bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B114: Innate immunity modulators to enhance oncolytic VSV-GP for the treatment of ovarian cancer
Authors: Kimpel Janine , Urbiola Carles R. , Dold Catherine , Marth Christian , Muik Alexander , Laer Dorothee Holm-von , Wollmann Guido
Published: November 2016

Oncolytic viruses (OV) that preferentially replicate in and kill tumor cells are promissing novel treatment option for advanced cancers. Through cell lysis, OV set tumor antigens free, which in combination with the OV adjuvant effect, unleashes a strong anti-tumor immune response. Here, we propose the use of the oncolytic VSV-GP for the treatment of ovarian cancer. Effective oncolytic activity of VSV-GP could be demonstrated in a panel of ovarian cancer cell lines. Analysis of the innate immune response of ovarian cancer cells to VSV-GP revealed IFN type I production and induction of an antiviral state of the cells as a potential mechanism leading to shortcomings in virotherapeutic treatment. In vivo, VSV-GP was tested in a subcutaneous ovarian cancer xenograft mouse model using the A2780 cell line. Treatment led to tumor remission, which was temporary in most mice resulting in tumor recurrance. In an orthotopic xenograft mouse model, intraperitoneal injection of the virus led to significantly prolonged survival compared to untreated animals. In addition, combination therapy of VSV-GP with the JAK1/2-inhibitor ruxolitinib was successfully tested in both models and found to enhance the oncolytic effect. The drug inhibited the signalling pathway induced by type I IFN and could thus be used to inhibit the antiviral innate immune response and enhance intratumoral viral replication. Importantly, despite inhibiting the antiviral response, no toxicity was observed in mice receiving up to 109 pfus (plaque forming units) VSV-GP via intraperitoneal application. In addition, using luciferase expressing VSV-GP, we found no off target tropism with ruxolitinib combination. In conclusion, VSV-GP was tested as a potent oncolytic virus to treat ovarian cancer. Restriction of viral replication due to the innate immune response could be overcome by the combination treatment of VSV-GP with the Jak-1/2 inhibitor ruxolitinib.

Citation Format: Janine Kimpel, Carles R. Urbiola, Catherine Dold, Christian Marth, Alexander Muik, Dorothee Holm-von Laer, Guido Wollmann. Innate immunity modulators to enhance oncolytic VSV-GP for the treatment of ovarian cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B114.
Abstract B133: Regulation of antiviral immune responses by RNase L
Authors: Clingan Jonathan , Eckard Sterling , Cooper Daphne , Ramos Hilario , Guillen Jaime , Canard Bruno , Gale Michael , Hesselberth Jay , Barton David , Stetson Daniel
Published: November 2016

Intracellular detection of RNA or DNA triggers distinct sensors that protect against virus infection: RNA activates the RIG-I-like Receptor (RLR)-MAVS pathway, whereas DNA activates the cyclic GMP-AMP Synthase (cGAS)-STING pathway. In addition, the oligoadenylate synthetases (OAS) detect foreign RNA and form 2'-5'-linked oligoadenylates (2-5A). The sole known function of 2-5A is to activate the endoribonuclease RNase L, which is thought to cleave cellular and viral RNAs indiscriminately into small fragments that activate the RLR response. We show here that, contrary to this prevailing view, RNase L-deficient cells have an enhanced antiviral response to RLR ligands. We find that the in vivo specificity of RNase L is restricted to ribosomal RNA and we establish RNase L as a specific regulator of protein translation, not an indiscriminate mediator of RNA decay. Our findings offer a revised view of the RNase L system, ascribing to it a negative regulatory role in the antiviral response and identifying rRNA as the primary target of RNase L activity.

Citation Format: Jonathan Clingan, Sterling Eckard, Daphne Cooper, Hilario Ramos, Jaime Guillen, Bruno Canard, Michael Gale, Jr., Jay Hesselberth, David Barton, Daniel Stetson. Regulation of antiviral immune responses by RNase L [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B133.
Abstract B142: Long non-coding RNA expression during CD8+ T cell differentiation and exhaustion
Authors: Hudson William , Kissick Haydn , Hashimoto Masao , Ahmed Rafi
Published: November 2016

Exhaustion of CD8+ T lymphocytes is a major barrier to effective clearance of chronic viral infection and cancer by the immune system. Transcriptional changes underlie the expansion and differentiation of a naive CD8+ T cell into various effector subsets, including the exhausted state. Experiments from other cell types have shown that the majority of the mammalian genome is transcribed, generating a large number of long, non-protein-coding RNAs (lncRNAs). These lncRNAs have been shown to play important roles in many cellular processes including histone modification, transcriptional regulation, and mRNA metabolism. To identify the role of lncRNAs in CD8+ T cell differentiation and exhaustion, we performed RNA-sequencing on functional and exhausted CD8+ T cells in both humans and mice. We identified over 1,000 expressed, previously un-annotated lncRNAs; of these, hundreds are differentially expressed over the course of CD8+ T cell differentiation. Exhausted CD8+ T cells express a unique set of lncRNAs, and this profile is altered with IL-2 treatment. These results suggest that lncRNAs play important roles in T cell differentiation and exhaustion, and further study is underway to determine their functional roles in anti-viral and anti-tumor immune responses.

Citation Format: William Hudson, Haydn Kissick, Masao Hashimoto, Rafi Ahmed. Long non-coding RNA expression during CD8+ T cell differentiation and exhaustion [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B142.
Abstract IA32: Visualizing tumor immune interaction in real time
Authors: Roberts Edward W. , Headley Mark B. , Broz Miranda , Boldjipour Bijan , Corbin Kaitlin , Binnewies Mikhail , Bins Adriaan , Gerard Audrey Audrey , Krummel Matthew
Published: November 2016

The nature of an immune response is rarely defined by a unanimous decisions by the participating cells; cells with seemingly opposing functions pervade many immune sites and tumors are no exception. Multiple DC and Macrophage subsets exert push/pull on T cell responses in tumors. Fundamentals of this are gleaned by live-imaging in connection with conventional methods such as flow-cytometry and immunofluorescence. Here, we broadly treat real-time imaging as a discovery tool to understand the tumor microenvironment (TME) and the diversity of cellular interactions that comprise host-tumor interactions. We have advanced this technology from sites of primary, spontaneous and aggressive tumors into sites of metastasis. The results promote the concept of seeking “allies” for tumor therapies within the TME and provide a basis for considering the balance of push/pull signals that determine the consensus immune response.

Citation Format: Edward W. Roberts, Mark B. Headley, Miranda Broz, Bijan Boldjipour, Kaitlin Corbin, Mikhail Binnewies, Adriaan Bins, Audrey Audrey Gerard, Matthew Krummel. Visualizing tumor immune interaction in real time [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA32.
Abstract PR03: HVEM (TNFRSF14) tumor suppressor in immune therapies of follicular lymphoma
Authors: Salloum Darin
Published: November 2016

Follicular lymphoma (FL) is among the most common and incurable forms of indolent B cell lymphoma. Somatic mutations that disrupt the HVEM (TNFRSF14) receptor gene in 28% of FL and include frequent homozygous lesions. The HVEM receptor interacts with the activating LIGHT and the inhibitory BTLA (B- and T- lymphocyte attenuator) receptors on B and T cells. Exactly, how HVEM mutations contribute to FL development is unknown. Here we show that the immune cell receptor HVEM (TNFRSF14) is a p53 response gene, and a frequent target of both somatic mutations, and recurrent chromosome 1p36 deletions in FL. Moreover, HVEM deficiency promotes FL development in vivo and establishes a favorable immune environment. Specifically, HVEM deficient lymphomas show an exaggerated activation of stromal components including follicular dendritic cells (FDCs) and increased recruitment of T follicular helper (TFH) cells that support B lymphocytes by secreting interleukins IL21 and IL4. Furthermore, HVEM loss stimulates B cell growth by disrupting an inhibitory BTLA (B and T Lymphocyte Attenuator) mediated signal. Notably, HVEM's tumor suppressor functions reside at the cell surface and extrinsic application of the HVEM ectodomain(P37-V202) can restore B cell growth control and block lymphoma growth in vivo. In addition, we demonstrate that CD19-specific, chimeric antigen receptor (CAR)-modified T cells that are further modified to constitutively secrete soluble HVEM ectodomain display significantly higher cytotoxicity against cancer B-cells with high BTLA expression in vivo.

Citation Format: Darin Salloum. HVEM (TNFRSF14) tumor suppressor in immune therapies of follicular lymphoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR03.
Treatment for Hearing Loss among the Elderly: Auditory Outcomes and Impact on Quality of Life
Authors: Manrique-Huarte Raquel , Calavia Diego , Huarte Irujo Alicia , Girón Laura , Manrique-Rodríguez Manuel
Published: November 2016

The study aim was to determine the benefit of cochlear implantation and hearing aids in older adults diagnosed with hearing loss and to evaluate the index of depression, anxiety and quality of life after such treatments. A retrospective cohort comprised 117 patients older than 65 years and diagnosed with moderate to profound hearing loss who were included and classified into 2 groups (treated vs. non-treated). A battery of tests including auditory (pure-tone average, disyllabic words in quiet at 65 dB SPL) and findings from a series of questions relevant to quality of life were compared between both groups. Auditory outcomes for disyllabic words were 58.21% for the cochlear implant-treated group and 82.8% for the hearing aid-treated group. There was a positive effect on anxiety, depression, health status and quality of life in the cochlear implant group versus the profound hearing loss control group. We conclude that older adults with moderate to profound hearing loss gain benefit from hearing aids or cochlear implants not only in terms of improved hearing function, but also in terms of positive effects on anxiety, depression, health status and quality of life.
Outcome Comparison of Allogeneic versus Autologous Stem Cell Transplantation in Transformed Low-Grade Lymphoid Malignancies: A Systematic Review and Pooled Analysis of Comparative Studies
Authors: Yun Seongseok , Vincelette Nicole D. , Abraham Ivo , Puvvada Soham , Anwer Faiz
Published: November 2016

Background: Some patients with low-grade lymphoid malignancies develop transformed disease, requiring stem cell transplantation (SCT). SCT outcomes in transformed low-grade lymphoid malignancies may differ from those of nontransformed disease or other aggressive non-Hodgkin lymphomas. We conducted a pooled analysis of the clinical outcomes of allogeneic versus high-dose therapy (HDT) with autologous SCT in adult patients with transformed low-grade lymphoid malignancies. Methods: A PubMed, EMBASE, and Cochrane search yielded 4 comparative studies reporting allogeneic versus HDT with autologous SCT outcomes in adults (age ≥18) with transformed low-grade lymphoid malignancies, including follicular, chronic/small lymphocytic, and marginal zone lymphoma. Risk ratio (RR) and 95% CI were calculated using random-effects models. Results: Rates for overall survival (OS) were 51.0 versus 69.5% (RR = 1.55, 95% CI 1.19-2.02, p = 0.001), rates of relapse were 37.3 versus 35.3% (RR = 1.04, 95% CI 0.70-1.55, p = 0.84), and rates of transplant-related mortality (TRM) were 33.3 versus 7.2% (RR = 4.52, 95% CI 2.75-7.43, p < 0.00001) for allogeneic versus autologous SCT. Previous rituximab treatment, reduced intensity conditioning regimen prior to SCT, or original pathology had no prognostic impact. Conclusion: HDT followed by autologous SCT was associated with lower TRM and a better OS, but there was no difference in relapse versus allogeneic SCT. Autologous SCT may be the better therapeutic option, considering the second chance of allogeneic SCT in the case of relapse.
Pelage Variation and Distribution of the Black Lion Tamarin, Leontopithecus chrysopygus
Authors: Garbino Guilherme Siniciato Terra , Rezende Gabriela Cabral , Valladares-Padua Claudio
Published: November 2016

The black lion tamarin, Leontopithecus chrysopygus, is endemic to the Atlantic Forest of the interior of the state of São Paulo in Brazil. Since the discovery of the species, authors have described variations in the pelage of L. chrysopygus, but the nature of this variation has remained unknown. We examined museum specimens and living animals to see if the pelage of L. chrysopygus varies individually, geographically or ontogenetically. We reviewed all known locality records of the species, and concluded that the pelage of L. chrysopygus varies individually and ontogenetically, but not geographically. The extent of the golden chromogenetic fields is larger in younger individuals, and the pelage becomes darker after successive moults. We examined 2 juveniles that presented a pelage similar to adult L. caissara. Geographically, there is a clear break in the phenotypes attributed to L. caissara and L. chrysopygus, precluding clinal variation and corroborating the specific status of the former. The separation between these 2 species is coincident with a tectonic fault known as the ‘Guapiara lineament', and may have been caused by a recent activation of this geological formation. We also suggest a historical contact zone between L. chrysopygus and the marmoset Callithrix aurita in the upper Rio Tietê region.
Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery
Authors: Bernabe-Garcia Mariela , López-Alarcon Mardia , Salgado-Sosa Alfredo , Villegas-Silva Raul , Maldonado-Hernandez Jorge , Rodríguez-Cruz Maricela , Rivas-Ruiz Rodolfo , Chavez-Sanchez Luis , Blanco-Favela Francisco A. , Mancilla-Ramirez Javier , Gordillo-Alvarez Virginia , Madrigal-Muñiz Olivia
Published: November 2016

Background: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. Methods: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. Results: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R2 model = 0.90) for shorter duration (β = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. Conclusions: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.
Poder demótico ao povo: o triunfo do dimotiki, o triunfo de Medeia
Authors: Bakogianni Anastasia
Published: November 2016

Este texto analisa uma produção moderna da Medeia de Eurípides (431 a.C.) nos últimos anos do século passado. A releitura da tragédia antiga, que é objeto desta minha discussão, foi apresentada no Teatro Nacional da Grécia, em 1997, e dirigida por Niketi Kontouri. Representativa de um ambiente específico que, acredito, foi promovido no estado moderno grego depois da resolução oficial relativa à infame “Questão da Língua”, essa montagem também oferece uma perspectiva singular a partir da qual se pode reexaminar a Medeia de Eurípides e a recepção do drama grego no mundo moderno.
Socioeconomic Deprivation and Survival After Heart Transplantation in England
Authors: Evans Jonathan D.W. , Kaptoge Stephen , Caleyachetty Rishi , Di Angelantonio Emanuele , Lewis Clive , Parameshwar K. Jayan , Pettit Stephen J.
Published: November 2016

Background—

Socioeconomic deprivation (SED) is associated with shorter survival across a range of cardiovascular and noncardiovascular diseases. The association of SED with survival after heart transplantation in England, where there is universal healthcare provision, is unknown.

Methods and Results—

Long-term follow-up data were obtained for all patients in England who underwent heart transplantation between 1995 and 2014. We used the United Kingdom Index of Multiple Deprivation (UK IMD), a neighborhood level measure of SED, to estimate the relative degree of deprivation for each recipient. Cox proportional hazard models were used to examine the association between SED and overall survival and conditional survival (dependant on survival at 1 year after transplantation) during follow-up. Models were stratified by transplant center and adjusted for donor and recipient age and sex, ethnicity, serum creatinine, diabetes mellitus, and heart failure cause. A total of 2384 patients underwent heart transplantation. There were 1101 deaths during 17 040 patient-year follow-up. Median overall survival was 12.6 years, and conditional survival was 15.6 years. Comparing the most deprived with the least deprived quintile, adjusted hazard ratios for all-cause mortality were 1.27 (1.04–1.55;
P
=0.021) and 1.59 (1.22–2.09;
P
=0.001) in the overall and conditional models, respectively. Median overall survival and conditional survival were 3.4 years shorter in the most deprived quintile than in the least deprived.

Conclusions—

Higher SED is associated with shorter survival in heart transplant recipients in England and should be considered when comparing outcomes between centers. Future research should seek to identify modifiable mediators of this association.
NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage
Authors: Bruder-Nascimento Thiago , Ferreira Nathanne S. , Zanotto Camila Z. , Ramalho Fernanda , Pequeno Isabela O. , Olivon Vania C. , Neves Karla B. , Alves-Lopes Rheure , Campos Eduardo , Silva Carlos Alberto A. , Fazan Rubens , Carlos Daniela , Mestriner Fabiola L. , Prado Douglas , Pereira Felipe V. , Braga Tarcio , Luiz Joao Paulo M. , Cau Stefany B. , Elias Paula C. , Moreira Ayrton C. , Câmara Niels O. , Zamboni Dario S. , Alves-Filho Jose Carlos , Tostes Rita C.
Published: November 2016

Background:

Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation.

Methods:

We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (
NLRP3
−/−
), caspase-1 knockout (
Casp-1
−/−
), and interleukin-1 receptor knockout (
IL-1R
−/−
) mice treated with vehicle or aldosterone (600 µg·kg
−1
·d
−1
for 14 days through osmotic mini-pump) while receiving 1% saline to drink.

Results:

Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow–derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure.

Conclusions:

Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.
Src Kinases Regulate Glutamatergic Input to Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension
Authors: Qiao Xin , Zhou Jing-Jing , Li De-Pei , Pan Hui-Lin
Published: November 2016

The elevated sympathetic outflow associated with hypertension is maintained by increased
N
-methyl-
d
-aspartate receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus. Synaptic NMDAR activity is tightly regulated by protein kinases, including the Src family of tyrosine kinases. We determined whether Src kinases play a role in increased NMDAR activity of PVN neurons projecting to the rostral ventrolateral medulla and in elevated sympathetic vasomotor tone in spontaneously hypertensive rats (SHRs). The Src protein level in the PVN was significantly greater in SHRs than in normotensive Wistar–Kyoto (WKY) rats and was not significantly altered by lowering blood pressure with celiac ganglionectomy in SHRs. Inhibition of Src kinase activity with 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) completely normalized the higher amplitudes of evoked NMDAR-mediated excitatory postsynaptic currents and puff NMDA–elicited currents of rostral ventrolateral medulla–projecting PVN neurons in SHRs. PP2 treatment also attenuated the higher frequency of NMDAR-mediated miniature excitatory postsynaptic currents of these neurons in SHRs. However, PP2 had no effect on NMDAR-excitatory postsynaptic currents or miniature excitatory postsynaptic currents of rostral ventrolateral medulla–projecting PVN neurons in WKY rats. NMDAR activity increased by an Src-activating peptide was blocked by PP2 but not by inhibition of casein kinase 2. In addition, microinjection of PP2 into the PVN not only decreased lumbar sympathetic nerve discharges and blood pressure but also eliminated the inhibitory effect of the NMDAR antagonist on sympathetic nerve activity and blood pressure in SHRs. Collectively, our findings suggest that increased Src kinase activity potentiates presynaptic and postsynaptic NMDAR activity in the PVN and sympathetic vasomotor tone in hypertension.
Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes
Authors: Bruno Rosa Maria , Duranti Emiliano , Ippolito Chiara , Segnani Cristina , Bernardini Nunzia , Di Candio Giulio , Chiarugi Massimo , Taddei Stefano , Virdis Agostino
Published: November 2016

We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor
N
-nitro-
l
-arginine methylester or the antioxidant tempol. Structure was evaluated by media–lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by
N
-nitro-
l
-arginine methylester on ACh was inversely related to age in both groups (
P
<0.0001) and blunted in HT versus NT for each age range. In NT, tempol enhanced endothelial function in the oldest subgroup; in HT, the potentiating effect started earlier. HT showed an increased M/L (
P
<0.001) versus control. In both groups, M/L was directly related to age (
P
<0.0001). M/L was greater in HT, starting from 31 to 45 years range. A significant age–hypertension interaction occurred (
P
=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper.
High-Normal Estimated Glomerular Filtration Rate in Early-Onset Preeclamptic Women 10 Years Postpartum
Authors: Paauw Nina D. , Joles Jaap A. , Drost José T. , Verhaar Marianne C. , Franx Arie , Navis Gerjan , Maas Angela H.E.M. , Lely A. Titia
Published: November 2016

Women with a history of preeclampsia have a 5- to 12-fold increased risk to develop end-stage kidney disease. Previous observations in small cohorts suggest that former preeclamptic (fPE) women have subtle abnormalities in renal hemodynamics and renal function, which might predispose them to renal failure in later life. In this study, we analyzed renal function in a cross-sectional cohort consisting of former early-onset preeclamptic (fPE, n=339) and former healthy pregnant women (fHP, n=332), overall with a mean age of 39 years at 10 years postpartum. Estimated glomerular filtration rate (eGFR), assessed by the modification of diet in renal disease (MDRD) and chronic kidney disease–epidemiology (CKD-epi) equations, and urinary protein:creatinine ratios were assessed 10 years postpartum. Median MDRD and CKD-epi eGFR did not significantly differ between fHP and fPE groups, whereas a comparison of distribution of eGFR revealed a shift toward a high-normal MDRD eGFR in the fPE group (χ
2
,
P
=0.02) with the same trend for CKD-epi eGFR (χ
2
,
P
=0.18). The odds ratio for fPE women having MDRD eGFR >110 mL/min per 1.73 m
2
was 1.6 (1.1–2.4). In addition, the median urinary protein:creatinine ratio was slightly higher in fPE (8.5 versus 7.1 mg/mmol;
P
<0.01) and correlated positively with both MDRD and CKD-epi eGFR in fPE women. No increased incidence of CKD in fPE women was observed. In conclusion, we demonstrate subtle changes in renal function in former early-onset preeclamptic women 10 years postpartum, characterized by a high-normal eGFR and a slightly higher protein excretion. Whether these subtle differences predispose to or predict long-term renal function loss in fPE women remains to be investigated.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR2668.
Coronary Artery Calcium Score Improves the Prediction of Occult Coronary Artery Stenosis in Ischemic Stroke Patients
Authors: Beigneux Ysoline , Sablayrolles Jean‐Louis , Varenne Olivier , Mas Jean‐Louis , Calvet David
Published: November 2016

Background

Coronary heart disease is a significant cause of morbidity and mortality in stroke patients. The coronary artery calcium score (
CACS
) has emerged as a robust and noninvasive predictor of coronary events. We assessed the predictive ability of
CACS
to identify stroke patients with severe (≥50%) occult coronary artery stenosis in a stroke/transient ischemic attack population, in addition to the
PRECORIS
score, based on Framingham Risk Score and presence of cervicocephalic artery stenosis, which was derived and validated for that purpose.

Methods and Results

We enrolled consecutive patients aged 45 to 75 years referred to our stroke unit with noncardioembolic ischemic stroke or transient ischemic attack, and no prior history of coronary disease. The presence of coronary stenosis was assessed with 64‐section computed tomography coronary angiography, and all patients had a detailed etiological work‐up.
CACS
was determined from computed tomography measurement using the Agatson score. The predictive value of
CACS
was assessed by logistic regression and reclassification method. Among 300 patients included in the study, 274 had computed tomography coronary angiography. Fifty patients (18%) had at least 1 coronary artery stenosis ≥50%. In multivariable analysis, after adjustment for the
PRECORIS
score,
CACS
was strongly associated with the presence of occult coronary artery stenosis (odds ratio=14.8 [1.8–120.3] for
CACS
[1–100] and 70.9 [8.9–562.0] for
CACS
>100). When
CACS
was added to the standard model, model fit was improved (
P
<0.001), Net Reclassification Improvement was 28.2% (
P
<0.001), and Integrated Discrimination Index was 18.2% (
P
<0.001).

Conclusions

In stroke/transient ischemic attack patients,
CACS
improves the prediction of occult coronary stenosis beyond classical risk factors.
Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women
Authors: Grøntved Anders , Koivula Robert W. , Johansson Ingegerd , Wennberg Patrik , Østergaard Lars , Hallmans Göran , Renström Frida , Franks Paul W.
Published: November 2016

Background

Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow‐up in middle‐aged men and women.

Methods and Results

We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10‐year period (1990–2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [
OR
]=0.85, 95%
CI
0.73–0.99), hypertension (
OR
=0.87, 95%
CI
0.79–0.95), hypertriglyceridemia (
OR
=0.85, 95%
CI
0.76–0.94), and impaired glucose tolerance (
OR
=0.88, 95%
CI
0.80–0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow‐up had lower odds of obesity (
OR
=0.61, 95%
CI
0.50–0.73), hypertension (
OR
=0.89, 95%
CI
0.80–0.98), hypertriglyceridemia (
OR
=0.80, 95%
CI
0.70–0.90), and impaired glucose tolerance (
OR
=0.82, 95%
CI
0.74–0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow‐up.

Conclusions

These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle‐aged men and women.
Combined Effects of Inflammatory Status and Carotid Atherosclerosis
Authors: Mayer Florian J. , Binder Christoph J. , Wagner Oswald F. , Schillinger Martin , Minar Erich , Mlekusch Wolfgang , Tsiantoulas Dimitris , Goliasch Georg , Hoke Matthias
Published: November 2016

Background and Purpose—

Inflammatory responses play a key role in atherogenesis. The aim of this study was to assess the prognostic value of hsCRP (high-sensitivity C-reactive protein) and to evaluate whether degree of carotid stenosis and serum levels of hsCRP jointly predict long-term mortality in asymptomatic patients with carotid atherosclerosis.

Methods—

One thousand sixty-five patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause-specific mortality.

Results—

During a median of 11.81 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. The risk of all-cause and cardiovascular mortality significantly increased in patients with elevated serum levels of hsCRP (the adjusted hazard ratio for cardiovascular mortality per increase of 1 mg/dL of hsCRP levels was 1.47;
P
<0.001). Patients with a high degree of carotid stenosis and increased hsCRP levels were particularly at risk of adverse outcome. Patients with carotid narrowing over 50% and hsCRP levels >0.29 mg/dL (=median) had nearly twice as high a risk of cardiovascular mortality compared with patients with carotid stenosis of <50% and hsCRP levels <0.29 mg/dL (adjusted hazard ratio 1.89;
P
<0.001). Improvement in risk stratification with combined assessment of carotid stenosis and hsCRP was confirmed by an improvement of the continuous net reclassification improvement with 18% for all-cause mortality and 15% for cardiovascular mortality compared with the degree of carotid stenosis alone (
P
<0.01).

Conclusions—

Measurement of hsCRP in combination with ultrasound investigations of the carotid arteries at a single time point provides additional prognostic information for patients with asymptomatic carotid atherosclerosis.
Justice for Darfur: The icc and Domestic Justice Initiatives Eleven Years after the un Security Council Referral
Authors: Sullo Pietro
Published: November 2016

This article provides a comprehensive overview of justice initiatives triggered by the International Criminal Court (icc) intervention in Sudan, assessing them in the light of the principle of complementarity against international fair trial standards. Particular attention is paid to the role that autochthonous justice initiatives might play to address the violence experienced in Darfur. The aim of this article hence includes providing an overview of the post-conflict justice scenario surrounding Sudan; discussing the rationale behind the adoption of the mechanisms established within this framework; and assessing the impact of the icc on the Sudanese justice system while simultaneously outlining possible strategies for the future.
The European Union’s Passenger Name Record Data Directive 2016/681: Is It Fit for Purpose?
Authors: Lowe David
Published: November 2016

In 2016 the eu introduced a Passenger Name Record data (pnr) Directive. In the eu there has been controversy over the acquisition and sharing of pnr data, related mainly to lack of safeguards and protection of personal data protection. This Article examines these issues related to earlier eu pnr agreements with third countries and why previous eu attempts to legislate in this area failed. By drawing a comparison with the 2011 pnr Directive proposal, the Article argues that by meeting the strict eu law on data protection as well as being necessary to assist in preventing and detecting acts of terrorism and serious crime it is submitted the 2016 Directive is fit for purpose and able to withstand scrutiny by the Court of Justice of the European Union.
Fascism’s Modernist Revolution: A New Paradigm for the Study of Right-wing Dictatorships
Authors: Griffin Roger
Published: November 2016

This article highlights the progress that has been made within fascist studies from seeing ‘fascist culture’ as an oxymoron, and assuming that it was driven by a profound animus against modernity and aesthetic modernism, to wide acceptance that it had its own revolutionary dynamic as a search for a Third Way between liberalism and communism, and bid to establish an alternative, rooted modern culture. Building logically on this growing consensus, the next stage is to a) accept that modernism is legitimately extended to apply to radical experimentation in society, economics, politics, and material culture; b) realize that seen from this perspective each fascism was proposing its own variant of modernism in both a socio-political and aesthetic sense, and that c) right-wing regimes influenced by fascism produced their own experiments in developing both a modern political regime and cultural modernism grounded in a unique national history.
The Myth of the New Man in Italian Fascist Ideology
Authors: Dagnino Jorge
Published: November 2016

This article addresses the key concept of the New Man within Fascist ideology, often considered as means and end of the Fascist revolution by the Fascists. Usually dismissed as an empty slogan by historians, it is argued in the following pages that the myth of the New Man is essential for a better understanding of the regime’s totalitarian and revolutionary aspirations along with its quest of creating an alternative modernity and a post-liberal and post-socialist type of civilisation based on the primacy of the collectivity - a realm where Italians could realise their full potential as human beings.
Australia’s economic transition, unemployment, suicide and mental health needs
Authors: Myles Nicholas , Large Matthew , Myles Hannah , Adams Robert , Liu Dennis , Galletly Cherrie
Published: November 2016

Objective:

There have been substantial changes in workforce and employment patterns in Australia over the past 50 years as a result of economic globalisation. This has resulted in substantial reduction in employment in the manufacturing industry often with large-scale job losses in concentrated sectors and communities. Large-scale job loss events receive significant community attention. To what extent these mass unemployment events contribute to increased psychological distress, mental illness and suicide in affected individuals warrants further consideration.

Methods:

Here we undertake a narrative review of published job loss literature. We discuss the impact that large-scale job loss events in the manufacturing sector may have on population mental health, with particular reference to contemporary trends in the Australian economy. We also provide a commentary on the expected outcomes of future job loss events in this context and the implications for Australian public mental health care services.

Results and conclusion:

Job loss due to plant closure results in a doubling of psychological distress that peaks 9 months following the unemployment event. The link between job loss and increased rates of mental illness and suicide is less clear. The threat of impending job loss and the social context in which job loss occurs has a significant bearing on psychological outcomes. The implications for Australian public mental health services are discussed.
The relationship of social support with well-being outcomes via work–family conflict: Moderating effects of gender, dependants and nationality
Authors: Drummond Suzie , O’Driscoll Michael P , Brough Paula , Kalliath Thomas , Siu Oi-Ling , Timms Carolyn , Riley Derek , Sit Cindy , Lo Danny
Published: November 2016

The impact of work–family conflict on well-being outcomes is well established, as is the role of social support in buffering perceptions of conflict. What is less well understood is how these relationships vary for different groups of respondents. Using a two-wave longitudinal design with a 12-month time lag and samples of employees (total N = 2183) from Australia, New Zealand, China and Hong Kong, the present research investigated whether the mediating relationships between social support, work–family conflict and well-being outcomes were moderated by gender, geographical region and the presence of dependants in the household. Supervisor support and family support were associated with lower work–family conflict, and hence reduced psychological strain and increased job and family satisfaction, for women and for employees in China and Hong Kong, but not for employees in Australia and New Zealand. However, the presence of dependants was not a significant moderator. Our findings illustrate the importance of exploring gender and national differences in work–family conflict research, particularly the investigation of cross-domain effects.
The Role of Dissemination as a Fundamental Part of a Research Project
Authors: Marín-González Esther , Malmusi Davide , Camprubí Lluís , Borrell Carme
Published: November 2016

Dissemination and communication of research should be considered as an integral part of any research project. Both help in increasing the visibility of research outputs, public engagement in science and innovation, and confidence of society in research. Effective dissemination and communication are vital to ensure that the conducted research has a social, political, or economical impact. They draw attention of governments and stakeholders to research results and conclusions, enhancing their visibility, comprehension, and implementation. In the European project SOPHIE (Evaluating the Impact of Structural Policies on Health Inequalities and Their Social Determinants and Fostering Change), dissemination was an essential component of the project in order to achieve the purpose of fostering policy change based on research findings. Here we provide our experience and make some recommendations based on our learning. A strong use of online communication (website, Twitter, and Slideshare accounts), the production of informative videos, the research partnership with civil society organizations, and the organization of final concluding scientific events, among other instruments, helped to reach a large public within the scientific community, civil society, and the policy making arena and to influence the public view on the impact on health and equity of certain policies.
Cumulative Effects of Growing Up in Separate and Unequal Neighborhoods on Racial Disparities in Self-rated Health in Early Adulthood
Authors: Kravitz-Wirtz Nicole
Published: November 2016

Evidence suggests that living in a socioeconomically deprived neighborhood is associated with worse health. Yet most research relies on cross-sectional data, which implicitly ignore variation in longer-term exposure that may be more consequential for health. Using data from the 1970 to 2011 waves of the Panel Study of Income Dynamics merged with census data on respondents’ neighborhoods (N = 1,757), this study estimates a marginal structural model with inverse probability of treatment and censoring weights to examine: (1) whether cumulative exposure to neighborhood disadvantage from birth through age 17 affects self-rated health in early adulthood, and (2) the extent to which variation in such exposure helps to explain racial disparities therein. Findings reveal that prolonged exposure to neighborhood disadvantage throughout childhood and adolescence is strikingly more common among nonwhite versus white respondents and is associated with significantly greater odds of experiencing an incidence of fair or poor health in early adulthood.
Immigration after Brexit
Authors: Portes Jonathan
Published: November 2016

This paper examines the short and long-term impacts of the UK referendum on migration flows and migration policy. Even in the short term – before any policy change – the vote will affect migration flows directly and indirectly through both economic and other channels. Post Brexit, two key issues will need to be addressed. Will the UK preserve a substantial measure of preference for EU citizens in any new system? And will policy tilt in a liberal or restrictive direction?
Building Democracy Anew
Authors: Couperus Stefan
Published: November 2016

This article interrogates the political semantics of neighborhood planning during and after the Second World War. It argues that as much as a geographical substrate for social and spatial planning, the neighborhood was an organizing principle in agendas of urban political reform in the 1940s and 1950s. Taking the case of Rotterdam, a severely bombed city that suffered from warfare in many respects, this article discloses the languages of political reform that informed an agenda of revitalizing urban democracy within the framework of the neighborhood. Two intertwined trajectories, encompassing public and private initiatives to institutionalize modes of neighborhood politics and democracy, will show how notions of democratic citizenship and the post-war institutional design of urban governance became irreconcilable in Rotterdam, but had a lasting impact on twentieth-century urbanism.
Recursive identification of time-varying non-linear cascade systems with static input and dynamic output non-linearities
Authors: Vörös Jozef
Published: November 2016

The paper deals with the recursive identification of time-varying non-linear dynamic systems using three-block cascade models with non-linear static, linear dynamic and non-linear dynamic blocks. These models are appropriate for systems with both actuator and sensor non-linearities. Multiple application of a decomposition technique provides special expressions for the corresponding non-linear model description that are linear in parameters. A modified recursive least-squares-based algorithm is used for estimation of the time-varying input polynomial and output backlash parameters. Simulation studies show the feasibility of proposed approach to estimate the model parameters and track their changes.
Two time-scale observer-based robust motion controller design and realization of a linear actuator
Authors: Wang Nan , Lin Weiyang , Yu Jinyong , Zhang An , Ye Chao
Published: November 2016

In this paper, an observer-based sliding mode controller is proposed for a high-accuracy motion plant to suppress the disturbances and improve the tracking performance. In particular, a two time-scale separation technology, which can recover the disturbance state in a faster time scale, is utilized to compensate the disturbances and improve the system robustness. The parameter identification is carried out to obtain the model coefficients with a high fitting rate. Such an identified model can allow the engineers to tune the controller’s gains highly enough when the system suffers from the measurement noises. Instead of the traditional low-pass filter, a differentiator is introduced for the velocity signal prediction and its discrete-time version is provided to attenuate the noises effect. To verify the effectiveness of the proposed approach, an adaptive robust control law is compared with the proposed one in terms of dynamic positioning error, robustness and rapid signal tracking, and the superiority and advantages can be illustrated by the experimental results.