bluuebunny/crossref_metadata_2025 huggingface dataset:
Labour market developments and their significance for VET in England: Current concerns and debates
Authors: Laczik Andrea , Mayhew Ken
Published: November 2015

This chapter discusses the relationship between the labour market and vocational education and training in England. For decades British governments have emphasised the need for more people to stay longer in the formal education system and at the same time have attempted to improve work-based training. They have also emphasised the centrality of vocational education and training in improving national productivity and growth and in alleviating distributional problems. We argue that education and training have made a more limited contribution to these objectives than governments might have hoped. This is because of a very imperfect match between the requirements of the labour market and what the vocational education and training system has produced. We suggest that a greater integration of industrial strategy and education and training policy is needed. More emphasis needs to be placed on apprenticeships and on lower level post-compulsory education rather than on higher education. Greater support is needed for educational interventions in early years in an attempt to reduce class bias in attainment and consequently in labour market opportunities. An overarching problem is that, whilst employer engagement has been a central theme of government policies, the extent of employer buy-in to these policies is unclear.
Impact of fatigue in patients with chronic obstructive pulmonary disease: results from an exploratory study
Authors: Antoniu Sabina Antonela , Petrescu Elena , Stanescu Raluca , Anisie Ecaterina , Boiculese Lucian
Published: November 2015

Introduction:

Fatigue, which is also present in the healthy population, is a common but understudied symptom in chronic obstructive pulmonary disease (COPD). We hypothesized that clinically significant fatigue is also frequent in COPD and can be associated with an increased disease burden.

Methods:

An exploratory analysis derived from an ongoing cross-sectional study was carried out to evaluate levels of fatigue and impact on health-related quality of life/health status in patients with COPD (COPD group; n = 20) and healthy subjects (control group; n = 5). Health-related quality of life was measured using the Short Form Health Survey 36 (SF-36), health status with the Clinical COPD Questionnaire (CCQ), and airways obstruction with postbronchodilator forced expiratory volume in 1 s (FEV1 %predicted). Fatigue was measured with the vitality score of the SF-36, its clinical significance being defined by values of 50 or less. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy scale for fatigue (FACIT-F).

Results:

Vitality scores were significantly worse in the COPD group (45.60 versus 76.25; p = 0.004). FACIT-F scores were significantly lower in the COPD group versus the control group (74.5 versus 95.0; p = 0.03). Clinically significant fatigue was detected in 60% of the COPD group, and was associated with a worse FEV1 %predicted (47.71 versus 65.82%; p = 0.016), worse symptoms burden (CCQ symptoms score 3.75 versus 2.43; p = 0.019), and worse overall health status (CCQ total score 3.30 versus 2.11; p = 0.011). Its link with systemic inflammation remains to be clarified further.

Conclusions:

Clinically significant fatigue is common among patients with COPD and is associated with an increased disease burden. It should therefore be integrated as a measure of disease prognosis and control in patients with COPD.
The Diabetic Retinopathy Screening Workflow
Authors: Bolster Nigel M. , Giardini Mario E. , Bastawrous Andrew
Published: November 2015

Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems’ use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound.
Antibiotic Prophylaxis Regimens in Trauma and Orthopaedic Surgery
Authors: Tucker Adam , Henderson L. , Moffatt R. , Abela R. , Troughton J. , McMullan R. , Wilson A.
Published: November 2015

Trauma, elective orthopaedics, and an aging population will result in an increasing health burden and work load. The move to surgical podiatrists in the National Health Service within the United Kingdom will shift the surgical workload away from orthopaedic surgeons. A devastating complication of foot and ankle surgery is postoperative infection. While postoperative infection is multifactorial in etiology, concomitant diabetes mellitus increases the general risk of trauma and orthopaedic surgical site infections up to 8-fold. We therefore undertook a prospective study of our unit antibiotic prophylaxis regimes. Fifty patients participated. Swabs were obtained using aseptic technique from the plantar aspect of the feet, between the toes, and subsequently cultured on agar plates. Specimens were then incubated for 48 hours before being exposed to antibiotic plates. Cultured organisms were classified as susceptible to an antibiotic regimen if susceptibility to cefuroxime, or susceptibility to either drug of the flucloxacillin/gentamicin combination, was demonstrated. Statistical analysis e was performed. A P value <.05 was considered significant. Fifty patients were recruited, 26 (52%) were male. Mean age of 53 ± 19.4 years. The cohort included 15 diabetic, of which 11 (73.3%) insulin-dependent, and 35 nondiabetic patients. Comparing flucloxacillin/gentamicin against cefuroxime overall, susceptibility was noted in 84% and 70%, respectively (P = .096). Resistance to cefuroxime was significantly higher in diabetics than in nondiabetics (53% vs 25%, P = .046). The same pattern was observed for the flucloxacillin/gentamicin regimen (33% vs 9%, P = .049). While both regimens are active against colonizing organisms in this prospective observational study, flucloxacillin and gentamicin provide greater coverage overall. We have demonstrated that the use of flucloxacillin/gentamicin provides better coverage against commensal bacterial flora compared with cefuroxime alone. This is of even greater importance in the case of the specific high-risk subgroups, such as diabetic patients.

Levels of Evidence: Level IV: Case Series
Managing uncertainty in mobile dating applications: Goals, concerns of use, and information seeking in Grindr
Authors: Corriero Elena Francesca , Tong Stephanie Tom
Published: November 2015

The current research used uncertainty management theory (UMT) as a framework to examine individuals’ experience of uncertainty within the context of Grindr, an all-male, location-based mobile dating application. In two studies, we first investigated the particular concerns associated with Grindr use. Results indicated that the unique affordances of Grindr generated six categories of user concerns associated with use of the mobile application. The second study confirmed that a specific set of user goals and concerns predicted daters’ desire for uncertainty, which in turn predicted information-seeking behavior. Findings clearly indicate that Grindr users’ responses to uncertainty were not limited to simple reduction strategies, but were dependent upon their desire for and tolerance of uncertainty in relation to their goals and concerns of application use. The current results also help to establish UMT’s predictive power and explanatory utility within the realm of interpersonal communication.
Bible Translation Overtaken by Change
Authors: del Corro Anicia
Published: November 2015

The article documents two Bible translation projects in the Philippines that took longer than usual to finish. The Pampango Bible took twenty-four years, and the Bolinao New Testament took thirty-five years. Accelerated change in the society generated changes in language preference with Tagalog competing with Pampango. From thirty barangays (the smallest political unit) in the 1970s that spoke Bolinao, this has been reduced to only six. Reasons cited are: easy access by land on the part of the Ilocanos; transport routes that once were by sea are now primarily by land, with good roads from the town of Bolinao to Manila; and a new bridge bringing an end to the isolation of the island towns of Anda and Santiago. One obvious sign of language endangerment is that young children are now unable to speak Bolinao, and only those in their fifties or sixties use Bolinao with ease.
Ideology and Bible Translation: Can Biblical Performance Criticism Help?
Authors: Esala Nathan
Published: November 2015

Biblical performance criticism (BPC) is a provincial practice with particular North American and European historical indices. When entering into a new context, this methodological genealogy needs to be recognized, because within those indices overt and covert interests are served. In order for BPC to be contextualized to serve local interests, it must recognize practices on the ground and how those practices have already been shaped or reshaped to serve local interests. I will highlight three practices in the Bik m context of Ghana to see how their ideological pathways have been (re)shaped to serve local interests: written Bible translation, oral tradition, and preaching. I will discuss two examples where written Bible translation has partially imitated the pathways of oral tradition and sermonic practice to better serve local interests. Then I will discuss the material dimensions of written Bibles and oral tradition as instructive for the way BPC materially contextualizes. Finally, I will suggest that if contextual Bible study as developed in South Africa could be adapted for the Bik m context, it could be helpful to Bible interpreters, translators, and performers as they seek to embed their Bible practices in locally controlled ways that foster local liberation.
Relevance Theory in the Performance of Revelation 17–19
Authors: Perry Peter S.
Published: November 2015

Relevance theory (RT) describes human communication as a cognitive process that tends to maximize contextual effects while minimizing processing effort. From an RT perspective, translation is a communication event in which a speaker/writer selects some contextual effects of a prior communication event to replicate with an acceptable amount of processing effort by new hearers in a different language. Performance is translation in that it shares the goal of replication of contextual effects; but while translators may desire verisimilitude above other goals, performers may have differently prioritized communicative objectives. Performance of a text provides Bible translators an opportunity to explore the effectiveness of verbal and non-verbal cues to maximize contextual effects and minimize processing effort for a specific audience. The performance of Revelation 17–19 offers a unique window into the cognitive effects of ambiguity and delayed processing, emotion and tone, space and distance that guide word choice, syntax, and visual formatting of a written translation. The non-verbal cues of performance correlate to the visual cues of a text in maximizing desired contextual effects while minimizing processing effort.
Translating New Testament Proverb-Like Sayings in the Style of Local Proverbs
Authors: Pluger Chris
Published: November 2015

This paper identifies a collection of “proverb-like” sayings found in the Greek New Testament and analyzes some of the grammatical and phonological features that characterize the collection. It then exemplifies the translation of several of these sayings into the Nsenga language as Nsenga proverbs, following the literary functional-equivalence (LiFE) approach described by E. R. Wendland. It is hoped that these “LiFE-like” Nsenga translations can serve as models for the translation of biblical proverbs into appropriate local literary forms in languages around the world.
Interpreting performance in offender supervision: The use of observation as a data collection method
Authors: Boxstaens Johan , Blay Ester , Pereto Anna Melendez , Décarpes Pascal
Published: November 2015

Empirical research on practicing offender supervision seems to be rather scarce in many European jurisdictions. Existing studies tend to be mostly descriptive and use interviews and surveys as methods of data collection. Moreover, comparative research on the practice of offender supervision is almost non-existent (Bauwens, 2011; Robinson and Svensson, 2013). This article describes and reflects on the exploratory work that has been done by researchers from different European jurisdictions in their effort to pilot observations as an innovative research method to study probation practice within a comparative framework. The authors briefly discuss observations as a method for collecting data in general. A description of the (ongoing) project of piloting observations as a method in comparative research and the methodological issues that arose, led to the development of a structured observation schedule that has been tested in Catalonia, Spain. We describe the first results of this study and discuss them in relation to our ongoing effort to assess the added value of observations in comparative research on probation practice.
Using vignette methodology to research the process of breach comparatively
Authors: Maguire Niamh , Beyens Kristel , Boone Miranda , Laurinavicius Alfredas , Persson Anders
Published: November 2015

Comparative research related to any aspect of the process of breach in either the pre-trial, sentencing or release phases is relatively rare. Comparative studies of decision making in the specific context of breach process are particularly lacking. One reason for the dearth of research in this area is the many challenges presented by comparative research across different jurisdictions. This article focuses on the development of a vignette methodology to explore the decision-making aspect of the breach process from a comparative perspective across a number of different European jurisdictions. The vignettes are designed to explore the decision-making aspects of two different types of breach process – the process of breach that follows on from a breach of conditions of early release from prison and the process that follows a breach of conditions attached to the completion of an unpaid work order. The article begins by contextualizing the research in debates about the relationship between compliance, legitimacy and rising prison populations. It critically examines the nature of vignette methodology and then discusses the specific challenges of using vignettes in comparative research as well as the development, piloting and evaluation of the decision-making vignettes in focus. We conclude by discussing some of the challenges we faced and particularly our challenge in terms of the development of the methodology – enhancing the comparability of the findings.
Examining Older Adults’ Perceptions of Usability and Acceptability of Remote Monitoring Systems to Manage Chronic Heart Failure
Authors: Evangelista Lorraine S. , Moser Debra K. , Lee Jung-Ah , Moore Alison A. , Ghasemzadeh Hassan , Sarrafzadeh Majid , Mangione Carol M.
Published: November 2015

Objective: This study was conducted to evaluate the feasibility, usability, and acceptability of using remote monitoring systems (RMS) in monitoring health status (e.g., vital signs, symptom distress) in older adults (≥55) with chronic heart failure (HF). Method: Twenty-one patients (52.4% women, mean age 73.1 ± 9.3) were trained to measure and transmit health data with an RMS. Data transmissions were tracked for 12 weeks. Results: All participants initiated use of RMS within 1 week; 71%, 14%, and 14% of patients transmitted daily health data 100%, ≥75%, and <75% of the time, respectively, for 12 weeks. Overall usability and acceptability of the RMS were 4.08 ± 0.634 and 4.10 ± 0.563, respectively (when scored on a range of 1-5, where 1 = strongly disagree and 5 = strongly agree). Discussion: Findings show that an RMS-based intervention can be successfully implemented in a group of older patients with chronic HF.
Clinical Utilization and Function of Tissue Doppler Imaging in Detecting Congenital Cardiomyopathies
Authors: Alexander Stacy
Published: November 2015

Hypertrophic cardiomyopathy (HCM) is caused by sarcomere genes and is the most common monogenic cardiovascular disorder. Left ventricular hypertrophy (LVH) is the classic hallmark sign for diagnosis; however, LVH may not manifest until adolescence or later in individuals who are mutation carriers. Genetic testing can identify individuals who carry pathogenic sarcomere mutations and have a clinical diagnosis of HCM—that is, mutation carriers who have not yet manifested LVH but are very likely to develop the disease. Evaluating this new patient subset with state-of-the-art echocardiography has shown evidence of early signs of left ventricular impairment. Tissue Doppler imaging is able to detect mutation carriers who may have altered diastolic function, by identifying individuals with reduced tissue Doppler velocities. This article reviews the findings of using tissue Doppler imaging in HCM and other forms of cardiomyopathy. Understanding this source of HCM presents an opportunity to predict and better manage disease.
Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphomas
Authors: Culjkovic-Kraljacic Biljana , Fernando Tharu M. , Marullo Rossella , Calvo-Vidal Nieves , Verma Akanksha , Yang ShaoNing , Tabbò Fabrizio , Gaudiano Marcello , Zahreddine Hiba , Goldstein Rebecca L. , Patel Jayeshkumar , Taldone Tony , Chiosis Gabriela , Ladetto Marco , Ghione Paola , Machiorlatti Rodolfo , Elemento Olivier , Inghirami Giorgio , Melnick Ari , Borden Katherine L. B. , Cerchietti Leandro
Published: November 2015

Key Points

eIF4E, a protein highly elevated in poor-prognostic lymphomas, simultaneously sustains expression of known driver oncogenes BCL6, BCL2, MYC. The tumorigenic form of Hsp90 is a novel partner protein in the process underlying a new therapeutic strategy for these aggressive lymphomas.
Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease
Authors: Solomon Joshua J. , Chung Jonathan H. , Cosgrove Gregory P. , Demoruelle M. Kristen , Fernandez-Perez Evans R. , Fischer Aryeh , Frankel Stephen K. , Hobbs Stephen B. , Huie Tristan J. , Ketzer Jill , Mannina Amar , Olson Amy L. , Russell Gloria , Tsuchiya Yutaka , Yunt Zulma X. , Zelarney Pearlanne T. , Brown Kevin K. , Swigris Jeffrey J.
Published: November 2015

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.

We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a “definite” or “possible” usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.

The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.

Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.
A voyage to Terra Australis: human-mediated dispersal of cats
Authors: Koch K. , Algar D. , Searle J. B. , Pfenninger M. , Schwenk K.
Published: November 2015

Background

Cats have been transported as human commensals worldwide giving rise to many feral populations. In Australia, feral cats have caused decline and extinction of native mammals, but their time of introduction and origin is unclear. Here, we investigate hypotheses of cat arrival pre- or post-European settlement, and the potential for admixture between cats of different invasion events. We analyse the genetic structure and diversity of feral cats from six locations on mainland Australia, seven Australian islands and samples from Southeast Asia and Europe using microsatellite and mitochondrial DNA data.

Results

Our results based on phylogeographic model selection are consistent with a European origin of cats in Australia. We find genetic distinctiveness of Australian mainland samples compared with Dirk Hartog Island, Flinders Island, Tasman Island and Cocos (Keeling) Island samples, and genetic similarities between some of the island populations. Historical records suggest that introduction of cats to these islands occurred at the time of European exploration and/or in connection with the pearling, whaling and sealing trades early in the 19th century. On-going influx of domestic cats into the feral cat population is apparently causing the Australian mainland populations to be genetically differentiated from those island populations, which likely are remnants of the historically introduced cat genotypes.

Conclusion

A mainly European origin of feral cats in Australia, with possible secondary introductions from Asia following the initial establishment of cats in Australia is reasonable. The islands surrounding Australia may represent founding populations and are of particular interest. The results of the study provide an important timeframe for the impact of feral cats on native species in Australia.
Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?
Authors: Carr Anitra C. , Shaw Geoffrey M. , Fowler Alpha A. , Natarajan Ramesh
Published: November 2015

Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.
Survival and Clinical Outcomes in Surgically Treated Patients With Metastatic Epidural Spinal Cord Compression: Results of the Prospective Multicenter AOSpine Study
Authors: Fehlings Michael G. , Nater Anick , Tetreault Lindsay , Kopjar Branko , Arnold Paul , Dekutoski Mark , Finkelstein Joel , Fisher Charles , France John , Gokaslan Ziya , Massicotte Eric , Rhines Laurence , Rose Peter , Sahgal Arjun , Schuster James , Vaccaro Alexander
Published: November 2015

Purpose

Although surgery is used increasingly as a strategy to complement treatment with radiation and chemotherapy in patients with metastatic epidural spinal cord compression (MESCC), the impact of surgery on health-related quality of life (HRQoL) is not well established. We aimed to prospectively evaluate survival, neurologic, functional, and HRQoL outcomes in patients with MESCC who underwent surgical management.

Patients and Methods

One hundred forty-two patients with a single symptomatic MESCC lesion who were treated surgically were enrolled onto a prospective North American multicenter study and were observed at least up to 12 months. Clinical data, including Brief Pain Inventory, ASIA (American Spinal Injury Association) impairment scale, SF-36 Short Form Health Survey, Oswestry Disability Index, and EuroQol 5 dimensions (EQ-5D) scores, were obtained preoperatively, and at 6 weeks and 3, 6, 9, and 12 months postoperatively.

Results

Median survival time was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. There was improvement at 6 months postoperatively for ambulatory status (McNemar test, P < .001), lower extremity and total motor scores (Wilcoxon signed rank test, P < .001), and at 6 weeks and 3, 6, and 12 months for Oswestry Disability Index, EQ-5D, and pain interference (paired t test, P < .013). Moreover, at 3 months after surgery, the ASIA impairment scale grade was improved (Stuart-Maxwell test P = .004). SF-36 scores improved postoperatively in six of eight scales. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma).

Conclusion

Surgical intervention, as an adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurologic, functional, and HRQoL outcomes, with acceptable risks in patients with a focal symptomatic MESCC lesion who have at least a 3 month survival prognosis.
Prospective Evaluation of the 21-Gene Recurrence Score Assay for Breast Cancer Decision-Making in Ontario
Authors: Levine Mark N. , Julian Jim A. , Bedard Philippe L. , Eisen Andrea , Trudeau Maureen E. , Higgins Brian , Bordeleau Louise , Pritchard Kathleen I.
Published: November 2015

Purpose

To evaluate the 21-gene recurrence score (RS) on decision-making in a population-based cohort.

Patients and Methods

Patients with axillary node-negative or nodal micrometastases, estrogen receptor–positive, and human epidermal growth factor receptor 2–negative breast cancer being considered for chemotherapy were eligible. All cancer treatment centers in Ontario, Canada, participated. Oncologists made a preliminary recommendation for endocrine therapy with or without chemotherapy on the basis of Adjuvant! Online (AOL) risk estimation. Patients were asked for their preference regarding chemotherapy. After RSs were available, patients returned for final decision-making. Patient satisfaction was measured by using the decisional conflict scale.

Results

Between January 2012 and July 2013, 1,000 patients were recruited. RSs were available for 979 patients. In 58% of patients, risk was categorized as low (RS, 0 to 18); in 33%, intermediate (RS, 19 to 30); and in 9%, high (RS, ≥ 31). Oncologists' recommendations pretest and post-test remained the same in 464 patients (48%), changed from unsure or chemotherapy to no chemotherapy in 365 (38%), and changed from unsure or no chemotherapy to chemotherapy in 143 (15%). After the test, oncologists recommended chemotherapy for 236 patients, 81% of whom received chemotherapy. Of 151 patients in whom risk was classified as intermediate by means of AOL, 41% were a low risk and 44% intermediate risk with RS. Of 298 patients at high risk with AOL, 16% had a high risk RS. None of 236 patients with grade I tumors had a high-risk RS. Mean total decisional conflict scale score significantly improved from pretest to post-test from 34 to 19 (P < .001).

Conclusion

The RS substantially influenced both oncologists' recommendations and patients' preferences for chemotherapy. The major effect was avoidance of chemotherapy when AOL indicated high or intermediate risk.
Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease
Authors: Geyer Holly , Scherber Robyn , Kosiorek Heidi , Dueck Amylou C. , Kiladjian Jean-Jacques , Xiao Zhijian , Slot Stefanie , Zweegman Sonja , Sackmann Federico , Fuentes Ana Kerguelen , Hernández-Maraver Dolores , Döhner Konstanze , Harrison Claire N. , Radia Deepti , Muxi Pablo , Besses Carlos , Cervantes Francisco , Johansson Peter L. , Andreasson Bjorn , Rambaldi Alessandro , Barbui Tiziano , Bonatz Karin , Reiter Andreas , Boyer Francoise , Etienne Gabriel , Ianotto Jean-Christophe , Ranta Dana , Roy Lydia , Cahn Jean-Yves , Maldonado Norman , Barosi Giovanni , Ferrari Maria L. , Gale Robert Peter , Birgegard Gunnar , Xu Zefeng , Zhang Yue , Sun Xiujuan , Xu Junqing , Zhang Peihong , te Boekhorst Peter A.W. , Commandeur Suzan , Schouten Harry , Pahl Heike L. , Griesshammer Martin , Stegelmann Frank , Lehmann Thomas , Senyak Zhenya , Vannucchi Alessandro M. , Passamonti Francesco , Samuelsson Jan , Mesa Ruben A.
Published: November 2015

Purpose

Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden.

Patients and Methods

Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly).

Results

The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S).

Conclusion

The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.
Racial Variation in the Uptake of Oncotype DX Testing for Early-Stage Breast Cancer
Authors: Roberts Megan C. , Weinberger Morris , Dusetzina Stacie B. , Dinan Michaela A. , Reeder-Hayes Katherine E. , Carey Lisa A. , Troester Melissa A. , Wheeler Stephanie B.
Published: November 2015

Purpose

Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake.

Methods

We used data from the Carolina Breast Cancer Study, phase III, a longitudinal, population-based study of 2,998 North Carolina women who received a diagnosis of breast cancer between 2008 and 2014. Our primary analysis used modified Poisson regression to determine the association between race and whether ODX testing was ordered among two strata: node-negative and node-positive breast cancer.

Results

A total of 1,468 women with estrogen receptor–positive, human epidermal growth factor receptor-2–negative, stage I or II breast cancer met inclusion criteria. Black patients had higher-grade and larger tumors, more comorbidities, younger age at diagnosis, and lower socioeconomic status than non-black women. Overall, 42% of women had ODX test results in their pathology reports. Compared with those who did not receive ODX testing, women who received ODX testing tended to be younger and have medium tumor size and grade. Our regression analyses indicated no racial disparities in ODX uptake among node-negative patients. However, racial differences were detected among node-positive patients, with black patients being 46% less likely to receive ODX testing than non-black women (adjusted relative risk, 0.54; 95% CI, 0.35 to 0.84; P = .006).

Conclusion

We did not find racial disparities in ODX testing for node-negative patients for whom ODX testing is guideline recommended and widely covered by insurers. However, our findings suggest that a newer, non–guideline-concordant application of ODX testing for node-positive breast cancer was accessed less by black women than by non-black women, reflecting more guideline concordant care among black women.
DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer
Authors: Thorsen Lise Bech Jellesmark , Offersen Birgitte Vrou , Danø Hella , Berg Martin , Jensen Ingelise , Pedersen Anders Navrsted , Zimmermann Sune Jürg , Brodersen Hans-Jürgen , Overgaard Marie , Overgaard Jens
Published: November 2015

Purpose

It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer.

Patients and Methods

In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat.

Results

A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease.

Conclusion

In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer.
Manufacturing Dissidence: Arts and Letters of North Korea's “Second Culture”
Authors: Hong Christine
Published: November 2015

Reading North Korean defector memoirs and Korean American “roots” narratives as forms of “second culture” relative to North Korea, namely, an alternative US-oriented culture whose representational authority is held as exceeding that of the socialist state of origin, this essay examines the ongoing Korean War as the backdrop for the neoconservative emergence of human rights critique of North Korea. Examining the transnational funding matrix behind the publication and international circulation of the North Korean defector memoir, specifically the National Endowment for Democracy's role in sponsoring such “human rights” writings, this essay reads the latter as weaponized forms of expression, defined by their instrumentality within an uneven global landscape of power and rendered lethal by the state of unresolved hostilities between the United States and North Korea. Positing the illegitimacy of North Korea, the defector memoir has been marshaled toward sovereignty-challenging, or regime-change, ends. Widely read as “human rights” literary forms, the defector memoir, alongside the Korean American “roots” narrative of North Korea, this essay argues, have served in the geopolitical arena as vehicles for “dissident” North Korean voices in place of an extant samizdat literature.
Loss of PGL-1 and PGL-3, a family of constitutive germ-granule components, promotes germline apoptosis in C. elegans
Authors: Min Hyemin , Shim Yhong-Hee , Kawasaki Ichiro
Published: November 2015

In Caenorhabditis elegans, the mechanisms regulating germline apoptosis remain largely unknown except for the core machinery. Mutants of pgl-1 and pgl-3 encoding a family of constitutive protein components of germline-specific P granules showed increased germline apoptosis under both physiological and DNA-damaged conditions. We found that the number of germ cells that lost PGL proteins increased significantly following UV irradiation, and that only those PGL-absent germ cells were selectively engulfed by gonadal sheath cells in adult hermaphrodite gonads. We further revealed that CEP-1, the p53 homolog, and CED-3 caspase promoted elimination of PGL-1 from germ cells following UV irradiation. Furthermore, protein levels of CED-4, the Apaf-1 homolog, and cytoplasmic translocation of SIR-2.1, a Sirtuin homolog, significantly increased in pgl mutants and increased even more following UV irradiation. CED-4 and SIR-2.1 were essential for high levels of germline apoptosis in pgl mutants. We conclude that PGL proteins suppress excessive germline apoptosis by repressing both the protein levels of CED-4 and the cytoplasmic translocation of SIR-2.1. Our study has revealed novel roles of PGL-1 and PGL-3 for the control of germline apoptosis.
PAK6 targets to cell-cell adhesions via its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape
Authors: Morse Elizabeth M. , Sun Xiaowen , Olberding Jordan R. , Ha Byung Hak , Boggon Titus J. , Calderwood David A.
Published: November 2015

The six serine/threonine kinases in the p21-activated kinase (PAK) family are important regulators of cell adhesion, motility and survival. PAK6, which is overexpressed in prostate cancer, was recently reported to localize to cell-cell adhesions and to drive epithelial cell colony escape. Here we report that PAK6 targeting to cell-cell adhesions occurs via its N-terminus, requiring both its Cdc42/Rac Interactive Binding (CRIB) domain and an adjacent polybasic region for maximal targeting efficiency. We find PAK6 localization to cell-cell adhesions is Cdc42-dependent, as Cdc42 knockdown inhibits PAK6 targeting to cell-cell adhesions. We further find the ability of PAK6 to drive epithelial cell colony escape requires kinase activity and is disrupted by mutations that perturb PAK6 cell-cell adhesion targeting. Finally, we demonstrate that all type II PAKs (PAK4, PAK5 and PAK6) target to cell-cell adhesions, albeit to differing extents, but PAK1 (a type I PAK) does not. Notably, the ability of a PAK isoform to drive epithelial colony escape correlates with its targeting to cell-cell adhesions. We conclude that PAKs have a broader role in the regulation of cell-cell adhesions than previously appreciated.
Wnt/β-catenin and LIF/Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal
Authors: Ye Shoudong , Zhang Dongming , Cheng Fei , Wilson Daniel , Mackay Jeffrey , He Kan , Ban Qian , Lv Feng , Huang Saifei , Liu Dahai , Ying Qi-Long
Published: November 2015

Activation of leukemia inhibitor factor (LIF)/Stat3 or Wnt/β-catenin signaling promotes mouse embryonic stem cell (mESC) self-renewal. A myriad of downstream targets have been identified in the individual signal pathway, but their common targets remain largely elusive. In this study, we found that the LIF/Stat3 and Wnt/β-catenin signaling pathways converge on Sp5 to promote mESC self-renewal. Forced Sp5 expression can reproduce partial effects of Wnt/β-catenin signaling but mimics most features of LIF/Stat3 signaling to maintain undifferentiated mESCs. Moreover, Sp5 is able to convert mouse epiblast stem cells to a naïve pluripotent state. Thus, Sp5 is an important component of the regulatory network governing mESC naïve pluripotency.
CULD is required for rhodopsin and TRPL channel endocytic trafficking and survival of photoreceptor cells
Authors: Xu Ying , Wang Tao
Published: November 2015

Endocytosis of G-protein-coupled receptors (GPCRs) and associated channels contributes to desensitization and adaptation of a variety of signaling cascades. In Drosophila, the major light sensing rhodopsin, Rh1, and the downstream ion channel, Transient Receptor Potential Like (TRPL), are endocytosed in response to light, but the mechanism is unclear. Using an RNA-Sequencing approach, we discovered CULD, a photoreceptor-cell enriched CUB- and LDLa-domain transmembrane protein that is required for endocytic trafficking of Rh1 and TRPL. CULD localized to endocytic Rh1- or TRPL-positive vesicles. Mutations in culd resulted in the accumulation of Rh1 and TRPL within endocytic vesicles, and disrupted the regular turnover of endocytic Rh1 and TRPL. In addition, loss of CULD induced light- and age-dependent retinal degeneration, and reduced levels of Rh1 but not TRPL suppressed retinal degeneration in culd null mutant flies. These data demonstrate that CULD plays an important role in the endocytic turnover of Rh1 and TRPL, and suggest that CULD-dependent rhodopsin endocytic trafficking is required for maintaining photoreceptor integrity.
VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling
Authors: Benn Andreas , Bredow Clara , Casanova Isabel , Vukičević Slobodan , Knaus Petra
Published: November 2015

Several vascular disorders, such as aberrant angiogenesis, atherosclerosis and pulmonary hypertension, have been linked to dysfunctional BMP signaling. Vascular hyperpermeability via distortion of endothelial cell adherens junctions is a common feature of these diseases, but the role of BMPs in this process has not been investigated. BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell–cell contacts, thereby modulating vascular permeability. Here we demonstrate that BMP6 induces hyperpermeabilization of human endothelial cells by inducing internalization and c-Src-dependent phosphorylation of VE-cadherin. Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. Our results provide first insights into the molecular mechanism of BMP-induced vascular permeability, a hallmark of various vascular diseases, and provide the basis for further investigations of BMPs as regulators of vascular integrity, both under physiological and pathophysiological conditions.
Menthol-induced bleaching rapidly and effectively provides experimental aposymbiotic sea anemones (Aiptasiasp.) for symbiosis investigations
Authors: Matthews Jennifer L. , Sproles Ashley E. , Oakley Clinton A. , Grossman Arthur R. , Weis Virginia M. , Davy Simon K.
Published: November 2015

Experimental manipulation of the symbiosis between cnidarians and photosynthetic dinoflagellates (Symbiodinium spp.) is critical to advance understanding of the cellular mechanisms involved in host–symbiont interactions, and overall coral reef ecology. The anemone Aiptasia sp. is a model for the cnidarian-dinoflagellate symbiosis, and notably it can be rendered aposymbiotic (i.e. dinoflagellate-free) and re-infected with a range of Symbiodinium types. Various methods exist for generating aposymbiotic hosts, however they can be hugely time-consuming and not wholly effective. Here, we optimise a method using menthol for production of aposymbiotic Aiptasia. The menthol treatment produced aposymbiotic hosts within just four weeks (97–100% symbiont loss), which was maintained long after treatment when anemones were held under a standard light/dark cycle. The ability of Aiptasia to form a stable symbiosis appeared unaffected by menthol exposure, as demonstrated by successful symbiosis re-establishment when experimentally re-infected. Furthermore, there was no significant impact on photosynthetic or respiratory performance of re-infected anemones.
Big brown bats (Eptesicus fuscus) emit intense search calls and fly in stereotyped flight paths as they forage in the wild
Authors: Hulgard Katrine , Moss Cynthia F. , Jakobsen Lasse , Surlykke Annemarie
Published: November 2015

The big brown bat, Eptesicus fuscus, uses echolocation for orientation and foraging, and scans its surroundings by aiming its sonar beam at obstacles and prey. All call parameters are highly adaptable and determine the bat's acoustic field of view and hence its perception of the echo scene. The intensity (source level) and directionality of the emitted calls directly contribute to the bat's acoustic field of view; however, the source level and directionality of the big brown bat's sonar signals have not been measured in the field. In addition, for bats, navigation and prey capture require that they process several streams of acoustic information. By using stereotypic flight paths in known areas, bats may be able to reduce the sensory processing load for orientation and therefore allocate echo processing resources to prey. Here we recorded the echolocation calls from foraging E. fuscus, in the field with a microphone array and estimated call intensity and directionality, based on reconstructed flight trajectories. The source levels were intense with an average max SL of 138 dB (rms re 20 µPa at 0.1 m.). Further, measurements taken from a subset of calls indicate that the echolocation signals in the field may be more directional than estimated in the lab (half amplitude angle=30° at 35 kHz). We also observed that E. fuscus appear to follow stereotypic flight paths, and propose that this could be a strategy to optimize foraging efficiency by minimizing the sensory processing load