bluuebunny/crossref_metadata_2025 huggingface dataset:
A Combination of Approved Antibodies Overcomes Resistance of Lung Cancer to Osimertinib by Blocking Bypass Pathways
Authors: Romaniello Donatella , Mazzeo Luigi , Mancini Maicol , Marrocco Ilaria , Noronha Ashish , Kreitman Matthew , Srivastava Swati , Ghosh Soma , Lindzen Moshit , Salame Tomer Meir , Onn Amir , Bar Jair , Yarden Yosef
Published: July 2018

Purpose: Because of emergence of resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), no targeted treatments are available for patients with lung cancer who lose sensitivity due to new mutations or bypass mechanisms. We examined in animals and in vitro an alternative therapeutic approach making use of antibodies.

Experimental Design: An osimertinib-sensitive animal model of lung cancer, which rapidly develops drug resistance, has been employed. To overcome compensatory hyperactivation of ERK, which we previously reported, an anti-EGFR antibody (cetuximab) was combined with other antibodies, as well as with a subtherapeutic dose of osimertinib, and cancer cell apoptosis was assayed.

Results: Our animal studies identified a combination of three clinically approved drugs, cetuximab, trastuzumab (an anti-HER2 mAb), and osimertinib (low dose), as an effective and long-lasting treatment that is able to prevent onset of resistance to osimertinib. A continuous schedule of concurrent treatment was sufficient for effective tumor inhibition and for prevention of relapses. Studies employing cultured cells and analyses of tumor extracts indicated that the combination of two mAbs and a subtherapeutic TKI dose sorted EGFR and HER2 for degradation; cooperatively enhanced apoptosis; inhibited activation of ERK; and reduced abundance of several bypass proteins, namely MET, AXL, and HER3.

Conclusions: Our in vitro assays and animal studies identified an effective combination of clinically approved drugs that might overcome resistance to irreversible TKIs in clinical settings. The results we present attribute the long-lasting effect of the drug combination to simultaneous blockade of several well-characterized mechanisms of drug resistance. Clin Cancer Res; 24(22); 5610–21. ©2018 AACR.

See related commentary by Fan and Yu, p. 5499
Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity
Authors: Baro Marta , Lopez Sambrooks Cecilia , Quijano Amanda , Saltzman W. Mark , Contessa Joseph
Published: July 2018

Purpose:

Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)–targeted therapies in glioma. We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.

Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1. The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles. The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging. A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.

Results:

NGI-1 reduced glycosylation, protein levels, and activation of most RTKs. NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation. NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest. Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls. Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.

Conclusions:

This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.

See related commentary by Wahl and Lawrence, p. 455
Targeted Therapy–based Combination Treatment in Rhabdomyosarcoma
Authors: van Erp Anke E.M. , Versleijen-Jonkers Yvonne M.H. , van der Graaf Winette T.A. , Fleuren Emmy D.G.
Published: July 2018

Targeted therapies have revolutionized cancer treatment; however, progress lags behind in alveolar (ARMS) and embryonal rhabdomyosarcoma (ERMS), a soft-tissue sarcoma mainly occurring at pediatric and young adult age. Insulin-like growth factor 1 receptor (IGF1R)-directed targeted therapy is one of the few single-agent treatments with clinical activity in these diseases. However, clinical effects only occur in a small subset of patients and are often of short duration due to treatment resistance. Rational selection of combination treatments of either multiple targeted therapies or targeted therapies with chemotherapy could hypothetically circumvent treatment resistance mechanisms and enhance clinical efficacy. Simultaneous targeting of distinct mechanisms might be of particular interest in this regard, as this affects multiple hallmarks of cancer at once. To determine the most promising and clinically relevant targeted therapy–based combination treatments for ARMS and ERMS, we provide an extensive overview of preclinical and (early) clinical data concerning a variety of targeted therapy–based combination treatments. We concentrated on the most common classes of targeted therapies investigated in rhabdomyosarcoma to date, including those directed against receptor tyrosine kinases and associated downstream signaling pathways, the Hedgehog signaling pathway, apoptosis pathway, DNA damage response, cell-cycle regulators, oncogenic fusion proteins, and epigenetic modifiers. Mol Cancer Ther; 17(7); 1365–80. ©2018 AACR.
CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a
Authors: Zhao Xiaohui , Xie Tian , Dai Ting , Zhao Wenhui , Li Jing , Xu Rui , Jiang Chao , Li Peiqiong , Deng Junyao , Su Xiaobo , Ma Ningfang
Published: July 2018

Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared with patients with low CHP2 expression. Moreover, it was demonstrated that overexpressing CHP2 significantly enhanced, whereas silencing endogenous CHP2 inhibited, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. In addition, overexpression of CHP2 accelerated, whereas inhibition of CHP2 retarded, G1–S phase cell-cycle transition in breast cancer cells. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor.

Implications: This study discovers a previously unrecognized role of CHP2 in the progression of breast cancer and supports the significance of this gene as a novel prognostic biomarker and a potential therapeutic target for breast cancer. Mol Cancer Res; 16(10); 1512–22. ©2018 AACR.
Macropinocytosis Fuels Prostate Cancer
Authors: Commisso Cosimo , Debnath Jayanta
Published: July 2018

Summary: Kim and colleagues identify necrotic debris as a macropinocytic cargo in PTEN-deficient prostate cancer cells, which is catabolized to generate the nutrients and biomass necessary to support tumor cell growth and metabolism in nutrient-limiting conditions. Cancer Discov; 8(7); 800–2. ©2018 AACR.

See related article by Kim et al., p. 866.
H2 Receptor Antagonists versus Proton Pump Inhibitors in Patients on Dual Antiplatelet Therapy for Coronary Artery Disease: A Systematic Review
Authors: Almufleh Aws , Ramirez F. Daniel , So Derek , Le May  Michel , Chong Aun-Yeong , Torabi Nazi , Hibbert Benjamin
Published: July 2018

Objectives: Mitigating the gastrointestinal (GI) bleeding risks of dual antiplatelet therapy (DAPT) is a common clinical concern. While proton pump inhibitors (PPIs) remain the most effective therapy, their adverse events warrant considering alternatives, including Histamine 2 receptor antagonists (H2RAs). Methods: We searched for randomized controlled trials in MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials, published from 1980 to 2016. After screening, 10 trials were eligible. We compared PPIs to H2RAs in patients on DAPT in terms of 2 clinical and one laboratory outcomes; GI complications, major adverse cardiovascular events (MACE) and high on-treatment platelet reactivity (HTPR). Clinical and statistical inter-study heterogeneity was low for all 3 outcomes (I2 = 0%, p > 0.05 for all). Results: Fixed effects meta-analysis suggested that PPIs were superior to H2RAs in preventing GI complications (OR 0.28, 95% CI 0.17–0.48) but with higher risk of HTPR (OR 1.28, 95% CI 1.030–1.60) though without a higher incidence of MACE (OR 0.99, 95% CI 0.55–1.77). Conclusions: PPIs are superior to H2RAs for gastroprotection in patients on DAPT. However, PPIs are associated with HTPR, with no significant difference demonstrated in MACE. Based on currently available data, the use of PPIs may be warranted in selected patients on DAPT deemed at risk for GI complications.
Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?
Authors: Abdelfattah Ramy , Kamran Haroon , Lazar Jason , Kassotis John
Published: July 2018

Objective: Caffeine has been considered a trigger for atrial fibrillation (AF). We conducted a meta-analysis including a dose-response analysis to assess the relationship between caffeine consumed and incidence of AF. Methods: Data from selected studies represented 176,675 subjects (AF in 9,987 [5.7%]). Caffeine content varied widely, ranging from 40 to 180 mg per cup of coffee. For purposes of the calculations in this study, we assumed 140 mg of caffeine in a standard 12-oz cup of coffee. Results: No significant difference was found in AF incidence when the subjects consuming less than 2 cups of coffee per day were compared to subjects with higher consumption, 1.068 (0.937–1.216). The risk of AF was higher among subjects consuming less than 2 cups of coffee daily when compared to higher daily consumption subjects. A lower incidence of AF was found among people consuming more than 436 mg daily. Conclusion: The incidence of AF is not increased by coffee consumption. In fact, we found a lower incidence of AF when caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence there is no association between caffeine intake and AF risk.
Understanding the Blind Spots of Psychosis: A Wittgensteinian and First-Person Approach
Authors: Van Duppen Zeno , Sips Rob
Published: July 2018

Background: Experiences of psychosis are often assumed to be strange, bizarre, or incomprehensible. The aim of this article is to offer a new step towards a better understanding of how the psychotic process affects a prereflective background. Methods: We use concepts from the philosophy of Ludwig Wittgenstein to clarify the first-person perspective on psychosis of one of the authors. Results: We describe the early psychotic process as breaking down the “nest of propositions,” shaking the scaffolds of our language games. Hereby, the prereflective background that forms our existential orientation in the world is fundamentally altered. We identify different aspects of this process: a dialectic of aha and anti-aha experiences, the experience of groundlessness, and blind spots. Acknowledging and exploring the depth and impact of this process on a person’s world may be a first step towards resolving their isolation and suffering. Philosophy can facilitate such an exploration, while interpersonal activation may offer structure and trust in the world, helping the patient to find solid ground in action and interaction. Conclusion: This article combines a philosophical approach with a first-person perspective on psychosis to illuminate aspects of psychosis that have not been described or elaborated on before. We argue that psychosis entails an experience of existential groundlessness. Our view has implications for treatment of and recovery from psychosis.
Ator, dobrador de tempo
Authors: Andraus Mariana Baruco Machado
Published: July 2018

Este artigo elabora uma reflexão sobre o conceito de tempo na arte do ator, estendendo-o ao dançarino e ao performer, em analogia com o conceito de “dobra”, presente na série de desenhos animados Avatar: a lenda de Aang. Também analisa a noção de tempo expandido existente nas linguagens da cena, tanto do ponto de vista da elaboração do gesto quanto da construção de roteiro dramatúrgico. Coloca a noção de tempo cênico em diálogo com a noção de subjetivação.
A Revolução Francesa em cena: o íntimo e o político em Ça Ira (1) Fin de Louis
Authors: Silva Igor De Almeida
Published: July 2018

Este ensaio apresenta um estudo do espetáculo Ça Ira (1) Fin de Louis, escrito e dirigido por Joël Pommerat. Inicialmente, busca-se estabelecer um diálogo entre Ça Ira e a histórica montagem de 1789, com direção de Ariane Mnouchkine. Em seguida, o espetáculo é examinado por meio de procedimentos recorrentes no trabalho de Pommerat, como, por exemplo, a neutralização do seu ponto de vista que expõe na peça situações, ideias e personagens sob diversas perspectivas. Por fim, este estudo baseia-se teoricamente no que Jean-Pierre Sarrazac chama de “teatros do íntimo” para observar a articulação entre o íntimo e o político em Ça Ira (1) Fin de Louis.
Magnetismo da revolução no exílio português de José Celso Martinez Corrêa (1974-1976)
Authors: Toledo Paulo Bio
Published: July 2018

O artigo debate o período de exílio que José Celso Martinez Corrêa e o Teatro Oficina viveram em Portugal durante a Revolução dos Cravos entre 1974 e 1976. A partir da reconstituição de um momento pouco documentado na trajetória do grupo, apresenta-se a hipótese de que o Oficina muda significativamente seus pressupostos estéticos e políticos quando em contato com o campo popular mais radical da revolução.
IL (Interleukin)-10–STAT3–Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction
Authors: Shirakawa Kohsuke , Endo Jin , Kataoka Masaharu , Katsumata Yoshinori , Yoshida Naohiro , Yamamoto Tsunehisa , Isobe Sarasa , Moriyama Hidenori , Goto Shinichi , Kitakata Hiroki , Hiraide Takahiro , Fukuda Keiichi , Sano Motoaki
Published: July 2018

Background:

Both osteopontin (OPN) and galectin-3 have been implicated in phagocytic clearance of dead cells and reparative fibrosis during wound healing. CD206
+
macrophages are involved in tissue repair through phagocytosis and fibrosis after myocardial infarction (MI). However, the relationship among OPN, galectin-3, and macrophage polarization in the context of MI remains unclear.

Methods:

The time course of
Spp1
(encoding OPN) expression in the heart after MI showed a strong activation of
Spp1
on day 3 after MI. To identify where in the body and in which cells the transcriptional activity of
Spp1
increased after MI, we analyzed EGFP (enhanced green fluorescent protein)-
Spp1
knockin reporter mice on day 3 after MI.

Results:

The transcriptional activity of
Spp1
increased only in CD206
+
macrophages in the infarct myocardium, and most of CD206
+
macrophages have strong transcriptional activation of
Spp1
after MI. The temporal expression pattern of
Lgal3
(encoding galectin-3) in cardiac macrophages after MI was similar to that of
Spp1
, and OPN is almost exclusively produced by galectin-3
hi
CD206
+
macrophages. Although both interleukin (IL)–4 and IL-10 were reported to promote CD206
+
macrophage-mediated cardiac repair after MI, IL-10– but not IL-4–stimulated CD11b
+
Ly6G
−
cells could differentiate into OPN-producing galectin-3
hi
CD206
+
macrophages and showed enhanced phagocytic ability. Inhibition of STAT3 tyrosine phosphorylation suppressed IL-10–induced expression of intracellular galectin-3 and transcriptional activation of
Spp1.
Knockdown of galectin-3 suppressed their ability to differentiate into OPN-producing cells, but not STAT3 activation. The tyrosine phosphorylation of STAT3 and the appearance rate of galectin-3
hi
CD206
+
cells on cardiac CD11b
+
Ly6G
−
cells in
Spp1
knockout mice were the same as those in wild-type mice.
Spp1
knockout mice showed vulnerability to developing post-MI left ventricular chamber dilatation and the terminal deoxynucleo-tidyltransferase 2‘-Deoxyuridine-5‘-triphosphate nick-end labeling (TUNEL)–positive cells in the infarcted myocardium after MI remained higher in number in
Spp1
knockout mice than in wild-type mice.

Conclusions:

OPN is almost exclusively produced by galectin-3
hi
CD206
+
macrophages, which specifically appear in the infarct myocardium after MI. The IL-10–STAT3–galectin-3 axis is essential for OPN-producing reparative macrophage polarization after myocardial infarction, and these macrophages contribute to tissue repair by promoting fibrosis and clearance of apoptotic cells. These results suggest that galectin-3 may contribute to reparative fibrosis in the infarct myocardium by controlling OPN levels.
Pharmacological Treatment of Arterial Hypertension in Children and Adolescents
Authors: Burrello Jacopo , Erhardt Elvira M. , Saint-Hilary Gaelle , Veglio Franco , Rabbia Franco , Mulatero Paolo , Monticone Silvia , D’Ascenzo Fabrizio
Published: July 2018

Pharmacological treatment is indicated in children and adolescents with hypertension unresponsive to lifestyle modifications, but there is not enough evidence to recommend 1 class of antihypertensive drugs over others. We performed a network meta-analysis to compare the results of available randomized clinical trials on pharmacological treatment of pediatric hypertension. From a total of 554 potentially relevant studies, 13 randomized placebo-controlled clinical trials enrolling ≥50 patients and a follow-up ≥4 weeks were included. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) after treatment were the coprimary end points. A total of 2378 pediatric patients, with a median age of 12 years, were included in the analysis. After a median follow-up of 35 days, lisinopril and enalapril were found to be superior to placebo in reducing SBP and DBP, whereas only for DBP, losartan was found to be superior to placebo and lisinopril and enalapril were found to be superior to eplerenone. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were associated with a greater SBP and DBP reduction compared with placebo, likewise the mineralocorticoid receptor antagonist was inferior to angiotensin-converting enzyme inhibitors in DBP reduction. The analysis was adjusted for study-level mean age, percentage of women, mean baseline blood pressure, and mean weight, only the latter significantly affected DBP reduction. According to the present analysis, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could represent the best choice as antihypertensive treatment for pediatric hypertension. However, because of the paucity of available data for the other classes of antihypertensive drugs, definitive conclusions are not allowed and further randomized controlled trials are warranted.
High Neutrophil-to-Lymphocyte Ratio Predicts Stroke-Associated Pneumonia
Authors: Nam Ki-Woong , Kim Tae Jung , Lee Ji Sung , Kwon Hyung-Min , Lee Yong-Seok , Ko Sang-Bae , Yoon Byung-Woo
Published: July 2018

Background and Purpose—

Although there are a variety of risk factors and predictive models for stroke-associated pneumonia (SAP), more objective and easily accessible markers are still needed. In this study, we evaluated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and SAP in patients with acute ischemic stroke.

Methods—

We assessed 1317 consecutive patients with acute ischemic stroke. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. The severity of pneumonia was rated using scores from the Pneumonia Severity Index, the quick Sequential Organ Failure Assessment, and the Acute Physiology and Chronic Health Evaluation II. The NLR was calculated after dividing absolute neutrophil counts by absolute lymphocyte counts.

Results—

Among the total patients, SAP occurred in 112 (9.0%) patients. Using a multivariable analysis, the NLR (adjusted odds ratio=1.55; 95% confidence interval, 1.15–2.11;
P
=0.005) remained significant after adjusting for confounders. In addition, age, atrial fibrillation, previous stroke history, initial National Institutes of Health Stroke Scale score, and high-sensitivity C-reactive protein were also significant, independent of NLR. The NLR was higher in the severe pneumonia group when it was assessed by Pneumonia Severity Index (
P
<0.001), quick Sequential Organ Failure Assessment (
P
<0.001), and Acute Physiology and Chronic Health Evaluation II scores (
P
=0.004). Furthermore, patients who had SAP had worse clinical outcomes both during hospitalization and after discharge.

Conclusions—

We demonstrated that a higher NLR predicted SAP in patients with acute ischemic stroke. The NLR may help to identify high-risk patients in time and provide clues for further studies about preventive antibiotic therapy.
Visual Image Statistics in the History of Western Art
Authors: Mather George
Published: July 2018

The history of Western visual art is traditionally divided into a succession of stylistic movements on the basis of the art-historical provenance and visual qualities of artworks. Little is known about how the visual statistics of Western artworks have changed over time, though this data could inform debate about the transitions between art movements. This longitudinal statistical study shows that two measures of the statistics of Western paintings remained relatively stable for 500 years, and similar to the values found in photographic images depicting the same subjects. Dramatic changes began in the late nineteenth century between the years 1878 and 1891, when the statistics of artworks became steadily more variable, and more frequently departed from values that are typical of representational images. This period can be considered as a major turning point that marks the beginning of the Modern Art movement. Statistically, abstract Modern art is more diverse than the representational art of any period. There is only limited evidence that aesthetic responses to paintings bear any relation to their visual statistics.
A new stygobiont species of Halocaridinides Fujino & Shokita, 1975 (Crustacea, Decapoda, Caridea, Atyidae) from caves on Socotra Island (Yemen), with notes on the genus
Authors: FRANSEN CHARLES H.J.M. , DAMME K. VAN
Published: July 2018

We describe a new species of stygobiont atyid shrimp of the genus Halocaridinides Fujino & Shokita, 1975 from subterranean brackish and freshwater environments on Socotra Island (Yemen). This is the first atyid shrimp discovered in the Socotra Archipelago. This Socotran endemic is the second species of Halocaridinides recorded from an Indian Ocean island and the first to occur in non-anchialine environments. The new species is characterized by the absence of eye pigmentation, a reduced rostrum and the presence of a single spine in the uropodal exopod diaeresis. Morphological variability in the robustness of the first and the second chelipeds, particularly obvious in the chelae, may indicate local speciation or phenotypical plasticity. At both extremes of the variation, animals with most slender (tenuis type) or robust (robustus type) morphologies occur. We discuss the Indo-Pacific distribution of the genus and the potential origin of the new Socotran species. An amended diagnosis for the genus and a key to all species are included.
Key to the currently recognized species of Limnias Schrank, 1803 (Rotifera, Monogononta, Gnesiotrocha, Flosculariidae)
Authors: WALLACE ROBERT LEE , KORDBACHEH AZAR , WALSH ELIZABETH J.
Published: July 2018

Although the most widely used key to the Rotifera subsumes six species of the sessile genus Limnias within two species groups (L. ceratophylli and L. melicerta), the original descriptions of these forms are sufficiently different to recognize them as distinct entities. We used these descriptions and all available literature on these species to develop dichotomous and formula keys to the six species based on easily recognizable morphological characters. As part of our review we added relevant ecological information from published sources, as well as our own data. We also discuss the need for additional observations of morphological, behavioral, life history, and genetic features to better understand the diversity of this widespread genus.
„Zabić Indianina w dziecku”. O kulturowym ludobójstwie w Kanadzie i sprawiedliwości tranzycyjnej z Kate Korycki rozmawia Anna Zawadzka [“Kill the Indian in the Child.” On cultural genocide and transitional justice in Canada. Kate Korycki in an interview by Anna Zawadzka]
Authors: Zawadzka Anna
Published: July 2018

“Kill the Indian in the Child.” On cultural genocide and transitional justice in Canada. Kate Korycki in an interview by Anna ZawadzkaThis is an interview with Kate Korycki on the reparations for the native population in Canada for what the Canadian government defined as “cultural genocide.” Kate Korycki was born in Warsaw and has lived in Toronto for 25 years. Until 2006 she worked for the Canadian Government in a ministry delivering federal social programs, like unemployment insurance and pensions. Her last job involved the implementation of the Common Experience Payment. This was the largest government program to offer reparations for the wrongs suffered by the indigenous population in Canada in residential schools, which were run for 150 years by the Catholic and Unitarian Churches. The schools have recently been characterized as sites of cultural genocide.Kate Korycki is completing her doctorate in political science at the University of Toronto. She holds an MA in Political Science from McGill University. Her broad research agenda concerns the politics of identity, belonging, and conflict. In her doctoral work she is concentrating on the politics of identity in time of transition. „Zabić Indianina w dziecku”. O kulturowym ludobójstwie w Kanadzie i sprawiedliwości tranzycyjnej z Kate Korycki rozmawia Anna ZawadzkaAnna Zawadzka przeprowadza wywiad z Kate Korycki na temat odszkodowań przyznanychrdzennym mieszkańcom w Kanadzie za to, co rząd kanadyjski określił mianem „kulturowego ludobójstwa”. Kate Korycki urodziła się w Warszawie i mieszka w Toronto od 25 lat. Do 2006 roku pracowała dla rządu kanadyjskiego, w ministerstwie spraw społecznych, takich jak bezrobocie czy emerytury. Jej ostatnia funkcja polegała na wdrożeniu „Zadośćuczynienia Wspólnego Doświadczania” (Common Experience Payment). Ten program był najszerszym gestem władz federalnych w postaci rządowych reparacji za krzywdy wyrządzone w szkołach rezydencyjnych wobec rdzennych mieszkańców w Kanadzie. Szkoły te były prowadzone przez 150 lat przez Kościół katolicki i unitariański. To właśnie działalność tych szkół została określona mianem kulturowego ludobójstwa.Kate Korycki pisze doktorat z nauk politycznych na Uniwersytecie w Toronto, po magisterium na Uniwersytecie Mcgill. Jej zainteresowania skupiają się na polityce tożsamości, przynależności i konflikcie.
Methods of Evaluation and Quantification of Microangiopathy in High Perfusion Microangiopathy (Chronic Venous Insufficiency and Diabetic Microangiopathy)
Authors: Cesarone M. R. , De Sanctis M. T. , Incandela L. , Belcaro G. , Griffin M. , Cacchio M.
Published: July 2018

Noninvasive tests have been developed to provide qualitative and quantitative information that can offer answers to most questions posed in venous diseases. While duplex scanning is used to assess the macrocirculation, microcirculatory methods assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess tissue viability and perfusion. Transcutaneous PO2 and PCO2 measurements are used to study venous hypertension, and strain-gauge plethysmography (SGP) is used to assess capillary filtration. In venous hypertension fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and therefore are an indication of the formation of edema, which is the most frequent sign of venous hypertension. Other methods such as the vacuum suction chamber and the edema tester can be used to assess changes due to treatment in chronic venous hypertension. These methods have been used and validated in several experimental and clinical studies. The techniques described in this article were used in controlled environmental conditions. Results were consistent with clinical problems and data from previous studies from our group and from data from other investigators.
Effects of the Total Triterpenic Fraction of Centella asiatica in Venous Hypertensive Microangiopathy: A Prospective, Placebo-Controlled, Randomized Trial
Authors: Cesarone M. R. , Belcaro G. , De Sanctis M. T. , Incandela L. , Cacchio M. , Bavera P. , Ippolito E. , Bucci M. , Griffin M. , Geroulakos G. , Dugall M. , Buccella S. , Kleyweght S. , Cacchio M.
Published: July 2018

The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included, After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F = 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F = 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p<0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (p<0.05). The difference in flux, signs and symptoms, and filtration was clinically important at 8 weeks. No side effects were observed. In conclusion venous microangiopathy was improved by TTFCA treatment.
Treatment of Edema and Increased Capillary Filtration in Venous Hypertension with Total Triterpenic Fraction of Centella asiatica: A Clinical, Prospective, Placebo-Controlled, Randomized, Dose-Ranging Trial
Authors: De Sanctis M. T. , Belcaro G. , Incandela L. , Cesarone M. R. , Griffin M. , Ippolito E. , Cacchio M.
Published: July 2018

The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal subjects before and after treatment for 4 weeks with total triterpenic fraction of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C (12 patients) was treated with placebo; and group D (10 normal subjects) was treated with TTFCA 60 mg thrice daily in a randomized study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AET (ankle edema tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of CFR, AC, and AET time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group. In conclusion, the improvement of signs and symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema. Dose ranging showed that 180 mg/day is more effective in improving symptoms and CFR.
Modification of the Echogenicity of Femoral Plaques after Treatment with Total Triterpenic Fraction of Centella aslatica: A Prospective, Randomized, Placebo-Controlled Trial
Authors: Incandela L. , Belcaro G. , Nicolaides A. N. , Cesarone M. R. , De Sanctis M. T. , Corsi M. , Bavera P. , Ippolito E. , Griffin M. , Geroulakos G. , Sabetai M. , Ramaswami G. , Veller M.
Published: July 2018

The aim of this study was to evaluate whether TTFCA (total triterpenic fraction of Centella asiatica), was effective, by modulating collagen production, in a period of 12 months, increasing the echogenicity of echolucent plaques at the femoral bifurcation. Hypoechoic atherosclerotic plaques have been found to be associated with an increased evidence of cerebrovascular events. In this type of plaques stromal composition is limited as the collagen component is generally very low; the plaque composition is mainly due to lipid accumulation or thrombosis. The aim of this study was the evaluation of echogenicity of hyperechoic plaques and how it could be modified by a drug acting on the modulation of collagen synthesis. Antiplatelet agents were used in all patients; cholesterol-lowering agents were used in 34% of patients in the treatment group and in 36% in the placebo group. TTFCA was used at the dose of 60 mg thrice daily (oral tablets). Of the 60 included subjects 26 completed the study in the treatment group and 24 in the placebo group. At inclusion the average GSM in the treatment group was 14 (SD 3) and 14.3 (SD 3) in controls. At 12 months GSM was increased up to 22.8 (SD 4) in the treatment group and it was 15 (SD 3) in controls. Considering texture no significant changes were observed in controls while a qualitative increase in homogenicity was observed in the TTFCA group. Plaque size measured at the beginning and at the end of the study showed a median increase in size, in controls (23%; range 0%–44%); it was unchanged in the TTFCA group (variation 7%; 4%–26%). In conclusion in the treatment group plaques increased in echogenicity and in homogenicity; size and stenosis remained unchanged. Modulating the scarring process within echolucent plaques (low echogenicity, high echolucency, with a very low collagen/stromal component), possibly by collagen modulation, makes plaques more stable. This has been achieved and documented in the present study by an increase in the gray-scale median (plaques become more echogenic, more ‘white’). The variation in GSM is generally associated with a lower risk of wall thrombosis, rupture and embolization. These observations indicate a positive action of TTFCA on the stabilization of hypoechoic, low-density femoral plaques
Voice Abnormalities and Laryngeal Pathology in Preterm Children
Authors: Hseu Anne , Ayele Nohamin , Kawai Kosuke , Woodnorth Geralyn , Nuss Roger
Published: July 2018

Introduction:

The prevalence of voice abnormalities in children born prematurely has been reported to be as high as 58%. Few studies have examined these abnormalities with laryngoscopic or videostroboscopic findings and characterized their laryngeal pathologies.

Objective:

To review voice abnormalities in patients with a history of prematurity and characterize the etiology of their voice problems. A secondary objective is to see if there is a correlation between the findings and the patient’s intubation and surgical history.

Methods:

A retrospective chart review was conducted of all preterm patients seen in voice clinic at a tertiary pediatric hospital. Demographic data, diagnoses, and office laryngoscopies were reviewed as well as any speech therapy evaluations and/or medical and surgical treatments.

Results:

Fifty-seven patients were included. Mean age at presentation was 5.1 (±4.3) years. Mean gestational age was 27.8 (±3.7) weeks. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) perceptual evaluations included a mean overall dysphonia severity of 46.6 (±24.2). Patients who had undergone prolonged intubation (⩾28 days) in the NICU or had prolonged NICU stays (>12 weeks) had significantly higher overall dysphonia severity scores. Thirty-three patients with vocal fold hypo- or immobility had significantly greater voice deviance in breathiness, loudness, and overall severity compared to those without vocal fold immobility. Of all patients, 35% were recommended surgical intervention and 49% voice therapy.

Conclusion:

Intubation greater than 28 days and prolonged NICU stays are associated with more severe dysphonia in premature patients. There should be a low threshold for clinical evaluation of dysphonia in this unique patient population.
Malignant Otitis Externa Outcomes: A Study of the University HealthSystem Consortium Database
Authors: Hatch Jonathan L. , Bauschard Michael J. , Nguyen Shaun A. , Lambert Paul R. , Meyer Ted A. , McRackan Theodore R.
Published: July 2018

Objective:

To characterize factors that affect outcomes for patients with malignant otitis externa (MOE).

Methods:

Retrospective review of inpatients with MOE was performed. Patient demographics, comorbid conditions, complications, procedures, and mortalities were analyzed.

Results:

A total of 786 patients with MOE were identified. The mean hospitalization length of stay (LOS) was 18.6 days (SD = 19.7). The overall mortality rate was 2.5% (n = 20), and complication rate was 4.3% (n = 34). Increasing age significantly and positively correlated with the incidence of MOE (r = 0.979, P < .0001). Factors that were associated with an increased rate of mortality were sepsis (odds ratio [OR] = 18.5; ES = 0.94; 95% CI, 0.47-1.42), congestive heart failure (OR = 3.1; ES = 0.42; 95% CI, 0.02-0.82), weight loss (OR = 10.2; ES = 1.23; 95% CI, 0.61-1.85), and coagulopathy (OR = 8.8; ES = 1.84; 95% CI, 0.91-2.77). Surgical intervention was performed in 19.2% (n = 151) of patients. Facial nerve involvement was present in 15.5% (n = 122) of patients and was associated with a significantly longer LOS of 12.9 days (SD = 19.6; ES = 0.21; 95% CI, 0.03-0.41).

Conclusions:

This large multi-institutional database study of MOE demonstrates that several patient factors impact the LOS and mortality. Patients at risk for unfavorable outcomes include the elderly, male gender, comorbidities, or cranial nerve involvement.
Facets of Trade Facilitation
Authors: Tantri Malini L. , Kumar C. Nalin
Published: July 2018

The theoretical underpinnings of trade facilitation (TF) would suggest a ‘balanced growth’ approach to expedite trade. However, taking the example of China and India, in this article, we explore how selective measures are capable of addressing issues related to TF. Both the economies offer very innovative interventions to address issues corresponding to TF, especially embedded in the way institutions are coordinated and integrated. As against the conventional idea that TF has to be initiated and carried forward only by the government, the ‘One Touch’ initiative in China provides a role for public–private partnership on issues pertaining to TF. This clearly demonstrates how, besides generating demand for trade-logistics services, the private sector itself can act as a source of supply to such services. The operation of Grapenet in India highlights the need to focus on sector-specific TF requirements along with meeting multilateral obligations. The One Touch initiative has to be appreciated as it was brought about in a context of the limited evolution of the information technology (IT) platform in China, and Grapenet has to be appreciated specifically because it brought a paperless integrated system in an agricultural context in India, where this sector’s preparedness for TF is less than that of the manufacturing sector.
Collaborators! Aftermath of Wartime Support for the INA among Indians in China
Authors: Sharma Nirmola
Published: July 2018

This article discusses the plight of the Indian community in China after the World War II. During the World War II, a sizeable number of Indian immigrants in China had been mobilised under the banner of the Indian National Army (INA), which was fighting for freedom from British colonial rule in alliance with Japan. This article seeks to understand the complex problems faced by the Indians in China in the aftermath of the War both because of the general dislocation they had suffered on account of war and occupation, and also because of their active or passive participation in a movement seen as ‘collaborationist’. It looks at how, for the British, Chinese and even Indian authorities, the issue of their status as ‘collaborators’ coloured the humanitarian issue of providing relief to a severely afflicted community. It also attempts to show how the wartime political activities of Indians in China not only had immediate consequences for them but also in some cases had an afterlife, which lasted for quite a few years after the War.
A novel industrial control architecture based on Software-Defined Network
Authors: Liang Geng , Li Wen
Published: July 2018

Traditionally, routers and other network devices encompass both data and control functions in most large enterprise networks, making it difficult to adjust the network infrastructure and operation to large-scale addition of end systems, virtual machines, and virtual networks in industrial comprehensive automation. A network organizing technique that has come to recent prominence is the Software-Defined Network (SDN). A novel SDN based industrial control network (SDNICN) was proposed in this paper. Intelligent network components are included in a SDNICN. Switches in SDNICN provided fundamental network interconnection for the whole industrial control network. Network controller is used for data transmission, forwarding and routing control between different layers. Service Management Center (SMC) is essentially responsible for managing various services used in industrial process control. SDNICN can not only greatly improve the flexibility and performance of industrial control network but also meet the intelligence and informatization of the future industry.
L'Organisation de la Statistique aux Pays-Bas
Authors: Methorst H. W.
Published: July 2018

I. — Aperçu historique du développement de la Statistique aux Pays-Bas, 34; II. — Organisation actuelle de la Statistique néerlandaise, 40; III. — Statistiques élaborées par le Bureau central, 43; IV. — La contrainte légale en matière de statistique, 47; V. — Dépouillement des matériaux de base, 48; VI. — Publications du Bureau central, 49; Observations sur quelques publications, 50.
Le Contentieux administratif en Suisse
Authors: Piller M. Joseph
Published: July 2018

I. — Préliminaires, p. 203; II. — Voies de recours des particuliers contre les actes des autorités administratives, p. 206; III. — Le contrôle juridictionnel de l'Administration, p. 207; IV. — Le contentieux administratif, p. 215; V. — Matières soumises aux organes juridictionnels, p. 220; VI. — La matière contentieuse administrative, p. 225; VII. — L'organisation des juridictions contentieuses administratives, p. 234; VIII. — La procédure: principes généraux, p. 240; IX. — La valeur juridique des décisions des Conseils ou Tribunaux contentieux administratifs, p. 246.
Le Mouvement des Idées et des Faits
Authors: Puget Henry
Published: July 2018

Pour aborder l'étude de l'administration américaine, p. 758. — Quelques indications sur le fonctionnement du parlement fédéral suisse, p. 767. — Le centenaire de la loi communale néerlandaise, p. 780. — Un projet de statut du personnel provincial et communal en Belgique, p. 784. — Handbook of organisation and methods techniques, p. 788. — Handbook on Secretarial practices, p. 793. — La conservation des sites en Allemagne et en Angleterre, p. 801. — Le bilan de la fonction publique en France, p. 806. — Les Fonds spéciaux en matière de travaux publics en Belgique, p. 813.
Notices Bibliographiques
Authors: J. M.
Published: July 2018

Aspects humains de l'Amérique au travail, p. 847. —Les finances de guerre du Canada, p. 849. —Les corporations de droit public chargées en Belgique du captage et de la distribution de l'eau potable, p. 857. —Les principes essentiels de l'urbanisme, p. 861.
The Administrative Regime Governing the French Regulations on Foreign Trade
Authors: Chapel Yves
Published: July 2018

by Yves Chapel

This is both a detailed account and a brief comment on the rules governing foreign trade in France. The author first comments on the three guiding principles of the relevant French legislation: 1) the individual has a right to import goods, within known procedures, 2) in the procedure of examination of applications, use is made of the services of organs which do not belong to the State as such, 3) there is a strong link with the control of currencies, and the administrative execution is markedly centralised.

Monsieur CHAPEL goes on to study the two fundamental legal provisions, and the agencies entrusted with their practical enforcement: Technical Directorates in the Ministries and « Technical Committees », the Office of Currency Control (« Office des Changes »), and finally delineates the actual working of this administrative machinery.

His conclusion is that the « Office des Changes » possibly enjoys excessive powers, even though they are indirect, and that this may point to a regrettable tendency towards « dirigism », but he adds that the French legislation is imbued with the principle that such concentration of powers in the hands of the State must be balanced by provisions enabling the individual to defend his interests. This hopeful attitude was justified by a recent liberation of some specified imports, a provision which is commented on in an additional note.