bluuebunny/crossref_metadata_2025 huggingface dataset:
MEK Inhibition Modulates Cytokine Response to Mediate Therapeutic Efficacy in Lung Cancer
Authors: Xie Mengyu , Zheng Hong , Madan-Lala Ranjna , Dai Wenjie , Gimbrone Nicholas T. , Chen Zhihua , Kinose Fumi , Blackstone Sarah A. , Smalley Keiran S.M. , Cress W. Douglas , Haura Eric B. , Rix Uwe , Beg Amer A.
Published: July 2019

Activating mutations in BRAF, a key mediator of RAS signaling, are present in approximately 50% of melanoma patients. Pharmacologic inhibition of BRAF or the downstream MAP kinase MEK is highly effective in treating BRAF-mutant melanoma. In contrast, RAS pathway inhibitors have been less effective in treating epithelial malignancies, such as lung cancer. Here, we show that treatment of melanoma patients with BRAF and MEK inhibitors (MEKi) activated tumor NF-κB activity. MEKi potentiated the response to TNFα, a potent activator of NF-κB. In both melanoma and lung cancer cells, MEKi increased cell-surface expression of TNFα receptor 1 (TNFR1), which enhanced NF-κB activation and augmented expression of genes regulated by TNFα and IFNγ. Screening of 289 targeted agents for the ability to increase TNFα and IFNγ target gene expression demonstrated that this was a general activity of inhibitors of MEK and ERK kinases. Treatment with MEKi led to acquisition of a novel vulnerability to TNFα and IFNγ-induced apoptosis in lung cancer cells that were refractory to MEKi killing and augmented cell-cycle arrest. Abolishing the expression of TNFR1 on lung cancer cells impaired the antitumor efficacy of MEKi, whereas the administration of TNFα and IFNγ in MEKi-treated mice enhanced the antitumor response. Furthermore, immunotherapeutics known to induce expression of these cytokines synergized with MEKi in eradicating tumors. These findings define a novel cytokine response modulatory function of MEKi that can be therapeutically exploited.

Significance:

Lung cancer cells are rendered sensitive to MEK inhibitors by TNFα and IFNγ, providing a strong mechanistic rationale for combining immunotherapeutics, such as checkpoint blockers, with MEK inhibitor therapy for lung cancer.

See related commentary by Havel, p. 5699
The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance
Authors: Beltran Himisha , Hruszkewycz Andrew , Scher Howard I. , Hildesheim Jeffrey , Isaacs Jennifer , Yu Evan Y. , Kelly Kathleen , Lin Daniel , Dicker Adam , Arnold Julia , Hecht Toby , Wicha Max , Sears Rosalie , Rowley David , White Richard , Gulley James L. , Lee John , Diaz Meco Maria , Small Eric J. , Shen Michael , Knudsen Karen , Goodrich David W. , Lotan Tamara , Zoubeidi Amina , Sawyers Charles L. , Rudin Charles M. , Loda Massimo , Thompson Timothy , Rubin Mark A. , Tawab-Amiri Abdul , Dahut William , Nelson Peter S.
Published: July 2019

Lineage plasticity has emerged as an important mechanism of treatment resistance in prostate cancer. Treatment-refractory prostate cancers are increasingly associated with loss of luminal prostate markers, and in many cases induction of developmental programs, stem cell–like phenotypes, and neuroendocrine/neuronal features. Clinically, lineage plasticity may manifest as low PSA progression, resistance to androgen receptor (AR) pathway inhibitors, and sometimes small cell/neuroendocrine pathologic features observed on metastatic biopsy. This mechanism is not restricted to prostate cancer as other malignancies also demonstrate lineage plasticity during resistance to targeted therapies. At present, there is no established therapeutic approach for patients with advanced prostate cancer developing lineage plasticity or small cell neuroendocrine prostate cancer (NEPC) due to knowledge gaps in the underlying biology. Few clinical trials address questions in this space, and the outlook for patients remains poor. To move forward, urgently needed are: (i) a fundamental understanding of how lineage plasticity occurs and how it can best be defined; (ii) the temporal contribution and cooperation of emerging drivers; (iii) preclinical models that recapitulate biology of the disease and the recognized phenotypes; (iv) identification of therapeutic targets; and (v) novel trial designs dedicated to the entity as it is defined. This Perspective represents a consensus arising from the NCI Workshop on Lineage Plasticity and Androgen Receptor-Independent Prostate Cancer. We focus on the critical questions underlying lineage plasticity and AR-independent prostate cancer, outline knowledge and resource gaps, and identify strategies to facilitate future collaborative clinical translational and basic studies in this space.
Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment
Authors: Nath Pulak Ranjan , Pal-Nath Dipasmita , Mandal Ajeet , Cam Margaret C. , Schwartz Anthony L. , Roberts David D.
Published: July 2019

Elevated CD47 expression in some cancers is associated with decreased survival and limited clearance by phagocytes expressing the CD47 counterreceptor SIRPα. In contrast, elevated CD47 mRNA expression in human melanomas was associated with improved survival. Gene-expression data were analyzed to determine a potential mechanism for this apparent protective function and suggested that high CD47 expression increases recruitment of natural killer (NK) cells into the tumor microenvironment. The CD47 ligand thrombospondin-1 inhibited NK cell proliferation and CD69 expression in vitro. Cd47−/− NK cells correspondingly displayed augmented effector phenotypes, indicating an inhibitory function of CD47 on NK cells. Treating human NK cells with a CD47 antibody that blocks thrombospondin-1 binding abrogated its inhibitory effect on NK cell proliferation. Similarly, treating wild-type mice with a CD47 antibody that blocks thrombospondin-1 binding delayed B16 melanoma growth, associating with increased NK cell recruitment and increased granzyme B and interferon-γ levels in intratumoral NK but not CD8+ T cells. However, B16 melanomas grew faster in Cd47−/− than in wild-type mice. Melanoma-bearing Cd47−/− mice exhibited decreased splenic NK cell numbers, with impaired effector protein expression and elevated exhaustion markers. Proapoptotic gene expression in Cd47−/− NK cells was associated with stress-mediated increases in mitochondrial proton leak, reactive oxygen species, and apoptosis. Global gene-expression profiling in NK cells from tumor-bearing mice identified CD47-dependent transcriptional responses that regulate systemic NK activation and exhaustion. Therefore, CD47 positively and negatively regulates NK cell function, and therapeutic antibodies that block inhibitory CD47 signaling can enhance NK immune surveillance of melanomas.
Choroidal Melanoma Simulating Adenoma of the Retinal Pigment Epithelium Arising at the Site of Congenital Hypertrophy of the Retinal Pigment Epithelium
Authors: Williams Jr. Basil K. , Di Nicola Maura , Lucio-Alvarez J. Antonio , Lally David R. , Shields Carol L.
Published: July 2019

Neoplasms of the retinal pigment epithelium (RPE) are rare tumors that can simulate choroidal melanoma, but clinical and imaging characteristics often differentiate these lesions. We report a 70-year-old male with an abruptly elevated pigmented lesion that arose at the site of congenital hypertrophy of the RPE and demonstrated associated exudation, as well as feeding and draining vessels, suggestive of RPE adenoma. Optical coherence tomography showed retinal elevation with serous retinal detachment adjacent to the mass, and ultrasonography revealed an abruptly elevated, moderately echodense mass of 6.4-mm thickness. Fluorescein ­angiography showed early tumor hypofluorescence, late ­tumor hyperfluorescence with staining and leakage, and ­retinal vessels buried under the mass, suggestive of a retinal tumor. The patient was monitored with the presumed diagnosis of RPE adenoma, but 3 months later, the growth was documented and fine-needle aspiration biopsy revealed choroidal melanoma. Management with I-125 plaque radiotherapy was performed leading to tumor regression and a thickness of 4.6 mm.
Ultrasound-Guided Transthoracic Fine-Needle Aspiration: A Reliable Tool in Diagnosis and Molecular Profiling of Lung Masses
Authors: Rodriguez Erika F. , Pastorello Ricardo , Osmani Lais , Hopkins Mark , Kryatova Maria , Kawamoto Satomi , Maleki Zahra
Published: July 2019

Introduction: Pulmonary adenocarcinoma is a major cause of mortality worldwide. The majority of patients present with advanced stage disease, and minimally invasive procedures are desirable for diagnosis and treatment plans. Herein, we report our experience with percutaneous/transthoracic needle aspiration (TT-NA) in the cytologic diagnosis of pulmonary adenocarcinoma. Material and Methods: After institutional review board approval, the cytopathology electronic data system was searched for all consecutive TT-NA of the lung masses from January 2011 to November 2015. Patients’ medical records were reviewed and cytologic materials were evaluated. Results: A total of 151 specimens were identified, with a mean age of 62.8 years; 62.9% of the patients had a prior history of malignancy. Carcinoma/adenocarcinoma was the most common (80%) diagnosis. The targeted lesions were predominantly located in the lung (56.3%, 81/151) and pleural based (27.8%, 42/151). The mean size of the lesions was 3.6 cm. Cytology specimens were adequate in 70.9% of the cases, while 72.8% (110/151) of the cases also had concurrent core biopsy. A malignant diagnosis was rendered in the majority of the cases (64.9%). In 71% of the cases, immunohistochemistry/histochemistry studies were successfully performed. Molecular/genetic studies were requested in 80% of the cases and had adequate material. Complications of the procedure were seen in 9.9% of the patients including pneumothorax (7.9%) and hemoptysis (1.9%). Conclusion: TT-NA is a relatively safe and reliable technique in the assessment of pulmonary lesions.
Mentalizing, Epistemic Trust and the Phenomenology of Psychotherapy
Authors: Fonagy Peter , Luyten Patrick , Allison Elizabeth , Campbell Chloe
Published: July 2019

This paper seeks to elucidate the phenomenological experience of psychotherapy in the context of the theory of mentalizing and epistemic trust. We describe two related phenomenological experiences that are the domain of psychotherapeutic work. The first is the patient’s direct experience of their own personal narrative being recognized, marked and reflected back to them by the therapist. Secondly, this intersubjective recognition makes possible the regulation and alignment of the patient’s imaginative capacity in relation to phenomenological experiences. In describing three aspects of the communication process that unfold in effective psychotherapeutic interventions – (1) the epistemic match, (2) improving mentalizing and (3) the re-emergence of social learning – the way in which any effective treatment is embedded in metacognitive processes about the self in relation to perceptual social reality is explained. In particular, attention is drawn to wider social determinants of psychopathology. We discuss the possible mechanism for the relationship between the socioeconomic environment and psychopathology, and the implications of this for psychotherapeutic treatment.
Changes in Adolescents’ Oral Health Status: Responsiveness of the Child Perception Questionnaire11–14
Authors: Aimée Nicole R. , van Wijk Arjen J. , Varjão Magmara M. , Paes Ana B. , Lourenço Jackeline , Mestrinho Heliana D. , Carvalho Joana Christina
Published: July 2019

Changes in oral health status following treatment should be assessed clinically as well as by patients’ reported outcomes. This study investigated changes on oral-health-related quality of life (OHRQoL) of adolescents enrolled in a comprehensive oral health care program for caries and gingival conditions. The sensitivity of the Child Perception Questionnaire11–14 (CPQ11–14) to detect clinical changes, that is, its responsiveness, was assessed. A total of 618 10–15-year adolescents answered the questionnaire before treatment and 560 at follow-up after 1 year. In the follow-up, 2 additional global transition judgment questions were asked. The adolescents were clinically and radiographically examined. At the baseline, 374 adolescents needed only nonoperative treatment, whereas 274 needed non- and operative treatments. After 1 year, the adolescents were regrouped according to the fulfillment of their treatment needs in Group 1 (n = 363) needing/receiving nonoperative treatment only; Group 2 (n = 98) needing/receiving both non- and operative treatments; Group 3 (n = 99) receiving nonoperative treatment only, while needing also operative treatment. The CPQ11–14 total mean change scores by the global transition judgment on self-perceived oral health status indicated significant differences (p < 0.001, ANOVA; internal responsiveness). The effect of the program for the treatment groups was significant (p = 0.014, ANCOVA; external responsiveness). The effect size for the change scores was of moderate magnitude. In conclusion, an overall improvement of adolescents’ OHRQoL was observed following 1-year oral health care program for caries and gingival conditions. The CPQ11–14 was internally and externally sensitive to detect substantial clinical changes. The CPQ11–14 seems appropriate for measuring long-term changes on adolescents’ OHRQoL.
Wall-Eyed Monocular Internuclear Ophthalmoplegia (WEMINO) and Millard-Gubler Syndromes in a Patient with Isolated Pontine Infarction: Topographic, Oculomotor, and Radiological Analysis of Two Very Uncommon Conditions
Authors: Ceballos-Lizarraga Ricardo , Palomino-Díaz Carlos , Romero-Figueroa José Ángel
Published: July 2019

The syndromes of wall-eyed monocular internuclear ophthalmoplegia and Millard-Gubler are very rare clinical complexes commonly caused by pontine infarction, hemorrhage, or tumors that compromise the paramedian tegmentum, medial longitudinal fascicle, and the basis pontis. We present the case of a 58-year-old female with an isolated pontine infarction characterized by acute vertigo, sudden horizontal diplopia due to ipsilateral internuclear ophthalmoplegia with exotropia, facial palsy and contralateral hemiparesis. This report analyzes, theorizes, and emphasizes the correlation between these atypical neurological findings, the pontine anatomy, and magnetic resonance imaging; encouraging the clinician to make expeditious diagnoses using the bedside skills and a high-quality oculomotor clinical examination. The phenotype and simultaneity of both syndromes makes this case a didactic exercise for the topo-diagnosis based on the neurology of eye movements, the intrinsic physiology of the pons, and the pathways that emerge or project towards it.
Experiência urbana e diferença geracional na formação da cultura popular japonesa
Authors: Oda Ernani
Published: July 2019

A popularidade da cultura popular japonesa (e.g. anime, manga) tem sido acompanhada de discursos essencialistas que retratam este fenômeno como reflexo de atributos supostamente imutáveis que teriam sido herdados desde tempos remotos. Embora este tipo de tese venha sendo corretamente criticada por diversos teóricos sociais, estes autores nem sempre oferecem esquemas teóricos alternativos. O objetivo deste trabalho é identificar elementos conceituais que contribuam para a formação de uma alternativa neste sentido. A partir da análise de uma corrente influente da sociologia da cultura no Japão, dois conceitos serão especialmente enfatizados: urbanização e diferença geracional. Estes dois conceitos permitem compreender de maneira mais clara a diversidade e a historicidade das condições sociais por trás da formação e transformação de diversos aspectos da cultura popular no Japão.
Senster: Reactivation of a Cybernetic Sculpture
Authors: Olszewska Anna , Długosz Marek
Published: July 2019

The turbulent history of Senster, a large cybernetic sculpture designed by Edward Ihnatowicz c. 1970, is divided in two periods: its creation and prematurely canceled display (1968–1974) and its recent reactivation (2017–2018). This article presents a comprehensive narrative of Senster's reactivation. It explains how the formulation of the conservation philosophy and methodology employed in the process was instrumental in delivering the solutions. Based on these observations, the authors propose a detailed strategy for the maintenance and reactivation of interactive embodied systems.
A monograph of Heterospathe (Areceae, Arecaceae) in New Guinea
Authors: PETOE PETER , BAKER WILLIAM J.
Published: July 2019

A revision of the genus Heterospathe Scheff. in New Guinea and immediately adjacent islands is presented. We recognise 14 species for this area. Taxonomic and nomenclatural changes are outlined, and each species is thoroughly described, mapped and illustrated. A key to the species in the area is included as well as preliminary IUCN Red List Assessments.
Psectrosciara Kieffer in Mexico (Diptera: Scatopsidae): two new species and additional records for the genus
Authors: HUERTA HERON , DZUL-MANZANILLA FELIPE , MANRIQUE-SAIDE PABLO , DE SOUZA AMORIM DALTON
Published: July 2019

Two new species of Psectrosciara Kieffer from Mexico—Psectrosciara ahuatla sp. nov. and Psectrosciara otumba sp. nov., both belonging to the scatopsiformis-group, are described and illustrated based on males and females collected in Neotropical (Acapulco and Nuxco in the State of Guerrero) and Nearctic (Coyotepec, in the State of Mexico) areas in Mexico. We have a new record of Psectrosciara serrata Cook from Jalisco (in the Biological Station of Chamela) and females from different parts of Mexico. A key for the species of Psectrosciara from Mexico is presented.
The spider wasp genus Telostholus Haupt, 1929 (Hymenoptera, Pompilidae) in Indonesia, with the description of three new species
Authors: LOKTIONOV VALERY M. , LELEJ ARKADY S.
Published: July 2019

Four species of the genus Telostholus Haupt, 1929 are reported from Indonesia, three of them are described and illustrated as new species: T. celebes Loktionov & Lelej, sp. nov. (Sulawesi), T. rinjani Loktionov & Lelej, sp. nov. (Lombok) and T. sulawesi Loktionov & Lelej, sp. nov. (Sulawesi). The genus Telostholus is newly recorded from the islands of Sulawesi and Lombok. A key to the Indonesian species is given for females.
A new skink of the genus Scincella Mittleman, 1950 (Squamata: Scincidae) from Ba Den Mountain, Tay Ninh Province, southern Vietnam
Authors: NGUYEN SANG NGOC , NGUYEN VU DANG HOANG , NGUYEN LUAN THANH , MURPHY ROBERT W.
Published: July 2019

Ba Den is an isolated mountain in southern Vietnam and home to two endemic species of lizards. Herein, we describe another endemic species, a new skink of the genus Scincella Mittleman, 1950, from the area based on morphological data, including hemipenial characters and nucleotide sequences of COI. The following morphological characters diagnose Scincella badenensis sp. nov.: medium size in adults (snout-vent length up to 64.4 mm); toes reach to fingers when limbs adpressed; midbody scale rows 32–36, smooth; paravertebral scales 67–71; dorsal scales not enlarged; ventral scale rows 68–74; supraoculars four; prefrontals in broad contact with one another; loreal scales two; tympanum deeply sunk, without auricular lobules; two enlarged anterior temporal scales; smooth lamellae beneath toe IV 18–20; pair of enlarged precloacal scales; hemipenes short, smooth and forked near the tip with two short lobes and two small terminal papillae; no dorsal pattern in males; and females with black interruptive vertebral line. The new species differs from its congeners by at least 10.4% uncorrected p-distance in COI sequences.
Potamocloeon edentatum sp. n. from Usambara Mountains in Tanzania (Ephemeroptera, Baetidae)
Authors: KLUGE NIKITA J.
Published: July 2019

Potamocloeon edentatum sp. n. is described based on all stages of both sexes associated by rearing from Usambara Mountains in Tanzania. Some key generic characters, i.e. mode of gonostyli development, genital musculature, patella-tibial suture of winged stages and texture of subimaginal tarsi, are described for Potamocloeon Gillies 1990 (= Maliqua Lugo-Ortiz & McCafferty 1997) for the first time.
Two Hexapleomera species from Japan, with a new species description and discussion of phylogenetic relationships within Hexapleomera (Crustacea: Tanaidacea)
Authors: TANABE YUKI , KAKUI KEIICHI
Published: July 2019

We describe Hexapleomera sasuke sp. nov. and provide a supplemental redescription of Hexapleomera urashima Tanabe et al., both of which are based on specimens collected in Japan. Hexapleomera sasuke closely resembles H. urashima, sharing a uropod with four articles, maxillipedal endites with two tiny dorso-subdistal and two distal spiniform setae, a labium with the palp fused to the outer lobe, and the pereopod-1 propodus with an inner subdistal plumose seta. The new species differs from H. urashima in having the basal article of pleopod 3 with three outer plumose setae, the chelipedal carpus with three or four dorsodistal simple setae, the region between the bases of the chelipedal dactylus and fixed finger with three or four simple setae, and deeply pigmented pleopodal rami. We determined partial sequences of the cytochrome c oxidase subunit I (COI) gene (655 nt) from H. sasuke, which proved to be 15.0–15.3% divergent from H. urashima in Kimura 2-parameter (K2P) distance; also in partial sequences of 18S rRNA gene (1888 nt after alignment), 0.8% divergent (K2P distance) was detected between two species. Based on morphology and molecular data, we discuss phylogenetic relationships within Hexapleomera, and propose two morphologically distinct groups, the robusta group and the wombat group.
A Geometric Interpretation of Southern Ocean Eddy Form Stress
Authors: Poulsen Mads B. , Jochum Markus , Maddison James R. , Marshall David P. , Nuterman Roman
Published: July 2019

An interpretation of eddy form stress via the geometry described by the Eliassen–Palm flux tensor is explored. Complimentary to previous works on eddy Reynolds stress geometry, this study shows that eddy form stress is fully described by a vertical ellipse, whose size, shape, and orientation with respect to the mean flow shear determine the strength and direction of vertical momentum transfers. Following a recent proposal, this geometric framework is here used to form a Gent–McWilliams eddy transfer coefficient that depends on eddy energy and a nondimensional geometric parameter α, bounded in magnitude by unity. The parameter α expresses the efficiency by which eddies exchange energy with baroclinic mean flow via along-gradient eddy buoyancy flux—a flux equivalent to eddy form stress along mean buoyancy contours. An eddy-resolving ocean general circulation model is used to estimate the spatial structure of α in the Southern Ocean and assess its potential to form a basis for parameterization. The eddy efficiency α averages to a low but positive value of 0.043 within the Antarctic Circumpolar Current, consistent with an inefficient eddy field extracting energy from the mean flow. It is found that the low eddy efficiency is mainly the result of that eddy buoyancy fluxes are weakly anisotropic on average. The eddy efficiency is subject to pronounced vertical structure and is maximum at ~3-km depth, where eddy buoyancy fluxes tend to be directed most downgradient. Since α partly sets the eddy form stress in the Southern Ocean, a parameterization for α must reproduce its vertical structure to provide a faithful representation of vertical stress divergence and eddy forcing.
Extraction of Revolving Channels of Drifters around Mesoscale Eddy Centers Based on Spatiotemporal Trajectory Clustering
Authors: Ma Chunyong , Li Siqing , Yang Yang , Yang Jie , Chen Ge
Published: July 2019

The global oceanic transports of energy, plankton, and other tracers by mesoscale eddies can be estimated by combining satellite altimetry and in situ data. However, the revolving channels of particles entrained by mesoscale eddies, which could help explain the dynamic process of eddies entraining materials, are still unknown. In this study, satellite altimeter and drifter data from 1993 to 2016 are adopted, and the normalized trajectory clustering algorithm (N-TRACLUS) is proposed to extract the revolving channels of drifters. First, the trajectories of drifters are normalized and clustered by using the density-based spatial clustering of applications with noise (DBSCAN) algorithm. Next, the revolving channels of drifters around the eddy center are extracted. The ring or arc pattern in the middle of a normalized eddy appears when drifters are uninterruptedly entrained by eddies for more than 30 days. Moreover, the revolving channels of drifters in cyclonic eddies are relatively closer to the eddy center than those in anticyclonic eddies. These revolving channels suggest the principal mode of materials’ continuous motion processes that are inside eddies.
Do Governance Indicators Matter for Economic Growth? The Case of Sri Lanka
Authors: Vinayagathasan T. , Ramesh R.
Published: July 2019

This study attempts to identify the impact of governance indicators on economic growth using time series data for Sri Lanka from 1996 to 2016 published by the World Bank. The Phillips–Perron (PP) unit root test confirmed that all the variables are integrated in order one and suggested the use of cointegration technique to identify the long-run relationship between the variables. All the lag length selection criteria except Schwarz Information Criterion (SIC) advocated the use of one lag as an optimal lag length for this study. Johansen cointegration method detected three cointegrating relationships among the variables. Further, this technique identified a significant and positive relationship between government effectiveness (GE) and gross domestic product per capita (GDPPC) in the long run. This result is in contrast to all the three traditional approaches, such as correlation test, scatter plot and ordinary least squared (OLS), in which they do not identify any clear relationship between them. Moreover, Johansen test found a negative and statistically significant link between political stability and absence of violence (PSAV) and GDPPC in the long run, while all three traditional approaches identified a positive correlation between them. The findings of this study indicate a negative association between rule of law (ROL) and GDPPC in the long run, which coincides with theory, some of the empirical studies and with findings of all three traditional approaches used in this study. Even though OLS did not identify a significant relationship between control of corruption (COC) and GDPPC, Johansen test, correlation test and scatter plot detected a significant and negative correlation between them in the long run as expected by the theoretical evidence. Granger’s causality test identified the bidirectional causality between GE and ROL and unidirectional causality between ROL and COC. However, relationship between governance variables and GDPPC vary based on the estimation methods. These findings suggest that the policymakers need to take considerable attention on the above when they formulate and implement policy to improve GE.
The Recent Evolution of Wisconsin Public Worker Unionism since Act 10
Authors: Nack David , Childers Michael , Kulwiec Alexia , Ibarra Armando
Published: July 2019

This paper examines the experience of four major public sector unions in Wisconsin since the passage of Wisconsin Act 10 in 2011. The four unions are the American Federation of State, County and Municipal Employees (AFSCME), the American Federation of Teachers (AFT-Wisconsin), the Service Employees International Union (SEIU), and the Wisconsin Education Association Council (WEAC), an affiliate of the National Education Association. Wisconsin’s prior legal framework for public sector collective bargaining is explained and compared to the new highly restrictive framework established by Act 10. That new framework, established by state legislation, is analyzed, as are its impacts on the membership, revenues, structures, and practices of the four unions. In general, we find the impacts to have been very dramatic, with a loss of active union membership averaging approximately 70 percent overall, and concomitant dramatic losses in union revenues and power. These shocks have engendered the restructuring of two of the unions examined, the downsizing of the third, and the de facto exiting from the state’s public sector in another. There have also been significant changes in representation practices in one union, but less so in the others. We conclude by discussing best union practices based on this experience, as well as considering what the recent public sector union history in Wisconsin may portend for public worker union membership nationwide, since the issuing of the Janus Decision by the U.S. Supreme Court.
Clinical Traits Characterizing an Exacerbation‐Prone Phenotype in Chronic Rhinosinusitis
Authors: Phillips Katie M. , Barbarite Eric , Hoehle Lloyd P. , Caradonna David S. , Gray Stacey T. , Sedaghat Ahmad R.
Published: July 2019

Objective

Acute exacerbation of chronic rhinosinusitis (AECRS) is associated with significant quality‐of‐life decreases. We sought to determine characteristics associated with an exacerbation‐prone phenotype in chronic rhinosinusitis (CRS).

Study Design

Cross‐sectional.

Setting

Tertiary care rhinology clinic.

Subjects

Patients with CRS (N = 209).

Methods

Patient‐reported number of sinus infections, CRS‐related antibiotics, and CRS‐related oral corticosteroids taken in the last 12 months were used as metrics for AECRS frequency. Sinonasal symptom burden was assessed with the 22‐item Sinonasal Outcome Test (SNOT‐22). Ninety patients reporting 0 for all AECRS metrics were considered to have had no AECRS in the prior 12 months. A total of 119 patients reported >3 on at least 1 AECRS metric and were considered as having an exacerbation‐prone phenotype. Characteristics associated with patients with an exacerbation‐prone phenotype were identified with exploratory regression analysis.

Results

An exacerbation‐prone phenotype was positively associated with comorbid asthma (adjusted odds ratio [ORadj] = 3.68, 95% CI: 1.42‐9.50, P =. 007) and SNOT‐22 (ORadj = 1.06, 95% CI: 1.04‐1.09, P <. 001). Polyps were negatively associated (ORadj = 0.27, 95% CI: 0.11‐0.68, P =. 005) with an exacerbation‐prone phenotype. SNOT‐22 score ≥24 identified patients with an exacerbation‐prone phenotype with a sensitivity of 93.3% and a specificity of 57.8%. Having either a SNOT‐22 score ≥24 with a nasal subdomain score ≥12 or a SNOT‐22 score ≥24 with an ear/facial discomfort subdomain score ≥3 provided >80% sensitivity and specificity for detecting patients prone to exacerbation.

Conclusions

In total, these results point to a CRS exacerbation‐prone phenotype characterized by high sinonasal disease burden with comorbid asthma but interestingly without polyps.
Pattern of Intraoperative Parathyroid Hormone and Calcium in the Treatment of Tertiary Hyperparathyroidism
Authors: Casarim André Luís Maion , Arcadipane Fernando Antonio Maria Claret , Martins Antonio Santos , Del Negro André , Rodrigues André Afonso Nimtz , Tincani Alfio Jose , Marchi Evaldo
Published: July 2019

Objective

Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues.

Study Design

Case series with planned data collection.

Setting

Tertiary referral medical center.

Subjects and Methods

The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of P <. 05.

Results

Thirty‐five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues (P =. 029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity (P =. 028).

Conclusions

Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.
A model for L1 grammatical attrition
Authors: Hicks Glyn , Domínguez Laura
Published: July 2019

This article proposes a formal model of the human language faculty that accommodates the possibility of ‘attrition’ (modification or loss) of morphosyntactic properties in a first language. Modeling L1 grammatical attrition entails a quite fundamental paradox: if the structure of the language faculty in principle allows for attrition of morphosyntax, why is it apparently so heavily constrained and rarely attested? We demonstrate that the attrition paradox can be resolved with a model that integrates a formally explicit generative grammar (eschewing classical parameters in favor of functional feature assemblies; see Chomsky, 2000, 2001) into a generalized model of language acquisition that decouples linguistic input from acquisitional intake (following Lidz and Gagliardi, 2015). This implementation makes specific predictions about the input and intake conditions that favor and disfavor L1 attrition. We explore these predictions for one of the most widely studied areas of attrition, namely the realization of pronominals.
Brain endothelial specific gene therapy improves experimental Sandhoff disease
Authors: Dogbevia Godwin , Grasshoff Hanna , Othman Alaa , Penno Anke , Schwaninger Markus
Published: July 2019

In Tay-Sachs and Sandhoff disease, a deficiency of the lysosomal enzyme β-hexosaminidase causes GM2 and other gangliosides to accumulate in neurons and triggers neurodegeneration. Although the pathology centers on neurons, β-hexosaminidase is mainly expressed outside of neurons, suggesting that gene therapy of these diseases should target non-neuronal cells to reconstitute physiological conditions. Here, we tested in Hexb−/− mice, a model of Sandhoff disease, to determine whether endothelial expression of the genes for human β-hexosaminidase subunit A and B ( HEXA, HEXB) is able to reduce disease symptoms and prolong survival of the affected mice. The brain endothelial selective vectors AAV-BR1-CAG- HEXA and AAV-BR1-CAG- HEXB transduced brain endothelial cells, which subsequently released β-hexosaminidase enzyme. In vivo intravenous administration of the gene vectors to adult and neonatal mice prolonged survival. They improved neurological function and reduced accumulation of the ganglioside GM2 and the glycolipid GA2 as well as astrocytic activation. Overall, the data demonstrate that endothelial cells are a suitable target for intravenous gene therapy of GM2 gangliosidoses and possibly other lysosomal storage disorders.
Dynamically vulcanized ethylene-methacrylic acid copolymer/nitrile butadiene rubber blends reinforced by zinc dimethacrylate
Authors: Liao Kerui , Liu Feifei , Wang Zhaobo
Published: July 2019

Thermoplastic vulcanizates (TPVs) based on ethylene-methacrylic acid (EMA) copolymer/nitrile butadiene rubber (NBR) blends were prepared by dynamic vulcanization where the NBR phase was reinforced by zinc dimethacrylate (ZDMA). The effect of ZDMA dosage on the mechanical properties, Mullins effect, and morphology of the TPVs was investigated systematically. Experimental results indicated that the mechanical properties of EMA/NBR TPVs were enhanced remarkably with the incorporation of ZDMA. Morphology study showed that the NBR particles with diameters of about 1–5 μm were dispersed evenly in the etched surface of EMA/NBR/ZDMA TPV. The Mullins effect could be observed in the stress–strain curves of EMA/NBR TPV and EMA/NBR/ZDMA TPV during the uniaxial loading–unloading cycles. Compared with those of EMA/NBR TPV, EMA/NBR/ZDMA TPV had the higher stress, residual deformation, and internal friction loss.
Autisme, j’accuse! Life-writing, autism and politics in the work of Hugo Horiot
Authors: Orchard Vivienne
Published: July 2019

Autism has generated a great deal of controversy, culturally, intellectually and politically. The context for this in recent years in France is unusual and has been the site of strong antagonism. These debates are political in terms of policy implications and disagreements along political lines but also entail the politics of knowledge, and the question of who has the right to speak for whom. Competing groups – parents, ‘experts’ and autistic adults have different claims to validity as knowledge-bearers. This epistemological validity is vital in creating wider public understanding and determining policy directions. Autism life-writing is a new phenomenon in French and contributes to this set of debates. In order to illuminate this further, this article will offer an account of the first best-selling memoir by an autistic individual in France. The book, L’Empereur, c’est moi, is by Hugo Horiot, and was published in 2013, at the height of the ‘autism battle’ in the French public sphere.
Le « corps républicain » et ses représentations dans les manuels scolaires de Paul Bert à la fin du XIXe siècle
Authors: Profillet Lucas , Laffage-Cosnier Sébastien , Vivier Christian
Published: July 2019

Paul Bert est un homme politique français incontournable du début de la IIIe République. Scientifique reconnu, républicain et ministre de l’Instruction publique du cabinet de Gambetta, il joue un rôle considérable dans la politique éducative et culturelle de la France par la mise en place des lois Jules Ferry. L’homme est aussi connu pour sa rédaction de manuels scolaires. L’analyse détaillée des manuels scolaires conçus par Paul Bert permet de comprendre le modèle corporel qui est donné à suivre à la jeunesse française. Que ce soit dans le discours de l’auteur ou dans l’iconographie qui l’accompagne, le corps est érigé en flambeau de la solution démocratique. Dans les manuels scolaires conçus par ce scientifique, le « corps républicain » représenté porte toujours la marque des normes sociales et culturelles qui lui sont imposées, autant de contraintes qui s’affichent comme les conditions sine qua non de son émancipation citoyenne future.
Model-based goodness-of-fit tests for the ordered stereotype model
Authors: Fernández Daniel , Liu Ivy , Arnold Richard , Nguyen Thuong , Spiess Martin
Published: July 2019

This paper presents two new model-based goodness-of-fit tests for the ordered stereotype model applied to an ordinal response variable. The proposed tests are based on the Lipsitz test, which partitions the subjects into G groups following the popular Hosmer–Lemeshow test for binary data. The tests construct an alternative model where group effects are added into the null model. If the model fits the data well then the null model is correct, and there should be no group effects. One of the main advantages of the ordered stereotype model is that it allows us to determine a new uneven spacing of the ordinal response categories, dictated by the data. The two proposed tests use this new adjusted spacing. One test uses the form of the original ordered stereotype model, and the other uses an ordinary linear model. We demonstrate the performance of both tests under a variety of scenarios. Finally, the results of the application in three examples are presented.
Abstract or concrete? The effect of climate change images on people’s estimation of egocentric psychological distance
Authors: Duan Ran , Takahashi Bruno , Zwickle Adam
Published: July 2019

Climate change has been widely perceived as a psychologically distant risk, largely viewed as separated from one’s direct experience. Using construal-level theory, we examined how the level of abstraction and concreteness of climate change imagery affects viewers’ perceived psychological distance of climate change, including spatial, temporal, social, and hypothetical (level of uncertainty) distances. Participants ( n = 402) were randomly assigned to one of two experimental conditions, one with abstract images and one with concrete images. Results show that the abstract and concrete images successfully activated people’s abstract and concrete mind-sets, respectively, and people who viewed abstract images were more likely to perceive climate change as a spatially and temporally distant issue.
India’s Huawei Conundrum
Authors: Khanapurkar Uday
Published: July 2019

Huawei, the Chinese telecom giant, has emerged as a key player in the provision of infrastructure required to support 5G wireless networks, the adoption of which will be foundational to recipient countries’ deployment of emerging technologies such as artificial intelligence and the Internet of things.   At the same time, however, security concerns with respect to Huawei’s ties to the Chinese army and state abound, prompting a number of countries to ban the company from supplying them said telecom infrastructure. India, however, is on the fence in this regard. This article assesses India’s Huawei conundrum through a conceptual framework of economic dependence wherein the costs of a ban and willingness to ban are examined in detail. It is argued that since the expected costs of banning Huawei equipment and the security risks of using them are both substantially high, India’s course of action must be to defer a quick decision and bargain for benefits and assurances.
Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib
Authors: Maral Senem , Bakanay Sule Mine , Kucuksahin Orhan , Dilek Imdat
Published: July 2019

Introduction

Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib.

Case report

A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE).

Management and outcome

Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse.

Discussion

Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.
Unraveling Escherichia coli’s Cloak: Identification of Phosphoethanolamine Cellulose, Its Functions, and Applications
Authors: Jeffries Jamie , Fuller Gerald G , Cegelski Lynette
Published: July 2019

Bacterial biofilms are complex, multicellular communities made up of bacteria enmeshed in a self-produced extracellular matrix (ECM) that protects against environmental stress. The ECM often comprises insoluble components, which complicates the study of biofilm composition, structure, and function. Wrinkled, agar-grown Escherichia coli biofilms require 2 insoluble macromolecules: curli amyloid fibers and cellulosic polymers. We quantified these components with solid-state nuclear magnetic resonance (NMR) and determined that curli contributed 85% of the isolated uropathogenic E coli ECM dry mass. The remaining 15% was cellulosic, but, surprisingly, was not ordinary cellulose. We tracked the identity of the unanticipated peak in the 13C NMR spectrum of the cellulosic component and discovered that E coli secrete phosphoethanolamine (pEtN)-modified cellulose. Cellulose is the most abundant biopolymer on the planet, and this marked the first identification of a naturally, chemically modified cellulose. To investigate potential roles of pEtN cellulose, we customized a newly designed live-cell monolayer rheometer and demonstrated that pEtN cellulose facilitated E coli attachment to bladder epithelial cells and acted as a glue, keeping curli cell associated. The discovery of pEtN cellulose opens questions regarding its biological function(s) and provides opportunities in materials science to explore this newly discovered biopolymer.
Brokers and Tours: Selling Urban Poverty and Violence in Latin America and the Caribbean
Authors: Dürr Eveline , Jaffe Rivke , Jones Gareth A.
Published: July 2019

This article explores how so-called “slum” tourism commodifies poverty and violence, transforming urban deprivation into a tourism product. In particular, we pay ethnographic attention to the role of brokers who mediate encounters between residents and tourists. The article explores how brokers—tour guides, art curators and civil society organizations—work to mediate power structures and enact a specific representational-performative politics. In so doing, brokers play a key role in aestheticizing and performing poverty and violence and converting disadvantaged spaces into a tourist product. We argue that brokers are vital to the reproduction of existing inequalities and to the formation of new social relationships and subjectivities.
Pornography addiction and the perimeters of acceptable pornography viewing
Authors: Taylor Kris , Gavey Nicola
Published: July 2019

In this study, we investigate how pornography addiction is constructed by members of the New Zealand public by analysing six 2016 newspaper articles focusing on pornography addiction, and the 1430 Facebook comments posted in response to them. Utilizing a critical discursive approach, we identified five interpretative repertoires employed to construct both the viewing of pornography and pornography itself in multiple ways. Our analysis suggests that although pornography remained poorly defined, it was at turns framed as both unnatural and natural to view. The naturalness of viewing pornography however was complicated by an explicit acceptance of pornography addiction, which was variously proposed as being similar to substance abuse, a threat to intimate relationships, and as a convenient excuse. Moreover, the pornography addict was reliably described as male, and implicitly placed within a monogamous heterosexual relationship, with pornography depicted as most threatening when impinging upon such relationships. As such, we argue that the construction of pornography addiction not only reifies morally conservative historical concerns, but also side-lines the ethical and political ramifications of normalized pornography viewership. The possible replacement of discussions about the content of pornography with debates about user effects indicates a rapid historical shift from concerns for community standards to concerns for personal responsibility.