bluuebunny/crossref_metadata_2025 huggingface dataset:
The best of respiratory infections from the 2015 European Respiratory Society International Congress
Authors: Polverino Eva , Bothamley Graham H. , Goletti Delia , Heyckendorf Jan , Sotgiu Giovanni , Aliberti Stefano
Published: July 2016

The breadth and quality of scientific presentations on clinical and translational research into respiratory infections at the 2015 European Respiratory Society (ERS) International Congress in Amsterdam, the Netherlands, establishes this area as one of the leadings fields in pulmonology. The host–pathogen relationship in chronic obstructive pulmonary disease, and the impact of comorbidities and chronic treatment on clinical outcomes in patients with pneumonia were studied. Various communications were dedicated to bronchiectasis and, in particular, to different prognostic and clinical aspects of this disease, including chronic infection withPseudomonasand inhaled antibiotic therapy. Recent data from the World Health Organization showed that Europe has the highest number of multidrug-resistant tuberculosis cases and the poorest countries have the least access to suitable treatments. Latent tuberculosis and different screening programmes were also discussed with particular attention to risk factors such as HIV infection and diabetes. Several biomarkers were proposed to distinguish between active tuberculosis and latent infection. Major treatment trials were discussed (REMOX, RIFQUIN and STREAM). The possibility of once-weekly treatment in the continuation phase (RIAQUIN) was especially exciting. The continuing rise ofMycobacterium abscessusas a significant pathogen was noted. This article reviews some of the best contributions from the Respiratory Infections Assembly to the 2015 ERS International Congress.
Utility of waist-to-height ratio in assessing the status of central obesity and related cardiometabolic risk profile among normal weight and overweight/obese children: The Bogalusa Heart Study
Authors: Mokha Jasmeet S , Srinivasan Sathanur R , DasMahapatra Pronabesh , Fernandez Camilo , Chen Wei , Xu Jihua , Berenson Gerald S
Published: July 2016

Background

Body Mass Index (BMI) is widely used to assess the impact of obesity on cardiometabolic risk in children but it does not always relate to central obesity and varies with growth and maturation. Waist-to-Height Ratio (WHtR) is a relatively constant anthropometric index of abdominal obesity across different age, sex or racial groups. However, information is scant on the utility of WHtR in assessing the status of abdominal obesity and related cardiometabolic risk profile among normal weight and overweight/obese children, categorized according to the accepted BMI threshold values.

Methods

Cross-sectional cardiometabolic risk factor variables on 3091 black and white children (56% white, 50% male), 4-18 years of age were used. Based on the age-, race- and sex-specific percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles) and overweight/obese (≥ 85th percentile). The risk profiles of each group based on the WHtR (<0.5, no central obesity versus ≥ 0.5, central obesity) were compared.

Results

9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5) and 19.8% among the overweight/obese were not (WHtR < 0.5). On multivariate analysis the normal weight centrally obese children were 1.66, 2.01, 1.47 and 2.05 times more likely to have significant adverse levels of LDL cholesterol, HDL cholesterol, triglycerides and insulin, respectively. In addition to having a higher prevalence of parental history of type 2 diabetes mellitus, the normal weight central obesity group showed a significantly higher prevalence of metabolic syndrome (p < 0.0001). In the overweight/obese group, those without central obesity were 0.53 and 0.27 times less likely to have significant adverse levels of HDL cholesterol and HOMA-IR, respectively (p < 0.05), as compared to those with central obesity. These overweight/obese children without central obesity also showed significantly lower prevalence of parental history of hypertension (p = 0.002), type 2 diabetes mellitus (p = 0.03) and metabolic syndrome (p < 0.0001).

Conclusion

WHtR not only detects central obesity and related adverse cardiometabolic risk among normal weight children, but also identifies those without such conditions among the overweight/obese children, which has implications for pediatric primary care practice.
Development of a two-step protocol for culture expansion of human annulus fibrosus cells with TGF-β1 and FGF-2
Authors: Chou Po-Hsin , Wang Shih-Tien , Ma Hsiao-Li , Liu Chien-Lin , Chang Ming-Chau , Lee Oscar Kuang-Sheng
Published: July 2016

Background

Different biologic approaches to treat disc regeneration, including growth factors (GFs) application, are currently under investigation. Human annulus fibrosus (hAF) repair or regeneration is one of the key elements for maintenance and restoration of nucleus pulposus function. However, so far there is no effective treatment for this purpose. The aim of the present study was to investigate the response of hAF cells to different combinations of GFs, and develop a protocol for efficient culture expansion.

Methods

hAF cells were harvested from degenerated disc tissues during surgical intervertebral disc removal, and hAF cells were expanded in a monolayer. The experiments were categorized based on different protocols with transforming growth factor (TGF-β1) and fibroblast growth factor (FGF-2) culture for 14 days: group 1 had no GFs (control group); group 2 received TGF-β1; group 3 received FGF-2; group 4 received both GFs; and group 5 (two-step) received both GFs for the first 10 days and TGF-β1 only for the next 4 days. Cell proliferation, collagen, and noncollagen extracellular matrix (ECM) production and genes expression were compared among these groups.

Results

At days 3, 7 and 10 of cultivation, groups 4 and 5 had significantly more cell numbers and faster cell proliferation rates than groups 1, 2, and 3. At 14 days of cultivation, significantly more cell numbers were observed in groups 3 and 4 than in group 5. The group 4 had the most cell numbers and the fastest proliferation rate at 14 days of cultivation. After normalization for cell numbers, group 5 (two-step) produced the most collagen and noncollagen ECM at 10 and 14 days of cultivation among the five groups. In group 5, ECM gene expression was significantly upregulated. High expression of matrix metalloproteinase-1 was upregulated with FGF-2 on the different days as compared to the other groups. Annulus fibrosus cell phenotypes were only marginally retained under the different protocols based on quantitative polymerase chain reaction results.

Conclusion

Taken together, the two-step protocol was the most efficient among these different protocols with the most abundant ECM production after normalization for cell numbers for culture expansion of hAF cells. The protocol may be useful in further cell therapy and tissue engineering approaches for disc regeneration.
Characterization of intercellular communication and mitochondrial donation by mesenchymal stromal cells derived from the human lung
Authors: Sinclair Kenneth Andrew , Yerkovich Stephanie Terase , Hopkins Peter Mark-Anthony , Chambers Daniel Charles
Published: July 2016

Background

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of repairing wounded lung epithelial cells by donating cytoplasmic material and mitochondria. Recently, we characterized two populations of human lung-derived mesenchymal stromal cells isolated from digested parenchymal lung tissue (LT-MSCs) from healthy individuals or from lung transplant recipients’ bronchoalveolar lavage fluid (BAL-MSCs). The aim of this study was to determine whether LT-MSCs and BAL-MSCs are also capable of donating cytoplasmic content and mitochondria to lung epithelial cells.

Methods

Cytoplasmic and mitochondrial transfer was assessed by co-culturing BEAS2B epithelial cells with Calcein AM or Mitotracker Green FM-labelled MSCs. Transfer was then measured by flow cytometry and validated by fluorescent microscopy. Molecular inhibitors were used to determine the contribution of microtubules/tunnelling nanotubes (TNTs, cytochalasin D), gap junctions (carbenoxolone), connexin-43 (gap26) and microvesicles (dynasore).

Results

F-actin microtubules/TNTs extending from BM-MSCs, LT-MSCs and BAL-MSCs to bronchial epithelial cells formed within 45 minutes of co-culturing cells. Each MSC population transferred a similar volume of cytoplasmic content to epithelial cells. Inhibiting microtubule/TNTs, gap junction formation and microvesicle endocytosis abrogated the transfer of cytoplasmic material from BM-MSCs, LT-MSCs and BAL-MSCs to epithelial cells. In contrast, blocking connexin-43 gap junction formation had no effect on cytoplasmic transfer. All MSC populations donated mitochondria to bronchial epithelial cells with similar efficiency. Mitochondrial transfer was reduced in all co-cultures after microtubule/TNT or endocytosis inhibition. Gap junction formation inhibition reduced mitochondrial transfer in BM-MSC and BAL-MSC co-cultures but had no effect on transfer in LT-MSC co-cultures. Connexin-43 inhibition did not impact mitochondrial transfer. Finally, bronchial epithelial cells were incapable of donating cytoplasmic content or mitochondria to any MSC population.

Conclusion

Similar to their bone marrow counterparts, LT-MSCs and BAL-MSCs can donate cytoplasmic content and mitochondria to bronchial epithelial cells via multiple mechanisms. Given that BM-MSCs utilize these mechanisms to mediate the repair of damaged bronchial epithelial cells, both LT-MSCs and BAL-MSCs will probably function similarly.
A novel ontology and machine learning driven hybrid cardiovascular clinical prognosis as a complex adaptive clinical system
Authors: Farooq Kamran , Hussain Amir
Published: July 2016

Purpose

This multidisciplinary industrial research project sets out to develop a hybrid clinical decision support mechanism (inspired by ontology and machine learning driven techniques) by combining evidence, extrapolated through legacy patient data to facilitate cardiovascular preventative care.

Methods

The proposed cardiovascular clinical decision support framework comprises of two novel key components:
(1) Ontology driven clinical risk assessment and recommendation system (ODCRARS) (2) Machine learning driven prognostic system (MLDPS). State of the art machine learning and feature selection methods are utilised for the prognostic modelling purposes. The ODCRARS is a knowledge-based system which is based on clinical expert’s knowledge, encoded in the form of clinical rules engine to carry out cardiac risk assessment for various cardiovascular diseases. The MLDPS is a non knowledge-based/data driven system which is developed using state of the art machine learning and feature selection techniques applied on real patient datasets. Clinical case studies in the RACPC, heart disease and breast cancer domains are considered for the development and clinical validation purposes. For the purpose of this paper, clinical case study in the RACPC/chest pain domain will be discussed in detail from the development and validation perspective.

Results

The proposed clinical decision support framework is validated through clinical case studies in the cardiovascular domain. This paper demonstrates an effective cardiovascular decision support mechanism for handling inaccuracies in the clinical risk assessment of chest pain patients and help clinicians effectively distinguish acute angina/cardiac chest pain patients from those with other causes of chest pain.

Conclusion

The new clinical models, having been evaluated in clinical practice, resulted in very good predictive power, demonstrating general performance improvement over benchmark multivariate statistical classifiers. Various chest pain risk assessment prototypes have been developed and deployed online for further clinical trials.
Erythrocyte zinc and serum copper in male and female adolescents according to puberty stage at different growth phases
Authors: Marques Andréa Grano , Sarni Roseli Oselka Sacardo , Lopes Luiz Anderson , Lopes Emilio , Amancio Olga Maria Silverio
Published: July 2016

Background

Considering that modification in body composition and growth velocity leads to alterations in zinc and copper nutritional status, the purpose of the study was to assess erythrocyte zinc and serum copper in adolescents of both genders, according to the stage of sexual maturity at different growth phases.

Methods

Two hundred and eighty-six adolescents were assessed, 157 were female, with body mass index Z-score between −2 and +2. Clinical biochemical measurements were assessed using atomic absorption spectrophotometry. Student’s t, Kruskal-Wallis, and Bonferroni tests were used.

Results

Median serum copper was superior, and zinc was inferior to respective reference values in all groups. Serum copper presented significant reduction in the final stages of pubertal development in males; in turn, erythrocyte zinc values increased linearly with the evolution of puberty stages in both genders. Comparison between genders in each stage of growth showed significant difference in peak acceleration and in deceleration for erythrocyte zinc and serum copper, with both being higher in females.

Conclusions

Serum copper is inversely influenced by modifications that occur with the evolution of puberty in males, whereas erythrocyte zinc is directly influenced in both genders, although always with deficient deposition. At peak acceleration and deceleration of growth, there is greater mobilization of erythrocyte zinc and serum copper in males, when compared with females, which does not occur at the onset of the acceleration of growth.
Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1
Authors: Smith Matthew , De Bono Johann , Sternberg Cora , Le Moulec Sylvestre , Oudard Stéphane , De Giorgi Ugo , Krainer Michael , Bergman Andries , Hoelzer Wolfgang , De Wit Ronald , Bögemann Martin , Saad Fred , Cruciani Giorgio , Thiery-Vuillemin Antoine , Feyerabend Susan , Miller Kurt , Houédé Nadine , Hussain Syed , Lam Elaine , Polikoff Jonathan , Stenzl Arnulf , Mainwaring Paul , Ramies David , Hessel Colin , Weitzman Aaron , Fizazi Karim
Published: July 2016

Purpose

Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC.

Patients and Methods

Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments.

Results

A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post–random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively).

Conclusion

Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.
Association of Chromosome 1q Gain With Inferior Survival in Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group
Authors: Gratias Eric J. , Dome Jeffrey S. , Jennings Lawrence J. , Chi Yueh-Yun , Tian Jing , Anderson James , Grundy Paul , Mullen Elizabeth A. , Geller James I. , Fernandez Conrad V. , Perlman Elizabeth J.
Published: July 2016

Purpose

The goal of this study was to analyze the association of copy number gain of 1q in favorable-histology Wilms tumors (FHWTs) with event-free survival (EFS) and overall survival (OS) within each tumor stage and with 1p and 16q copy number loss and/or loss of heterozygosity.

Methods

Unilateral FHWTs from 1,114 patients enrolled in National Wilms Tumor Study-5 that were informative for 1p and 16q microsatellite markers (previously determined) and informative for 1q gain, 1p loss, and 16q loss using multiplex ligation-dependent probe amplification were analyzed.

Results

Eight-year EFS was 86% (95% CI, 84% to 88%) for the entire cohort. Of 1,114 patients, 317 tumors (28%) displayed 1q gain. Eight-year EFS was 77% for those with 1q gain and 90% for those lacking 1q gain (P < .001). Eight-year OS was 88% for those with 1q gain and 96% for those lacking 1q gain (P < .001). Within each disease stage, 1q gain was associated with inferior EFS (stage I, 85% v 95%; P = .0052; stage II, 81% v 87%; P = .0775; stage III, 79% v 89%; P = .01; stage IV, 64% v 91%; P = .001). OS was significantly inferior in patients with stage I (P < .0015) and stage IV disease (P = .011). With multivariable analysis, 1q gain was associated with an increased relative risk of relapse of 2.4 (P < .001), whereas 1p loss was not, despite significance on univariable analysis.

Conclusion

Gain of 1q is associated with inferior survival in unilateral FHWTs and may be used to guide risk stratification in future studies.
Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status?
Authors: Tisnado Diana , Malin Jennifer , Kahn Katherine , Landrum Mary Beth , Fletcher Robert , Klabunde Carrie , Clauser Steven , Rogers Selwyn O. , Keating Nancy L.
Published: July 2016

Purpose:

Chemotherapy prolongs survival in patients with advanced non–small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists’ recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations.

Methods:

We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients’ performance status and symptoms and physicians’ demographic and practice characteristics with chemotherapy recommendations.

Results:

Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P < .001). Compared with patient factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses.

Conclusion:

Strong consensus among oncologists exists for chemotherapy in patients with advanced non–small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk–benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care.
Relationships Among Financial Distress, Emotional Distress, and Overall Distress in Insured Patients With Cancer
Authors: Meeker Caitlin R. , Geynisman Daniel M. , Egleston Brian L. , Hall Michael J. , Mechanic Karen Y. , Bilusic Marijo , Plimack Elizabeth R. , Martin Lainie P. , von Mehren Margaret , Lewis Bianca , Wong Yu-Ning
Published: July 2016

Purpose:

Recent studies have demonstrated increasing rates of financial toxicities and emotional distress related to cancer treatment. This study assessed and characterized the relationships among financial distress, emotional symptoms, and overall distress in patients with cancer.

Methods:

A cross-sectional sample of patients with cancer who visited our outpatient medical oncology and psychiatry clinics completed a pen-and-paper survey. The survey assessed demographics; cost concerns; and financial, emotional, and overall distress.

Results:

One hundred twenty insured patients completed the survey. Sixty-five percent reported clinically significant overall distress scores, with the same percentage reporting at least one emotional problem (worry, anxiety, depression, etc). Twenty-nine percent scored in the range of high to overwhelming financial distress. By using structural equation modeling, we found that financial distress was associated with overall distress. This association was both direct (accounting for 76% of the effect) and indirect (accounting for 24% of the effect) via mediation by emotional distress.

Conclusion:

This cohort of patients with cancer reported significant levels of emotional distress, financial distress, and overall distress. These factors were interrelated, with both financial and emotional distress contributing to overall distress. Interventions targeted at alleviating financial distress may help to decrease levels of overall distress.
Positron Emission Tomography–Computed Tomography (PET-CT) Versus No PET-CT in the Management of Potentially Resectable Colorectal Cancer Liver Metastases: Cost Implications of a Randomized Controlled Trial
Authors: Serrano Pablo E. , Gafni Amiram , Gu Chu-Shu , Gulenchyn Karen Y. , Julian Jim A. , Law Calvin , Hendler Aaron L. , Moulton Carol-Anne , Gallinger Steven , Levine Mark N.
Published: July 2016

Purpose:

To evaluate whether positron emission tomography (PET) combined with computed tomography (PET-CT) is cost saving, or cost neutral, compared with conventional imaging in management of patients with resectable colorectal cancer liver metastases.

Methods:

Cost evaluation of a randomized trial that compared the effect of PET-CT on surgical management of patients with resectable colorectal cancer liver metastases. Health care use data ≤ 1 year after random assignment was obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (ie, Ministry of Health). Mean costs with 95% credible intervals (CrI) were estimated by using a Bayesian approach.

Results:

The estimated mean cost per patient in the 263 patients who underwent PET-CT was $45,454 CAD (range, $1,340 to $181,420) and in the 134 control patients, $40,859 CAD (range, $279 to $293,558), with a net difference of $4,327 CAD (95% CrI, −$2,207 to $10,614). The primary cost driver was hospitalization for liver surgery (difference of $2,997 CAD for PET-CT; 95% CrI, −$2,144 to $8,010), which was mainly a result of a longer length of hospital stay for the PET-CT arm (median, 7 v 6 days; P = .03) and a higher postoperative complication rate (20% v 10%; P = .01). Baseline characteristics were similar between groups, including the number of liver segments involved with cancer, number of segments resected, and type of liver resection performed. No difference in survival was detected between arms.

Conclusion:

PET-CT was associated with limited clinical benefit and a nonsignificant increased cost. Universal funding of PET-CT in the management of patients with resectable colorectal cancer liver metastases does not seem justified.
Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients
Authors: Hatfield Laura A. , Huskamp Haiden A. , Lamont Elizabeth B.
Published: July 2016

Purpose:

Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide.

Methods:

We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients.

Results:

Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99).

Conclusion:

First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings.
Treatment of Stage IIIA Non–Small-Cell Lung Cancer: A Concise Review for the Practicing Oncologist
Authors: Santana-Davila Rafael , Martins Renato
Published: July 2016

Stage IIIA non–small-cell lung cancer occurs in a heterogenous group of patients for whom the best treatment is multimodality therapy with chemotherapy, radiation, and surgery in a select group of individuals. This clinical review intends to answer the most common questions that clinicians face in the decision about the best management in this group.
Allogeneic Hematopoietic Stem-Cell Transplantation for Myelofibrosis: A Practical Review
Authors: Farhadfar Nosha , Cerquozzi Sonia , Patnaik Mrinal , Tefferi Ayalew
Published: July 2016

Myelofibrosis is a myeloproliferative neoplasm with cardinal features of extramedullary hematopoiesis, hepatosplenomegaly, cytopenias, and constitutional symptoms that result in shortened survival and leukemic transformation. It is a disease predominantly of the elderly, and currently available therapies only offer symptom control without curative benefit or ability to alter disease progression. Allogeneic hematopoietic stem-cell transplant (HSCT) is the only potentially curative intervention; however, this is only feasible in younger and medically fit patients and selectively offered to those with high-risk disease. Despite ongoing advancements, HSCT is associated with substantial morbidity and mortality, and the determination of which patients with myelofibrosis are ideal candidates and the selection of the opportune moment to proceed with transplantation remains challenging. This review summarizes our current recommendations for the role of and indications for HSCT in myelofibrosis.
Césaire's Apocalyptic Word
Authors: Drabinski John E.
Published: July 2016

The postcolonial moment is animated by a single, fecund question: What does it mean to begin? Whether it is a vision of cultural retrieval, syncretic memory work, or a first production of the unprecedented, this moment is oriented toward the new as a question of resistance, revolution, and, ultimately, an unshackled future. But, as with any theorizing of the future, this moment is also bound up with the question of memory work: What is the past? And what is the past to the future? This essay takes up the question of beginning in Aimé Césaire's critical work and early poetry. In particular, it explores the relation between apocalypse and prophecy in Notebook of a Return to the Native Land and draws out some of the implications for such thinking after Césaire and négritude. Beginning with that key moment in Notebook in which Césaire demands “the end of the world,” the essay traces Césaire's apocalyptic and establishes it as a precondition of the work of two post-Césairean trends: existentialism (Frantz Fanon) and what I call the Afro-postmodern (Edouard Glissant).
What Neoliberalism Could Not Do, the MAS Can: Divergences and Compatibility between Political Forms and Capital Accumulation in Bolivia
Authors: Lohman Huascar Salazar
Published: July 2016

Recently, the policies promoted by the government of the Movement to Socialism Party (Movimiento al Socialismo; MAS) have shown themselves to be increasingly and explicitly tied to the interests of old and new dominant elites. In contrast to the neoliberal era, when domination was confronted with broad popular resistance, the recent capitulation to old and new dominant elites has become feasible thanks to the new forms of organization of state control that were established with Evo Morales's presidency in 2006 and during subsequent political-economic transformations. This article examines how the political form on which Morales's government was founded instituted a narrative and practice that penetrated and disarticulated popular—mainly communitarian—forces that once resisted neoliberal politics, effectively making the Bolivian socio-economic structure more permeable to transnational capital.
Marx's “Universal Passport”; or, Critique as a Practice of Translation
Authors: Ryan Dermot
Published: July 2016

This essay opens by outlining the ways Marx uses the idea of translation to explain his theoretical practice and its relationship to classical political economy. Recognizing the moment of science in the emergent field of political economy, Marx declares that the ideological distortions in the discourse arise because political economists are speaking “the language of commodities.” In this sense, Marx's “science” is the practice of translation. Building on the grounding insight that scientific knowledge descends into ideology by misrecognizing the correct terrain of its concepts, Marx's writings from Capital onward (and the history of their reception) exhibit a very real tension between political economy as a universal language of concepts called forth by capital (as a universalizing set of social processes) and political economy as a practice that vigilantly attends to the (im)possibility of translating its categories to address different social and historical contexts.
Marxism, Communism, and Translation: An Introduction
Authors: Ertürk Nergis , Serin Özge
Published: July 2016

In introducing this special issue of boundary 2, this essay seeks to challenge the derivative conception of Marxist-communist translation that posits a hierarchical distinction between universal and particular forms of Marxism and communism. Reconceptualizing translation (via Walter Benjamin) as a necessary structural possibility inherent in the original texts, the essay argues that translation is a constitutive feature of all Marxisms and communisms (including Marx's and Lenin's) across time and space. The essay traces the importance of translation as both an actual practice and an important concept-metaphor in Marx's and Lenin's writings. If their writings may all too conveniently be construed as prophecies that lost their historical force in mistranslation (among other misfortunes), we might say that our obligation today is to translate Marx and Lenin more extensively and more vigorously—not despite but precisely because of their inexhaustible translatability. Insofar as an ostensibly original Marx, or Marxism-communism, has always exceeded its historical realization, we ought to affirm its difference as a universalizable in the so-called postcommunist historical present.
The Use-Value of Idioms: The Language of Marxism and Language as Such
Authors: Serin Özge
Published: July 2016

Through a consideration of Turkish Marxist intellectual Hikmet Kıvılcımlı's (1902–71) translation of Wage Labor and Capital, this essay examines the relation between conceptual translation and language in the historical conjuncture of the Kemalist revolution that brought about a radical transformation in language. Moving from Kıvılcımlı's language, suffused with idioms, slang, West Thracian dialectal phonations, colloquialisms, gallicisms, Turkish neologisms, and Arabic and Persian loanwords in the preface to the equivalential chains of Western, Ottoman, and new Turkish words in the translation, the essay uncovers Kıvılcımlı's ambivalence toward the excess of language over concepts. Kıvılcımlı seeks to dispel the effects of linguistic anarchy and perform an impossible leap over conceptual language by creating a short circuit between Marxian thought and Turkish idioms. If the Marxian text is to have a performative force, Kıvılcımlı insists, it must first necessarily become common in both senses of the word, that is, both open to the use of all and typical, ordinary, and perhaps even banal, akin to a conventional formula, a proverb, or an idiom that could be told, recited, and used by anyone and everyone, time and again but always singularly.
Of Race: The Exorbitant Du Bois
Authors: Hesse Barnor
Published: July 2016

Nahum Chandler, in his remarkably evocative book X—The Problem of the Negro as a Problem for Thought, works with the Derridean idea of the exorbitant to argue that W. E. B. Du Bois's thinking exceeds and transforms the terms of Western critical thought on modernity. Du Bois is credited with conceptualizing the idea of “the Negro” as derivable from the formations of colonial and racialized modernity, which as formations are conventionally foreclosed by Western critical thought. In the spirit of a Derridean supplement to Chandler's argument, this essay suggests Chandler's otherwise compelling account of Du Bois nevertheless obscures an alternative, conceptually richer way in which Du Bois's thought is exorbitant to his own thinking on the question of race. This involves understanding the constitution of race as a colonial-political practice that is named here as “race governance.”
The Radical Vision of Si-lan Chen: The Politics of Dance in an Age of Global Crisis
Authors: Sine Elizabeth E.
Published: July 2016

This essay explores the making of a radical cultural politics amid the global crisis of the 1930s and 1940s through a study of the life and work of dancer Si-lan Chen. Born in Trinidad to Afro-Caribbean and Chinese parents, trained as a ballerina in Moscow, and an active supporter of Chinese and other anti-imperialist movements, Chen toured the global South, worked in the United States, and returned to the West Indies during the early 1940s to play an integral role in the making of a transnational Caribbean cultural politics. Sine's research traces how Chen continually defied the racial, gender, national, and aesthetic boundaries she encountered in her life as she advanced a radical political vision that was global in its scope as well as its aspirations. Sine highlights how Chen challenged the rationalist premises governing modern, Western thought and stressed the interconnectivity of global popular emancipatory movements.
Journal Work: Africa Is a Country
Authors: Jacobs Sean
Published: July 2016

This essay, more a series of observations, explores the history and politics of the media and analysis online site Africa Is a Country (africasacountry.com), which the author founded in 2009. Exploring changes to the blogosphere and social media and their implications for websites focusing on the African continent and its diaspora, the essay makes reference to the historical antecedents of cultural journals, both online and offline, including Transition, Kwani!, and Chimurenga Chronic, and debates some of the challenges facing online publishing, such as editorial control, management, political orientation, and focus.
The (Anti)Social Life of a Digital Journal in the Era of Global Info-Capitalism
Authors: Sharma Ashwani
Published: July 2016

By reflecting on running the open-access online “race” journal darkmatter, the author examines the crisis of academic journal publishing. This crisis is manifested by the transformations in the economics of journal production, especially with the rise of open-access publishing and the neoliberalization of the academy; the developments in digital communications; and the global consolidation of Western corporate publishing power in “info-capitalism.” The evolution of darkmatter is poised in terms of negotiating this crisis as opportunity and risk. The digital journal is able to produce a range of multimedia outputs addressing the interdisciplinary fields of race and postcolonial study. The challenge of emerging Web projects and the proliferation of online information potentially repositions darkmatter as the privileged site for the publication of scholarly research. The essay speculates on this critical journal in a time of “information overload” as a site of “autonomous resistance” in the increasing commodification of knowledge.
Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation
Authors: Roa-Espitia Ana L. , Hernández-Rendón Eva R. , Baltiérrez-Hoyos Rafael , Muñoz-Gotera Rafaela J. , Cote-Vélez Antonieta , Jiménez Irma , González-Márquez Humberto , Hernández-González Enrique O.
Published: July 2016

Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton.
Multiple sensory modalities used by squid in successful predator evasion throughout ontogeny
Authors: York Carly A. , Bartol Ian K. , Krueger Paul S.
Published: July 2016

Squid rely on multiple sensory systems for predator detection. In this study we examine the role of two sensory systems, the lateral line analogue and vision, in successful predator evasion throughout ontogeny. Squid Doryteuthis pealeii and Lolliguncula brevis were recorded using high-speed videography in the presence of natural predators under light and dark conditions with their lateral line analogue intact and ablated via a pharmacological technique. Paralarval squid showed reduced escape responses when ablated; however, no differences were found between light and dark conditions, as was previously shown in juveniles and adults, indicating that the lateral line analogue is integral for predator detection early in life. Vision does play a role in survival as ablated squid in dark conditions had lower survivorship than all other treatments. Throughout ontogeny, squid oriented themselves anteriorly towards the oncoming predator, maximizing sensory input to the lateral line analogue system and providing better positioning for tail-first escape jetting, the preferred escape mode. Ablated juveniles and adults had lower response times, escape velocities and peak acceleration than non-ablated individuals, indicating that the lateral line analogue enables squid to respond quicker and with more powerful jets to a predator and maximize escape success. Our findings reveal that the lateral line analogue plays a role in predator detection and successful escape response at the earliest life stages, and continues to contribute to successful evasion by aiding visual cues in juvenile and adult squid.
Repeatability of locomotor performance and of morphology – locomotor performance relationships
Authors: Conradsen Cara , Walker Jeffrey A. , Perna Catherine , McGuigan Katrina
Published: July 2016

There is good evidence that natural selection drives the evolution of locomotor performance, but the processes that generate among individual variation in locomotion, the substrate upon which selection acts, are relatively poorly understood. We measured prolonged swimming performance, Ucrit, and morphology in a large cohort (n=461) of wildtype zebrafish, Danio rerio, at ∼6 months and again at ∼9 months. Using mixed model analyses to estimate repeatability as the intraclass correlation coefficient, we determined that Ucrit was significantly repeatable (r = 0.55; 95% CI: 0.45 -0.64). Performance differences between the sexes (males 12% faster than females) and changes with age (decreasing 0.07% per day) both contributed to variation in Ucrit and, therefore, the repeatability estimate. Accounting for mean differences between sexes within the model decreased the estimate of Ucrit repeatability to 21% below the naïve estimate, while fitting age in the models increased the estimate to 14% above the naïve estimate. Greater consideration of factors such as age and sex is therefore necessary for the interpretation of performance repeatability in wild populations. Body shape significantly predicted Ucrit in both sexes in both assays, with the morphology – performance relationship significantly repeatable at the population level. However, morphology was more strongly predicative of performance in older fish, suggesting a change in the contribution of morphology relative to other factors such as physiology and behaviour. The morphology – performance relationship changed with age to a greater extent in males than females.
Thyroid hormone influences muscle mechanics in carp (Cyprinus carpio) independently from SERCA activity
Authors: James Rob S. , Little Alexander G. , Tallis Jason , Seebacher Frank
Published: July 2016

Thyroid hormone is a key regulator of metabolism, and in zebrafish hypothyroidism decreases sustained and burst swimming performance. These effects are accompanied by decreases in both metabolic scope and the activity of sarco-endoplasmic reticulum ATPase (SERCA) in zebrafish. Our aim was to determine whether thyroid hormone affects skeletal muscle contractile function directly and whether these effects are mediated by influencing SERCA activity. We show that hypothyroidism reduces sustained locomotor performance but not sprint performance in carp (Cyprinus carpio). We accept our hypothesis that hypothyroidism reduces force production in isolated skeletal muscle, when compared to T2, but we reject the hypothesis that this effect is mediated by influencing SERCA activity. Blocking SERCA activity with thapsigargin reduced muscle fatigue resistance, but hypothyroidism had no effect on fatigue. Hence, thyroid hormone plays a role in determining isolated skeletal muscle mechanics, but its effects are more likely to be mediated by other mechanisms than affecting SERCA activity.
Discrimination of fast click series produced by tagged Risso's dolphins (Grampus griseus) for echolocation or communication
Authors: Arranz P. , DeRuiter S. L. , Stimpert A. K. , Neves S. , Friedlaender A. S. , Goldbogen J. A. , Visser F. , Calambokidis J. , Southall B. L. , Tyack P. L.
Published: July 2016

Early studies that categorized odontocete pulsed sounds had few means of discriminating signals used for biosonar-based foraging from those used for communication. This capability to identify the function of sounds is important for understanding and interpreting behavior; it is also essential for monitoring and mitigating potential disturbance from human activities. Archival tags were placed on free-ranging Grampus griseus to quantify and discriminate between pulsed sounds used for echolocation-based foraging and those used for communication. Two types of rapid click-series pulsed sounds, buzzes and burst pulses, were identified as produced by the tagged dolphins and classified using a Gaussian mixture model based on their duration, association with jerk (i.e., rapid change of acceleration), and temporal association with click trains. Buzzes followed regular echolocation clicks and coincided with a strong jerk signal from accelerometers on the tag. They consisted of series averaging 359 ± 210 (mean ± SD) clicks with an increasing repetition rate and relatively low amplitude. Burst pulses consisted of relatively short click series averaging 45 ± 54 clicks with decreasing repetition rate and longer inter-click interval that were less likely to be associated with regular echolocation and the jerk signal. These results suggest that the longer, relatively lower amplitude, jerk-associated buzzes are used in this species to capture prey, mostly during the bottom phase of foraging dives, as seen in other odontocetes. In contrast, the shorter, isolated burst pulses that are generally emitted by the dolphins while at or near the surface are used outside of a direct, known foraging context.
Relative contributions of the structural and catalytic roles of Rrp6 in exosomal degradation of individual mRNAs
Authors: Mukherjee Kaustav , Gardin Justin , Futcher Bruce , Leatherwood Janet
Published: July 2016

The RNA exosome is a conserved complex for RNA degradation with two ribonucleolytic subunits, Dis3 and Rrp6. Rrp6 is a 3′–5′ exonuclease, but it also has a structural role in helping target RNAs to the Dis3 activity. The relative importance of the exonuclease activity and the targeting activity probably differs between different RNA substrates, but this is poorly understood. To understand the relative contributions of the exonuclease and the targeting activities to the degradation of individual RNA substrates in Schizosaccharomyces pombe, we compared RNA levels in an rrp6 null mutant to those in an rrp6 point mutant specifically defective in exonuclease activity. A wide range of effects was found, with some RNAs dependent mainly on the structural role of Rrp6 (“protein-dependent” targets), other RNAs dependent mainly on the catalytic role (“activity-dependent” targets), and some RNAs dependent on both. Some protein-dependent RNAs contained motifs targeted via the RNA-binding protein Mmi1, while others contained a motif possibly involved in response to iron. In these and other cases Rrp6 may act as a structural adapter to target specific RNAs to the exosome by interacting with sequence-specific RNA-binding proteins.