bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodality Treatment Involving Radiotherapy for Advanced Liver-Confined Hepatocellular Carcinoma
Authors: Yoon Hong In , Seong Jinsil
Published: November 2014

Background: Advanced-stage hepatocellular carcinoma (HCC) has an extremely poor prognosis although sorafenib, which is the treatment of choice, has provided survival benefits. Among advanced diseases, liver-confined HCC, which invades the vasculature without extrahepatic metastasis, requires novel therapeutic management beyond using sorafenib alone. Currently, the Korean Liver Cancer Study Group and National Comprehensive Cancer Network guidelines recommend combined radiotherapy (RT) and chemotherapy for some selected cases. For advanced liver-confined HCC, focal liver irradiation, RT technological development, and optimal selection of RT-suitable patients enable clinicians to use RT-involving multimodality treatments based on oncologic principles, such as concurrent chemoradiotherapy, which represent effective multimodality treatments for several types of malignancy. Summary: In this review, we discuss the need to develop novel therapeutic approaches for liver-confined HCC and clinical applications of RT-involving multimodality treatments for advanced liver-confined HCC. Conclusion: RT-involving multimodality treatments can enhance the overall therapeutic successes for advanced liver-confined HCC and also provide potential cures to some patients via conversion to a resectable condition.
Characteristics of Long-Term Survivors following Sorafenib Treatment for Advanced Hepatocellular Carcinoma: Report of a Workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan
Authors: Tanaka Katsuaki , Shimada Mitsuo , Kudo Masatoshi
Published: November 2014

Background: Little data are available on the long-term survival of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC). Summary: During a consensus workshop at the 50th annual meeting of the Liver Cancer Study Group of Japan held in Kyoto (June 5-6, 2014), experts met to discuss the characteristics of long-term (>3 years) survivors of advanced HCC following sorafenib treatment. A total of 70 long-term survivors following sorafenib treatment at eight institutions were included, and the long-term survival rate (>3 years) at each institution ranged from 2.6 to 6.9% (mean, 4.5). The long-term survival-related factors presented can be categorized as follows: (1) conversion options, including hepatic resection following successful sorafenib treatment, (2) additional salvage options when progressive disease is confirmed, (3) long-term sorafenib treatment, (4) effective post-sorafenib options to prolong postprogression survival, and (5) good pretreatment liver function. Sorafenib monotherapy exceeding 3 years is rare, and most of the patients receiving sorafenib required other treatment modalities in the form of multidisciplinary therapy. Conclusion: The overview obtained from the workshop reflects the pattern of management in practice for long-term survivors following sorafenib treatment for HCC in Japan and may also provide valuable information for other countries.
Efficacy and Safety of Telaprevir-Based Antiviral Treatment for Elderly Patients with Hepatitis C Virus
Authors: Takita Masahiro , Hagiwara Satoru , Kudo Masatoshi , Kouno Masashi , Chishina Hirokazu , Arizumi Tadaaki , Kitai Satoshi , Yada Norihisa , Inoue Tatsuo , Minami Yasunori , Ueshima Kazuomi
Published: November 2014

Background: Telaprevir-based antiviral therapy has been the primary treatment for chronic hepatitis C genotype 1 at a high viral load since November 2011. On the other hand, a number of patients have been reported to require withdrawal from or reduced doses of drugs due to side effects, such as eruptions, anemia, and renal dysfunction. In addition, as hepatitis C patients are growing older, it is imperative to investigate the tolerability of triple combination therapy for elderly patients. Subjects and Methods: The study subjects comprised 35 patients who received telaprevir combination therapy after November 2011. They were divided into group A (age: <65 years; n = 21) and group B (age: ≥65 years; n = 14) in order to compare the treatment completion rate, sustained virological response at week 24 (SVR24), and adverse events between the groups. Results: The treatment completion rate was 82.8% (29/35) in all subjects, 90.4% (19/21) in group A, and 78.5% (11/14) in group B. The rate was lower in group B but without a significant difference between the groups (p = 0.804). The SVR24 rate was 88.5% (31/35) in all subjects, 90.4% (19/21) in group A, and 85.7% (12/14) in group B, without a significant difference between the groups (p = 0.161). Conclusion: Although the incidence of anemia was higher in group B, there was no significant difference in the treatment completion or SVR24 rate between the groups. Telaprevir combination therapy is suggested to be tolerable for elderly hepatitis C patients.
Ultrasound Elastography Correlates Treatment Response by Antiviral Therapy in Patients with Chronic Hepatitis C
Authors: Yada Norihisa , Sakurai Toshiharu , Minami Tomohiro , Arizumi Tadaaki , Takita Masahiro , Inoue Tatsuo , Hagiwara Satoru , Ueshima Kazuomi , Nishida Naoshi , Kudo Masatoshi
Published: November 2014

Objective: To investigate the relationship between tissue elasticity before and after antiviral therapy and shear wave as well as strain elastography. Methods: FibroScan and real-time tissue elastography were performed before and after antiviral therapy for chronic hepatitis C, and treatment efficacy and elastographic findings were comparatively analyzed. Elasticity was evaluated by measuring liver stiffness (LS) in kilopascals using FibroScan, and the liver fibrosis index (LFI) was assessed by real-time tissue elastography. Results: LS and LFI correlated well before and after therapy (r = 0.567, p = 0.003 and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LS increased in 4 of 5 patients. Patients with an increase in both LS and LFI were all in the non-SVR group (3/3, 100%). In addition, LS increased in all patients except 1 in the non-SVR group (4/5, 80%). In the SVR group, both LS and LFI decreased in all patients except 1 (18/19, 94.7%). In the patient with an increase in LS despite achieving SVR, LS decreased quickly after alcohol cessation. Conclusions: With a few exceptions, SVR improved LS. All patients with an increase in LFI were in the non-SVR group, even though LFI decreased in 2 patients. Our findings suggest that an LFI increase indicates lack of treatment efficacy with antiviral therapy. LFI may be useful for the assessment of treatment efficacy in patients with worsening of LS despite achieving SVR with antiviral therapy.
Late-Onset Paraplegia after Complete Response to Two Cycles of Ipilimumab for Metastatic Melanoma
Authors: O'Kane Grainne M. , Lyons Tomas G. , Colleran Gabrielle C. , Ahmad Marzuki Wan , Alken Scheryll , Kavanagh Eoin C. , Fitzpatrick David , Murray Brian , Kelly Catherine M.
Published: November 2014

Background: Ipilimumab has been shown to improve overall survival in patients with metastatic melanoma; however, complete responses (CRs) are uncommon. Immune-related side effects usually involve the skin or gastrointestinal tract. Neurologic events occur less frequently but are well described. Case Report: We report the case of a 58-year-old man with metastatic melanoma who commenced ipilimumab post spinal decompression and radiation. He developed a colitis post cycle 2 and ipilimumab was discontinued. Imaging, however, documented a radiological CR. 8 weeks later, he developed paraplegia and a myelitis despite an ongoing radiological CR. Steroid use resulted in some improvement radiologically, without clinical improvement. Conclusion: We report myelitis with consequent paraplegia as a potential neurological immune-related side effect of ipilimumab. We further describe a patient with a CR after 2 cycles of ipilimumab in the setting of radiation.
Assessment of Cardiac Autonomic Nervous System Involvement in Systemic Sclerosis via Exercise Heart Rate Recovery
Authors: Karakulak Ugur Nadir , Okutucu Sercan , Şahiner Levent , Maharjan Naresh , Aladag Elifcan , Akdogan Ali , Kilic Levent , Kaya Ergun Baris , Aytemir Kudret , Tokgozoglu Lale
Published: November 2014

Objective: To assess exercise heart rate recovery (HRR) indices in patients with systemic sclerosis (SSc) for an assessment of their cardiac autonomic function. Subjects and Methods: Thirty-five patients with diffuse or limited SSc and 35 healthy controls were enrolled. All subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. Results: The SSc and control groups were similar in age (45.2 ± 11.6 vs. 43.9 ± 10.0 years), had identical gender ratios (31 female/4 male in both groups) and similar left ventricular ejection fraction (66.5 ± 5.1 vs. 67.7 ± 5.9%). The mean HRR1 (21.8 ± 4.4 vs. 27.7 ± 4.3 bpm, p = 0.001), HRR2 (43.8 ± 6.3 vs. 47.6 ± 4.4 bpm, p = 0.004) and HRR3 (58.8 ± 10.3 vs. 63.6 ± 7.3 bpm, p = 0.031) values were significantly lower in the SSc group than in the healthy controls. HRR indices were similar in the limited and diffuse SSc subgroups. Conclusions: The patients with SSc had lower HRR indices than normal subjects. Cardiac autonomic functions might be involved in SSc, even in patients without cardiac symptoms.
Overexpression of Tumor-Associated Trypsin Inhibitor (SPINK1/TATI) in Hepatitis C-Associated Hepatocellular Carcinoma: Potential Implications for Viral Hepatocarcinogenesis
Authors: Hass Holger G. , Jobst Jürgen , Vogel Ulrich , Scheurlen Michael , Nehls Oliver
Published: November 2014

Background: The molecular pathomechanisms leading to hepatitis C virus (HCV)-induced hepatocarcinogenesis remain unclear. This study investigated the molecular pathways and key genes underlying HCV-positive hepatocellular carcinoma (HCC) using gene expression profiling. Methods: Oligonucleotide arrays (Affymetrix HU133A) were used to determine and compare the tissue-specific gene expression profiles in 39 cases of HCV-positive or -negative HCC and non-malignant liver tissue. The expression values of the most overexpressed genes were validated by real-time polymerase chain reaction (RT-PCR). Results: 837 genes or expressed sequence tags (ESTs) were significantly differently expressed in HCV-positive HCC versus healthy tissue: 414 were upregulated and 423 were downregulated (p < 0.05; > 2-fold change in ≥ 70% of the samples). A specific gene expression profile for HCV-positive HCC was obtained using 2-dimensional cluster analysis and was confirmed using supervised neuronal network modeling. The most consistently overexpressed gene coded for serine protease inhibitor Kazal-type 1 (SPINK1)/tumor-associated trypsin inhibitor (TATI) (median fold change, 19.7; significantly overexpressed in 90% of the samples). SPINK1/TATI was coregulated with matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of metalloproteinases (TIMPs)). Conclusions: Gene expression profiling identified specific dysregulated molecular pathways and SPINK1/TATI as the most overexpressed gene in HCV-positive HCC. These data highlight the importance of SPINK1/TATI as a tumor marker for HCV-induced HCC and may lead to a better understanding of HCV-induced hepatocarcinogenesis.
Mangiferin Attenuate Sepsis-Induced Acute Kidney Injury via Antioxidant and Anti-Inflammatory Effects
Authors: He Liyu , Peng Xiaofei , Zhu Jiefu , Chen Xian , Liu Hong , Tang Chengyuan , Dong Zheng , Liu Fuyou , Peng Youming
Published: November 2014

Background: Acute kidney injury (AKI) is a frequent and serious complication of sepsis. A growing body of evidence now suggests that inflammatory reactions and tubular dysfunction induced by oxidative stress involved in the mechanisms of the disease. This study aimed to determine the role of anti-inflammatory and anti-oxidant activities of mangiferin (MA) in sepsis-induced AKI. Methods: We investigated the effects of MA on apoptosis of rat kidney proximal tubular cell (RPTC), together with renal function and morphological alterations of mice undergoing cecal-ligation and puncture (CLP). The levels of oxidative stress in kidney tissues were also determined. Moreover, we mainly focus on the effects of MA in regulating the production of NLRP3 and Nrf2 in the present study. Results: The exposure to LPS (5 Vg/ml) yielded a signiﬁcant increase of apoptosis in RPTC cells, which was largely inhibited by MA pretreatment. MA attenuates renal dysfunction and ameliorates the morphological changes in the septic mice induced by CLP. MA inhibits oxidative stress, decreases serum levels of IL-1F and IL-18, and prevents tubular epithelial cells apoptosis in kidneys of CLP mice model. Data in this study also suggest that MA promotes Nrf2 expression and suppresses renal NLRP3 inflammasome activation. Conclusion: In summary, MA protects against sepsis-induced AKI through NLRP3 inflammasome inhibition and Nrf2 up-regulation. Thus, the mangiferin could thus be a promising candidate for development of a multi-potent drug. i 2014 S. Karger AG, Basel
Supraclavicular Lymphadenopathy: Should It Be Perceived as the Virchow's Node of Head and Neck Tumors?
Authors: Acar Turker , Savas Recep , Kocacelebi Kenan , Guneyli Serkan
Published: November 2014

Background: In this study, we aimed to determine the correlation between supraclavicular lymph node involvement (SLNI) and metastatic potential, frequency, and metastases predilection sites in patients diagnosed with various head and neck tumors (HNT) and staged via positron emission tomography/computed tomography (PET/CT) imaging. We also investigated the impact of different variables on SLNI. Patients and Methods: 270 patients diagnosed with HNT were enrolled in the study (194 males and 96 females, mean age 54.9 ± 14.7 years (range 18-89 years)). Results: Nasopharyngeal carcinoma demonstrated significant SLNI (p < 0.01); however, other subtypes of HNT did not. In all HNT studied, no apparent metastatic predilection tendency for the supraclavicular region was observed, as opposed to the well-described Virchow's node. Age, gender, tumor size, and systemic metastases were not identified as statistically significant variables contributing to SLNI. Multivariate regression analysis revealed an increased cervical (p < 0.01) and thoracic (p = 0.001) lymph node involvement in patients with SLNI. Conclusion: SLNI with the possibility of metastasis was more frequently observed in nasopharyngeal carcinoma, advancing the nodal status without significantly influencing the T and M stages. A careful evaluation of this very small region is of critical importance for proper nodal staging in nasopharyngeal cancer patients.
Quality of Life under Capecitabine (Xeloda®) in Patients with Metastatic Breast Cancer: Data from a German Non-Interventional Surveillance Study
Authors: Müller Volkmar , Fuxius Stefan , Steffens Claus-Christoph , Lerchenmüller Christian , Luhn Birgit , Vehling-Kaiser Ursula , Hurst Ursula , Hahn Lars-Jörgen , Soeling Ulrike , Wohlfarth Tim , Zaiss Matthias
Published: November 2014

Aim: This non-interventional surveillance study (NIS) collected data on the quality of life (QoL) of patients treated with capecitabine as mono- or combination chemotherapy in an outpatient setting. Methods: Capecitabine was administered orally for 14 days of each 21-day cycle. The main parameters of interest were QoL, compliance, patient and physician satisfaction, handling of hand-foot syndrome (HFS), and efficacy. The statistics were descriptive; some differences were compared using confidence intervals (CIs). Results: 735 patients from 161 centers received at least 1 dose of capecitabine. The median duration of observation was 5.5 months overall. The QoL global score was 53% (mean from the entire study population at all times), without any correlation to HFS. The overall response rate (ORR) was 35.1%, and the disease control rate (DCR) 64.4%. The median progression-free survival (PFS) was overall 6.81 months (95% CI 6.32-7.63 months) and it was significantly higher in patients with HFS (8.4 months, 95% CI 7.5-9.2 months, hazard ratio (HR) 0.60; p < 0.0001). The safety and tolerability of capecitabine were considered acceptable. The HFS incidence (all grades) was 27.1%. Conclusions: Capecitabine had a favorable risk-benefit relation in outpatient therapy. The QoL remained stable over the course of the investigation, indicating good compliance. HFS was a strong predictor of longer PFS and had no negative impact on the global QoL.
Analysis of the Discriminative Methods for Diagnosis of Benign and Malignant Solitary Pulmonary Nodules Based on Serum Markers
Authors: Wang Wanping , Liu Mingyue , Wang Jing , Tian Rui , Dong Junqiang , Liu Qi , Zhao Xianping , Wang Yuanfang
Published: November 2014

Background: Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Methods: Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. Results: The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). Conclusion: This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN.
Prognostic Impact of C-Reactive Protein in Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Rocha Pedro , Morgan Charity J. , Templeton Arnoud J. , Pond Gregory R. , Naik Gurudatta , Sonpavde Guru
Published: November 2014

Background: Serum C-reactive protein (CRP) demonstrates a prognostic impact in small studies of metastatic prostate cancer (MPC). Methods: A systematic review was conducted to identify publications and presentations exploring the association of serum CRP and overall survival (OS) in MPC, both castration-sensitive and castration-resistant. Heterogeneity among trials was assessed using Cochrane's Q statistic, and the I2 statistic was used to quantify inconsistency. The assumption of homogeneity was considered invalid if p < 0.1. All statistical tests were 2-sided, and p < 0.05 was considered significant. Results: 6 studies were eligible, totaling 659 evaluable patients. 2 studies evaluated castration-sensitive men receiving androgen deprivation, while the remaining 4 studies evaluated castration-resistant men receiving docetaxel-based chemotherapy. Men with higher CRP had significantly worse OS than those with lower CRP (hazard ratio (HR) = 1.42, p < 0.001, 95% confidence interval (CI) 1.17-1.73). In trials of castration-sensitive men, high CRP yielded a HR = 1.92 (p = 0.005, 95% CI 1.22-3.03; I2 = 0). In castration-resistant men, high CRP yielded HR = 1.35 (p = 0.003, 95% CI 1.11-1.65; I2 = 78.6%). Conclusion: This meta-analysis suggests a detrimental impact for CRP on OS in MPC. Prospective validation is justified to enhance prognostication and trial design, given the affordability, ready availability, and large dynamic range of CRP.
Gastroduodenal Intussusception, Intermittent Biliary Obstruction and Biochemical Pancreatitis due to a Gastric Hyperplastic Polyp
Authors: Chahla Elie , Kim Michael A. , Beal Brandon T. , Alkaade Samer , Garrett Robert W. , Omran Louay , Ogawa Michael T. , Taylor Jason R.
Published: November 2014

We present the case of a 76-year-old man with gastroduodenal intussusception secondary to a gastric hyperplastic polyp. Intussusception in the adult population occurs infrequently. Our patient presented with gastroduodenal intussusception, which is very uncommon and accounts for <10% of all types of intussusception. This case is unique in that partial endoscopic resection of the gastric hyperplastic polyp resolved the patient's gastroduodenal intussusception, biliary obstruction and biochemical pancreatitis without the need for surgical intervention.
Leading from the Margins
Authors: Adeney Frances
Published: November 2014

This article outlines mission theologies and practices of women trainees for mission in Brazil. The women are from theusa, Central America, and Brazil and assigned to mission work in Brazil with theus-based “Mission Society”. Nine interviews from a missionary training session in July 2008 are analyzed in order to: (1) articulate the spoken mission theology of women trainees; (2) identify everyday practices that women mission trainees engage in related to their mission calling and work; (3) relate the dislocation experienced by the women to sustaining practices and character traits they developed by utilizing the lived experience of their everyday practices; (4) describe the fuller theology of mission that results and make suggestions for incorporating women’s mission theologies based on practices into stated mission theologies, showing how everyday practices of women doing mission can enhance missiological understandings.
Minimal Faith and Irenic Ideals in Seventeenth-Century Scholarly Circles
Authors: Nellen Henk
Published: November 2014

This article shows how the Dutch humanist Hugo Grotius (1583–1645), inspired by his friend Isaac Casaubon, sought to introduce a procedure for mitigating strife in the Christian church. He proclaimed a division between a set of self-evident, universally accepted key tenets, to be endorsed by all believers, and a larger number of secondary, not completely certain articles of faith, which were to be left open for friendly debate. The doctrine of the Trinity belonged to the second category; it should be treated in a careful, detached way, in words that did not go beyond the terminology of the Bible. However, defenders of this irenic stance laid themselves open to severe criticism: the example of the conservative Lutheran theologian Abraham Calovius illustrates how they were censured for giving up divinely inspired truth for a chimerical unionist ideal which cajoled them into reintroducing the early Christian heresy of Arianism, now called Socinianism.
“An End to Unjust Inequality in the World”
Authors: Balmer Randall
Published: November 2014

Since the emergence of the Religious Right in the late 1970s, American evangelicalism has commonly been associated with conservative politics. An examination of nineteenth-century evangelicalism, however, suggests a different affinity. Antebellum evangelicals marched in the vanguard of social change with an agenda that almost invariably advocated for those on the margins of society, including women and African Americans. Evangelicals were involved in peace crusades and the temperance movement, a response to social ills associated with rampant alcohol consumption in the early republic. They advocated equal rights for women, including voting rights. Evangelicals in the North crusaded against slavery. Although Horace Mann, a Unitarian from Massachusetts, is the person most often associated with the rise of common schools, Protestants of a more evangelical stripe were early advocates of public education, including leaders in Ohio, Michigan, and Kentucky. Some evangelicals, including Charles Grandison Finney, even excoriated capitalism as inconsistent with Christian principles.
G. Banna’s and A. Fadlallah’s Views on Dancing
Authors: Alagha Joseph
Published: November 2014

This article discusses the concept of purposeful art (al-fann al-hadif), which is ideologically motivated art that caters to Muslim religious sensibilities, in opposition to lowbrow art (al-fann al-habit) that does not. It compares Gamal al-Banna’s attempt in Egypt to include dance into the concept with the views of the Lebanese Ayatullah Fadlallah, the late ideologue and early mentor of the Shi‘ite resistance movement Hizbullah. The main question is how purposeful art – particularly dancing as an illustration of the sensitivity of body in public space – is legitimized by the jurisprudential notion ofhasanat(good deeds) in the Sunni tradition by al-Banna andmaslaha(interest, advantage) in the Shi‘ite tradition by Fadlallah and Hizbullah. By promoting resistance art (al-fann al-muqawim), Hizbullah reveals its new face. It contests public space through artistic cultural productions, including dancing, which leave room for the female body to perform on a stage characterized by gender mixing, for a mixed audience. Hizbullah believes that art is humanity and it promotes democracy. al-Banna, Fadlallah, and Hizbullah concur that “Islam”, as it is lived out by its followers, finds a necessary expression in social practices; it is the art form of dancing that is more controversial.
Toward a Theory of “Islamist Movements”
Authors: Gould Mark
Published: November 2014

I differentiate conceptually between Islamist and other religious movements directed towards religious and political institutions and, for each of these, between movements that endeavor to transform (1) role relationships, (2) collectivity structures, (3) normative expectations, and (4) value orientations in these institutions. I construct a value-added theory that specifies the necessary and sufficient conditions generating each of these types of movements. Movements are directed at one of these components of social action dependent on the nature of strain present for actors within the system. Their direction is guided by the nature of the opportunity structure present in the social order under examination. Religious disorders, religious movements that violate institutionalized norms and attempt to reconstruct one or more aspects of an institutionalized religious structure, emerge when religious value-commitments and obligations are deflated and actors adopt a calculating orientation towards them. A parallel set of religious movements that do not violate institutionalized norms will emerge when all of the variables are present except a deflation of value-commitments.
A re-description of the fossil damselfly Eolestes syntheticus Cockerell, 1940 (Odonata: Zygoptera: Eolestidae n. fam.) with description of new taxa from the Eocene of North America
Authors: GREENWALT DALE E. , BECHLY GÜNTER
Published: November 2014

The enigmatic species Eolestes syntheticus Cockerell, 1940, from the Early Eocene of North America, previously attributed to the lestoid family Synlestidae, is re-examined in light of the discovery of new material from the Middle Eocene Kishenehn Formation in northwestern Montana. E. syntheticus and a new species, Eolestes ramosus sp. n., are attributed to a new family Eolestidae fam. n.. In addition, a new genus and species very closely related to Lestidae but assigned to family unknown, Lutetialestes uniformis sp. n., is described from the Kishenehn Formation.
New observations on Myxozoa of the goldline sea bream Sarpa salpa L. 1758 (Teleostei : Sparidae) from the Mediterranean coast of Tunisia
Authors: LAAMIRI SAYEF
Published: November 2014

A member of the Sparidae family, the goldline sea bream Sarpa salpa (Linnaeus, 1758) collected from the Gulf of Tunis and the Bay of Bizerte in Northeast Tunisia, Western Mediterranean, were examined for the myxozoan parasites. During the parasitological exposure, a total of 7 myxosporean are found including 6 coelozoic species belong to the genus Ceratomyxa Thélohan, 1892 infected the gallbladder of their host of which 3 known species have been previously described, C. arcuata Thélohan, 1892, C. pallida Thélohan, 1895 and C. herouardi Georgévitch, 1916 and 3 species seem different in morphology to Ceratomyxa spp already known from Mediterranean Sea or from other localities in the wide world. These species are Ceratomyxa sp. 1, Ceratomyxa sp. 2 and Ceratomyxa sp. 3. Only one histozoic species belongs to the genus Henneguya Thélohan, 1892, Henneguya sp. identified for the first time infecting the mesentery vessels of S. salpa. The myxosporean parasite C. arcuata Thélohan, 1892 is reported for the first time in Tunisian waters from the goldline sea bream which represents as new host records. In addition to the Monoparasitism, the phenomenon of Polyparasitism was observed between the current species in both sampling sites with two types: Biparasitism and Triparasitism. The most frequent Polyparasitism was a Biparasitism-type between C. herouardi and C. pallida with frequency 16.97%. For all the species, no serious pathogenic changes have been recorded in the host organ or in the outward appearance of the fish. Morphological features, site of infection into the host, parasite prevalence and mean intensity of each myxosporean found during this survey are determined and their taxonomic affinities to other species are discussed.
Trigonal Ice Crystals in Earth’s Atmosphere
Authors: Murray Benjamin J. , Salzmann Christoph G. , Heymsfield Andrew J. , Dobbie Steven , Neely Ryan R. , Cox Christopher J.
Published: November 2014

We are all familiar with the hexagonal shape of snow and ice crystals, and it is well established that their sixfold symmetry is derived from the arrangement of water molecules in a hexagonal crystal structure. However, atmospheric ice crystals with only threefold rotational symmetry are often observed, which is inconsistent with the hexagonal crystal structure of ordinary ice. These crystals are found in a wide range of different cloud types ranging from upper-tropospheric cirrus to contrails and diamond dust and they form at temperatures ranging from about −84° to −5°C. Recent experimental studies of ice crystal structures have shown that ice under a wide range of atmospheric conditions does not always conform to the standard hexagonal crystal structure. Instead, sequences of the hexagonal structure can be interlaced with cubic sequences to create stacking-disordered ice. This degrades the symmetry of the crystal structure so that, instead of having a hexagonal structure, they have a trigonal structure with a corresponding threefold symmetry. Hence, this implies that atmospheric ice crystals with threefold symmetry are made of stacking-disordered ice. We conclude that the presence of trigonal crystals in the atmosphere is consistent with rare Parry arc halos and also show that they have distinct radiative properties compared with hexagonal ice.
Sensitivity of Tropical Cyclone Feedback on the Intensity of the Western Pacific Subtropical High to Microphysics Schemes
Authors: Sun Yuan , Zhong Zhong , Lu Wei
Published: November 2014

The Advanced Research version of Weather Research and Forecasting (WRF-ARW) Model is used to examine the sensitivity of a simulated tropical cyclone (TC) track and the associated intensity of the western Pacific subtropical high (WPSH) to microphysical parameterization (MP) schemes. It is found that the simulated WPSH is sensitive to MP schemes only when TCs are active over the western North Pacific. WRF fails to capture TC tracks because of errors in the simulation of the WPSH intensity. The failed simulation of WPSH intensity and TC track can be attributed to the overestimated convection in the TC eyewall region, which is caused by inappropriate MP schemes. In other words, the MP affects the simulation of the TC activity, which influences the simulation of WPSH intensity and, thus, TC track. The feedback of the TC to WPSH plays a critical role in the model behavior of the simulation. Further analysis suggests that the overestimated convection in the TC eyewall results in excessive anvil clouds and showers in the middle and upper troposphere. As the simulated TC approaches the WPSH, the excessive anvil clouds extend far away from the TC center and reach the area of the WPSH. Because of the condensation of the anvil clouds’ outflows and showers, a huge amount of latent heat is released into the atmosphere and warms the air above the freezing level at about 500 hPa. Meanwhile, the evaporative (melting) process of hydrometers in the descending flow takes place below the freezing level and cools the air in the lower and middle troposphere. As a result, the simulated WPSH intensity is weakened, and the TC turns northward earlier than in observations.
Wind and Temperature Oscillations Generated by Wave–Turbulence Interactions in the Stably Stratified Boundary Layer
Authors: Sun Jielun , Mahrt Larry , Nappo Carmen , Lenschow Donald H.
Published: November 2014

The authors investigate atmospheric internal gravity waves (IGWs): their generation and induction of global intermittent turbulence in the nocturnal stable atmospheric boundary layer based on the new concept of turbulence generation discussed in a prior paper by Sun et al. The IGWs are generated by air lifted by convergence forced by the colliding background flow and cold currents near the ground. The buoyancy-forced IGWs enhance wind speed at the wind speed wave crests such that the bulk shear instability generates large coherent eddies, which augment local turbulent mixing and vertically redistribute momentum and heat. The periodically enhanced turbulent mixing, in turn, modifies the air temperature and flow oscillations of the original IGWs. These turbulence-forced oscillations (TFOs) resemble waves and coherently transport momentum and sensible heat. The observed momentum and sensible heat fluxes at the IGW frequency, which are due to either the buoyancy-forced IGWs themselves or the TFOs, are larger than turbulent fluxes near the surface. The IGWs enhance not only the bulk shear at the wave crests, but also local shear over the wind speed troughs of the surface IGWs. Temporal and spatial variations of turbulent mixing as a result of this wave-induced turbulent mixing change the mean airflow and the shape of the IGWs.
Shear Capacity as Prognostic for Nocturnal Boundary Layer Regimes
Authors: van Hooijdonk Ivo G. S. , Donda Judith M. M. , Clercx Herman J. H. , Bosveld Fred C. , van de Wiel Bas J. H.
Published: November 2014

Field observations and theoretical analysis are used to investigate the appearance of different nocturnal boundary layer regimes. Recent theoretical findings predict the appearance of two different regimes: the continuously turbulent (weakly stable) boundary layer and the relatively “quiet” (very stable) boundary layer. A large number of nights (approximately 4500 in total) are analyzed using an ensemble averaging technique. The observations support the existence of these two fundamentally different regimes: weakly stable (turbulent) nights rapidly reach a steady state (within 2–3 h). In contrast, very stable nights reach a steady state much later after a transition period (2–6 h). During this period turbulence is weak and nonstationary. To characterize the regime, a new parameter is introduced: the shear capacity. This parameter compares the actual shear after sunset with the minimum shear needed to sustain continuous turbulence. In turn, the minimum shear is dictated by the heat flux demand at the surface (net radiative cooling), so that the shear capacity combines flow information with knowledge of the boundary condition. It is shown that the shear capacity enables prediction of the flow regimes. The prognostic strength of this nondimensional parameter appears to outperform the traditional ones like the similarity parameter z/L and the gradient Richardson number Ri as a regime indicator.
Policies of media and cultural integration in Germany: From guestworker programmes to a more integrative framework
Authors: Bozdağ Çiğdem
Published: November 2014

After the arrival of the first labour migrants in Germany in the 1960s, a gradual change in the perception of migrants in German politics took place: from guests ( Gastarbeiter) and foreigners ( Ausländer) to citizens as members of a new form of ‘us’ that is constructed within diversity. These transformations were reflected in Germany’s migration-related policies throughout recent history. This article focuses on media-related policies for cultural integration, which go hand in hand with the developments in the general migration policy framework, analysing different phases after the 1960s. In general, we observe an increasing institutionalization of integration policies, a more comprehensive understanding of the role of the media for integration purposes and a diversification of measures, even more rapidly after the enactment of the Immigration Act in 2004. Cultural diversity is now emphasized as an enriching factor for the German mediascape. However, there continues to be a need for long-term policies in order to improve media diversity in practice.
Perception management – Deterring potential migrants through information campaigns
Authors: Heller Charles
Published: November 2014

How are images used in the aim of governing migration? This article probes this question through the example of the International Organization for Migration’s (IOM) information campaigns (ICs) in Cameroon, through which it seeks to ‘manage the perception’ of potential illegal(ized) migrants to the European Union (EU). Taking the self-reflexive perspective of a filmmaker who has documented migrants’ rights violations in several projects and is thus struck by the use of imagery of suffering migrants as a deterrent, I first draw a comparison with the practice of colonial educational cinema, which I argue bares many similarities with the IOM’s ICs. Second, I inscribe them within broader trends in migration management, which have in common a simultaneous spatial expansion beyond the EU’s boundaries and a broadening of the domains they attempt to shape. I then attend to the particular ‘media dispositif’ the IOM constitutes in its campaign in Cameroon and question the actual effects of its campaigns.
Multiple myeloma: a model for scientific and clinical progress
Authors: San Miguel Jesus
Published: November 2014

Multiple myeloma (MM) is a unique cancer paradigm for investigating the mechanisms involved in the transition from a premalignant condition (monoclonal gammopathy of undetermined significance) into a malignant disease (MM). In the pathogenesis of myeloma, the dialogue between plasma cells and their microenvironment is as important as the genotypic characteristics of the tumor clone. MM is genetically highly complex, with almost all patients displaying cytogenetic abnormalities and frequent intraclonal heterogeneity that play a critical role in the outcome of the disease. In fact, it is likely that myeloma will soon no longer be considered as a single entity. This, along with the availability of an unexpected number of new treatment possibilities, has reinforced the need for better tools for prognosis and for monitoring treatment efficacy through minimal residual disease techniques. The outcome of MM patients has significantly improved in the last 2 decades, first through the introduction of high-dose therapy followed by autologous stem cell transplantation and, more recently, due to the use of proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide). Moreover, the need to reexamine the diagnostic criteria of early MM and the possibility of early intervention opens up new therapeutic avenues. New drugs are also emerging, including second- and third-generation proteasome inhibitors and immunomodulators, monoclonal antibodies, histone deacetylase inhibitors, and kinesin spindle protein inhibitors, among others. Our goal is to find a balance among efficacy, toxicity, and cost, with the ultimate aim of achieving a cure for this disease.
BCR pathway inhibition as therapy for chronic lymphocytic leukemia and lymphoplasmacytic lymphoma
Authors: Wiestner Adrian
Published: November 2014

Chronic lymphocytic leukemia (CLL) and lymphoplasmacytic lymphoma (LPL) are malignancies of mature B cells. In LPL, mutations of the adaptor protein MYD88 (L265P) in the Toll-like receptor pathway have been recognized recently as being a hallmark of the disease and indicate a dependence of the tumor on this pathway. In CLL, functional studies have implicated BCR activation in the tissue microenvironment as a pivotal pathway in the pathogenesis. Bruton's tyrosine kinase (BTK) and the PI3Kδ isoform are essential for BCR signaling and also seem to be required for signal transduction in LPL cells, even if the role of BCR signaling in this disease remains less well defined. Ibrutinib, a covalent inhibitor of BTK approved by the Food and Drug Administration as a second-line treatment for CLL, and idelalisib, a selective inhibitor of PI3Kδ, achieve excellent clinical responses in both diseases irrespective of classic markers indicating high-risk disease. Several additional inhibitors targeting BTK and PI3Kδ, as well as the spleen tyrosine kinase, have entered clinical trials. This review discusses the biologic basis for kinase inhibitors as targeted therapy for CLL and LPL and summarizes the clinical experience with these agents.
Indolent lymphoma: follicular lymphoma and the microenvironment—insights from the microscope
Authors: Harris Nancy Lee
Published: November 2014

Follicular lymphomas (FLs) are neoplasms of germinal center (GC) B cells, which retain many of the morphologic, immunophenotypic, genetic, and functional features of normal GC B cells. Both normal GCs and neoplastic follicles of FL also contain non-neoplastic cells (microenvironment) that influence and are influenced by the GC and FL B cells and are likely important for tumor cell survival. Many insights into the nature of the GC/FL microenvironment have come from morphologic and immunophenotypic analysis, both before and after the discoveries from gene expression profiling. This chapter reviews what we have learned from the microscope and highlights the pitfalls involved in trying to enumerate cells in the microenvironment for clinical prognostication.
Indolent lymphoma: follicular lymphoma and the microenvironment—insights from gene expression profiling
Authors: Rimsza Lisa M. , Jaramillo Melba C.
Published: November 2014

As shown with gene expression profiling (GEP), the development and progression of follicular lymphoma (FL) involves complex interactions between neoplastic B cells and the surrounding microenvironment. GEP further reveals that the tumor microenvironment may predict survival in patients with FL and influence the response to therapy and the risk of transformation. Here, we briefly review GEP technology and summarize the role of the tumor microenvironment in FL diagnosis, prognosis, and transformation. Genes expressed by infiltrating T cells and macrophages appear to be the most important predictors of survival, clinical behavior, and outcome. These findings provide a basis for future studies into the pathogenesis and pathophysiology of FL and may ultimately provide guidance in the choice of therapy and the identification of potential therapeutic targets.
Therapeutic targeting of microenvironment in follicular lymphoma
Authors: Nowakowski Grzegorz S. , Ansell Stephen M.
Published: November 2014

Immune and nonimmune microenvironmental factors play a critical role in the progression, transformation, and resistance to therapy in follicular lymphoma (FL). A recent increase in our understanding of the role of microenvironment in FL biology has led to the development of novel therapeutic strategies targeting the nonimmune and immune microenvironment. These include immunomodulatory drugs, immune checkpoint inhibitors, immnunoconjugates, and small-molecule inhibitors with an impact on the microenvironment in addition to direct antitumor activity. These agents are now at different stages of clinical development, ranging from early clinical trials in relapsed disease to phase 3 studies in the upfront setting, including combinations with other agents such as monoclonal antibodies and chemotherapy. It is important to recognize that, although the current upfront therapy of FL is associated with favorable outcomes in the majority of patients, a significant proportion experience early disease progression and develop treatment resistance and transformation to aggressive lymphoma. Although the development of “chemo-free” combinations using drugs targeting the microenvironment offers a promising approach to minimize toxicity, the identification of patients at risk of relapse and the use of biomarkers allowing the personalization of therapy will likely play a major role in the development of maintenance strategies. Against this landscape of currently available therapy options, this chapter discusses the clinical status of therapies targeting the microenvironment in FL.
The genomic landscape of acute lymphoblastic leukemia in children and young adults
Authors: Mullighan Charles G.
Published: November 2014

Our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL) has been greatly advanced by genomic profiling and sequencing studies. These efforts have characterized the genetic basis of recently described and poorly understood subtypes of ALL, including early T-cell precursor ALL, Philadelphia chromosome–like (Ph-like) ALL, and ALL with intrachromosomal amplification of chromosome 21, and have identified several rational therapeutic targets in high-risk ALL, notably ABL1-class and JAK-STAT inhibitors in Ph–like ALL. Deep sequencing studies are also refining our understanding of the genetic basis of clonal heterogeneity and relapse. These studies have elucidated the nature of clonal evolution during disease progression and identified genetic changes that confer resistance to specific therapeutic agents, including CREBBP and NT5C2. Genomic profiling has also identified common and rare inherited genetic variants that influence the risk of developing leukemia. These efforts are now being extended to ALL in adolescents and adults with the goal of fully defining the genetic landscape of ALL to further improve treatment outcomes in high-risk populations.
Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia
Authors: Alexander Sarah
Published: November 2014

For children with acute lymphoblastic leukemia, the identification of those at higher risk of disease recurrence and modifying therapy based on this risk is a critical component to the provision of optimal care. The specific definitions of high-risk ALL vary across cooperative groups, but the themes are consistent, being largely based on leukemia biology and disease response. Intensification of conventional chemotherapy for those with high-risk disease has led to improved outcomes. It is anticipated that the development of rational targeted therapy for specific biologically unique subsets of children with leukemia will contribute to ongoing progress in improving the outcomes for children with acute lymphoblastic anemia.