size was significantly smaller in high-quality studies (six studies; OR = 0.86; 95% CI, 0.75–0.99), as compared with low-quality studies (10 studies; OR = 0.74; 95% CI, 0.69–0.81). The results were consistent across sex, study quality, study design, and geographic location. In conclusion, meta-analysis of published observational studies indicates that physical activity is associated with reduced risk of gastric cancer. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of gastric cancer, in addition to a myriad of other health benefits. Cancer Prev Res; 7(1); 12–22. ©2013 AACR.
Gain or Loss? Sunscreen Efficiency after Cosmetic Pretreatment of the Skin
Authors: Kluschke F. , Weigmann H.J. , Schanzer S. , Meinke M. , Vergou T. , Sterry W. , Lademann J.
Published: September 2013

Sunscreens are a key pillar of the multimodal protection strategy against short- and long-term impacts of intermittent and continuous UV exposure. Hitherto, an unanswered part of current scientific discourse is the question whether a cosmetic pretreatment has an impact on distribution and adhesiveness of sunscreens on the skin and therefore affects UV protection. In order to evaluate the homogeneity of sunscreen filter distribution, water resistance as a parameter of adhesiveness and effective UV protection of sunscreens after a pretreatment with cream or lotion was investigated in 18 volunteers who were examined before and after swimming, using the established combination of the tape stripping procedure and UV/VIS spectroscopy. It was shown that a cosmetic skin pretreatment affects neither filter homogeneity nor effective UV protection prior to water contact. However, compared to nonpretreated skin, a considerable loss of water resistance is caused. Therefore, using a cream or lotion before application of sunscreens is not to be recommended.
Prosodic Variation for Topic Shift and Other Functions in Local Contrasts in Conversation
Authors: Zellers Margaret
Published: September 2013

Speakers and listeners have been shown to use phonetic cues to help them in tracking the ongoing structure of conversational interaction, but fragmentation between qualitative and quantitative research means that the forms and functions of these cues have been given varying characterizations. The current study explores prosodic variation in contrastive structures in conversational data, using a combined methodology adopting aspects from both qualitative (conversation analysis) and quantitative (experimental phonetics/phonology) approaches. Statistical and conversation-analytical methods used together reveal relationships between prosodic variation and interactional function, such as variations in pitch range across adjacent turns being linked to the presence of ‘stepwise' topic changes.
Interactions of heparin and a covalently-linked antithrombin-heparin complex with components of the fibrinolytic system
Authors: Chander Ankush , Atkinson Helen M. , Stevic Ivan , Berry Leslie R. , Kim Paul Y. , Chan Anthony K. C.
Published: September 2013

Unfractionated heparin (UFH) is used as an adjunct during thrombolytic therapy. However, its use is associated with limitations, such as the inability to inhibit surface bound coagulation factors. We have developed a covalent conjugate of antithrombin (AT) and heparin (ATH) with superior anticoagulant properties compared with UFH. Advantages of ATH include enhanced inhibition of surface-bound coagulation enzymes and the ability to reduce the overall size and mass of clots in vivo. The interactions of UFH or ATH with the components of the fibrinolytic pathway are not well understood. Our study utilised discontinuous second order rate constant (k2
) assays to compare the rates of inhibition of free and fibrin-associated plasmin by AT+UFH vs ATH. Additionally, we evaluated the effects of AT+UFH and ATH on plasmin generation in the presence of fibrin. The k2
values for inhibition of plasmin were 5.74 ± 0.28 x 106 M-1 min-1 and 6.39 ± 0.59 x 106 M-1 min-1 for AT+UFH and ATH, respectively. In the presence of fibrin, the k2
values decreased to 1.45 ± 0.10 x 106 M-1 min1 and 3.07 ± 0.19 x 106 M-1 min-1 for AT+UFH and ATH, respectively. Therefore, protection of plasmin by fibrin was observed for both inhibitors; however, ATH demonstrated superior inhibition of fibrin-associated plasmin. Rates of plasmin generation were also decreased by both inhibitors, with ATH causing the greatest reduction (approx. 38-fold). Nonetheless, rates of plasmin inhibition were 2–3 orders of magnitude lower than for thrombin, and in a plasma-based clot lysis assay ATH significantly inhibited clot formation but had little impact on clot lysis. Cumulatively, these data may indicate that, relative to coagulant enzymes, the fibrinolytic system is spared from inhibition by both AT+UFH and ATH, limiting reduction in fibrinolytic potential during anticoagulant therapy.
Comparison of the CHADS2, CHA2DS2 -VASc and HAS-BLED scores for the prediction of clinically relevant bleeding in anticoagulated patients with atrial fibrillation: The AMADEUS trial
Authors: Apostolakis Stavros , Lane Deirdre A. , Buller Harry , Lip Gregory Y. H.
Published: September 2013

Many of the risk factors for stroke in atrial fibrillation (AF) are also important risk factors for bleeding. We tested the hypothesis that the CHADS2 and CHA2DS2-VASc scores (used for stroke risk assessment) could be used to predict serious bleeding, and that these scores would compare well against the HAS-BLED score, which is a specific risk score designed for bleeding risk assessment. From the AMADEUS trial, we focused on the trial’s primary safety outcome for serious bleeding, which was “any clinically relevant bleeding”. The predictive value of HAS-BLED/CHADS2/CHA2DS2-VASc were compared by area under the curve (AUC, a measure of the c-index) and the Net Reclassification Improvement (NRI). Of 2,293 patients on VKA, 251 (11%) experienced at least one episode of “any clinically relevant bleeding” during an average 429 days follow up period. Incidence of “any clinically relevant bleeding” rose with increasing HAS-BLED/CHADS2/CHA2DS2-VASc scores, but was statistically significant only for HAS-BLED (p<0.0001). Only HAS-BLED demonstrated significant discriminatory performance for “any clinically relevant bleeding” (AUC 0.60, p<0.0001). There were significant AUC-differences between HAS-BLED (which had the highest AUC) and both CHADS2 (p<0.001) and CHA2DS2VASc (p=0.001). The HAS-BLED score also demonstrated significant NRI for the outcome of “any clinically relevant bleeding” when compared with CHADS2 (p=0.001) and CHA2DS2-VASc (p=0.04). In conclusion, the HAS-BLED score demonstrated significant discriminatory performance for “any clinically relevant bleeding” in anticoagulated patients with AF, whilst the CHADS2 and CHA2DS2-VASc scores did not. Bleeding risk assessment should be made using a specific bleeding risk score such as HAS-BLED, and the stroke risk scores such as CHADS2 or CHA2DS2-VASc scores should not be used.
Renal Dysfunction, Stroke Risk Scores (CHADS
2
, CHA
2
DS
2
-VASc, and R
2
CHADS
2
), and the Risk of Thromboembolic Events After Catheter Ablation of Atrial Fibrillation
Authors: Kornej Jelena , Hindricks Gerhard , Kosiuk Jedrzej , Arya Arash , Sommer Philipp , Husser Daniela , Rolf Sascha , Richter Sergio , Piorkowski Christopher , Gaspar Thomas , Lip Gregory Y.H. , Bollmann Andreas
Published: September 2013

Background—

There are limited data on the predictive value of stroke risk scores for thromboembolic events (TEs) after catheter ablation of atrial fibrillation (AF). Our objectives were to report the incidence of TEs after AF ablation in a large contemporary AF ablation cohort and to investigate the impact of renal dysfunction and the value of stroke risk stratification scores (CHADS
2
, CHA
2
DS
2
-VASc, and R
2
CHADS
2
) for predicting TE after AF ablation.

Methods and Results—

Using the Leipzig Heart Center AF Ablation Registry, we documented TEs in patients undergoing radiofrequency AF catheter ablation. TE was defined as stroke, transient ischemic attack, or systemic embolism. Study population (N=2069; 66% men; 60±10 years; 62% paroxysmal AF; mean CHADS
2
, 1.2±0.9; CHA
2
DS
2
-VASc, 2.1±1.4; and R
2
CHADS
2
, 1.3±1.1) were followed up for a median 18 (Q1–Q3, 12–29) months (ie, 3078 patient-years). Overall, 31 TEs occurred, with 16 events within 30 days of ablation and 15 TEs (0.72%) during the follow-up period. On multivariate analysis, CHADS
2
(
P
<0.001), R
2
CHADS
2
(
P
<0.001), and CHA
2
DS
2
-VASc (
P
=0.003) scores were independent predictors of TEs during follow-up, and AF recurrence conferred a nonsignificant trend for increased TE risk (
P
=0.071–0.094). The CHA
2
DS
2
-VASc score further differentiated TE risk in patients with CHADS
2
and R
2
CHADS
2
0 to 1 (0.13% if CHA
2
DS
2
-VASc was 0–1 and 0.71% if CHA
2
DS
2
-VASc was >2) and had the best predictive value in patients with AF recurrences (c-index 0.894,
P
=0.022 versus CHADS
2
,
P
=0.031 versus R
2
CHADS
2
).

Conclusions—

CHADS
2
, CHA
2
DS
2
-VASc, and R
2
CHADS
2
scores were associated with TE risk. The CHA
2
DS
2
-VASc score differentiated TE risk in the low-risk strata based on CHADS
2
and R
2
CHADS
2
scores and may be superior in the subgroup with AF recurrences.
Loss of Collectrin, an Angiotensin-Converting Enzyme 2 Homolog, Uncouples Endothelial Nitric Oxide Synthase and Causes Hypertension and Vascular Dysfunction
Authors: Cechova Sylvia , Zeng Qing , Billaud Marie , Mutchler Stephanie , Rudy Christine K. , Straub Adam C. , Chi Liqun , Chan Fang R. , Hu Jun , Griffiths Robert , Howell Nancy L. , Madsen Kirsten , Jensen Boye L. , Palmer Lisa A. , Carey Robert M. , Sung Sun-Sang J. , Malakauskas Sandra M. , Isakson Brant E. , Le Thu H.
Published: September 2013

Background—

Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid transporters. In rodents, the renal expression of collectrin is increased after subtotal nephrectomy and during high-salt feeding, raising the question of whether collectrin has any direct role in blood pressure regulation.

Methods and Results—

Using a susceptible genetic background, we demonstrate that deletion of collectrin results in hypertension, exaggerated salt sensitivity, and impaired pressure natriuresis. Collectrin knockout mice display impaired endothelium-dependent vasorelaxation that is associated with vascular remodeling, endothelial nitric oxide synthase uncoupling, decreased nitric oxide production, and increased superoxide generation. Treatment with Tempol, a superoxide scavenger, attenuates the augmented sodium sensitivity in collectrin knockout mice. We report for the first time that collectrin is expressed in endothelial cells. Furthermore, collectrin directly regulates
l
-arginine uptake and plasma membrane levels of CAT1 and y
+
LAT1 amino acid transporters in endothelial cells. Treatment with
l
-arginine modestly lowers blood pressure of collectrin knockout mice.

Conclusions—

Collectrin is a consequential link between the transport of
l
-arginine and endothelial nitric oxide synthase uncoupling in hypertension.
The Greek Historia monachorum in Aegypto and Athanasius’ Life of Antony
Authors: Cain Andrew
Published: September 2013

Abstract

This article examines possible literary sources underlying the Greek Historia monachorum in Aegypto, which was composed anonymously in the last decade of the fourth century, and argues that the Life of Antony, which Athanasius had released some forty years earlier, exercised a demonstrable influence over it.
An Investigation of the Aerosol Indirect Effect on Convective Intensity Using Satellite Observations
Authors: Wall Christina , Zipser Edward , Liu Chuntao
Published: September 2013

The effect of the environment on individual clouds makes it difficult to isolate the signal of the aerosol indirect effect, particularly at larger spatial and temporal scales. This study uses observations from the Tropical Rainfall Measuring Mission (TRMM), CloudSat, and Aqua satellites to identify convective cloud systems in clean and dirty environments. The Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol index is collocated with radar precipitation features (RPFs) from TRMM and congestus cloud features (CFs) from CloudSat. The Interim ECMWF Re-Analysis (ERA-Interim) is interpolated to identify the environmental profile surrounding each feature. Regions in Africa, the Amazon, the Atlantic Ocean, and the southwestern United States are examined. TRMM features in the Africa and Amazon regions are more intense and have higher lightning flash rates under dirty background conditions. RPFs in the southwestern United States are more intense under clean background conditions. The Atlantic region shows little difference in intensity. The differences found in the mean thermodynamic profile for RPFs forming in clean and dirty environments could explain these differences in convective intensity.

Congestus identified with CloudSat show smaller differences between clouds forming in clean and dirty environments in Africa and the Amazon. Congestus in clean environments have higher reflectivities and generally larger widths, but no trend is seen in cloud-top height. The signal of the aerosol indirect effect is so small that it is very difficult to detect confidently using these methods. The environment must be considered in any study of the aerosol indirect effect, because important environmental changes can occur as aerosols are introduced to an air mass.
Quantifying the Strength and Delay of Climatic Interactions: The Ambiguities of Cross Correlation and a Novel Measure Based on Graphical Models
Authors: Runge Jakob , Petoukhov Vladimir , Kurths Jürgen
Published: September 2013

Lagged cross-correlation and regression analysis are commonly used to gain insights into interaction mechanisms between climatological processes, in particular to assess time delays and to quantify the strength of a mechanism. Exemplified on temperature anomalies in Europe and the tropical Pacific and Atlantic, the authors study lagged correlation and regressions analytically for a simple model system. A strong dependence on the influence of serial dependencies or autocorrelation is demonstrated, which can lead to misleading conclusions about time delays and also obscures a quantification of the interaction mechanism.

To overcome these possible artifacts, the authors propose a two-step procedure based on the concept of graphical models recently introduced to climate research. In the first step, graphical models are used to detect the existence of (Granger) causal interactions that determine the time delays of a mechanism. In the second step, a certain partial correlation and a regression measure are introduced that allow one to specifically quantify the strength of an interaction mechanism in a well interpretable way that enables the exclusion of misleading effects of serial correlation as well as more general dependencies. The potential of the approach to quantify interactions between two and more processes is demonstrated by investigating teleconnections of ENSO and the mechanism of the Walker circulation.

The article is intended to serve as a guideline to interpret lagged correlations and regressions in the presence of autocorrelation and introduces a powerful approach to analyze time delays and the strength of an interaction mechanism.
Distinguishing Interannual Variations of the Northern and Southern Modes of the East Asian Winter Monsoon
Authors: Chen Zhang , Wu Renguang , Chen Wen
Published: September 2013

The East Asian winter monsoon (EAWM)-related climate anomalies have shown large year-to-year variations in both the intensity and the meridional extent. The present study distinguishes the interannual variations of the low-latitude and mid- to high-latitude components of the EAWM to gain a better understanding of the characteristics and factors for the EAWM variability. Through composite analysis based on two indices representing the northern and southern components (modes) of the EAWM variability, the present study clearly reveals features unique to the northern and southern mode. The northern mode is associated with changes in the mid- to high-latitude circulation systems, including the Siberian high, the Aleutian low, the East Asian trough, and the East Asian westerly jet stream, whereas the southern mode is closely related to circulation changes over the global tropics, the North Atlantic, and North America. A strong northern mode is accompanied by positive, negative, and positive surface temperature anomalies in the Indochina Peninsula, midlatitude Asia, and northeast Russia, respectively. A strong southern mode features lower temperature over tropics and higher temperature over mid- to high-latitude Asia. While the southern mode is closely related to El Niño–Southern Oscillation (ENSO), the northern mode does not show an obvious relation to the tropical sea surface temperature (SST) change or to the North Atlantic Oscillation (NAO)/Arctic Oscillation (AO) on the interannual time scale. Distinct snow cover and sea ice changes appear as responses to wind and surface temperature changes associated with the two modes and their effects on the EAWM variability need to be investigated in the future.
Affective team climate
Authors: Levecque Katia , Roose Henk , Vanroelen Christophe , Rossem Ronan Van
Published: September 2013

In occupational health research, the demand–control–support (DCS) model has attracted a great deal of attention. Although this model emphasizes the interaction between workers and their work environment, the DCS framework has mainly been tested at the micro-level. The present study shows that combining the DCS model with insights from organizational climate studies offers a fruitful theoretical framework by which to address variation in psychological distress in team workers. Hierarchical logistic regression using data on 1,098 workers from 97 teams in a car factory in Belgium reveals that a positive perception of the affective climate in one’s team lowers levels of psychological distress. In addition, the team’s affective climate, emerging from and reproduced within everyday social interaction between team members, plays a significant role of its own in the well-being of team members. When the affective team climate is positive, all team members benefit in terms of distress levels, even those workers who hold a negative perception of their emotional work environment. Part of the health effects of a positive climate runs through moderating the health-damaging effects of high job demands.
A Relational Theory of Earnings Inequality
Authors: Avent-Holt Dustin , Tomaskovic-Devey Donald
Published: September 2013

Most research on earnings adopts economist’s human capital model. In doing so, social scientists, explicitly or implicitly, cede primacy to the labor supply and demand mechanisms of neoclassical economics. In contrast we develop a model that treats actors’ claims as the central mechanism generating inequalities. In this model earnings are most proximately a result of negotiation between actors embedded in a set of social relations within organizations, a process we refer to as relational claims-making. Institutional and competitive aspects of organizational environments, as well as social distinctions within organizations themselves, provide resources and constraints on the persuasiveness and plausibility of wage claims by actors. Market mechanisms are not causally proximate to the production of wage inequality, but rather are an aspect of actor’s environments with the potential to influence the plausibility of particular claims.
A comparison between the predictive capability of matrix cracking, damage and failure criteria for fibre reinforced composite laminates: Part A of the third world-wide failure exercise
Authors: Kaddour AS , Hinton MJ , Smith PA , Li S
Published: September 2013

This paper provides a set of concluding remarks on Part A of the third world-wide failure exercise where a comparison has been made between the capabilities of 12 different mathematical models for predicting the evolution of matrix cracking, damage and failure in continuous fibre-reinforced polymer composites when subjected to multi-axial loading. The originators (or their collaborators) of those theories have employed their methods to 13 carefully selected challenging problems (test cases) addressing the cracking and damage evolution arising from ply thickness, lay-up sequence, size effects and a variety of loading conditions (biaxial, bending, thermal loading and loading-unloading) of a number of unidirectional and multi-directional glass and carbon epoxy laminates. These covered eight different lay-ups consisting of 0°, [0°/90°/0°], [0°/90°8/0°], [0°/90°]s, [±45°]s, [±50°]s, [30°/90°/−30°/90°]s and a family of [0°m/45°m/90°m/−45°m]s, [45°/0°/90°/−45°]s and [0°/45°/−45°/90°]s quasi-isotropic laminates. Key features in each theory are identified including: types of damage models employed, whether linear or nonlinear analysis was carried out, reliance on software and numerical methods and identification of modes of damage. The results of stress–strain curves, crack density and damage curves have been superimposed and bar charts were constructed to show similarities and differences between the predictions of the various theories.
The Domestic Sources of Donor Credibility
Authors: Eng Man Yan , Urpelainen Johannes
Published: September 2013

Donors often condition foreign aid to recipients on policy adjustments. How do domestic interest groups influence a donor’s ability to credibly commit to implementing threats and promises? In our model, domestic interest groups in the donor country can mobilize to support the donor’s implementation of punishments and rewards. The expectation of such mobilization influences the credibility of threats and promises at the prior contracting stage. The analysis produces three central findings. First, the donor chooses to rely on a single instrument when the domestic interest group exhibits a strong preference for that instrument, even if the cost of using that instrument is relatively high. Second, for credibility reasons the donor often promises generous rewards or threatens ruthless sanctions that seem out of proportion. Finally, the donor cannot simultaneously make credible threats and promises unless domestic interest groups mobilize to support both instruments. We examine the case of US foreign aid to Israel and Palestine to illustrate these theoretical propositions.
Legislative Governance in Times of International Terrorism
Authors: König Thomas , Finke Daniel
Published: September 2013

How do political parties with different policy-making interests and veto power respond to international terrorism—can coalition parties and bicameral legislatures overcome their policy-making tensions and form a unified front for adopting counterterrorist measures? This study examines German counterterrorist legislation before and after the attacks of 9/11 by using a dictionary-based computerized text analysis. Our findings demonstrate that in times of low threat, the level of intra-coalition and bicameral conflict decreases the likelihood of counterterrorist legislation. However, in the event of a high external threat, this effect disappears despite the continuing divergence in partisan policy preferences. This suggests that a high external threat imposes inaction costs on political parties, which they attempt to avoid by adopting counterterrorist measures in the legislative arena.
Physiological Awareness Is Negatively Related to Inhibitory Functioning in Tourette Syndrome
Authors: Eddy Clare M. , Rickards Hugh E. , Cavanna Andrea E.
Published: September 2013

In Tourette syndrome (TS), tics are characteristically preceded by subjective bodily experiences referred to as premonitory sensations. Premonitory sensory phenomena play a key role in behavior therapy for tics, the success of which has also been suggested to be related to inhibitory functioning. We investigated whether TS was associated with altered internal physiological awareness and how this may interact with the neuropsychological characteristics of TS. We compared the awareness of bodily sensations and inhibitory functioning in 18 adult patients with uncomplicated TS and 18 healthy controls. We also explored relationships between these factors, tic severity, and premonitory sensations. Patients with TS exhibited significantly higher scores on the Private Body Consciousness (PBC) scale and inhibitory deficits on traditional and emotional Stroop tests. PBC scores were not correlated with premonitory sensations or tic severity. However, inhibitory functioning was negatively related to PBC scores and premonitory sensations. Relationships between inhibitory performance and tic severity were complex. In conclusion, patients with TS exhibit increased PBC in addition to inhibitory deficits. Aspects of inhibitory functioning are related to PBC, premonitory sensations, and tic severity. Complex interplay between neuropsychological and neurophysiological mechanisms could therefore determine tic severity and the success of behavioral treatments.