bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Credit Surge in Historical Context
Authors: Ohnsorge Franziska , Yu Shu
Published: March 2017

Benign financing conditions since the global financial crisis and, more recently, rising financing needs have fueled a rapid increase in credit to the nonfinancial private sector, especially to the corporate sector in emerging markets and developing economies (EMDEs). In this paper, we first compare post-crisis credit booms with pre-crisis episodes of credit booms and document some distinctive features of post-crisis credit booms. We find that, credit booms in commodity-importing EMDEs in the immediate wake of the global financial crisis have subsided since 2012 but have left a legacy of credit to the nonfinancial private sector that has been considerably higher than in previous credit booms. In contrast, since 2014, credit growth in several commodity-exporting EMDEs has been near the pace observed in past credit booms. We then benchmark current credit-to-gross domestic product (GDP) ratios against thresholds identified in the literature as early warning indicators. Most EMDEs are still some distance away from those thresholds. However, since recent credit booms have not been accompanied by investment surges/booms, GDP growth may contract more when credit booms unwind.
Policy Inconsistencies and the Political Economy of Currency Crises
Authors: Amri Puspa D. , Willett Thomas D.
Published: March 2017

Formal models of currency crises have shown that inconsistencies between countries' domestic and exchange rate policies are a major cause of currency crises. To understand why such prolonged inconsistencies exist, we need to go beyond standard economic models and take political economy and behavioral considerations into account. We sketch out ways in which such considerations can be taken into account and highlight recent research that is useful for this project. We also offer some directions for future research and a brief guide to the empirical identification of currency crises and to the measurements of some of the relevant political and economic policy variables.
Structural Economic Vulnerability, Trade Policy and FDI Inflows
Authors: Gnangnon Sèna Kimm , Iyer Harish
Published: March 2017

This paper investigates two questions: first, how does countries' structural economic vulnerability (EVI) affect their foreign direct investment (FDI) inflows; second, how does EVI influence FDI inflows when host countries further liberalize their trade policies. The empirical analysis provides evidence that EVI influences negatively FDI inflows and that, in the context of greater trade policy liberalization, this vulnerability deters FDI only when it exceeds a certain threshold. These results call for enhanced cooperation between national governments and the international community to address developing countries, least-developed countries' EVI in order to ensure greater FDI inflows, which are critical for their economic development.
Hydrogen storage in a heterogeneous sandstone formation: dimensioning and induced hydraulic effects
Authors: Pfeiffer Wolf Tilmann , Beyer Christof , Bauer Sebastian
Published: March 2017

Large-scale energy storage in the geological subsurface (e.g. by storing hydrogen gas) may help to mitigate effects of a fluctuating energy production arising from the extensive use of renewable energy sources. The applicability of hydrogen (H
2
) storage in a porous sandstone formation is investigated by defining a usage scenario and a subsequent numerical simulation of a storage operation at an existing anticlinal structure in the North German Basin. A facies modelling approach is used to obtain 25 heterogeneous and realistic parameter sets. The storage operation consists of the initial filling with nitrogen used as cushion gas, the initial filling with H
2
, and six withdrawal periods with successive refilling and shut-in periods. It is found that, on average, the storage can sustain a continuous power output of 245 MW for 1 week when using five storage wells, while peak performance can be as high as 363 MW, indicating that the storage is mainly limited by the achievable extraction rates. The median of the maximum pressure perturbation caused by this storage is around 3 bars and can be observed at a distance of 5 km from the wells.
The Energy of Data
Authors: Székely Gábor J. , Rizzo Maria L.
Published: March 2017

The energy of data is the value of a real function of distances between data in metric spaces. The name energy derives from Newton's gravitational potential energy, which is also a function of distances between physical objects. One of the advantages of working with energy functions (energy statistics) is that even if the data are complex objects, such as functions or graphs, we can use their real-valued distances for inference. Other advantages are illustrated and discussed in this review. Concrete examples include energy testing for normality, energy clustering, and distance correlation. Applications include genome studies, brain studies, and astrophysics. The direct connection between energy and mind/observations/data in this review is a counterpart of the equivalence of energy and matter/mass in Einstein's E=mc2.
Rationale for the use of statins in liver disease
Authors: Schierwagen Robert , Uschner Frank Erhard , Magdaleno Fernando , Klein Sabine , Trebicka Jonel
Published: March 2017

The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.
Mild hypothermia preserves myocardial conduction during ischemia by maintaining gap junction intracellular communication and Na+ channel function
Authors: Nassal Michelle M. J. , Wan Xiaoping , Dale Zack , Deschênes Isabelle , Wilson Lance D. , Piktel Joseph S.
Published: March 2017

Acute cardiac ischemia induces conduction velocity (CV) slowing and conduction block, promoting reentrant arrhythmias leading to sudden cardiac arrest. Previously, we found that mild hypothermia (MH; 32°C) attenuates ischemia-induced conduction block and CV slowing in a canine model of early global ischemia. Acute ischemia impairs cellular excitability and the gap junction (GJ) protein connexin (Cx)43. We hypothesized that MH prevented ischemia-induced conduction block and CV slowing by preserving GJ expression and localization. Canine left ventricular preparations at control (36°C) or MH (32°C) were subjected to no-flow prolonged (30 min) ischemia. Optical action potentials were recorded from the transmural left ventricular wall, and CV was measured throughout ischemia. Cx43 and Na+ channel (NaCh) remodeling was assessed using both confocal immunofluorescence (IF) and/or Western blot analysis. Cellular excitability was determined by microelectrode recordings of action potential upstroke velocity (d V/d tmax) and resting membrane potential (RMP). NaCh current was measured in isolated canine myocytes at 36 and 32°C. As expected, MH prevented conduction block and mitigated ischemia-induced CV slowing during 30 min of ischemia. MH maintained Cx43 at the intercalated disk (ID) and attenuated ischemia-induced Cx43 degradation by both IF and Western blot analysis. MH also preserved d V/d tmax and NaCh function without affecting RMP. No difference in NaCh expression was seen at the ID by IF or Western blot analysis. In conclusion, MH preserves myocardial conduction during prolonged ischemia by maintaining Cx43 expression at the ID and maintaining NaCh function. Hypothermic preservation of GJ coupling and NaCh may be novel antiarrhythmic strategies during resuscitation.

NEW & NOTEWORTHY Therapeutic hypothermia is now a class I recommendation for resuscitation from cardiac arrest. This study determined that hypothermia preserves gap junction coupling as well as Na+ channel function during acute cardiac ischemia, attenuating conduction slowing and preventing conduction block, suggesting that induced hypothermia may be a novel antiarrhythmic strategy in resuscitation.
Annexin A2 contributes to lung injury and fibrosis by augmenting factor Xa fibrogenic activity
Authors: Schuliga Michael , Jaffar Jade , Berhan Asres , Langenbach Shenna , Harris Trudi , Waters David , Lee Peter V. S. , Grainge Christopher , Westall Glen , Knight Darryl , Stewart Alastair G.
Published: March 2017

In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into factor Xa (FXa), a coagulant protease with fibrogenic actions. Extracellular annexin A2 binds to FXa, augmenting activation of the protease-activated receptor-1 (PAR-1). In this study, the contribution of annexin A2 in lung injury and fibrosis was investigated. Annexin A2 immunoreactivity was observed in regions of fibrosis, including those associated with fibroblasts in lung tissue of IPF patients. Furthermore, annexin A2 was detected in the conditioned media and an EGTA membrane wash of human lung fibroblast (LF) cultures. Incubation with human plasma (5% vol/vol) or purified FXa (15–50 nM) evoked fibrogenic responses in LF cultures, with FXa increasing interleukin-6 (IL-6) production and cell number by 270 and 46%, respectively ( P < 0.05, n = 5–8). The fibrogenic actions of plasma or FXa were attenuated by the selective FXa inhibitor apixaban (10 μM, or antibodies raised against annexin A2 or PAR-1 (2 μg/ml). FXa-stimulated LFs from IPF patients ( n = 6) produced twice as much IL-6 as controls ( n = 10) ( P < 0.05), corresponding with increased levels of extracellular annexin A2. Annexin A2 gene deletion in mice reduced bleomycin-induced increases in bronchoalveolar lavage fluid (BALF) IL-6 levels and cell number (* P < 0.05; n = 4–12). Lung fibrogenic gene expression and dry weight were reduced by annexin A2 gene deletion, but lung levels of collagen were not. Our data suggest that annexin A2 contributes to lung injury and fibrotic disease by mediating the fibrogenic actions of FXa. Extracellular annexin A2 is a potential target for the treatment of IPF.
Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice
Authors: Chatel Benjamin , Messonnier Laurent A. , Hourdé Christophe , Vilmen Christophe , Bernard Monique , Bendahan David
Published: March 2017

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice ( P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls ( P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice.

NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD.
Pancreatic Cancer Progression Relies upon Mutant p53-Induced Oncogenic Signaling Mediated by NOP14
Authors: Du Yongxing , Liu Ziwen , You Lei , Hou Pengjiao , Ren Xiaoxia , Jiao Tao , Zhao Wenjing , Li Zongze , Shu Hong , Liu Changzheng , Zhao Yupei
Published: March 2017

Mutant p53 (mutp53) proteins promote tumor invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying sustained activation of mutp53 oncogenic signaling is currently unclear. In this study, we report that NOP14 nucleolar protein (NOP14) expression is upregulated in PDAC tumors and metastatic tissue specimens. NOP14 overexpression promoted cell motility, whereas NOP14 inhibition decreased invasive capacity of PDAC cells. In vivo invasion assays conducted on established subcutaneously, orthotopically, and intravenously injected tumor mouse models also indicated NOP14 as a promoter of PDAC metastasis. Mechanistically, mutp53 was validated as a functional target of NOP14; NOP14 primed tumor invasion and metastasis by increasing the stability of mutp53 mRNA. The NOP14/mutp53 axis suppressed p21 expression at both the transcriptional and posttranscriptional levels via induction of miR-17-5p in PDAC cells. In vivo, high NOP14 expression in PDAC patient tumors correlated with local metastasis and lymph invasion. Overall, our findings define a novel mechanism for understanding the function of NOP14 in the metastatic cascade of PDAC. Targeting NOP14 allows for effective suppression of tumor invasion in a mutp53-dependent manner, implicating NOP14 inhibition as a potential approach for attenuating metastasis in p53-mutant tumors. Cancer Res; 77(10); 2661–73. ©2017 AACR.
Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients
Authors: Dolstra Harry , Roeven Mieke W.H. , Spanholtz Jan , Hangalapura Basav N. , Tordoir Marleen , Maas Frans , Leenders Marij , Bohme Fenna , Kok Nina , Trilsbeek Carel , Paardekooper Jos , van der Waart Anniek B. , Westerweel Peter E. , Snijders Tjeerd J.F. , Cornelissen Jan , Bos Gerard , Pruijt Hans F.M. , de Graaf Aniek O. , van der Reijden Bert A. , Jansen Joop H. , van der Meer Arnold , Huls Gerwin , Cany Jeannette , Preijers Frank , Blijlevens Nicole M.A. , Schaap Nicolaas M.
Published: March 2017

Purpose: Older acute myeloid leukemia (AML) patients have a poor prognosis; therefore, novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting a unique scalable NK-cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPC) from partially HLA-matched umbilical cord blood units.

Experimental Design: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30 × 106/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.

Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1 × 104 T cells/kg and <3 × 105 B cells/kg body weight. HSPC-NK cells were well tolerated, and neither graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting being given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL15 plasma levels. Moreover, donor chimerism up to 3.5% was found in bone marrow. Interestingly, in vivo HSPC-NK cell maturation was observed, indicated by the rapid acquisition of CD16 and KIR expression, while expression of most activating receptors was sustained. Notably, 2 of 4 patients with minimal residual disease (MRD) in bone marrow before infusion became MRD negative (<0.1%), which lasted for 6 months.

Conclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential “off-the-shelf” translational immunotherapy approach in AML. Clin Cancer Res; 23(15); 4107–18. ©2017 AACR.
Pooled Clustering of High-Grade Serous Ovarian Cancer Gene Expression Leads to Novel Consensus Subtypes Associated with Survival and Surgical Outcomes
Authors: Wang Chen , Armasu Sebastian M. , Kalli Kimberly R. , Maurer Matthew J. , Heinzen Ethan P. , Keeney Gary L. , Cliby William A. , Oberg Ann L. , Kaufmann Scott H. , Goode Ellen L.
Published: March 2017

Purpose: Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC).

Experimental Design: Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information.

Results: Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had downregulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (P < 0.001) and with rate of optimal surgical debulking (≤1 cm, P = 1.9E−4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (P = 0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors compared with >28% in other subtypes; P = 0.02).

Conclusions: HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. Clin Cancer Res; 23(15); 4077–85. ©2017 AACR.
Elevated Serum Uric Acid Level Predicts Rapid Decline in Kidney Function
Authors: Kuwabara Masanari , Bjornstad Petter , Hisatome Ichiro , Niwa Koichiro , Roncal-Jimenez Carlos A. , Andres-Hernando Ana , Jensen Thomas , Milagres Tamara , Sato Yuka , Garcia Gabriela , Ohno Minoru , Lanaspa Miguel A. , Johnson Richard J.
Published: March 2017

Background: While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease, it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5 years in a general Japanese population. Methods: This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30-85 years) in our analyses whose data were available between 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73 m2 at baseline. In addition to examining the entire cohort (n = 12,578), we stratified our analyses by baseline eGFR groups: 60-90, 90-120, and ≥120 mL/min/1.73 m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR, and rapid eGFR decline (defined as the highest quartile of change in eGFR), adjusted for age, gender, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. Results: After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR 1.27, 95% CI 1.17-1.38), and 1 mg/dL increase in SUA over 5 years was associated with 3.77-fold greater odds of rapid eGFR decline (OR 3.77, 95% CI 3.35-4.26). Conclusions: Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5 years.
Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia
Authors: Mashima Kyoko , Ito Daisuke , Kameyama Masashi , Osada Takashi , Tabuchi Hajime , Nihei Yoshihiro , Yoshizaki Takahito , Noguchi Eri , Tanikawa Mariko , Iizuka Takashi , Date Yugaku , Ogata Yuji , Nakahara Tadaki , Iwabuchi Yu , Jinzaki Masahiro , Murakami Koji , Suzuki Norihiro
Published: March 2017

Background: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain β amyloid (Aβ) burden begins and progresses. Our study aimed to determine the prevalence of Aβ deposition in PD without dementia using amyloid PET. Methods: This was a cross-sectional study on 33 patients with PD without dementia, of whom 21 had normal cognition and 12 met the criteria for PD-mild cognitive impairment. All subjects underwent neuropsychological assessment and [18F] florbetaben (FBB) PET. Results: All subjects had Lewy body-related disorders, displaying a significantly reduced myocardial [123I] metaiodobenzylguanidine uptake. The cortical FBB-binding pattern in all subjects, including APOE e4 carriers, suggested negative Aβ deposition. Conclusion: Patients with PD without dementia exhibit an extremely low prevalence of Aβ positivity compared with those reported in cognitively normal elderly controls. Further longitudinal imaging studies and long-term follow-up are needed; however, our findings provide novel insights for understanding Aβ metabolism in PD.
A NECESSIDADE DE PARÂMETROS PARA A EFETIVAÇÃO DO DIREITO À SAÚDE: A JUDICIALIZAÇÃO DO ACESSO AO HORMÔNIO DO CRESCIMENTO NO ESTADO DO PARÁ
Authors: Verbicaro Loiane Prado , Santos Andreza Casanova Vongrapp
Published: March 2017

O presente trabalho é resultado de pesquisa acerca da aquisição do medicamento somatropina, o hormônio do crescimento, pela Secretaria de Saúde Pública do Estado do Pará no período que compreende os anos de 2009 a 2013. O estudo teve como objetivo analisar os efeitos da judicialização do acesso ao medicamento com base na medida liminar exarada, nos autos da Ação Civil Pública n. 0021681-17.2011.8.14.0301, que determinou ao Estado do Paráo fornecimento do medicamento Hormotrop® – Somatropina 12 UI para todas as crianças e adolescentes com deficiência na produção de hormônio do crescimento; e demonstrar, através de um caso concreto, a necessidade de estabelecer parâmetros que possam subsidiar o Poder Judiciário na análise das ações que visam a efetivar o direito à saúde. Foi realizada pesquisa bibliográfica sobre os aspectos jurídicos que envolvem o processo de judicialização da saúde, bem como sobre os aspectos técnicos e psicológicos atinentes ao uso do hormônio do crescimento e acerca das políticas públicas relacionadas a seu acesso. Os dados coletados demonstraram que houve mudança no padrão de consumo do medicamento somatropina a partir do ano de 2011 – mesmo período em que foi proferida a decisão liminar na referida ação civil pública. Tal conclusão suscita a necessidade de estabelecer parâmetros baseados em critérios técnicos na análise das ações que envolvem questões relacionadas a medicamentos, em um contexto de crescente judicialização da política e das relações sociais no Brasil.
DIREITO SANITÁRIO GLOBAL: TEMAS, ATORES E PROCESSOS
Authors: Freitas Roberta de
Published: March 2017

Proteger a saúde pública e melhorar os indicadores individuais de saúde envolve cada vez mais inovações na legislação nacional e internacional. Além das tradicionais organizações internacionais voltadas para a saúde (Organização Pan-Americana da Saúde, Organização Mundial da Saúde), nota-se no cenário global um incremento de outros atores que dispõem de normas e regulamentos próprios e que repercutem e interferem de forma direta ou indireta na área da saúde, tais como a Organização Mundial do Comércio, o Banco Mundial, fundações privadas etc. O presente artigo não tem por objetivo esgotar a reflexão conceitual sobre o Direito Sanitário Global, mas procura caracterizá-lo a partir de três elementos que o integram: temas, atores e processos políticos de negociação.
A EFETIVAÇÃO JURÍDICO-POLÍTICA DO DIREITO À SAÚDE NO SUPREMO TRIBUNAL FEDERAL: A REFERÊNCIA PARADIGMÁTICA DA SL 47-AGR/PE
Authors: Dallari Sueli Gandolfi , Maggio Marcelo Paulo
Published: March 2017

A saúde é direito fundamental, essencial à proteção e à manutenção da vida, pressuposto da dignidade da pessoa humana, possuindo papel de destaque na complexa realidade social que integramos. Como tal, deve ser incansavelmente protegido, respeitado e garantido mediante políticas sociais e econômicas, em prol do interesse de cada indivíduo e da própria sociedade, consoante, inclusive, previsto na ordem constitucional. Nesse contexto, instado a se pronunciar, o Supremo Tribunal Federal, na qualidade de guardião da Constituição, tem a incumbência de proferir respostas capazes de proporcionar o bem-estar físico, mental e social devido a todos, em sintonia com o constitucionalmente previsto, no intuito de garantir adequado alcance jurídico e/ou político em suas decisões. Por isso, mostra-se relevante avaliar se a atuação da Corte, frente a casos concretos, efetivamente consegue respeitar a boa técnica jurídica e/ou política e, com essa finalidade, por enquadrá-la na condição de paradigma, optou-se por eleger o decisum prolatado no âmbito da Suspensão de Liminar 47 – Agravo Regimental do Estado de Pernambuco.
Plasmin Cleaves Von Willebrand Factor at K1491-R1492 in the A1–A2 Linker Region in a Shear- and Glycan-Dependent Manner In Vitro
Authors: Brophy Teresa M. , Ward Soracha E. , McGimsey Thomas R. , Schneppenheim Sonja , Drakeford Clive , O’Sullivan Jamie M. , Chion Alain , Budde Ulrich , O’Donnell James S.
Published: March 2017

Objective—

Previous studies have demonstrated a role for plasmin in regulating plasma von Willebrand factor (VWF) multimer composition. Moreover, emerging data have shown that plasmin-induced cleavage of VWF is of particular importance in specific pathological states. Interestingly, plasmin has been successfully used as an alternative to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif) in a mouse model of thrombotic thrombocytopenic purpura. Consequently, elucidating the molecular mechanisms through which plasmin binds and cleaves VWF is not only of basic scientific interest but also of direct clinical importance. Our aim was to investigate factors that modulate the susceptibility of human VWF to proteolysis by plasmin.

Approach and Results—

We have adapted the VWF vortex proteolysis assay to allow for time-dependent shear exposure studies. We show that globular VWF is resistant to plasmin cleavage under static conditions, but is readily cleaved by plasmin under shear. Although both plasmin and ADAMTS13 cleave VWF in a shear-dependent manner, plasmin does not cleave at the Tyr1605-Met1606 ADAMTS13 proteolytic site in the A2 domain. Rather under shear stress conditions, or in the presence of denaturants, such as urea or ristocetin, plasmin cleaves the K1491-R1492 peptide bond within the VWF A1–A2 linker region. Finally, we demonstrate that VWF susceptibility to plasmin proteolysis at K1491-R1492 is modulated by local N-linked glycan expression within A1A2A3, and specifically inhibited by heparin binding to the A1 domain.

Conclusions—

Improved understanding of the plasmin–VWF interaction offers exciting opportunities to develop novel adjunctive therapies for the treatment of refractory thrombotic thrombocytopenic purpura.
Identification of Cadherin 2 (
CDH2
) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Mayosi Bongani M. , Fish Maryam , Shaboodien Gasnat , Mastantuono Elisa , Kraus Sarah , Wieland Thomas , Kotta Maria-Christina , Chin Ashley , Laing Nakita , Ntusi Ntobeko B.A. , Chong Michael , Horsfall Christopher , Pimstone Simon N. , Gentilini Davide , Parati Gianfranco , Strom Tim-Matthias , Meitinger Thomas , Pare Guillaume , Schwartz Peter J. , Crotti Lia
Published: March 2017

Background—

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous condition caused by mutations in genes encoding desmosomal proteins in up to 60% of cases. The 40% of genotype-negative cases point to the need of identifying novel genetic substrates by studying genotype-negative ARVC families.

Methods and Results—

Whole exome sequencing was performed on 2 cousins with ARVC. Validation of 13 heterozygous variants that survived internal quality and frequency filters was performed by Sanger sequencing. These variants were also genotyped in all family members to establish genotype–phenotype cosegregation. High-resolution melting analysis followed by Sanger sequencing was used to screen for mutations in cadherin 2 (
CDH2
) gene in unrelated genotype-negative patients with ARVC. In a 3-generation family, we identified by whole exome sequencing a novel mutation in
CDH2
(c.686A>C, p.Gln229Pro) that cosegregated with ARVC in affected family members. The
CDH2
c.686A>C variant was not present in >200 000 chromosomes available through public databases, which changes a conserved amino acid of cadherin 2 protein and is supported as the causal mutation by parametric linkage analysis. We subsequently screened 73 genotype-negative ARVC probands tested previously for mutations in known ARVC genes and found an additional likely pathogenic variant in
CDH2
(c.1219G>A, p.Asp407Asn).
CDH2
encodes cadherin 2 (also known as N-cadherin), a protein that plays a vital role in cell adhesion, making it a biologically plausible candidate gene in ARVC pathogenesis.

Conclusions—

These data implicate
CDH2
mutations as novel genetic causes of ARVC and contribute to a more complete identification of disease genes involved in cardiomyopathy.
Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death
Authors: Ghasemzadeh Nima , Hayek Salim S. , Ko Yi-An , Eapen Danny J. , Patel Riyaz S. , Manocha Pankaj , Al Kassem Hatem , Khayata Mohamed , Veledar Emir , Kremastinos Dimitrios , Thorball Christian W. , Pielak Tomasz , Sikora Sergey , Zafari A. Maziar , Lerakis Stamatios , Sperling Laurence , Vaccarino Viola , Epstein Stephen E. , Quyyumi Arshed A.
Published: March 2017

Background—

Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification.

Methods and Results—

C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden’s index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43–2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points.

Conclusions—

SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.
New earthworm species of Righiodrilus (Clitellata, Glossoscolecidae) from eastern Amazonia
Authors: SANTOS BIANCA TAMIRES SILVA DOS , BARTZ MARIE LUISE CAROLINE , HERNÁNDEZ-GARCÍA LUIS MANUEL , ROUSSEAU GUILLAUME XAVIER , MARTINS MARLUCIA BONIFÁCIO , JAMES SAMUEL WOOSTER
Published: March 2017

Three new species of the glossoscolecid earthworm genus Righiodrilus are described from material collected in northern Pará and Maranhão States, Brazil. Rhigiodrilus gurupi n. sp. is characterized by four pairs of post-testicular spermathecae in xiv–xvii. Rhigiodrilus viseuensis n. sp. is distinguished by tubercula pubertatis in xix–xxiii and clitellum in xvi–xxiii. Rhigiodrilus moju n. sp. is the only species in the genus that lacks tubercula pubertatis. We provide an updated key and a distribution map for all species of Righiodrilus.
Phylogenetic analysis of the Neotropical Pristimantis leptolophus species group (Anura: Craugastoridae): molecular approach and description of a new polymorphic species
Authors: RIVERA-CORREA MAURICIO , JIMÉNEZ-RIVILLAS CARLOS , DAZA JUAN M.
Published: March 2017

Pristimantis, distributed throughout the New World tropics, is the most speciose vertebrate genus. Pristimantis presents an enormous morphological diversity and is currently divided into several demonstrably non-monophyletic phenetic species groups. With the purpose of increasing our understanding of Pristimantis systematics, we present the first phylogenetic analysis using molecular evidence to test the monophyly and infer evolutionary relationships within the Pristimantis leptolophus group, an endemic group of frogs from the highlands of the Colombian Andes. Our phylogenetic reconstruction recovers the group as monophyletic with high support, indicating general concordance between molecular data and morphological data. In addition, we describe a new polymorphic species lacking conspicuous tubercles, a regular attribute among species of the P. leptolophus species group and endemic from the Páramo de Sonsón complex (Antioquia, Colombia). The phylogenetic position of the new species is inferred and other systematic implications in the light of our results are discussed.
Predictive Nomogram of RAGE Genetic Polymorphisms and Metabolic Risk Factors for Myocardial Infarction Risk in a Han Chinese Population
Authors: Li Weiming , Li Yingxue , Zhang Zhiyong , Xia Kun , Shang Xiaoming , Yang Xinchun , Wang Lefeng , Zhang Qi
Published: March 2017

We investigated the association of 4 well-characterized polymorphisms in receptor for the advanced glycation end-product ( RAGE) gene with myocardial infarction (MI) risk and the changes in metabolic risk factors among 717/612 patients/controls, with the aim of constructing a predictive nomogram. The genotype/allele distributions differed significantly between the 2 groups for T-429C ( Pgenotype/allele = .004/.001) and G1704T ( P < .001/.001). T-429C was significantly associated with MI risk, especially under a recessive model (adjusted odds ratio: 2.24, 95% confidence interval: 1.33-3.79, P = .003). For G1704T, significance was detected under additive (1.37; 1.12-1.67; P = .002) and recessive (3.86; 2.27-6.57; P < .001) models. There were significant differences in blood pressure and low-density lipoprotein cholesterol (LDL-C) across T-429C genotypes and in total cholesterol and LDL-C across G1704T genotypes. The overall best multifactor dimensionality reduction model included dyslipidemia, G1704T, and T-429C. Further predictive nomogram on 2 significant polymorphisms, blood pressure and lipids, showed a better predictive capability (concordance index = 0.716, P < .001). Altogether, we identified 2 polymorphisms of RAGE, T-429C and G1704T, which interacted with metabolic risk factors associated with the occurrence of MI. We also constructed a genetic–metabolic nomogram that can better predict MI risk.
Income Inequality, Entrepreneurial Activity, and National Business Systems: A Configurational Analysis
Authors: Lewellyn Krista B.
Published: March 2017

This article explores how and why high levels of income inequality result from configurations of different types of entrepreneurial activities and elements of the institutional context in a multicountry sample. A configurational approach is used to unpack the complexities associated with how income inequality arises from different types of entrepreneurial activities embedded in different institutional contexts associated with Whitley’s national business systems dimensions. The findings from fuzzy-set qualitative comparative analysis reveal that high levels of both high-growth and necessity entrepreneurial activity are associated with income inequality in certain contexts that are characterized by distinct institutional complementarities.
Need–Supply Fit in an Activity-Based Flexible Office: A Longitudinal Study During Relocation
Authors: Gerdenitsch Cornelia , Korunka Christian , Hertel Guido
Published: March 2017

Combinations of concentrated work and interactions are facilitated by office environments such as activity-based flexible offices (A-FOs). A-FOs are characterized by activity-based workspaces, an open-plan layout, and desk sharing. Although there is a growing enthusiasm for replacing cellular offices with A-FOs, the effects of such changes on office workers are still unclear. Within this three-wave longitudinal study, we investigated the changes (time lag of 1 and 8 months after the redesign) in perceived need–supply fit, distraction, interaction across teams, and workspace satisfaction during relocation from a cellular office to an A-FO. Moreover, as previous case studies indicated individual differences in the use of A-FOs, we considered participants’ perceived need–supply fit as a moderator indicating an appropriate use of A-FO supplies. We found a linear increase of perceived need–supply fit, a decrease in distraction, and a significant interaction effect where workspace satisfaction and interaction across teams increased more strongly for participants reporting a better perceived need–supply fit.
“Fili d’oro”: Literature, painting, and blindness in D’Annunzio’s Notturno
Authors: Mirabile Andrea
Published: March 2017

This article analyzes the relationships between literature and the arts in D’Annunzio’s Notturno. The verbal and the visual constantly intersect in the poet’s corpus. Nevertheless, the Notturno is unique: according to the narrator, he composes the text during a period of semi-blindness caused by a war-related accident. Consequently, the protagonist is unable to see his favorite works of art, which are described through the filters of memory, desire, and imagination. D’Annunzio’s nocturnal ekphrasis blends wake and dream, asceticism and eroticism, narrative linearity and poetical fragmentation. Vision and writing deconstruct their own conventional separations: the elements of each form mingle in a dimension that reflects simultaneously the influence of the Decadent age and the birth of Modernism. Despite the scarce scholarly attention devoted to the Notturno outside the borders of Italy, D’Annunzio’s text anticipates the current debates on the aporias of sight (Derrida), the ambiguous temporality of the visual arts (Didi-Huberman), and the contradictory distinction between ‘internal’ and ‘external’ vision (Belting).
Factors that affect the empathy constructs among a sample of clinical social workers in Kuwait
Authors: Al-Ma’seb Hend
Published: March 2017

Empathy is an important tool that clinical social workers use during their interventions with clients. This study aims to explore the knowledge base on empathy among clinical social workers in Kuwait. It investigates the relationship between empathy and three constructs and some demographic variables. The sample ( N = 527) consisted of clinical social workers practicing in Kuwait. The findings revealed significant relationships (1) between empathy, compassionate contextual assessment, intrinsic help and emotional support, and gender; (2) between empathy, compassionate contextual assessment, and participants’ majors in college; and (3) between empathy, intrinsic help and emotional support, and participants’ income.
Biodegradable glycerol-based polymeric composites filled with industrial waste materials
Authors: Kasetaite Sigita , Ostrauskaite Jolita , Grazuleviciene Violeta , Bridziuviene Danguole , Rainosalo Egidija
Published: March 2017

The aim of this work was preparation and investigation of the polymeric composites from naturally occurring materials with the properties similar to those of conventional polymer composites and which can degrade to harmless substances after use. The other target of this work was to estimate the applicability of industrial waste materials as fillers in the polymeric composites and thus to offer a potential exploitation of biodegradable waste materials as an alternative to disposal. In this study, the polymeric composites were prepared by photopolymerization of glycerol diglycidyl ether and different industrial waste materials (rapeseed cake, phosphogypsum and horn meal) using a mixture of triarylsulfonium hexafluoroantimonates as photoinitiator. The effect of the amount and nature of the industrial waste materials on the kinetics of photopolymerization, values of contact angle and surface free energy, mechanical, thermal, rheological properties, swelling in water and biodegradability of the polymeric composites was studied. The incorporation of the selected industrial waste fillers into glycerol-based polymeric composites increased swelling in water, adhesiveness, biodegradability and reduced Young modulus values.
Students’ Value Orientations in Contemporary China: Analysis of Measurement Invariance and Latent Mean Differences in Comparison With Students From Germany and Russia
Authors: Heim E. , Scholten S. , Maercker A. , Xiu D. , Cai D. , Gao Z. H. , Lu S. , Sang Z. Q. , Wei J. , Kochetkov Y. , Margraf J.
Published: March 2017

The present study examined Chinese students’ personal value orientations according to the Schwartz value theory in comparison with students from Germany and Russia. The theory postulates 10 value orientations grouped into four higher-order factors: conservation versus openness to change and self-transcendence versus self-enhancement. Schwartz’ value orientations have been extensively investigated in Europe but less in East Asian countries such as China. We hypothesized that Chinese students would score higher on conservation and self-enhancement than German and Russian students, but lower on self-transcendence. Regarding openness to change, a null hypothesis was formulated. Students from China ( n = 9,601), Germany ( n = 1,118), and Russia ( n = 3,890) completed the Portrait Values Questionnaire (PVQ-21). To ensure methodological preconditions for cross-cultural comparison, measurement invariance of the PVQ-21 was tested. In a first step, confirmatory Factor Analysis (CFA) was conducted separately for each country. Due to the high correlation between the 10 values, the four higher-order dimensions were studied separately. Configural, metric, and scalar invariance models were tested using multigroup CFA. Full metric and partial scalar invariance models held for all higher-order factors. Thereafter, latent means of values were compared across samples. As a result, Chinese students scored highest on the four higher-order dimensions when compared with Russian and German samples, thus the hypotheses were only partly confirmed. Results of this study could reflect the value conflicts emerging from various cultural influences in contemporary China: Young people are confronted with daily negotiation between Confucian tradition and the rapid economic development.
Stereotype Threat and Stereotype Reactance: The Effect of Direct and Indirect Stereotype Manipulations on Performance of Palestinian Citizens of Israel on Achievement Tests
Authors: Hakim Caesar , Kurman Jenny , Eshel Yohanan
Published: March 2017

The role of stereotype threat in performance of Palestinian citizens of Israel (PCI) on the psychometric exam (parallel to the SAT in the United States) was investigated. Two experiments, conducted in field settings, examined the role of stereotype threat in performance of PCI students in psychometric-like tests. Experiment 1, conducted on 135 Arab high school students, indicated that activation of the stereotype pertaining to the lower academic ability of PCI lowered participants’ performance relative to a control group. Experiment 2, which included 115 Arab students who participated in preparatory courses for the psychometric tests, showed that a direct manipulation of the stereotype led to stereotype reactance and increased performance, whereas an indirect manipulation activated the stereotype and resulted in lowered performance. These findings suggest that activating a stereotype threat or a stereotype reactance is contingent on the manipulation employed. Practical implications of these results are discussed.
Associations Between Methamphetamine Use, Housing Status, and Incarceration Rates Among Men Who Have Sex With Men and Transgender Women
Authors: Anderson-Carpenter Kaston D. , Fletcher Jesse B. , Reback Cathy J.
Published: March 2017

The present study examined associations between methamphetamine use and social factors among men who have sex with men (MSM) and transgender women. Over a 4-year period, 7,419 HIV outreach encounters were conducted with MSM ( n = 6,243) and transgender women ( n = 1,176). Logistic and negative binomial regressions estimated associations between sociodemographics, incarceration history, housing status, and methamphetamine use. Incarceration history was associated with marginal housing or homelessness (adjusted odds ratio [AOR] = 3.4) and with increased likelihood (AOR = 6.00) and adjusted incidence rate ratio (AIRR = 3.57) of methamphetamine use. African American/Black MSM and transgender women were more likely to report a recent incarceration history compared with non-African American/Black participants (AOR = 2.18). Incarceration history was associated with a HIV-positive status (AOR = 1.69), and transgender women were 5.2 times more likely to report recent incarceration relative to MSM. Understanding these associations may provide a basis for developing interventions that account for the social factors influencing health outcomes among these two high-risk populations.