bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the Eda Pathway on Tooth Root Development
Authors: Fons Romero J.M. , Star H. , Lav R. , Watkins S. , Harrison M. , Hovorakova M. , Headon D. , Tucker A.S.
Published: August 2017

The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig’s epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.
Workplace Bullying and Turnover Intention: Exploring Work Engagement as a Potential Mediator
Authors: Coetzee Melinde , van Dyk Jeannette
Published: August 2017

Employees’ turnover intentions may entail expensive consequences for companies. The study examined the mediating effect of work engagement in the relationship between workplace bullying and turnover intention. Using a cross-sectional sample of 373 employees, structural equation modeling and mediation analysis showed that perceptions of work- and person-related bullying were linked to low levels of vigor and dedication which in turn were associated with high turnover intention. Work engagement partially mediated the effect of high workplace bullying on high turnover intention. The results were interpreted from a social cognitive perspective and recommendations for practice were made.
Takes Two to Tango: Essential Practices of Highly Effective Transfer Partnerships
Authors: Fink John , Jenkins Davis
Published: August 2017

Objective: The objective of this study was to describe practices of 2- and 4-year institutional partnerships effective in supporting transfer student success. Method: Using student records from the National Student Clearinghouse (NSC) for the entire 2007 fall cohort of first-time-in-college community college students nationwide, researchers identified partnerships of 2- and 4-year institutions that were more effective than expected (controlling for student and institutional characteristics) in enabling community college entrants to transfer to a 4-year institution and earn a bachelor’s degree. Based on this methodology, and in partnership with the Aspen Institute’s College Excellence Program, researchers visited six pairs of 2- and 4-year college transfer partnerships identified as high performers, interviewing more than 350 faculty, student-facing and senior-level staff, and transfer students. Results: From these in-depth interviews, researchers identified a set of essential transfer practices common among these highly effective institutional partnerships. The practices were grouped under three broad strategies: (a) make transfer a priority, (b) create clear programmatic pathways with aligned high-quality instruction, and (c) provide tailored transfer advising. Contributions: This study offers a set of essential transfer practices culled from national fieldwork to 2- and 4-year institutional transfer partnerships identified using NSC data as highly effective in supporting transfer student success.
Feline Herpesvirus Pneumonia: Investigations Into the Pathogenesis
Authors: Monne Rodriguez Josep Maria , Leeming Gail , Köhler Kernt , Kipar Anja
Published: August 2017

Feline herpesvirus type 1 (FeHV-1) is one of the etiological agents of feline respiratory disease. FeHV-1 is an epitheliotropic and cytopathic virus that mainly causes rhinitis and conjunctivitis, although pneumonia is also occasionally seen. In this study, the authors investigated the pathogenesis of FeHV-1-associated pneumonia, comparing natural cases with viral infection of tracheal ring and cell cultures in vitro, using histology, immunohistology, double immunofluorescence, and transmission electron microscopy as investigative tools. The results confirm that FeHV-1 targets both respiratory epithelial cells and pneumocytes and indicate that FeHV-1 pneumonia is the consequence of continuous cell-to-cell viral spread from the upper airways via the trachea into the lungs. They provide strong evidence that FeHV-1–infected cells die primarily via apoptosis, following loss of cell-to-cell contact, rounding, and detachment. However, virus-induced lesions in vivo are dominated by marked neutrophil infiltration and extensive necrosis with less prominent apoptosis; in the airways, the tissue necrosis can extend into the submucosa. The necrosis appears to result from virus-induced neutrophil influx and release of proteolytic enzymes, such as matrix metalloproteinase-9, from the neutrophils.
Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs
Authors: Ford Jordan , McEndaffer Laura , Renshaw Randall , Molesan Alex , Kelly Kathleen
Published: August 2017

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%–45%) and 2 of 41 controls (5%; 95% CI, 0.1%–16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.
Dietary Supplements Commonly Used by Cancer Survivors: Are There Any Benefits?
Authors: Marian Mary J.
Published: August 2017

Following a cancer diagnosis, dietary supplements are reportedly used by 20%–80% of individuals. Supplements are most commonly used by breast cancer survivors, followed by patients with prostate, colorectal, and lung cancers, which is not surprising since these are the most common types of cancer diagnosed in adults. Reasons cited for such use include improving quality of life, reducing symptoms related to treatment and/or the disease process, and recommendation from medical practitioners; family and friends may also be an influence. However, controversy surrounds the use of dietary supplements, particularly during treatment—specifically, whether supplements affect treatment efficacy is unknown. This article discusses the evidence related to common dietary supplements used to prevent cancer or a recurrence.
Nurse researchers’ perspectives on research ethics in China
Authors: Gu Can , Ye Man , Wang Xiaomin , Yang Min , Wang Honghong , Khoshnood Kaveh
Published: August 2017

Background:

In China, research ethics is a subject of increasingly formal regulation. However, little is known about how nursing researchers understand the concept of research ethics and the ways in which they can maintain ethical standards in their work.

Aim:

The aim of this study is to examine nursing researchers’ perspectives on research ethics in China.

Research design:

We conducted a descriptive qualitative study. Qualitative research methods enabled us to gain an in-depth understanding of nursing researchers’ views on research ethics.

Participants and research context:

We carefully selected and extensively interviewed 28 nursing researchers, nursing faculty, and clinical nurses who had been involved in research or who may undertake research in the future. We collected data between October 2014 and March 2015.

Ethical considerations:

This study was approved by the institutional review boards of Yale University and Central South University.

Findings:

We grouped the data into five categories based on the interviewees’ responses: (1) perceptions of ethics, bioethics, and research ethics; (2) perception of the ethics review process; (3) perception of the function of institutional review boards; (4) the need for comprehensive ethical guidelines for future studies; and (5) ethical challenges faced by the interviewees.

Discussion and conclusion:

This study contributes new insights into nursing researchers’ views on research ethics in China and finds considerable shortcomings in researchers’ understanding and implementation of ethical principles. Intensive educational efforts are needed to provide nursing researchers, institutional review board members, and even study subjects with accurate and up-to-date information and guidance on research ethics. In addition, while Western research ethics theoretically have guided Chinese clinical research for several years, the ways in which nursing researchers have implemented these ethical standards highlight the differences between the Eastern and Western ethical paradigms. This finding suggests the need for ethical standards that are more tailored to the Chinese context.
Handmaidens of History? Exploring English, Hindi and Sanskrit Textbooks for Schools
Authors: Roy Kumkum
Published: August 2017

The article explores the ways in which concerns of history, in terms of content, concepts and methodology, find space or do not find space within textbooks used for teaching languages. These may be more important as sites of ‘knowledge’ than social science books, because the latter are often regarded as insignificant within the formal schooling system.

 How are great men (and women) constructed? What are regarded as ‘suitable’ examples of historical achievements? How is change understood and explained? Are there spaces for escaping from a normative, increasingly homogeneous and homogenised understanding of the past dominated by the preoccupations of a visible, majoritarian middle class? These are some of the questions raised.
Evolution of accounting education in Italy, 1890–1935
Authors: Lazzini Arianna , Iacoviello Giuseppina , Ferraris Franceschi Rosella
Published: August 2017

This article focuses on the development of the study of accounting in the Italian education system between the nineteenth and twentieth centuries. It also focuses on the subsequent formation of a scientific and experimental forma mentis that would prepare students for administrative and managerial activities in industry, commerce and public administration. Starting from the second half of the nineteenth century – when the presence of accounting in education was limited to secondary school and implemented with sporadic educational initiatives by private bodies – and covering approximately the 50 years after the unification of Italy, this study analyses, through the lens of Foucault’s power–knowledge relationship, the institutional and structural measures adopted by the State to develop the study of accounting in Italy, in the period 1890–1935.
The Process of Primary Desistance From Intimate Partner Violence
Authors: Walker Kate , Bowen Erica , Brown Sarah , Sleath Emma
Published: August 2017

This study examined the interaction between structure and agency for individuals in the first or early phase of primary desistance (1 year offending free) from intimate partner violence (IPV). Narrative accounts of perpetrators, survivors, and IPV program facilitators were analyzed using Thematic Analysis. Changes in the self and the contexts, structures, and conditions were necessary to promote desistance. Perpetrators made behavioral and cognitive changes taking on different identities (agentic role) by removing external stressors and instability within the confines of a supportive environment (structural role). Findings provide a theoretical framework of desistance from IPV that integrates social processes and subjective change.
Evaluating Structural Change Approaches to Health Promotion: An Exploratory Scoping Review of a Decade of U.S. Progress
Authors: Asada Yuka , Lieberman Lisa D. , Neubauer Leah C. , Hanneke Rosie , Fagen Michael C.
Published: August 2017

Structural change approaches—also known as policy and environmental changes—are becoming increasingly common in health promotion, yet our understanding of how to evaluate them is still limited. An exploratory scoping review of the literature was conducted to understand approaches and methods used to evaluate structural change interventions in health promotion and public health literature. Two analysts—along with health sciences librarian consultation—searched PubMed, Web of Science, and EMBASE for peer-reviewed U.S.-based, English language studies published between 2005 and 2016. Data were extracted on the use of evaluation frameworks, study designs, duration of evaluations, measurement levels, and measurement types. Forty-five articles were included for the review. Notably, the majority (73%) of studies did not report application of a specific evaluation framework. Studies used a wide range of designs, including process evaluations, quasi- or nonexperimental designs, and purely descriptive approaches. In addition, 15.6% of studies only measured outcomes at the individual level. Last, 60% of studies combined more than one measurement type (e.g., site observation + focus groups) to evaluate interventions. Future directions for evaluating structural change approaches to health promotion include more widespread use and reporting of evaluation frameworks, developing validated tools that measure structural change, and shifting the focus to health-directed approaches, including an expanded consideration for evaluation designs that address health inequities.
Florid Intussusceptive-like Microvascular Dysangiogenesis in a Preterm Lung
Authors: De Paepe Monique E , V Benny Merline Kocheekkaran , Priolo Lauren , Luks Francois I , Shapiro Svetlana
Published: August 2017

The cellular mechanisms underlying the microvascular dysangiogenesis of bronchopulmonary dysplasia (chronic lung disease of the newborn) remain largely undetermined. We report unusual pulmonary vascular findings in a 27-week-gestation male newborn who died on the second day of life from intractable respiratory failure, following a pregnancy complicated by prolonged membrane rupture and persistent severe oligohydramnios. As expected, postmortem examination revealed pulmonary hypoplasia (lung/body weight ratio: 2.23%; 10th percentile for 27 weeks: 2.59%). In addition, lung microscopy revealed complex networks of non-sprouting, tortuous, and bulbously dilated capillaries, randomly distributed in widened airspace septa. Anti-smooth muscle actin immunohistochemistry demonstrated immunoreactive central densities within capillary lumina, suggestive of intravascular pillar formation. The plexus-forming, non-sprouting type of angiogenesis and apparent transluminal pillar formation are consistent with intussusceptive (“longitudinal splitting”) angiogenesis. In concordance with previous observations made in human fetal lung xenografts, these findings support the notion that human postcanalicular lungs have the capacity to switch from sprouting to non-sprouting, intussusceptive-like angiogenesis, possibly representing an adaptive response activated by hemodynamic flow alterations and/or hypoxia. The possible relationship between the intussusceptive-like vascular changes observed in this case and the microvascular dysangiogenesis characteristic of bronchopulmonary dysplasia remains to be determined.
Soft Tissue Perineurioma in a Child With Neurofibromatosis Type 1
Authors: Al-Adnani Mudher
Published: August 2017

Soft tissue perineurioma is a rare benign peripheral nerve sheath tumor, especially in children. This manuscript presents an unusual case of soft tissue perineurioma in a 10-year-old boy with neurofibromatosis type 1. The patient presented with a lump in the region of the right breast. A subcutaneous, well circumscribed mass was removed. The cut surface was cream with a vaguely nodular appearance. Histology showed a spindle cell lesion with variable architecture and biphasic morphology. There was no nuclear atypia or pleomorphism. The differential diagnosis and other soft tissue lesions that can be seen in neurofibromatosis type 1 are discussed.
Morton ordering of 2D arrays for efficient access to hierarchical memory
Authors: Walker David W
Published: August 2017

This article investigates the recursive Morton ordering of two-dimensional arrays as an efficient way to access hierarchical memory across a range of heterogeneous computer platforms, ranging from manycore devices, multicore processors, clusters and distributed environments. A brief overview of previous research in this area is given, and algorithms that make use of Morton ordering are described. These are then used to investigate the efficiency of the Morton ordering approach by performance experiments on different processors. In particular, timing results are presented for matrix multiplication, Cholesky factorization and fast Fourier transform algorithms. The use of the Morton ordering approach leads naturally to algorithms that are recursive and exposes parallelism at each level of recursion. Thus, the approach advocated in this talk not only provides convenient and efficient access to hierarchical memory but also provides a basis for exploiting parallelism.
The Ancient Walls of Damascus and the Siege of Mouaddamiyya: A Historical and Spatial Analysis of Bounded Place and Cultural Identity
Authors: Halabi Nour
Published: August 2017

Throughout the Syrian crisis, the presence of material and symbolic boundaries to culture became a particularly salient element of the continuously unfolding political turmoil. As one terrorist group, Daesh, or the Islamic State of Iraq and Syria, seeks to unite the vast area of the Middle East under the political, religious, and cultural administration of a “Greater State of Syria,” or “al-Sham,” this article revisits the historical spatial organization of Damascus and the construction of city boundaries and walls as factors that contributed to the cultivation of spatially grounded cleavages within Syrian and Damascene identity. In the latter section of this article, I reflect on the impact of these cleavages on the Syrian crisis by focusing on the public response to the siege of the Mouaddamiyya neighborhood.
Acceptability of a vocational advice service for patients consulting in primary care with musculoskeletal pain: A qualitative exploration of the experiences of general practitioners, vocational advisers and patients
Authors: Sanders Tom , Wynne-Jones Gwenllian , Nio Ong Bie , Artus Majid , Foster Nadine
Published: August 2017

Aims: Using qualitative interviews, this study explored the experiences of GPs, vocational advisers and patients towards a new vocational advice (VA) service in primary care. Methods: This study was nested within the Study of Work and Pain (SWAP) cluster randomised controlled trial. The SWAP trial located a VA service within three general practices in Staffordshire. Interviews took place with 10 GPs 12 months after the introduction of the VA service, four vocational advisers whilst the VA service was running and 20 patients on discharge from the VA service. The data were analysed using the constant comparative method, which is a variation of grounded theory. Results: The key factors determining the acceptability and perceived effectiveness of the VA service from the perspective of the three groups of stakeholders were (1) the timing of referrals to the VA, (2) the perceived lack of patient demand for the service and (3) role uncertainty experienced by VAs. Conclusions: Early vocational intervention may not be appropriate for all musculoskeletal patients with work difficulties. Indeed, many patients felt they did not require the support of a VA, either because they had self-limiting work difficulties and/or already had support mechanisms in place to return to work. Future VA interventions may be better implemented in a targeted way so that appropriate patients are identified with characteristics which can best be addressed by the VA service.
Rawls and racial justice
Authors: Matthew DC
Published: August 2017

This article discusses the adequacy of Rawls’ theory of justice as a tool for racial justice. It is argued that critics like Charles W Mills fail to appreciate both the insights and limits of the Rawlsian framework. The article has two main parts spread out over several different sections. The first is concerned with whether the Rawlsian framework suffices to prevent racial injustice. It is argued that there are reasons to doubt whether it does. The second part is concerned with whether a Rawlsian framework has the resources to rectify past racial injustice. It is argued that it has more resources to do this than Mills allows. This second part of the article centers on two Rawlsian ideas: ideal theory and the fair equality of opportunity (FEO) principle. It is argued that ideal theory is essential for the kind of rectificatory work that Mills wants nonideal theory to do, and that where there is a socioeconomic legacy of past injustice, it is hard to see how FEO could be implemented if it did no rectificatory work, a result which means that there is less need to turn to nonideal theory at all.
Inversion of magnetic fields inside pipelines: Modeling, validations, and applications
Authors: Xinjing Huang , Guanren Chen , Yu Zhang , Jian Li , Tianshu Xu , Shili Chen
Published: August 2017

Spherical detector is a novel and promising approach for pipeline inspections with high signal-to-noise ratio and low risk of blockage. As the magnetic signals are recorded in a rotating frame by the rolling spherical detector, it is difficult to directly deploy the raw periodic signals for magnetic inspections, such as pipeline orientation calculations and the identifications of girth welds, turning points, and other pipe features. Against this backdrop, a magnetic inversion approach for transforming the measured magnetic signals from the rotating sensor frame into the stationary pipe frame is developed and demonstrated both analytically and experimentally. By comparing the transformed values with that measured by a sensor moving on a straight route, the inversion approach is proven to hold for an arbitrary fixed rotation axis, with the average and maximum errors mostly less than 1 and 2 µT, respectively. Field experiments demonstrate that the magnetic inversion can expose and enhance hidden or imperceptible magnetic anomalies and pipeline turning points and improve pipeline route calculation accuracy via secondary alignments. The results will promote the spherical detector to play a greater role in pipeline inspections.
Peaks Over Threshold–based detector design for structural health monitoring: Application to aerospace structures
Authors: Rébillat Marc , Hmad Ouadie , Kadri Farid , Mechbal Nazih
Published: August 2017

Structural health monitoring offers new approaches to interrogate the integrity of complex structures. The structural health monitoring process classically relies on four sequential steps: damage detection, localization, classification, and quantification. The most critical step of such process is the damage detection step since it is the first one and because performances of the following steps depend on it. A common method to design such a detector consists of relying on a statistical characterization of the damage indexes available in the healthy behavior of the structure. On the basis of this information, a decision threshold can then be computed in order to achieve a desired probability of false alarm. To determine the decision threshold corresponding to such desired probability of false alarm, the approach considered here is based on a model of the tail of the damage indexes distribution built using the Peaks Over Threshold method extracted from the extreme value theory. This approach of tail distribution estimation is interesting since it is not necessary to know the whole distribution of the damage indexes to develop a detector, but only its tail. This methodology is applied here in the context of a composite aircraft nacelle (where desired probability of false alarm is typically between 10−4 and 10−9) for different configurations of learning sample size and probability of false alarm and is compared to a more classical one which consists of modeling the entire damage indexes distribution by means of Parzen windows. Results show that given a set of data in the healthy state, the effective probability of false alarm obtained using the Peaks Over Threshold method is closer to the desired probability of false alarm than the one obtained using the Parzen-window method, which appears to be more conservative.
Treatment strategies for autoimmune encephalitis
Authors: Shin Yong-Won , Lee Soon-Tae , Park Kyung-Il , Jung Keun-Hwa , Jung Ki-Young , Lee Sang Kun , Chu Kon
Published: August 2017

Autoimmune encephalitis is one of the most rapidly growing research topics in neurology. Along with discoveries of novel antibodies associated with the disease, clinical experience and outcomes with diverse immunotherapeutic agents in the treatment of autoimmune encephalitis are accumulating. Retrospective observations indicate that early aggressive treatment is associated with better functional outcomes and fewer relapses. Immune response to first-line immunotherapeutic agents (corticosteroids, intravenous immunoglobulin, plasma exchange, and immunoadsorption) is fair, but approximately half or more of patients are administered second-line immunotherapy (rituximab and cyclophosphamide). A small but significant proportion of patients are refractory to all first- and second-line therapies and require further treatment. Although several investigations have shown promising alternatives, the low absolute number of patients involved necessitates more evidence to establish further treatment strategies. In this review, the agents used for first- and second-line immunotherapy are discussed and recent attempts at finding new treatment options are introduced.
The Neural Correlates of Cognitive Objectification
Authors: Bernard Philippe , Rizzo Tiziana , Hoonhorst Ingrid , Deliens Gaétane , Gervais Sarah J. , Eberlen Julia , Bayard Clémence , Deltenre Paul , Colin Cécile , Klein Olivier
Published: August 2017

At an early stage of visual processing, human faces and bodies are typically associated with larger N170s when presented in an inverted (vs. upright) position, indexing the involvement of configural processing. We challenged this view and hypothesized that sexualized bodies would not be sensitive to inversion, thereby suggesting that they would be processed similarly to objects. Participants saw sexualized male and female bodies, nonsexualized male and female bodies, as well as objects in both upright and inverted positions while we recorded the N170. Results indicated that inverted (vs. upright) nonsexualized male and female bodies were associated with larger N170 amplitudes. In contrast, no N170 amplitude inversion effect emerged for sexualized male and female bodies or objects. These results suggest that sexualized bodies are processed similarly to objects and quite differently than nonsexualized bodies. We discuss the results and their implications in the light of the literatures in person perception and objectification.
Kardiovize Brno 2030, a prospective cardiovascular health study in Central Europe: Methods, baseline findings and future directions
Authors: Movsisyan Narine K , Vinciguerra Manlio , Lopez-Jimenez Francisco , Kunzová Šárka , Homolka Martin , Jaresova Jana , Cífková Renata , Sochor Ondřej
Published: August 2017

Background

Atherosclerotic cardiovascular disease is highly prevalent in Eastern and Central Europe, where the incidence is the highest in the world. The Kardiovize Brno 2030 study was designed as a prospective cohort study to investigate the complex relationships of cardiovascular disease and outcomes with a range of biological, psychosocial, environmental, behavioral, and economic factors in an urban population of the Czech Republic.

Methods

We randomly selected a 1% sample of the city of Brno residents aged 25–64 years stratified by sex and age. The study assessed traditional and novel cardiovascular disease risk factors, including sociodemographic and smoking status, physical activity, diet, depression, stress, body fat, cardio-ankle vascular index, and intima media thickness, complemented by blood tests; biological samples were stored for future analyses.

Results

The study enrolled 2160 participants (54.8% women), with a mean age of 47 ± 11.3 years. They were mostly full-time employed (75.6%) and married (62.1%). Hyperlipidemia was highly prevalent (70.7% in men, and 67.1% in women, NS). Hypertension and diabetes mellitus were more prevalent in men than in women (54.3% vs. 38.7% and 7.1% vs. 3.5%, respectively, P < 0.001 for both). A total of 25.3% of men and 21.9% of women smoked, whereas 20.0% and 43.0% of men and 18.1% and 26.6% of women were obese and overweight, respectively.

Conclusions

Cardiovascular risk factors are highly prevalent in the city of Brno, an urban population from Central Europe. The Kardiovize Brno 2030 study will provide unique multidimensional and longitudinal cardiovascular health data from a region where epidemiological studies are scarce.
Measuring the impact of multiple sclerosis: Enhancing the measurement performance of the Multiple Sclerosis Impact Scale (MSIS-29) using Rasch Measurement Theory (RMT)
Authors: Cleanthous Sophie , Cano Stefan , Kinter Elizabeth , Marquis Patrick , Petrillo Jennifer , You Xiaojun , Wakeford Craig , Sabatella Guido
Published: August 2017

Background

Study objectives were to evaluate the Multiple Sclerosis Impact Scale (MSIS-29) and explore an optimized scoring structure based on empirical post-hoc analyses of data from the Phase III ADVANCE clinical trial.

Methods

ADVANCE MSIS-29 data from six time-points were analyzed in a sample of patients with relapsing–remitting multiple sclerosis (RRMS). Rasch Measurement Theory (RMT) analysis was undertaken to examine three broad areas: sample-to-scale targeting, measurement scale properties, and sample measurement validity. Interpretation of results led to an alternative MSIS-29 scoring structure, further evaluated alongside responsiveness of the original and revised scales at Week 48.

Results

RMT analysis provided mixed evidence for Physical and Psychological Impact scales that were sub-optimally targeted at the lower functioning end of the scales. Their conceptual basis could also stand to improve based on item fit results. The revised MSIS-29 rescored scales improved but did not resolve the measurement scale properties and targeting of the MSIS-29. In two out of three revised scales, responsiveness analysis indicated strengthened ability to detect change.

Conclusion

The revised MSIS-29 provides an initial evidence-based improved patient-reported outcome (PRO) instrument for evaluating the impact of MS. Revised scoring improves conceptual clarity and interpretation of scores by refining scale structure to include Symptoms, Psychological Impact, and General Limitations.

Clinical trial

ADVANCE (ClinicalTrials.gov identifier NCT00906399).
Pigmentary Maculopathy as the Presenting Sign of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome
Authors: Schechet Sid A. , Sheyman Alan T.
Published: August 2017

We report a case of an asymptomatic 40-year-old African American male who was referred to our clinic for evaluation of bilateral macular drusen. Medical history was remarkable only for diabetes mellitus type 1. Fundoscopy revealed a peculiar, bilateral pigmentary maculopathy. Further imaging included autofluorescence imaging that showed an irregular hypo- and hyperautofluorescent pattern consistent with severe retinal pigment epithelial (RPE) dysfunction. Optical coherence tomography supported outer retinal layer loss and RPE atrophy. Fluorescein angiography and electroretinography were also performed. Further discussion with the patient yielded a family history where 4 older siblings died in their teenage years from strokes and seizures. The patient was referred to a geneticist who ultimately diagnosed him with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, and genetic testing of his mitochondrial deoxyribonucleic acid identified an A3234G point mutation in the MT-TL1 gene.
Role of anthracycline and comprehensive geriatric assessment for elderly patients with diffuse large B-cell lymphoma
Authors: Lin Richard J. , Behera Madhusmita , Diefenbach Catherine S. , Flowers Christopher R.
Published: August 2017

Survival outcome for elderly patients with newly diagnosed diffuse large B-cell lymphoma remains suboptimal in the rituximab era. In this systematic review, we summarize available evidence relevant to the inclusion of anthracycline in upfront chemoimmunotherapy for these elderly patients and highlight the need of prospective clinical trials. With limited prospective data, we find that pretreatment comprehensive geriatric assessment accurately predicts survival and treatment-related toxicities, suggesting its potential role in guiding overall treatment decision-making.
Replication and validation of genetic polymorphisms associated with survival after allogeneic blood or marrow transplant
Authors: Karaesmen Ezgi , Rizvi Abbas A. , Preus Leah M. , McCarthy Philip L. , Pasquini Marcelo C. , Onel Kenan , Zhu Xiaochun , Spellman Stephen , Haiman Christopher A. , Stram Daniel O. , Pooler Loreall , Sheng Xin , Zhu Qianqian , Yan Li , Liu Qian , Hu Qiang , Webb Amy , Brock Guy , Clay-Gilmour Alyssa I. , Battaglia Sebastiano , Tritchler David , Liu Song , Hahn Theresa , Sucheston-Campbell Lara E.
Published: August 2017

Key Points

Candidate SNP associations with survival outcomes after URD transplant are most likely false-positive findings. Over 85% of candidate SNPs are not linked to a biochemical function; of those that are, about half are not linked to the candidate gene.
Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer
Authors: Gainor Justin F. , Tseng Diane , Yoda Satoshi , Dagogo-Jack Ibiayi , Friboulet Luc , Lin Jessica J. , Hubbeling Harper G. , Dardaei Leila , Farago Anna F. , Schultz Katherine R. , Ferris Lorin A. , Piotrowska Zofia , Hardwick James , Huang Donghui , Mino-Kenudson Mari , Iafrate A. John , Hata Aaron N. , Yeap Beow Y. , Shaw Alice T.
Published: August 2017

Purpose

The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements in 1% to 2% of non–small-cell lung cancers (NSCLCs), which confer sensitivity to treatment with the anaplastic lymphoma kinase (ALK)/ROS1/mesenchymal-epithelial transition factor inhibitor crizotinib. Currently, insights into patterns of metastatic spread and mechanisms of crizotinib resistance among patients with ROS1-positive disease are limited.

Patients and Methods

We reviewed clinical and radiographic imaging data of patients with ROS1- and ALK-positive NSCLC to compare patterns of metastatic spread at initial metastatic diagnosis. To determine molecular mechanisms of crizotinib resistance, we analyzed repeat biopsy specimens from a cohort of patients with ROS1-positive disease who progressed on crizotinib.

Results

We identified 39 and 196 patients with advanced ROS1- and ALK-positive NSCLC, respectively. Patients with ROS1-positive disease had significantly lower rates of extrathoracic metastases ( ROS1, 59.0%; ALK, 83.2%; P = .002), including lower rates of brain metastases ( ROS1, 19.4%; ALK, 39.1%; P = .033), at initial metastatic diagnosis. Despite similar overall survival between patients with ALK- and ROS1-positive NSCLC treated with crizotinib (median, 3.0 v 2.5 years, respectively; P = .786), patients with ROS1-positive NSCLC also had a significantly lower cumulative incidence of brain metastases (34% v 73% at 5 years; P < .001). In addition, we identified 16 patients who underwent a total of 17 repeat biopsies after progression on crizotinib. ROS1 resistance mutations were identified in 53% of specimens, including nine (64%) of 14 non–brain metastasis specimens. ROS1 mutations included G2032R (41%), D2033N (6%), and S1986F (6%).

Conclusion

Compared with ALK rearrangements, ROS1 rearrangements are associated with lower rates of extrathoracic metastases, including fewer brain metastases, at initial metastatic diagnosis. ROS1 resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, which underscores the need to develop novel ROS1 inhibitors with activity against these resistant mutants.
A Literary Remittance: Juan C. Laya’sHis Native Soiland the Rise of Realism in the Filipino Novel in English
Authors: Nadal Paul
Published: August 2017

This essay recovers a once celebrated but now forgotten Filipino novel in English, Juan Cabreros Laya’s His Native Soil (1941), which marked the emergence of realism during the Philippine Commonwealth’s slow, decade-long transition to independence from the United States. Whereas the novel was originally praised as a landmark text in Philippine literature in English, His Native Soil was later dismissed by postwar critics as an imitative, formally flawed, and stylistically inferior work. Taking up Roberto Schwarz’s challenge to advance a reading practice that takes into account the difference between literature and social structure in the colonial periphery, I argue that rather than viewing His Native Soil’s improbabilities of plot and tonal dissonances as artistic flaws, they are more meaningfully read as the author’s attempt to adapt the realist protocols of the bildungsroman to capture the double-edged nature of independence: the adoption of a trade policy that would economically bind together the Philippines and the United States and that would render political freedom impossible for Filipinos unless relations of colonial dependency were to be continued after independence.
Agentive Modals
Authors: Mandelkern Matthew , Schultheis Ginger , Boylan David
Published: August 2017

This essay proposes a new theory of agentive modals: ability modals and their duals, compulsion modals. After criticizing existing approaches—the existential quantificational analysis, the universal quantificational analysis, and the conditional analysis—it presents a new account that builds on both the existential and conditional analyses. On this account, the act conditional analysis, a sentence like ‘John can swim across the river’ says that there is some practically available action (in a sense the essay makes precise) that is such that if John tries to do it, he swims across the river. The essay argues that the act conditional analysis avoids the problems faced by existing accounts of agentive modality and shows how the act conditional analysis can be extended to an account of generic agentive modal claims. The upshot is a new vantage point on the role of agentive modal ascriptions in practical discourse: ability ascriptions serve as a kind of hypothetical guarantee, and compulsion ascriptions as a kind of nonhypothetical guarantee.
Tail regeneration and other phenomena of wound healing and tissue restoration in lizards
Authors: Jacyniak Kathy , McDonald Rebecca P. , Vickaryous Matthew K.
Published: August 2017

Wound healing is a fundamental evolutionary adaptation with two possible outcomes: scar formation or reparative regeneration. Scars participate in re-forming the barrier with the external environment and restoring homeostasis to injured tissues, but are well understood to represent dysfunctional replacements. In contrast, reparative regeneration is a tissue-specific program that near-perfectly replicates that which was lost or damaged. Although regeneration is best known from salamanders (including newts and axolotls) and zebrafish, it is unexpectedly widespread among vertebrates. For example, mice and humans can replace their digit tips, while many lizards can spontaneously regenerate almost their entire tail. Whereas the phenomenon of lizard tail regeneration has long been recognized, many details of this process remain poorly understood. All of this is beginning to change. This Review provides a comparative perspective on mechanisms of wound healing and regeneration, with a focus on lizards as an emerging model. Not only are lizards able to regrow cartilage and the spinal cord following tail loss, some species can also regenerate tissues after full-thickness skin wounds to the body, transections of the optic nerve and even lesions to parts of the brain. Current investigations are advancing our understanding of the biological requirements for successful tissue and organ repair, with obvious implications for biomedical sciences and regenerative medicine.
A survey of working conditions within biomedical research in the United Kingdom
Authors: Riddiford Nick
Published: August 2017

Background: Recent articles have presented a bleak view of career prospects in biomedical research in the US. Too many PhDs and postdocs are trained for too few research positions, creating a “holding-tank” of experienced senior postdocs who are unable to get a permanent position. Coupled with relatively low salaries and high levels of pressure to publish in top-tier academic journals, this has created a toxic environment that is perhaps responsible for a recently observed decline in biomedical postdocs in the US, the so-called “postdocalypse”.

Methods: To address the gulf of information relating to working habits and attitudes of UK-based academic biomedical researchers, a link to an online survey was included in an article published in the Guardian newspaper. Survey data were collected between 21st March 2016 and 6th November 2016 and analysed to examine discrete profiles for three major career stages: PhD, postdoc and principal investigator.

Results: Overall, the data presented here echo trends observed in the US: The 520 UK-based biomedical researchers responding to the survey reported feeling disillusioned with academic research, due to the low chance of getting a permanent position and the long hours required at the bench. Also like the US, large numbers of researchers at each distinct career stage are considering leaving biomedical research altogether.

Conclusions: There are several systemic flaws in the academic scientific research machine – for example the continual overproduction of PhDs and the lack of stability in the early-mid stages of a research career - that are slowly being addressed in countries such as the US and Germany. These data suggest that similar flaws also exist in the UK, with a large proportion of respondents concerned about their future in research. To avoid lasting damage to the biomedical research agenda in the UK, addressing such concerns should be a major priority.
Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data
Authors: Zhang Chao , Bijlard Jochem , Staiger Christine , Scollen Serena , van Enckevort David , Hoogstrate Youri , Senf Alexander , Hiltemann Saskia , Repo Susanna , Pipping Wibo , Bierkens Mariska , Payralbe Stefan , Stringer Bas , Heringa Jaap , Stubbs Andrew , Bonino Da Silva Santos Luiz Olavo , Belien Jeroen , Weistra Ward , Azevedo Rita , van Bochove Kees , Meijer Gerrit , Boiten Jan-Willem , Rambla Jordi , Fijneman Remond , Spalding J. Dylan , Abeln Sanne
Published: August 2017

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data.
Second ISCB Latin American Student Council Symposium (LA-SCS) 2016
Authors: Monzon Alexander Miguel , Hasenahuer Marcia A. , Mancini Estefanía , Coimbra Nilson , Cravero Fiorella , Cáceres-Molina Javier , Ramírez-Sarmiento César A. , Palopoli Nicolas , Meysman Pieter , Parra R. Gonzalo
Published: August 2017

This report summarizes the scientific content and activities of the second edition of the Latin American Symposium (LA-SCS), organized by the Student Council (SC) of the International Society for Computational Biology (ISCB), held in conjunction with the Fourth Latin American conference from the International Society for Computational Biology (ISCB-LA 2016) in Buenos Aires, Argentina, on November 19, 2016.