bluuebunny/crossref_metadata_2025 huggingface dataset:
Nodal Signaling as a Developmental Therapeutics Target in Oncology
Authors: Kalyan Aparna , Carneiro Benedito A. , Chandra Sunandana , Kaplan Jason , Chae Young Kwang , Matsangou Maria , Hendrix Mary J.C. , Giles Francis
Published: May 2017

The tumor microenvironment is a vital feature of oncogenesis and tumor progression. There are several parallels between cancer cells and early developmental stem cells, including their plasticity and signaling mechanisms. In early fetal development, Nodal is expressed for endodermal and mesodermal differentiation. This expression has been shown reemerge in the setting of epithelial cancers, such as breast and melanoma. High Nodal expression correlates to an aggressive tumor grade in these malignancies. Nodal signal begins with its interaction with its coreceptor, Cripto-1, leading to activation of Smad2/Smad3 and ultimately downstream transcription and translation. Lefty is the natural inhibitor of Nodal and controls Nodal signaling during fetal development. However, cancer cells lack the presence of Lefty, thus leading to uncontrolled tumor growth. Given this understanding, inhibition of the Nodal pathway offers a new novel therapeutic target in oncology. Mol Cancer Ther; 16(5); 787–92. ©2017 AACR.
Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses NF2 Loss–Driven Tumorigenesis
Authors: Cooper Jonathan , Xu Qingwen , Zhou Lu , Pavlovic Milica , Ojeda Virginia , Moulick Kamalika , de Stanchina Elisa , Poirier John T. , Zauderer Marjorie , Rudin Charles M. , Karajannis Matthias A. , Hanemann C. Oliver , Giancotti Filippo G.
Published: May 2017

Inactivation of NF2/Merlin causes the autosomal-dominant cancer predisposition syndrome familial neurofibromatosis type 2 (NF2) and contributes to the development of malignant pleural mesothelioma (MPM). To develop a targeted therapy for NF2-mutant tumors, we have exploited the recent realization that Merlin loss drives tumorigenesis by activating the E3 ubiquitin ligase CRL4DCAF1, thereby inhibiting the Hippo pathway component Lats. Here, we show that MLN4924, a NEDD8-activating enzyme (NAE) inhibitor, suppresses CRL4DCAF1 and attenuates activation of YAP in NF2-mutant tumor cells. In addition, MLN4924 sensitizes MPM to traditional chemotherapy, presumably as a result of collateral inhibition of cullin-RING ubiquitin ligases (CRL) involved in DNA repair. However, even in combination with chemotherapy, MLN4924 does not exhibit significant preclinical activity. Further analysis revealed that depletion of DCAF1 or treatment with MLN4924 does not affect mTOR hyperactivation in NF2-mutant tumor cells, suggesting that loss of Merlin activates mTOR independently of CRL4DCAF1. Intriguingly, combining MLN4924 with the mTOR/PI3K inhibitor GDC-0980 suppresses the growth of NF2-mutant tumor cells in vitro as well as in mouse and patient-derived xenografts. These results provide preclinical rationale for the use of NAE inhibitors in combination with mTOR/PI3K inhibitors in NF2-mutant tumors.
Pre- and Post-Transplant Treatment of Viral Hepatitis C
Authors: Mutimer David
Published: May 2017

Background: Hepatitis C (HCV) is a common cause of liver failure and liver cancer, and is a frequent indication for liver transplantation (LT). Until recently, a majority of transplanted patients were viraemic at the time of transplantation and they inevitably underwent recurrent infection of the graft. Prior to the availability of specific direct-acting antiviral (DAA) drugs, HCV infection was seldom successfully treated before or after transplantation. Key Messages: During the past 2 years, the use of interferon-free DAA therapy has transformed the management of patients post-LT and of patients on the transplant waiting list. DAA treatment post-LT can eradicate infection and normalize liver function tests in a majority of treated patients. An improvement in long-term graft and patient outcome can be anticipated. DAA treatment of patients with liver failure awaiting LT eliminates infection and is associated with an improvement in the liver function for a majority of treated patients. The majority still require transplantation, though some may improve sufficiently and quickly enough to be removed from the LT waiting list. Conclusions: Eventually, as greater numbers of patients with compensated cirrhosis are successfully treated with DAAs, HCV-associated liver failure may become an uncommon indication for LT.
The Gut Microbiota and the Hepatologist: Will Our Bugs Prove to be the Missing Link?
Authors: Pallen Mark J. , Quraishi Mohammed N.
Published: May 2017

The advent of next-generation sequencing has enabled in-depth analysis to study the composition and function of the gut microbiota in a culture-independent manner. Consequently, this has led to rapid interest in understanding the pathogenesis and progression of chronic liver disease in relation to perturbations of the gut microbiota. Animal models and human studies have demonstrated its crucial role in contributing to disease mechanisms in alcoholic and non-alcoholic liver disease and more recently in primary sclerosing cholangitis. There is increasing evidence to suggest that the gut microbiota and its components influence the development and modulation of chronic liver damage through direct communication via the portal system, metabolite production, alterations in gut barrier integrity, liver/gut immune axis and bile acid metabolism. The impact of microbiota-directed therapies for liver disease is still in its infancy. Better understanding of its role in disease mechanisms will lead to a more targeted approach in modulation of gut microbiota to influence both progression and complications of liver disease. This review discusses the current evidence for the gut microbiota-liver axis and its role in the development, progression and treatment of liver disease.
Treating Hepatobiliary Cancers: The Oncology Way
Authors: Galle Peter Robert
Published: May 2017

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. HCC represents more than 90% of primary liver cancers. There is growing incidence of HCC worldwide. In the western world, HCC arises in a cirrhotic background in up to 90% of cases, and cirrhosis itself is a progressive disease that affects patient survival. Thus, outcome in patients with HCC and the chances for anti-tumor treatment and it is results are dependent not only on tumor-associated factors but also on the liver function. Cholangio carcinoma is the second most common primary liver tumor with an estimated incidence of 1:100,000. Cholangiocarcinoma can be sub-classified as intrahepatic (iCCA), perihilar or distal where iCCA arises within the liver parenchyma. Overall, the incidence of iCCA seems to be increasing globally. This may be attributed to a global increase of risk factors shared between HCC and iCCA, such as viral hepatitis, liver cirrhosis, diabetes mellitus, obesity, NASH, and others.
Stemness in Liver Cancer
Authors: Thorgeirsson Snorri S.
Published: May 2017

Cancer cells possessing “stemness,” or stem-cell properties, are referred to as cancer stem cells (CSC) or cancer-initiating cells. The concept that these cells rest at the apex of the cancer hierarchy is an evolving theme in cancer research. These cells are by definition primarily responsible for the initiation and propagation of tumors as well as relapse after therapy, and they are therefore of major scientific interest. Several studies indicate that hepatocellular carcinomas that harbor phenotypic features of stem cells and progenitor cells constitute a subclass of therapeutically challenging cancers that are associated with a particularly poor prognosis. We recently demonstrated that any cell type in the mouse hepatic lineage can undergo oncogenic reprogramming into a CSC by activating different cell type-specific pathways [1]. Identification of common and cell of origin-specific phenotypic and genetic changes could provide new therapeutic targets for liver cancer.
Nutrition and Liver Health
Authors: Jackson Alan A.
Published: May 2017

Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools that would enable a more precise nutritional diagnosis, but these require systematic investigation and application. For the present, approaches that place emphasis on being able to control the metabolic state without exposing the liver to unnecessary metabolic stress remain the basis for successful nutritional support.
What Comes after Ursodeoxycholic Acid in Primary Biliary Cholangitis?
Authors: Wong Lin Lee , Hegade Vinod S. , Jones David E.J.
Published: May 2017

Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by chronic cholestasis. Treatment with the accepted primary therapy ursodeoxycholic acid (UDCA) has been shown to be associated with delayed disease progression probably through reduced impact of cholestatic injury on the target biliary epithelial cells. Patients with inadequate response to UDCA (which can be identified through validated biochemical criteria) are at increased risk of disease progression, need for liver transplantation, and death. Obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second-line therapy in PBC and has been recently licensed by the Food and Drug Administration and European Medicines Agency for use in patients showing an inadequate response to UDCA or who are unable to tolerate it. Although evidence for biochemical improvement by OCA is compelling, there is, as yet, no evidence that OCA improves hard clinical outcomes or quality of life. In addition, OCA may not be suitable for PBC patients with pruritus as it can worsen the symptom. Other novel agents currently in clinical development may have better side-effect profile. Fibrates have the potential but currently lack high quality evidence to support their routine clinical use in PBC. Symptom management of PBC is challenging and ASBT inhibitors and rituximab are being evaluated for pruritus and fatigue, respectively.
Treatment with Enriched Environment Reduces Neuronal Apoptosis in the Periinfarct Cortex after Cerebral Ischemia/Reperfusion Injury
Authors: Chen Xiuping , Zhang Xin , Xue Li , Hao Chizi , Liao Weijing , Wan Qi
Published: May 2017

Background/Aims: Enriched environment (EE) has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism remains unclear. The purpose of this study was to investigate the effect of EE treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury. Methods: The cerebral I/R injury was established by middle cerebral artery occlusion (MCAO). A set of behavioral tests including the modified neurological severity score (mNSS), limb-placing test and foot-fault test were conducted. The infarct volume and the neuronal survival rate were evaluated by Nissl staining. The morphology and ultrastructure of ischemic neurons was examined by transmission electron microscopy. Neuronal apoptosis was assessed by double labeling of TdT-mediated dUTP-biotin nick end labeling (TUNEL) with NeuN. The expressions of apoptosis-related proteins were tested by western blotting and immunohistochemical labeling. Results: EE treatment improved neurological function, reduced infarct volume, increased neuronal survival rate and alleviated the morphological and ultrastructural damage of neurons (especially mitochondria) after I/R injury. EE treatment reduced the neuronal apoptosis, increased B cell lymphoma/leukemia-2 (Bcl-2) protein levels while decreased Bcl-2-associated X protein (Bax), cytochrome c, caspase-3 expressions and Bax/Bcl-2 ratio in the periinfarct cortex after cerebral I/R injury. Conclusion: Our findings suggest that EE treatment inhibits neuronal apoptosis in the periinfarct cortex after focal cerebral I/R injury, which may be one of the possible mechanisms underlying the neuroprotective effects of EE.
Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (Viscum album L.) Extract
Authors: Sakalli Çetin Esin , Tetiker Hasan , İlhan Çelik Özgür , Yılmaz Nigar , Ciğerci İbrahim Hakkı
Published: May 2017

Background: The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay. Material and Methods: 32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out. Results: MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly. Conclusion: This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.
Increased Risk of Bullous Pemphigoid after First-Ever Stroke: A Population-Based Study
Authors: Shen Ai-Ling , Lin Hsiu-Li , Lin Hsiu-Chen , Tseng Yuan-Fu , Hsu Chien-Yeh , Chou Che-Yi
Published: May 2017

Background: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. Methods: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. Results: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. Conclusions: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.
Comparison of the Outcomes of Trabeculectomy with 5-Fluorouracil versus Ologen Implant in Primary Open-Angle Glaucoma
Authors: Shihadeh Wisam , Massad Ihab , Khader Yousef , Al-Rawi Ahmed , Alshalakhti Tala
Published: May 2017

Purpose: To compare the outcomes of trabeculectomy with 5-fluorouracil (5-FU) versus Ologen™ implant in patients with primary open-angle glaucoma. Methods: A retrospective chart review was performed of patients with primary open-angle glaucoma who underwent trabeculectomy using either Ologen or 5-FU over 12 consecutive months. The patients had moderate-to-advanced primary open-angle glaucoma and uncontrolled intraocular pressure (IOP) on maximally tolerated medical treatment. Fornix-based trabeculectomy was performed on all patients by the same surgeon. The outcomes that were recorded and analyzed included the IOP level and number of glaucoma medications before and after surgery as well as the complications. All patients were followed for at least 3 months. Results: A total of 58 eyes (of 47 patients) were included in this study. The eyes were divided into 2 groups: the 5-FU group (n = 30, 51.7%) and the Ologen group (n = 28, 48.3%). The demographics and preoperative clinical features were not significantly different between the 2 groups. Repeated-measures analysis showed a significant decrease in IOP after trabeculectomy in both groups, with a marked decrease at day 1 after surgery. The amount of relative change at postoperative day 1 was significantly higher in the Ologen group (62.1 vs. 45.2%; p = 0.025). After this, there were no significant changes over time in IOP measurements in either group. In all the eyes, there was a significant drop in the number of antiglaucoma medications used after the surgery (p < 0.005), i.e. from 4.0 to 1.4 and from 4.3 to 1.0 in the 5-FU and Ologen groups, respectively, with no significant differences between groups (p = 0.303). Complications were few and minor in both groups. Bleb revision was needed in 2 eyes in the 5-FU group and in 4 eyes in the Ologen group. Conclusion: The efficacy and safety of trabeculectomy with 5-FU was similar to that with Ologen. Further studies with a larger number of patients and longer follow-up periods are needed.
Risk for Incident Heart Failure: A Subject‐Level Meta‐Analysis From the Heart “OMics” in AGEing (HOMAGE) Study
Authors: Jacobs Lotte , Efremov Ljupcho , Ferreira João Pedro , Thijs Lutgarde , Yang Wen‐Yi , Zhang Zhen‐Yu , Latini Roberto , Masson Serge , Agabiti Nera , Sever Peter , Delles Christian , Sattar Naveed , Butler Javed , Cleland John G. F. , Kuznetsova Tatiana , Staessen Jan A. , Zannad Faiez , Pinet Florence , Pizard Anne , Rouet Philippe , Leenders Joost , Diez Javier , Odili Augustine , Wei Fang‐Fei , Newman Anne , Papadimitrious Lampros , Davoli Marina , Mureddu Gian Francesco , Ford Ian , Jukema Wouter , Stott David J. , Poulter Neil
Published: May 2017

Background

To address the need for personalized prevention, we conducted a subject‐level meta‐analysis within the framework of the Heart “OMics” in AGEing (HOMAGE) study to develop a risk prediction model for heart failure (HF) based on routinely available clinical measurements.

Methods and Results

Three studies with elderly persons (Health Aging and Body Composition [Health ABC],
Valutazione della PREvalenza di DIsfunzione Cardiaca asinTOmatica e di scompenso cardiaco
[PREDICTOR], and Prospective Study of Pravastatin in the Elderly at Risk [PROSPER]) were included to develop the
HF
risk function, while a fourth study (Anglo‐Scandinavian Cardiac Outcomes Trial [ASCOT]) was used as a validation cohort. Time‐to‐event analysis was conducted using the Cox proportional hazard model. Incident
HF
was defined as
HF
hospitalization. The Cox regression model was evaluated for its discriminatory performance (area under the receiver operating characteristic curve) and calibration (Grønnesby‐Borgan χ
2
statistic). During a follow‐up of 3.5 years, 470 of 10 236 elderly persons (mean age, 74.5 years; 51.3% women) developed
HF
. Higher age, BMI, systolic blood pressure, heart rate, serum creatinine, smoking, diabetes mellitus, history of coronary artery disease, and use of antihypertensive medication were associated with increased
HF
risk. The area under the receiver operating characteristic curve of the model was 0.71, with a good calibration (χ
2
7.9,
P
=0.54). A web‐based calculator was developed to allow easy calculations of the
HF
risk.

Conclusions

Simple measurements allow reliable estimation of the short‐term
HF
risk in populations and patients. The risk model may aid in risk stratification and future
HF
prevention strategies.
Host-Parasite list updating of Ciliates and fermentation in the digestive tract of wild miscellaneous herbivores in South Africa (RSA)
Authors: BOOYSE D. G. , DEHORITY B. A.
Published: May 2017

This article is dedicated to the Author, Burk Dehority, who became very ill with cancer. Fortunately he confirmed or corrected all identifications on ciliates in this article. This paper was 80% finished when he became ill. He unfortunately passed away in February 2016.
An Assessment of Recent and Future Temperature Change over the Sichuan Basin, China, Using CMIP5 Climate Models
Authors: Bannister Daniel , Herzog Michael , Graf Hans-F. , Hosking J. Scott , Short C. Alan
Published: May 2017

The Sichuan basin is one of the most densely populated regions of China, making the area particularly vulnerable to the adverse impacts associated with future climate change. As such, climate models are important for understanding regional and local impacts of climate change and variability, like heat stress and drought. In this study, climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) are validated over the Sichuan basin by evaluating how well each model can capture the phase, amplitude, and variability of the regionally observed mean, maximum, and minimum temperature between 1979 and 2005. The results reveal that the majority of the models do not capture the basic spatial pattern and observed means, trends, and probability distribution functions. In particular, mean and minimum temperatures are underestimated, especially during the winter, resulting in biases exceeding −3°C. Models that reasonably represent the complex basin topography are found to generally have lower biases overall. The five most skillful climate models with respect to the regional climate of the Sichuan basin are selected to explore twenty-first-century temperature projections for the region. Under the CMIP5 high-emission future climate change scenario, representative concentration pathway 8.5 (RCP8.5), the temperatures are projected to increase by approximately 4°C (with an average warming rate of +0.72°C decade−1), with the greatest warming located over the central plains of the Sichuan basin, by 2100. Moreover, the frequency of extreme months (where mean temperature exceeds 28°C) is shown to increase in the twenty-first century at a faster rate compared to the twentieth century.
Projected Future Changes of Tropical Cyclone Activity over the Western North and South Pacific in a 20-km-Mesh Regional Climate Model
Authors: Zhang Chunxi , Wang Yuqing
Published: May 2017

A high-resolution regional atmospheric model is employed to project the late twenty-first-century changes of tropical cyclone (TC) activity over the western North Pacific (WP) and southwest Pacific (SP). The model realistically reproduces the basic features of the TC climatology in the present-day simulation. Future projections under the representative concentration pathway 4.5 (RCP45) and 8.5 (RCP85) scenarios are investigated. The results show no significant change of TC genesis frequency (TCGF) in the WP by RCP45 due to the cancellation of the reduction over the western part and the increase over the eastern part together with a considerable decrease of TCGF by RCP85 due to the excessive TCGF reduction in the western part. The TCGF over the SP consistently decreases from RCP45 to RCP85. Despite the fact that the simulated maximum surface wind speeds are below 52 m s−1, the change with more strong TCs and fewer weak TCs is robust. The future changes in the TC genesis locations and translational speeds modulate the TC lifetime and frequency of occurrence. The TC genesis potential index (GPI) is used to evaluate the projected TCGF changes. The results show that low-level vorticity and midtropospheric vertical velocity largely contribute to the reduction of GPI in the western part of the WP, while vertical wind shear and midtropospheric vertical velocity mainly contribute to the decrease of GPI over the SP. The weakening of the monsoon trough is found to be responsible for the decreases of GPI and TCGF over the western part of the WP.
Estimation of the Tropical Pacific Ocean State 2010–13
Authors: Verdy Ariane , Cornuelle Bruce , Mazloff Matthew R. , Rudnick Daniel L.
Published: May 2017

A data-assimilating ⅓° regional dynamical ocean model is evaluated on its ability to synthesize components of the Tropical Pacific Ocean Observing System. The four-dimensional variational data assimilation (4DVAR) method adjusts initial conditions and atmospheric forcing for overlapping 4-month model runs, or hindcasts, that are then combined to give an ocean state estimate for the period 2010–13. Consistency within uncertainty with satellite SSH and Argo profiles is achieved. Comparison to independent observations from Tropical Atmosphere Ocean (TAO) moorings shows that for time scales shorter than 100 days, the state estimate improves estimates of TAO temperature relative to an optimally interpolated Argo product. The improvement is greater at time scales shorter than 20 days, although unpredicted variability in the TAO temperatures implies that TAO observations provide significant information in that band. Larger discrepancies between the state estimate and independent observations from Spray gliders deployed near the Galápagos, Palau, and Solomon Islands are attributed to insufficient model resolution to capture the dynamics in strong current regions and near coasts. The sea surface height forecast skill of the model is assessed. Model forecasts using climatological forcing and boundary conditions are more skillful than climatology out to 50 days compared to persistence, which is a more skillful forecast than climatology out to approximately 20 days. Hindcasts using reanalysis products for atmospheric forcing and open boundary conditions are more skillful than climatology for approximately 120 days or longer, with the exact time scale depending on the accuracy of the state estimate used for initializing and on the reanalysis forcing. Estimating the model representational error is a goal of these experiments.
Ethnic inequality and coups in sub-Saharan Africa
Authors: Houle Christian , Bodea Cristina
Published: May 2017

Does ethnic inequality breed coups? The recent literature on civil war shows both that inequality between ethnic groups induces war and, importantly, that civil wars and coups, although fundamentally different, are related. The literature on coups d’état, however, has yet to theorize and test the effect of ethnic inequality on coups. The link is plausible because many coups are ‘ethnic coups’, which depend on the capacity of plotters to mobilize their co-ethnics. We argue that large income and wealth disparities between ethnic groups accompanied by within-group homogeneity increase the salience of ethnicity and solidify within-group preferences vis-à-vis the preferences of other ethnic groups, increasing the appeal and feasibility of a coup. We use group-level data for 32 sub-Saharan African countries and 141 ethnic groups between 1960 and 2005 and provide the first large-N test to date of the effect of ethnic inequality on coups. Between- and within-group inequality measures are constructed based on survey data from the Afrobarometer and the Demographic and Health Surveys. We find strong support for our hypothesis: between-ethnic-group inequality (BGI) increases the likelihood that an ethnic group stages a coup only when within-ethnic-group inequality (WGI) is low. Coups remain frequent in sub-Saharan Africa and coups are the main threat to democracy in the region, by harming democratic consolidation and economic development, and by provoking further political instability. Our work provides a novel rationale to be concerned about ethnic inequality, showing that when ethnic and income cleavages overlap, destabilizing coups d’état are more likely.
The effects of military and non-military government expenditures on private consumption
Authors: Lorusso Marco , Pieroni Luca
Published: May 2017

In this article, we provide evidence that civilian and military government spending have specific characteristics that can affect private consumption differently. Our vector autoregressive (VAR) estimates for the US economy for the period 1960–2013 show that civilian expenditure induces a positive and significant response on private consumption, whereas military spending has a negative impact. We also analyze the effects of these public spending components for the subsamples 1960–79 and 1983–2013, respectively. Our results show that the main transmission channels of both civilian and military expenditures have changed over time. We adopt a new Keynesian approach and develop a dynamic stochastic general equilibrium (DSGE) model in order to simulate the empirical evidence. Both the larger persistence of shocks in military spending and the different financing mechanisms, which account for the propensity of policymakers to use budget deficits to finance wars, mimic the differences in the empirical responses of private consumption. Simulated impulse response functions of alternative specification models prove the robustness of our analysis. In particular, we assess the impact of civilian and military shocks in the presence of different (i) shares of heterogeneous households, (ii) price rigidities, and (iii) monetary reactions in response to different government shocks.
Assessing window area and potential for electricity savings by using daylighting and hybrid ventilation in office buildings in southern Brazil
Authors: Rupp Ricardo Forgiarini , Ghisi Enedir
Published: May 2017

The aim of this study is to develop a method to assess window area based on electricity consumption in office buildings in southern Brazil. The method may be used in the preliminary building design process in order to help choose an adequate window area to minimize its impact on energy consumption, depending on climate, building size, solar orientation, and mode of operation. The method also considered thermal comfort and daylighting performance. Four cases were investigated: Case 1, building operating with artificial lighting and air-conditioning; Case 2, considering integration of daylight and artificial light with air-conditioning; Case 3, building operating with hybrid ventilation and artificial lighting; and Case 4, considering integration of daylight and artificial light with hybrid ventilation. EnergyPlus and Daysim simulation programs were used to estimate the electricity consumption for each model. The integration of daylighting with artificial light (Case 2) generates more potential for energy savings (PES) than hybrid ventilation (Case 3). Case 4 showed PES ranging from 4.2% to 64.9%, allowing larger window areas with lower consumption, resulting in the highest PES.
Interlanguage and Cross-Generational Assimilation: Past Tense Unmarking in Hispanicized English
Authors: Callahan Erin
Published: May 2017

This study analyzes an emerging variety of North Carolina Hispanicized English in terms of the grammatical variable of past tense marking. It compares variation in Durham, North Carolina, Hispanicized English at increasing lengths of residency to generational varieties of Hispanicized English in a comparison sample, another contact-influenced ethnic variety of English, spoken by a longstanding Chicano community in south Texas. In this way, it tests the hypothesis that interlanguage (socio)linguistic development may in fact recapitulate generational changes in different sociodemographic speech settings. Results indicate that for the speakers in this study, the -t/-d variable indicates not only the constraints of the phonological process of deletion, but two morphosyntactic constraints: (1) the effects of verb class and (2) a grammatical process of past tense unmarking.
Global stabilization for switched stochastic nonlinear systems via unbounded time-varying scaling
Authors: Song Zhibao , Zhai Junyong , Zhu Zhengwei
Published: May 2017

This paper is concerned with the problem of global stabilization for switched stochastic nonlinear systems under arbitrary switchings. Based on the unbounded time-varying scaling of states, we design a state feedback controller to render the closed-loop switched system asymptotically stable in probability. Two examples are given to demonstrate the effectiveness of the proposed control scheme.
Linear active disturbance rejection control approach for load frequency control of two-area interconnected power system
Authors: Huang Congzhi , Li Jing , Mu Shicai , Yan Huaicheng
Published: May 2017

The performance optimization of the load frequency control problem for two-area interconnected power system is investigated by employing the gravitational search algorithm based linear active disturbance rejection control approach. Firstly, the load frequency control problem of a two-area power system with two identical non-reheated turbine units is formulated, taking into account the external step disturbance and parameters perturbation. Then, the essentials of the second order process oriented linear active disturbance rejection control approach are presented, where the parameters optimization procedure based on the gravitation search algorithm is proposed. Finally, the effectiveness of the proposed approach in the load frequency control problem is validated by the given extensive simulation examples. The disturbance rejection ability and the robustness with respect to the parameter perturbation of the proposed approach are also demonstrated.
Model predictive control with feedback correction for optimal energy dispatch of a networked microgrid
Authors: Zhou Xuping , Yan Huaicheng , Zhang Hao , Peng Chen
Published: May 2017

The novel model predictive control with feedback correction designed in this paper aims to optimize the energy dispatch and minimize the operation costs of a microgrid, which contributes to the improvement of pollution emissions and economic growth. The microgrid communication is based on power line communication, thus more accurate prediction models of photovoltaic and wind power generations of a networked microgrid can be designed from weather forecast information transmitted by power line communication. The prediction model for micro gas turbines and the loads of a microgrid are also proposed for optimization of the model predictive control. The rolling optimization model is updated by the latest forecast information to get minimization costs and optimal energy dispatch. The feedback correction designs predictions of generation and loads prediction errors to give an adjustment of the prediction model. Then the energy optimization dispatch will be updated by the adjusted prediction, so the most optimal dispatch will be obtained. Finally, the data of a microgrid in the Zhejiang province is applied in simulation and the minimization costs are compared with ideal costs to verify the performance and effectiveness of the proposed model predictive control strategy.
Knowledge, behaviour and microbial load of workers handling dental solid waste in a public health service in Brazil
Authors: Vieira Cristina Dutra , Tagliaferri Thaysa Leite , Carvalho Maria Auxiliadora Roque de , Oliveira Camilla Aparecida Silva de , Magalhães Paula Prazeres , Santos Simone Gonçalves dos , Farias Luiz de Macêdo
Published: May 2017

Healthcare wastes are those generated inside healthcare services, including dental clinics. Workers coming into close proximity to hazardous healthcare waste are potentially at risk. In an attempt to assess the knowledge and attitudes of workers dealing with infectious waste, a questionnaire was administered. The biological risk was investigated by evaluating the microbial load and screening some clinically relevant micro-organisms in the nasal mucosa, hands and coats of these workers. The results showed that 66.6% of the study population had incomplete primary education. Only two workers have had their blood tested to confirm anti-HBs levels. Microbial load evaluation on hand surfaces of morning workers showed statistically significant lower microbial loads after the workday when compared with the beginning of the work period. It is important to highlight that some clinically relevant bacteria, such as Pseudomonas aeruginosa and Klebsiella pneumoniae were isolated from worker’s hands. This study revealed the need for more training programmes regarding awareness of safe waste disposal protocols and also the necessity of discussing vaccination and its implications. Data regarding microbial loads of the worker’s hands, mostly at the beginning of the workday when handwashing is recommended worldwide, emphasise that hygiene measures should receive more attention during training exercises.
Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus
Authors: Willis R , Smikle M , DeCeulaer K , Romay-Penabad Z , Papalardo E , Jajoria P , Harper B , Murthy V , Petri M , Gonzalez E B
Published: May 2017

Background

The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes.

Methods

The serum levels of several aPL, 25-hydroxy-vitamin D, pro-inflammatory cytokines including IFNα, IL-1β, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican ( n = 45) and Hopkins ( n = 267) lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/β2glycoprotein antigenic complexes (oxLβ2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were used.

Results

Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients, respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLβ2Ag and IL-6 were elevated in the Jamaican cohort, and IFNα, IL-1β and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8, and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines.

Conclusions

Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle complexities of vitamin D’s relationship with cytokine production and disease activity in these patients.
Roles of silent information regulator 1–serine/arginine-rich splicing factor 10–lipin 1 axis in the pathogenesis of alcohol fatty liver disease
Authors: Li Yuanyuan , Zhou Junying
Published: May 2017

Alcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to alcoholic liver disease (ALD). With the continued ethanol consumption, alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including alcoholic steatohepatitis, fibrosis/cirrhosis, and even eventually progress to hepatocellular carcinoma and liver failure. Furthermore, cell trauma, inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of ethanol-mediated liver lesions. AFLD is characterized by excessive fat deposition in liver induced by excessive drinking, which is related closely to the raised synthesis of fatty acids and triglyceride, reduction of mitochondrial fatty acid β-oxidation, and the aggregation of very-low-density lipoprotein (VLDL). Although little is known about the cellular and molecular mechanisms of AFLD, it seems to be correlated to diverse signal channels. Massive studies have suggested that liver steatosis is closely associated with the inhibition of silent information regulator 1 (SIRT1) and the augment of lipin1 β/α ratio mediated by ethanol. Recently, serine/arginine-rich splicing factor 10 (SFRS10), a specific molecule functioning in alternative splicing of lipin 1 (LPIN1) pre-mRNAs, has emerged as the central connection between SIRT1 and lipin1 signaling. It seems a new signaling axis, SIRT1–SFRS10–LPIN1 axis, acting in the pathogenesis of AFLD exists. This article aims to further explore the interactions among the above three molecules and their influences on the development of AFLD.

Impact statement

ALD is a major health burden in industrialized countries as well as China. AFLD, the earliest and reversible form of ALD, can progress to hepatitis, fibrosis/cirrhosis, even hepatoma. While the mechanisms, by which ethanol consumption leads to AFLD, are complicated and multiple, and remain incompletely understood. SIRT1, SFRS10, and LIPIN1 had been separately reported to participate in lipid metabolism and the pathogenesis of AFLD. Noteworthy, we found the connection among them via searching articles in PubMed and we had elaborated the connection in detail in this minireview. It seems a new signaling axis, SIRT1–SFRS10–LIPIN1 axis, acting in the pathogenesis of AFLD exists. Further study aimed at SIRT1–SFRS10–LIPIN1 signaling system will possibly offer a more effective therapeutic target for AFLD.
ITIM receptors: more than just inhibitors of platelet activation
Authors: Coxon Carmen H. , Geer Mitchell J. , Senis Yotis A.
Published: May 2017

Since their discovery, immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit signaling from immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors in almost all hematopoietic cells, including platelets. However, a growing body of evidence has emerged demonstrating that this is an oversimplification, and that ITIM-containing receptors are versatile regulators of platelet signal transduction, with functions beyond inhibiting ITAM-mediated platelet activation. PECAM-1 was the first ITIM-containing receptor identified in platelets and appeared to conform to the established model of ITIM-mediated attenuation of ITAM-driven activation. PECAM-1 was therefore widely accepted as a major negative regulator of platelet activation and thrombosis for many years, but more recent findings suggest a more complex role for this receptor, including the facilitation of αIIbβ3-mediated platelet functions. Since the identification of PECAM-1, several other ITIM-containing platelet receptors have been discovered. These include G6b-B, a critical regulator of platelet reactivity and production, and the noncanonical ITIM-containing receptor TREM-like transcript-1, which is localized to α-granules in resting platelets, binds fibrinogen, and acts as a positive regulator of platelet activation. Despite structural similarities and shared binding partners, including the Src homology 2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2, knockout and transgenic mouse models have revealed distinct phenotypes and nonredundant functions for each ITIM-containing receptor in the context of platelet homeostasis. These roles are likely influenced by receptor density, compartmentalization, and as-yet unknown binding partners. In this review, we discuss the diverse repertoire of ITIM-containing receptors in platelets, highlighting intriguing new functions, controversies, and future areas of investigation.
PD-1 blockade for relapsed lymphoma post–allogeneic hematopoietic cell transplant: high response rate but frequent GVHD
Authors: Haverkos Bradley M. , Abbott Diana , Hamadani Mehdi , Armand Philippe , Flowers Mary E. , Merryman Reid , Kamdar Manali , Kanate Abraham Sebastian , Saad Ayman , Mehta Amitkumar , Ganguly Siddhartha , Fenske Timothy S. , Hari Parameswaran , Lowsky Robert , Andritsos Leslie , Jagasia Madan , Bashey Asad , Brown Stacey , Bachanova Veronika , Stephens Deborah , Mineishi Shin , Nakamura Ryotaro , Chen Yi-Bin , Blazar Bruce R. , Gutman Jonathan , Devine Steven M.
Published: May 2017

Key Points

Checkpoint blockade via anti–PD-1 mAbs was associated with a high overall response rate in relapsed Hodgkin lymphoma allo-HCT patients. Checkpoint blockade via anti–PD-1 mAbs after allo-HCT can be complicated by rapid onset of severe and treatment-refractory GVHD.
Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin
Authors: Mantia Charlene , Uhlmann Erik J. , Puligandla Maneka , Weber Griffin M. , Neuberg Donna , Zwicker Jeffrey I.
Published: May 2017

Key Points

Therapeutic enoxaparin was associated with a greater than threefold increased risk of major ICH in patients with glioma. The PANWARDS risk score was a sensitive predictor of major ICH in glioma.
Laurence Alan Boxer, M.D. (1940–2017)
Authors: Dinauer Mary C
Published: May 2017

A memorial for Laurence Alan Boxer, M.D.
Niels Borregaard, M.D. (1951–2017)
Authors: Cowland Jack B , Horn Charlotte , Nauseef William M
Published: May 2017

A memorial for Niels Borregaard, M.D., Ph.D.
Yuliy Sannikov: Winner of the 2016 Clark Medal
Authors: Athey Susan , Skrzypacz Andrzej
Published: May 2017

Yuliy Sannikov is an extraordinary theorist who has developed methods that offer new insights in analyzing problems that had seemed well-studied and familiar: for example, decisions that might bring about cooperation and/or defection in a repeated-play prisoner's dilemma game, or that affect the balance of incentives and opportunism in a principal–agent relationship. His work has broken new ground in methodology, often through the application of stochastic calculus methods. The stochastic element means that his work naturally captures situations in which there is a random chance that monitoring, communication, or signaling between players is imperfect. Using calculus in the context of continuous-time games allows him to overcome tractability problems that had long hindered research in a number of areas. He has substantially altered the toolbox available for studying dynamic games. This essay offers an overview of Sannikov's research in several areas.