bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic internal mammary lymph nodes or mimickers on parasternal ultrasonography: focusing on their distribution and depth
Authors: Jeong Chae Jin , Bae Jung Min , Park So Yoon , Han Boo-Kyung , Ko Eun Sook , Ko Eun Young
Published: April 2017

Background

Ultrasonography (US) is an important tool to evaluate the status of internal mammary lymph node (IMN). US features of metastatic IMNs could help determine when biopsy should be performed.

Purpose

To compare US features of metastatic IMNs to those of benign entities.

Material and Methods

In women with suspected IMN metastasis on US, their intercostal space (ICS) abnormalities were classified into metastatic IMN, benign IMN, and lymph node (LN) mimickers. US features, distribution, and depth of abnormalities in one ICS and involved ICS level were analyzed.

Results

Among 66 ICS abnormalities in 53 women, 46 were metastatic IMNs, ten were benign IMNs, and ten were LN mimickers. For metastatic IMNs, the second ICS was the most commonly involved ICS (n = 22), followed by the first (n = 13), the third (n = 8), and the fourth (n = 3). ICS level distribution of metastatic IMNs was not significantly ( P = 0.5407) different from that of non-metastatic lesions. Metastatic IMNs were predominantly seen in the posterior layer of ICS, significantly ( P < 0.0001) different from LN mimickers. Both metastatic IMNs and non-metastatic lesions were evenly distributed over the upper, middle, and lower part (in craniocaudal direction) of one ICS.

Conclusion

Metastatic IMNs are more likely to be found in the posterior layer of ICS. This can help distinguish them from LN mimickers. Any part (upper, middle, or lower) of one ICS in craniocaudal direction could be involved. The second ICS was the most commonly involved level.
World Politics in Colour
Authors: Ling L. H. M.
Published: April 2017

Racism reflects how we think and act as much as what. It manifests in terms of biology, geography, and culture but reflects an episteme that normalises Self and Other into a bordered binary. Here, a trialectical epistemology can help. It dissolves racialised realities by showing how opposites exist in each other, thereby constituting a three-ness – e.g. self-in-other and other-in-self – that links Self and Other despite mutual antagonisms. From such trialectics, epistemic compassion can arise. It enables learning from the Other through what Buddhists call ‘interbeing’ or the recognition that ‘you are in me, and I in you’. Reciprocity thus becomes key. The Self cannot violate the Other without also violating itself; likewise, loving the Other effectively loves the Self. Flat, monochromatic binaries like ‘black’ versus ‘white’ cannot continue and colour revivifies world politics, both literally and figuratively. I apply trialectics to the ‘border problem’ between India and China as an analogy.
The right to a human in the loop: Political constructions of computer automation and personhood
Authors: Jones Meg Leta
Published: April 2017

Contributing to recent scholarship on the governance of algorithms, this article explores the role of dignity in data protection law addressing automated decision-making. Delving into the historical roots of contemporary disputes between information societies, notably European Union and Council of Europe countries and the United States, reveals that the regulation of algorithms has a rich, culturally entrenched, politically relevant backstory. The article compares the making of law concerning data protection and privacy, focusing on the role automation has played in the two regimes. By situating diverse policy treatments within the cultural contexts from which they emerged, the article uncovers and examines two different legal constructions of automated data processing, one that has furnished a right to a human in the loop that is intended to protect the dignity of the data subject and the other that promotes and fosters full automation to establish and celebrate the fairness and objectivity of computers. The existence of a subtle right across European countries and its absence in the US will no doubt continue to be relevant to international technology policy as smart technologies are introduced in more and more areas of society.
Levofloxacin-Induced Acute Immune-Mediated Thrombocytopenia of Rapid-Onset
Authors: Shih Andrew W. , Lam Andy S. , Warkentin Theodore E.
Published: April 2017

Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient has been receiving the implicated drug for at least 1 week, due to newly forming drug-dependent antibodies (“typical-onset” D-ITP). A “rapid-onset” form of D-ITP can occur when previous sensitization has occurred, where antibodies have thus already been formed, and a precipitous platelet count fall occurs upon reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the rapid-onset form with a well-documented previous exposure has not been described. We report a 76-year-old male treated with levofloxacin for acute exacerbation of chronic obstructive pulmonary disease. After a single 750 mg oral dose of levofloxacin, his platelet count fell from 187 to 5 × 109/L (nadir) over 4 days. Other causes of thrombocytopenia were ruled out. He had received a previous course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and treatment with intravenous immunoglobulin and dexamethasone resulted in platelet count recovery. Levofloxacin-dependent antibodies were not detectable, consistent with the known low sensitivity of laboratory tests for drug-dependent antibodies, presumably indicating antibodies against levofloxacin metabolites, as is indirectly supported by the abrupt but relatively slow platelet count decline observed. This case illustrates a rapid-onset presentation of levofloxacin-induced D-ITP in the setting of previous drug exposure.
E-Personality of the Young Indian Online Shopper: A Scale Validation
Authors: Singh Vinita , Chaudhuri Ranjan , Verma Sanjeev
Published: April 2017

The Internet is the most important tool for online shopping. Online shopping in India is growing at an exponential rate and the trend is expected to continue in the years to come. The current research was undertaken to understand the personality traits of young online shoppers. There is a need to develop appropriate scales for measuring the traits which are dominant, and hence applicable in the Indian context. As part of the review of previous literature as well as exploratory studies conducted by various experts in the field, the author developed a pool of items related to the e-personality traits of the online shoppers. Using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability and validity of the scale were confirmed. A four-factor scale consisting of innovativeness, need for uniqueness, novelty seeking behaviour and opinion leadership was developed. This study is the first step towards identifying factors that influence the young Indian online shopper’s personality or e-profile.
Digitalisation, between disruption and evolution
Authors: Valenduc Gérard , Vendramin Patricia
Published: April 2017

This article questions the disruptive nature of the current process of digitalisation from a retrospective point of view. Four aspects of this process are considered: digitised information as a strategic economic resource; the nature and pace of industrial revolutions; the contested nature of the link between technology and employment; and the shift from flexible work practices towards virtual work. The article reviews some salient research findings from the past three decades and confronts them with recent publications concerning the future of work in the digital economy. It argues that the current wave of digitalisation combines, on the one hand, continuing trends in the analysis of the information society or knowledge-based society, and, on the other hand, significant breakthroughs the scope and impacts of which must be carefully assessed, avoiding any return to technological determinism.
Mechanisms Mediating Functional Hyperemia in the Brain
Authors: Nippert Amy R. , Biesecker Kyle R. , Newman Eric A.
Published: April 2017

Neuronal activity within the brain evokes local increases in blood flow, a response termed functional hyperemia. This response ensures that active neurons receive sufficient oxygen and nutrients to maintain tissue function and health. In this review, we discuss the functions of functional hyperemia, the types of vessels that generate the response, and the signaling mechanisms that mediate neurovascular coupling, the communication between neurons and blood vessels. Neurovascular coupling signaling is mediated primarily by the vasoactive metabolites of arachidonic acid (AA), by nitric oxide, and by K+. While much is known about these pathways, many contentious issues remain. We highlight two controversies, the role of glial cell Ca2+ signaling in mediating neurovascular coupling and the importance of capillaries in generating functional hyperemia. We propose signaling pathways that resolve these controversies. In this scheme, capillary dilations are generated by Ca2+ increases in astrocyte endfeet, leading to production of AA metabolites. In contrast, arteriole dilations are generated by Ca2+ increases in neurons, resulting in production of nitric oxide and AA metabolites. Arachidonic acid from neurons also diffuses into astrocyte endfeet where it is converted into additional vasoactive metabolites. While this scheme resolves several discrepancies in the field, many unresolved challenges remain and are discussed in the final section of the review.
Carrel
Authors: Gloviczki Peter Joseph
Published: April 2017

This autoethnography examines the role of a specific place—a library carrel—as a space within which to engage in ongoing conversations about the cultural importance of brevity, information quality, and connection and disconnection, among individuals and their machines. I hope this short article contributes to dialogues about knowledge production and consumption within the present-day cultural environment.
Structured Expert Consensus on Actinic Keratosis: Treatment Algorithm Focusing on Daylight PDT
Authors: Calzavara-Pinton Piergiacomo , Hædersdal Merete , Barber Kirk , Basset-Seguin Nicole , Del Pino Flores María Emilia , Foley Peter , Galimberti Gaston , Gerritsen Rianne , Gilaberte Yolanda , Ibbotson Sally , Peris Ketty , Sapra Sheetal , Sotiriou Elena , Torezan Luis , Ulrich Claas , Guillemot Jonathan , Hendrich Janek , Szeimies Rolf-Markus
Published: April 2017

Background:

A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK).

Objectives:

To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information.

Methods:

A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options.

Results:

The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation.

Conclusions:

The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician’s clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields.
Personalized medicine: what are the challenges for health services?
Authors: Ricciardi Walter
Published: April 2017

Genetics and genomics, together with other biomedical sciences and digital technologies, have a vital role to play in transforming health services to become systems that can work for health in the 21st century in ways that are affordable and that respond to individuals’ requirement for more autonomy. Health services should embrace this agenda and implement changes in the organization of care.
Thermal stress analysis of one- and two-dimensional functionally graded plates subjected to in-plane heat fluxes
Authors: Demirbas M Didem , Apalak M Kemal
Published: April 2017

This study addresses the thermal stress analysis of one- and two-dimensional functionally graded plates subjected to in-plane heat fluxes. The material composition variation is assumed in-plane, not through the plate thickness according to a power-law distribution in terms of the volume fraction of the constituents. The mathematical model considers the spatial derivatives of local mechanical and thermal properties. The heat transfer and Navier equations of the two-dimensional thermo-elastic model were discretized using the finite difference method, and the set of linear equations were solved using the pseudo singular value method. The performance of both one- and two-dimensional functionally gradient material plates was investigated under two types of in-plane fluxes: one-edge and two-edges. For each type of heat fluxes, one- and two-dimensional functionally gradient material plates exhibited different displacement, stress and strain distributions. The temperature levels and distributions were affected with increasing ceramic constituent in the composition variation of the plate. One-dimensional functionally gradient material plate was more suitable for an one-edge heat flux along the direction of material composition variation, whereas two-dimensional functionally gradient material plate was more effective on the relieving the thermal stresses for a two-edges heat flux.
How was it for you? The Interview Society and the irresistible rise of the (poorly analyzed) interview
Authors: Silverman David
Published: April 2017

Atkinson and Silverman’s (1997) depiction of the Interview Society analysed the dominance of interview studies that seek to elicit respondents ‘experiences’ and ‘perceptions’. Their article showed that this vocabulary is deeply problematic, assuming an over-rationalistic account of behaviour and a direct link between the language of people’s accounts and their past and present psychic states. In this article, using a Constructionist approach, I develop these ideas, by asking what sort of data are we trying to retrieve through interviews, i.e. what do interviews reveal? I go on to examine and discount the claimed intellectual auspices for most interview studies and the way in which interview data are usually analysed. I conclude by showing how the reliability of interview transcripts can be improved and the analysis of interview data made more robust.
Doing laboratory ethnography: reflections on method in scientific workplaces
Authors: Stephens Neil , Lewis Jamie
Published: April 2017

Laboratory ethnography extended the social scientist’s gaze into the day-to-day accomplishment of scientific practice. Here we reflect upon our own ethnographies of biomedical scientific workspaces to provoke methodological discussion on the doing of laboratory ethnography. What we provide is less a ‘how to’ guide and more a commentary on what to look for and what to look at. We draw upon our empirical research with stem cell laboratories and animal houses, teams producing robotic surgical tools, musicians sonifying data science, a psychiatric genetics laboratory, and scientists developing laboratory grown meat. We use these cases to example a set of potential ethnographic themes worthy of pursuit: science epistemics and the extended laboratory, the interaction order of scientific work, sensory realms and the rending of science as sensible, conferences as performative sites, and the spaces, places and temporalities of scientific work.
Interactionism and digital society
Authors: Housley William , Smith Robin James
Published: April 2017

In this article we consider the extent to which interactionist ideas can inform the analysis of current socio-technical trends and practices that surround the emerging contours of digital society. We make reference to four field domains of inquiry that are relevant to this task and highlight how established interactionist insights can be carried forward and inform future studies in this developing area.
Code-switching in newly formed multinational project teams
Authors: Vigier Mary , Spencer-Oatey Helen
Published: April 2017

Based on an ethnographic-like case study comprising observations and interviews with members of three newly formed multinational project teams, our study explores the micro-processes of interactional teamwork and captures how the three teams develop strategies for managing the challenges of code-switching in their interactions. Findings from our study suggest that teams interpret the impact of code-switching challenges differently in spite of the fact that they are performing similar activities, suggesting that adopting (clearly defined) rules for managing interactions may not be as effective as the presence of other factors within the teams. Our findings extend theory on the use of a common working language in multinational teams and go beyond this by illustrating how individual teams establish practices for handling the challenges of code-switching and the effects of these on team interactions.
UPDis: A user-assisted projection technique for distance information
Authors: Neves Tácito TAT , Fadel Samuel G , Hilasaca Gladys M , Fatore Francisco M , Paulovich Fernando V
Published: April 2017

Multidimensional projection techniques have become essential analytical tools. Typically, they map data from a high-dimensional space into a low-dimensional visual space, preserving distance or neighborhood structures on the produced layout. Despite the advances, with faster and highly precise techniques, existing methods still carry deficiencies that impair their use as exploratory tools. An example is the mismatching that can occur between what the user considers similar/dissimilar and what is conveyed by the visual representation. Recently, a class of projection techniques aims at addressing this limitation, allowing users to control the projection process by changing the distance relationships using small data samples. Among such methods, Local Affine Multidimensional Projection has proved to be the state-of-the-art regarding the effectiveness of user intervention. Although Local Affine Multidimensional Projection has attained a relative success, it is limited to certain application domains. Since it relies on feature vector representations with data instances described by vectors embedded into a Euclidean space, scenarios that offer only distance information or a distance function cannot be handled. In this article, we present a novel multidimensional projection technique, called User-assisted Projection Technique for Distance Information, which takes advantage of the solid mathematical framework provided by Local Affine Multidimensional Projection, adapting it to scenarios where only distance information or a distance function is available. The results show that User-assisted Projection Technique for Distance Information is as fast, accurate, robust, and flexible as the existing state-of-the-art techniques, enabling the application of the refined user control provided by Local Affine Multidimensional Projection on domains not previously covered. Its versatility is illustrated in an application that involves the organization of book collections that employs an external source of information for the recommendation of new readings.
Analysis of “A New Optimized Percutaneous Access System for CIPII”
Authors: Renard Eric
Published: April 2017

While only used initially in cases with resistance to subcutaneous insulin therapy, intraperitoneal insulin therapy provides an overall more stable glucose control than subcutaneous insulin therapy thanks to its pharmacokinetics as pointed by Garcia-Verdugo et al from the experience of implantable insulin pumps. The expansion of these devices has been limited by underdelivery issues and high cost. The availability of a new percutaneous access to intraperitoneal route could allow a similar glucose control with less constraints of follow-up and expected lower cost. Currently reported clinical experience does not allow a reliable assessment of its main risk of infection which could impair its sustained usability. Because intraperitoneal insulin could allow a fully automated closed-loop insulin delivery, a specific interest for its means of performance is relevant.
Estimating the Illumination Direction From Three-Dimensional Texture of Brownian Surfaces
Authors: Pont Sylvia C. , van Doorn Andrea J. , Koenderink Jan J.
Published: April 2017

We studied whether human observers can estimate the illumination direction from 3D textures of random Brownian surfaces, containing undulations over a range of scales. The locally Lambertian surfaces were illuminated with a collimated beam from random directions. The surfaces had a uniform albedo and thus texture appeared only through shading and shadowing. The data confirm earlier results with Gaussian surfaces, containing undulations of a single scale. Observers were able to accurately estimate the source azimuth. If shading dominated the images, the observers committed 180° errors. If cast shadows were present, they resolved this convex-concave-ambiguity almost completely. Thus, observers relied on second-order statistics in the shading regime and used an unidentified first-order cue in the shadow regime. The source elevations could also be estimated, which can be explained by the observers’ exploitation of the statistical homogeneity of the stimulus set. The fraction of the surface that is in shadow and the median intensity are likely cues for these elevation estimates.
Opportunities for Engaging Patients in Kidney Research
Authors: Demian Maryam N. , Lam Ngan N. , Mac-Way Fabrice , Sapir-Pichhadze Ruth , Fernandez Nicolas
Published: April 2017

Purpose:

The purpose of this review is to provide a summary of the rationale for engaging patients in research as well as to review the established and envisioned advantages and strategies for patient-researcher partnerships. The authors of this article, which include a patient and 4 researchers in kidney disease, discuss the expected benefits and opportunities for patient engagement in their respective research programs. The 4 research programs span the spectrum of kidney disease and focus on enhancing bone health, increasing living donor kidney transplants, improving medication adherence, and preventing kidney transplant rejection.

Sources of Information:

The sources of information for this review include published studies on the topics of patient engagement and the 4 research programs of the new investigators.

Key Findings:

(1) Patient, health care provider, and researcher partnerships can contribute useful insights capable of enhancing research in kidney disease. (2) Regardless of the research program, there are various strategies and opportunities for engagement of patients with lived experience across the various stages of research in kidney disease. (3) Envisioned advantages of patient-researcher partnerships include: targeting patient-identified research priorities, integrating patients’ experiential knowledge, improving study design and feasibility through patient-researcher input, facilitating dissemination of research findings to other patients, effectively responding to patient concerns about studies, and inspiring researchers to conduct their research.

Limitations:

The limitations of the current review include the relative scarcity of literature on patient engagement within the field of kidney disease.

Implications:

The findings of the current review suggest that it will be important for future studies to identify optimal strategies for patient engagement in setting research priorities, study design, participant recruitment, execution of research projects, and knowledge dissemination and translation.
Online Training in Mind-Body Therapies: Different Doses, Long-term Outcomes
Authors: Kemper Kathi J. , Rao Nisha , Gascon Gregg , Mahan John D.
Published: April 2017

Background.

There is a high rate of burnout among health professionals, driving diverse attempts to promote resilience and well-being to counter this trend. The purpose of this project was to assess the dose-response relationship between the number of hours of online mind-body skills training for health professionals and relevant outcomes a year later.

Methods.

Among 1438 registrants for online training (including up to 12 hours of training on mind-body practices) between December 2013 and November 2015, we analyzed responses from the first 10% who responded to an anonymous online survey between December 1, 2015 and February 1, 2016. Questions included the type and frequency of mind-body practice in the past 30 days and whether the online training had any impact on personal life or professional practice. Standardized measures were used to assess stress, mindfulness, confidence in providing compassionate care, and burnout.

Results.

The 149 respondents represented a variety of ages and health professions; 55% completed one or more mind-body training modules an average of 14 months previously. Most (78%) engaged in one or more mind-body practices in the 30 days before the survey; 79% reported changes in self-care and 71% reported changes in the care of others as a result of participating. Increasing number of hours of training were significantly associated with practicing mind-body skills more frequently; increasing practice frequency was associated with less stress and burnout, which were associated with missing less work. Greater practice frequency was also associated with improvements in stress, mindfulness, and resilience, which were associated with increased confidence in providing compassionate care.

Conclusion.

Online training in mind-body therapies is associated with changes in self-reported behavior one year later; increasing doses of training are associated with more frequent practice which is associated with less stress, burnout, and missing work, and higher levels of mindfulness, resilience, and confidence in providing compassionate care. Additional studies are needed to compare mind-body skills training with other interventions designed to improve resilience and compassion while decreasing burnout in health professionals.
Development and Validation of the iDI: A Short Self-Rating Disability Instrument for Low Back Pain Disorders
Authors: Rolli Salathé Cornelia , Elfering Achim , Tuschel Alexander , Ogon Michael , Mayer H. Michael , Boos Norbert
Published: April 2017

Study Design:

Cross-sectional and longitudinal validation study.

Objective:

Development and validation of a short, reliable, and valid questionnaire for the assessment of low back pain–related disability.

Methods:

The iDI was created in a stepwise procedure: (1) its development was based on the literature and theoretical consideration; (2) outcome data were collected and evaluated in a pilot study; (3) final validations were performed based on an international multicenter spine surgery outcome study including 514 patients; (4) the iDI was programmed for a tablet computer (iPad) and tested for its clinical practicability.

Results:

The final version of the iDI comprises of 8 simple questions related to different aspects of disability with a 5-point Likert-type answer scale. The iDI compared very well to the Oswestry Disability Index in terms of reliability and validity. The iDI was demonstrated to be suitable for data assessment on a tablet computer (iPad).

Conclusions:

The iDI is a short, valid, and practicable tool that facilitates routine quality assessment in terms of low back pain–related disability.
Factors Associated With Improved Function and Maintenance of Sports Activities at 5 to 10 Years After Autologous Hamstring ACL Reconstruction in Young Men
Authors: Hetsroni Iftach , van-Stee Mischa , Marom Niv , Koch Jonathan E. J. , Dolev Eran , Maoz Guy , Nyska Meir , Mann Gideon
Published: April 2017

Background:

There are limited data regarding associated factors of return to sports activities at more than 5 years after anterior cruciate ligament (ACL) reconstruction.

Purpose:

To test interrelationships between patient characteristics, concomitant articular lesions, graft laxity, and maintenance of sports activities at 5 to 10 years after ACL reconstruction. It was hypothesized that at 5 to 10 years after the operation in young adult men, maintenance of greater activity level and better knee function would be associated with greater preinjury activity level, younger age at reconstruction, absence of concomitant articular lesions, and minimal graft laxity at follow-up.

Study Design:

Case series; Level of evidence, 4.

Methods:

One hundred six men with autologous hamstring ACL reconstruction between the ages of 18 and 35 years were reviewed at 5 to 10 years after surgery. Excluded patients had contralateral ACL tear, revision reconstruction, or another injury impairing function. Fifty-five patients were eligible and available for follow-up. Independent variables included preinjury Tegner score, time interval from injury to surgery, smoking status, age, articular lesions, KT side-to-side difference, and pivot-shift grade. Main outcome measures were Tegner activity level, International Knee Documentation Committee (IKDC) subjective score, and Knee injury and Osteoarthritis Outcome Scale (KOOS) score at 5 to 10 years after surgery.

Results:

Greater Tegner activity level at follow-up was associated in a regression model with greater preinjury Tegner activity level (correlation coefficient, 0.423; P = .01), lower KT difference (correlation coefficient, –0.278; P = .04), and negative pivot shift (correlation coefficient, –0.277; P = .05). Younger age at operation predicted return to greater Tegner activity level in a univariate analysis (correlation coefficient, –0.266; P = .05) but not in a regression model (not significant). Chondral lesions at surgery predicted lower IKDC subjective scores (71.4 ± 14.3 vs 84.1 ± 11.5; P < .01) and KOOS scores but did not affect maintenance of sports activities.

Conclusion:

At 5 to 10 years after autologous hamstring ACL reconstruction in young men, predictors of greater sports activity level are primarily high preinjury activity level and reestablishment of knee laxity. Younger age at operation and moderate chondral lesions have lower impact in this respect.
Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults
Authors: Gardner Rebecca A. , Finney Olivia , Annesley Colleen , Brakke Hannah , Summers Corinne , Leger Kasey , Bleakley Marie , Brown Christopher , Mgebroff Stephanie , Kelly-Spratt Karen S. , Hoglund Virginia , Lindgren Catherine , Oron Assaf P. , Li Daniel , Riddell Stanley R. , Park Julie R. , Jensen Michael C.
Published: April 2017

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.
IRP2 as a potential modulator of cell proliferation, apoptosis and prognosis in nonsmall cell lung cancer
Authors: Khiroya Heena , Moore Jasbir S. , Ahmad Nabeel , Kay Jamie , Woolnough Kerry , Langman Gerald , Ismail Iyad , Naidu Babu , Tselepis Chris , Turner Alice M.
Published: April 2017

IREB2is a gene that produces iron regulatory protein 2 (IRP2), which is critical to intracellular iron homeostasis and which relates to the rate of cellular proliferation.IREB2lies in a lung cancer susceptibility locus. The aims were to assess 1) the relationship between iron loading, cell proliferation and IRP2 expression in lung cancer; 2) the potential of iron related pathways as therapeutic targets; and 3) the relevance of IRP2 in operated lung cancer patients.

Cells of two nonsmall cell cancer (NSCLC) lines and primary bronchial epithelial cells (PBECs) were cultured with and without iron; and proliferation, apoptosis and migration were assessed. Reverse transcriptase PCR and Western blot were used to assess expression of iron homeostasis genes/proteins. Iron chelation and knockdown ofIREB2were usedin vitroto explore therapeutics. A cohort of operated NSCLC patients was studied for markers of systemic iron status, tumour IRP2 staining and survival.

Iron loading caused cell proliferation in cancer cell lines, which were less able to regulateIREB2expression than PBECs. Iron chelation resulted in a return of proliferation rates to baseline levels; knockdown ofIREB2had a similar effect. IRP2-positive tumours were larger (p=0.045) and higher percentage staining related to poorer survival (p=0.079).

Loss of iron regulation represents a poor prognostic marker in lung cancer.
The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment
Authors: Ferretti Elisa , Corcione Anna , Pistoia Vito
Published: April 2017

IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA+CD45RO+ T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sézary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts—germinal center B cells—produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.
Improving Access to Cancer Treatments: The Role of Biosimilars
Authors: Chopra Rakesh , Lopes Gilberto
Published: April 2017

Biologics play a key role in cancer treatment and are principal components of many therapeutic regimens. However, they require complex manufacturing processes, resulting in high cost and occasional shortages in supply. The cost of biologics limits accessibility of cancer treatment for many patients. Effective and affordable cancer therapies are needed globally, more so in developing countries, where health care resources can be limited. Biosimilars, which have biologic activity comparable to their corresponding reference drugs and are often more cost effective, have the potential to enhance treatment accessibility for patients and provide alternatives for decision makers (ie, prescribers, regulators, payers, policymakers, and drug developers). Impending patent expirations of several oncology biologics have opened up a vista for the development of corresponding biosimilars. Several countries have implemented abbreviated pathways for approval of biosimilars; however, challenges to their effective use persist. Some of these include designing appropriate clinical trials for assessing biosimilarity, extrapolation of indications, immunogenicity, interchangeability with the reference drug, lack of awareness and possibly acceptance among health care providers, and potential political barriers. In this review, we discuss the potential role and impact of biosimilars in oncology and the challenges related to their adoption and use. We also review the safety and efficacy of some of the widely used biosimilars in oncology and other therapeutic areas (eg, bevacizumab, darbepoetin, filgrastim, rituximab, and trastuzumab).
Estrogen Deficiency Exacerbates Type 1 Diabetes–Induced Bone TNF-α Expression and Osteoporosis in Female Mice
Authors: Raehtz Sandi , Bierhalter Hayley , Schoenherr Daniel , Parameswaran Narayanan , McCabe Laura R.
Published: April 2017

Estrogen deficiency after menopause is associated with rapid bone loss, osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized by hypoinsulinemia and hyperglycemia, is also associated with bone loss and increased fracture risk. With better treatment options, T1D patients are living longer; therefore, the number of patients having both T1D and estrogen deficiency is increasing. Little is known about the mechanistic impact of T1D in conjunction with estrogen deficiency on bone physiology and density. To investigate this, 11-week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose streptozotocin injection. Microcomputed tomographic analysis indicated a marked reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that was far greater than the reductions (~50%) in BVF in either the OVX and T1D groups. Osteoblast markers, number, and activity were significantly decreased in T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly, marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone expression analyses revealed that tumor necrosis factor (TNF)–α levels were highest in T1D-OVX mice and correlated with bone loss, and osteoblast and osteocyte death. In vitro studies indicate that estrogen deficiency and high glucose enhance TNF-α expression in response to inflammatory signals. Taken together, T1D combined with estrogen deficiency has a major effect on bone inflammation, which contributes to suppressed bone formation and osteoporosis. Understanding the mechanisms/effects of estrogen deficiency in the presence of T1D on bone health is essential for fracture prevention in this patient population.
SNAP-25 gene family members differentially support secretory vesicle fusion
Authors: Arora Swati , Saarloos Ingrid , Kooistra Robbelien , van de Bospoort Rhea , Verhage Matthijs , Toonen Ruud F.
Published: April 2017

Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that Snap-25-null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days in vitro (DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable extents – SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.
Elements of logic, rhetoric and eristic for expert witnesses giving oral opinions at court hearings
Authors: Kosmowski Wojciech
Published: April 2017

Celem tego artykułu jest przybliżenie biegłym, przede wszystkim psychiatrom, innym lekarzom, a także psychologom podstawowych wiadomości z dziedziny logiki, retoryki i erystyki przydatnych w ich praktyce zawodowej. Umiejętności te nie są bowiem standardowym elementem kształcenia profesjonalistów z tych dziedzin, choć niewątpliwie należą do elementów klasycznego kształcenia. Posiadanie wiedzy specjalistycznej i wybitnych nawet umiejętności diagnozowania, prowadzenia terapii i stawiania prognoz nie przekłada się automatycznie na zdolność prowadzenia skutecznej argumentacji. W pracy posłużono się metodą Cardijna (widzieć – osądzić – działać).
Zdarza się, że dobrze przygotowana opinia sądowo – psychiatryczna i psychologiczna ulegnie podważeniu na rozprawie z powodów poza merytorycznych, na skutek pewnych zabiegów erystycznych i retorycznych. Część z biegłych po takich doświadczeniach rezygnuje z wydawania opinii.
Aby uniknąć takich sytuacji w tej pracy zawarto najważniejsze definicje w zakresie logiki, retoryki i erystyki. Wskazano przykłady rachunku zdań, wybrane modele rozumowania, figury retoryczne i zabiegi erystyczne mające zastosowanie w przedstawianiu ekspertyz specjalistycznych. Tym przykładom towarzyszą propozycje odpowiadania na argumenty używane przez osoby chcące podważyć wydane przez biegłych opinie. Zaproponowano także schemat przygotowania odpowiedzi na pytania i wątpliwości stron postępowania.
Book Reviews
Authors: Shen Wenjing
Published: April 2017

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an email from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor. The following books are reviewed in this issue of Interfaces, 47(2), March–April 2017: Forest Value Chain Optimization and Sustainability, Sophie D’Amours, Mustapha Ouhimmou, Jean-François Audy, and Yan Feng, eds.; Rise of the Robots: Technology and the Threat of a Jobless Future, Martin Ford.
Healthcare law and ethics, 12. Ethics: everyone's business?
Authors: Barber Chris
Published: April 2017

This series on healthcare ethics began with the idea that healthcare law and healthcare ethics are major aspects of the working lives of all healthcare professionals, including healthcare assistants (HCAs) and, given the nature of the healthcare world in which these healthcare professionals work, are likely to be increasingly important. This final article will draw together themes explored throughout this series within the context of healthcare funding constraints.
The Barnstaple Leg Club, Devon
Authors: Kingsley Andrew , Hampton Sylvie , Lindsay Ellie , Renyi Roland
Published: April 2017

Andrew Kingsley, Sylvie Hampton, Ellie Lindsay and Roland Renyi discuss how the social model of care has proved its worth in the South West of England
Managing coeliac disease
Authors: Kochhar Suneeta
Published: April 2017

The gastrointestinal condition can be painful and distressing for patients, writes Kochhar Suneeta
Research roundup: April 2017
Authors: Greener Mark
Published: April 2017

In brief

People with alcohol dependency are more likely to develop or die from a range of diseases, including several conditions with less well-known links to excessive drinking In eczema, moisturisers, particularly combined with active treatment, prolong time to flare, reduce the number of flares and are steroid sparing Antidepressants seem to be associated with an increased risk of hip fracture People with one of 18 autoimmune diseases may be especially likely to develop dementia
Prescribing in patients with chronic kidney disease
Authors: Johnston Sheila
Published: April 2017

Chronic kidney disease (CKD), stages 3-5, affects about 9% of adults in the UK. It is expected that around half of these patients will progress to end-stage kidney disease. CKD often exists with other long-term conditions such as diabetes. We know that patients with advanced kidney disease can carry a symptom burden similar to that of advanced cancer. Early intervention with medicines aimed at retarding the rate of renal decline and managing the symptoms associated with CKD can be important in improving patients' quality of life and reducing their symptom burden. Prescribing in this group of patients can be challenging as there are many considerations to take into account due to the impaired renal function.
‘CPD that has a strong focus on pupil outcomes’
Authors: Clay Bridget
Published: April 2017

Bridget Clay outlines how the DfE ‘Standard’ for professional development offers a clear route map for improvement, which can be supported by her organisation.
A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model
Authors: Decambron A. , Manassero M. , Bensidhoum M. , Lecuelle B. , Logeart-Avramoglou D. , Petite H. , Viateau V.
Published: April 2017

Objectives

To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects.

Materials and Methods

Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation.

Results

A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 sd 1089 mm3 versus 782 sd 507 mm3; p = 0.09). Bone union was consistent with autograft (1960 sd 518 mm3). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% sd 5% versus 94% sd 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs.

Discussion

Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1.