bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Conceptualization, Design, and Evaluation of Appealing, Meaningful, and Playable Digital Games for Older People
Authors: Sayago Sergio , Rosales Andrea , Righi Valeria , Ferreira Susan M. , Coleman Graeme W. , Blat Josep
Published: August 2015

While older people tend to be regarded as actual, or potential, players of digital games within literature on game studies, human–computer interaction, and gerontechnology, they are also often considered nonavid users of digital technologies. This contradiction prompted us to conduct a literature review, which revealed (a) insufficient involvement of older people within the design of games targeted toward this group and (b) insufficient understanding of their everyday digital gameplay. In this article, we present the conceptualization, design, and evaluation of digital games that active older people found to be sufficiently appealing, playable, and meaningful. A 6-month ethnography of the play experiences of 170 older people helped us to conceptualize these games, which were codesigned through playful everyday activities. To facilitate the development of these games, we designed and evaluated an online game creation platform, which enabled 99 older people with different cultural backgrounds to create, play, and contribute to games.
Virtual Warlords
Authors: Milik Oskar
Published: August 2015

EVE Online grants individuals the anonymity and freedom to act in any way they wish, going so far as to encourage and reward in-game criminal behavior toward other players. This design might lead some to expect anarchy within this digital universe. Instead, this virtual world is highly ordered, containing large organizations led by powerful leaders. To gain understanding of how such social structures operate, this project observes speeches made by heads of organizations in EVE Online to determine the categorization tools used to maintain order in a potentially chaotic environment. It finds that by focusing on group identity, leaders emphasize their role and responsibility for creating and maintaining organizational culture. Additionally, by crafting a narrative of territorial conflict and their own role as a warlord and military leader, they encourage ruthlessness on the part of their membership and establish a social system based upon the individual leader.
Muscle Dysmorphia and the Perception of Men’s Peer Muscularity Preferences
Authors: Lin Linda , DeCusati Frank
Published: August 2015

Research suggests that peer muscularity norms preferences are related to men’s body image, but little information is known about how perceptions of specific peer group norms preferences are related to men’s body image disturbances and specific health behaviors. This study investigated how men perceived the muscularity preferences of male, female, close, and distant peers and whether the perceptions of specific peer preferences were related to muscle dysmorphia and steroid use. Data on muscle dysmorphia and the perceptions of peer muscularity norms were collected from 117 male college students. Results indicated that men perceived distant and male peers as having the most exaggerated preferences for muscularity and that those perceptions were not an accurate reflection of their distant male peers’ reported preferences. Results also indicated that perceptions of close female peer muscularity preferences were predictive of symptoms of muscle dysmorphia, but this relationship did not exist for other peer groups, suggesting that the perceptions of close female peer preferences may play a role in the development of muscle dysmorphia. No relationship was found between perceptions of peer muscularity preferences and steroid use.
The Physical Activity–Related Barriers and Facilitators Perceived by Men Living in Rural Communities
Authors: Gavarkovs Adam G. , Burke Shauna M. , Petrella Robert J.
Published: August 2015

Men, especially those living in rural areas, experience chronic disease at higher rates than the general population. Physical activity is a well-established protective factor against many chronic diseases; however, only a small fraction of men are meeting national guidelines for physical activity. The purpose of this study was to examine the perceived physical activity–related barriers and facilitators experienced by men living in rural areas in Canada. Participants completed a paper-and-pencil or online survey and asked to select personally relevant physical activity-related barriers and facilitators from a list of 9 and 10 choices, respectively. A total of 149 men completed the survey (50.3% between the ages of 18 and 55 years; 43.0% older than 55 years). Participants were predominantly from rural areas and smaller communities. Overall, the response options “I’m too tired,” “I don’t have enough time,” and “I think I get enough exercise as work” were the three most frequently cited barriers to regular physical activity. The response options “Personal motivation to be healthy,” “I enjoy it,” and “Support from family and/or friends” were the three most often cited facilitators to physical activity. Results are similar to those shown in other populations. Results can be used to inform the development of policies and programs that aim to increase the physical activity levels of men living in rural areas and small communities.
Self-Rated Health and Health Care Access Associated With African American Men’s Health Self-Efficacy
Authors: Thompson Terry , Mitchell Jamie A. , Johnson-Lawrence Vicki , Watkins Daphne C. , Modlin Charles S.
Published: August 2015

Health self-efficacy, a measure of one’s self-assurance in taking care of their own health, is known to contribute to a range of health outcomes that has been under examined among African American men. The purpose of this investigation was to identify and contextualize predictors of general health self-efficacy in this population. A cross-sectional sample of surveys from 558 African American was examined. These men were older than 18 years, could read and write English, and attended a hospital-based community health fair targeting minority men in 2011. The outcome of interest was health self-efficacy, which was assessed by asking, “Overall, how confident are you in your ability to take good care of your health?” Responses ranged from 1 ( not confident at all) to 5 ( completely confident). Covariates included age, self-rated health, health insurance status, having a regular physician, and being a smoker. The mean age of participants was 54.4 years, and 61.3% of participants indicated confidence in their ability to take good care of their health. Older age and being a smoker were inversely associated with the outcome. Good self-rated health, having health insurance, and having a regular doctor were positively associated with reports of health self-efficacy. Findings suggest that multiple points of connection to the health care system increase the likelihood of health self-efficacy for this sample and interventions to support older African American men who may evaluate their own health status as poor and who may face barriers to health care access are implicated.
The shear stess profile of the pivotal fenestrated endograft at the level of the renal branches: A computational study for complex aortic aneurysms
Authors: Georgakarakos Efstratios , Xenakis Antonios , Bisdas Theodosios , Georgiadis George S , Schoretsanitis Nikolaos , Antoniou George A , Lazarides Miltos
Published: August 2015

Purpose

This study investigated the impact of the variant angulations on the values and distribution of wall shear stress on the renal branches and the mating vessels of a pivotal fenestrated design.

Methods

An idealized endograft model of two renal branches was computationally reconstructed with variable angulations of the left renal branch. These ranged from the 1:30' to 3:30' o'clock position, corresponding from 45° to 105° with increments of 15°. A fluid-structure-interaction analysis was performed to estimate the wall shear stress.

Results

The proximal part of the renal branch preserved quite constant wall shear stress. The transition zone between its distal end and the renal artery showed the highest values compared to the proximal and middle segments, ranging from 8.9 to 12.4 Pa. The lowest stress values presented at 90° whereas the highest at 45°. The post-mating arterial segment showed constantly low stress values regardless of the pivotal branch angle (6.3 to 6.6 Pa). The 45° configuration showed a distribution of the highest stress posteriorly whereas the 105°-angulation anteriorly.

Conclusions

The variant horizontal branch orientation influences the wall shear stress distribution across its length and affects its values only at its transition with the mating vessel. These findings and their potential association with adverse effects deserve further clinical validation.
Mortality outcomes of ruptured abdominal aortic aneurysms and rural presentation
Authors: Munday Emily , Walker Stuart
Published: August 2015

Objectives

Centralisation of vascular surgery services has coincided with a move towards endovascular repair of ruptured abdominal aortic aneurysms with the goal to improve patient outcomes. The aim of this study was to assess the effect of rural presentation and transfer times on survival from ruptured abdominal aortic aneurysm.

Design

A retrospective review.

Materials

All patients presenting with ruptured abdominal aortic aneurysm to public hospitals in Tasmania between July 2006 and April 2013.

Methods

Demographic data, Glasgow aneurysm score, Hardman index, transfer times, operative technique and 30-day mortality were collected from medical records.

Results

Over the study period 127 patients presented to public hospitals in Tasmania with ruptured abdominal aortic aneurysm. A total of 27 presented to north west hospitals where no vascular surgery service is provided (NWRH), 23 to a northern hospital where an intermittent vascular surgery service is provided (LGH) and 77 to the state tertiary vascular surgery service (RHH). Of these, 4 (14.8%) died at NWRH, 6 (26.1%) died at LGH and 43 (55.8%) died at RHH without operation. Of the 35 patients transferred from NWRH and LGH to RHH, 5 died without operation. Median time from presentation to theatre at RHH if transferred from NWRH was 6.25 hours, from the LGH 4.75 hours, compared to 2.75 hours when presenting directly to RHH. Open repair was performed in 41 patients and endovascular repair in 23 patients. Overall 30-day mortality in those treated at RHH was 26.6% (39.0% for open repair, 4.3% for endovascular repair). Mortality for intended operative patients initially presenting to non-RHH hospitals was 33.3% vs. 32.3% for those initially presenting to RHH. p Value 0.93.

Conclusion

There was no clinical or statistical disadvantage to rural presentation and transfer for patients presenting with ruptured abdominal aortic aneurysm in Tasmania. Endovascular repair has a role despite long transfer times.
Palestinian television and public participation
Authors: Abuzanouna Bahjat
Published: August 2015

This article examines the Palestinians perceptions towards the role of Palestine TV and Al-Aqsa TV in providing a platform for open discussion and create an arena for different groups to communicate freely with each other. Focus groups with a range of participants, from university students and human rights activists, to journalists and non-governmental organization employees were deployed. The article argues that the two political factions are trying to manipulate the public and conceal information that affects their power. It provides an overview of comments, and views expressed by the participants during the focus group sessions in response to a set of questions. The key findings of the study were, in the view of many respondents, that the two television channels, Palestine TV and Al-Aqsa TV, were controlled by the two political parties – Fatah and Hamas, respectively and that this has compromised the media’s function to public participation.
Behind the high-tech fetish: Children, work and media use across classes in India
Authors: Banaji Shakuntala
Published: August 2015

A dearth of media might seem idyllic to urban parents tired of being pestered for an iPad or the latest game. But given the increasing focus amongst Western scholars and educators on theorising digital media as a conduit to conviviality, creativity and civic participation, insights can be gained from the lives and narratives of media-rich and media-deprived children in areas of the global south. Using original observations and in-depth qualitative interviews with rural and urban Indian children aged 9–17, this article discusses the media, work, learning and anxieties they face in everyday life. These data are analysed drawing on frameworks developed to understand child work and children’s agency in the fields of critical sociology and social anthropology. Findings suggest the need for a revised analysis of media use and cultural meaning in middle and low income contexts as strongly inflected by children’s social class, their responsibilities, labour, contextual knowledge and embeddedness in diverse non-mediated communities.
Parsimonious Description of Glucose Variability in Type 2 Diabetes by Sparse Principal Component Analysis
Authors: Fabris Chiara , Facchinetti Andrea , Fico Giuseppe , Sambo Francesco , Arredondo Maria Teresa , Cobelli Claudio ,   on behalf of the MOSAIC EU Project Consortium
Published: August 2015

Background:

Abnormal glucose variability (GV) is a risk factor for diabetes complications, and tens of indices for its quantification from continuous glucose monitoring (CGM) time series have been proposed. However, the information carried by these indices is redundant, and a parsimonious description of GV can be obtained through sparse principal component analysis (SPCA). We have recently shown that a set of 10 metrics selected by SPCA is able to describe more than 60% of the variance of 25 GV indicators in type 1 diabetes (T1D). Here, we want to extend the application of SPCA to type 2 diabetes (T2D).

Methods:

A data set of CGM time series collected in 13 T2D subjects was considered. The 25 GV indices considered for T1D were evaluated. SPCA was used to select a subset of indices able to describe the majority of the original variance.

Results:

A subset of 10 indicators was selected and allowed to describe 83% of the variance of the original pool of 25 indices. Four metrics sufficient to describe 67% of the original variance turned out to be shared by the parsimonious sets of indices in T1D and T2D.

Conclusions:

Starting from a pool of 25 indices assessed from CGM time series in T2D subjects, reduced subsets of metrics virtually providing the same information content can be determined by SPCA. The fact that these indices also appear in the parsimonious description of GV in T1D may indicate that they could be particularly informative of GV in diabetes, regardless of the specific type of disease.
Decreased eGFR as a Risk Factor for Heart Failure in 13 781 Individuals With Type 1 Diabetes
Authors: Vestberg Daniel , Rosengren Annika , Olsson Marita , Gudbjörnsdottir Soffia , Haraldsson Börje , Svensson Ann-Marie , Lind Marcus
Published: August 2015

Background:

Impaired renal function is a well-known risk factor of cardiovascular disease, but its relation to heart failure in individuals with type 1 diabetes has been sparsely studied. The aim of our study was to quantify the risk increase for development of heart failure with decreasing kidney function in individuals with type 1 diabetes.

Methods:

Three equations were used to calculate eGFR (estimated glomerular filtration rate) for individuals with T1D and no known heart failure in the Swedish National Diabetes Registry. Proportional hazards regression models were constructed to evaluate the association between eGFR and hospitalization for heart failure (HF).

Results:

Among 13 781 individuals (mean age 41.1 [SD 13.3] years at baseline), 330 (2.4%) were hospitalized for HF over median follow-up of 7.0 years. Renal function was normal (eGFR > 90 mL/min/1.73 m2) in 67% of individuals according to the Cockcroft-Gault formula, compared to 51% and 41% according to the Chronic Kidney Disease Epidemiology (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulas. For eGFR 45-60 ml/min/1.73 m2, hazard ratios (HRs) for hospitalization (reference >90 mL/min/1.73 m2) were 3.18 (95% CI 2.17, 4.65), 2.12 (1.16, 3.08), and 2.44 (1.69, 3.55) using the Cockcroft-Gault, MDRD, and CKD-EPI formulas. With eGFR <30 ml/min/1.73 m2 there was a HR of 3.78 (2.15, 5.91), 3.44 (2.14, 5.51), and 3.51 (2.21, 5.51) compared to normal kidney function (>90 mL/min/1.73 m2).

Conclusions:

In individuals with T1D, risk of hospitalization for heart failure was over 2 times greater at eGFR 45-60 ml/min/1.73 m2 and more than 3 times greater at eGFR <30 ml/min/1.73 m2 when compared to normal eGFR.
Liberals Condemn Sacrilege Too
Authors: Frimer Jeremy A. , Tell Caitlin E. , Haidt Jonathan
Published: August 2015

Are social conservatives the only ones who use concerns about sacred objects or practices when making moral judgments, such as when they defend the “sanctity of marriage”? Or do liberals condemn sacrilege too? A third possibility is that all talk about sanctity and sacrilege is merely post hoc justification of moral judgments based solely on the perception of harm to sentient or anthropomorphized beings. We present evidence that liberals, like conservatives, morally condemn harmless violations of their own sacred objects. In most cases of liberal sacrilege (e.g., environmental destruction), sentient beings suffer. To deconflate desecration from harm, we examined a context in which someone altered an object that was lifeless yet sacred to a group of liberals—the mountain Cerro Torre. Three studies found that liberals condemned the alteration of the mountain as a harmless desecration. Defending sacred values may bind group members into a cohesive moral community.
Negative Stereotypes Cause Christians to Underperform in and Disidentify With Science
Authors: Rios Kimberly , Cheng Zhen Hadassah , Totton Rebecca R. , Shariff Azim F.
Published: August 2015

Despite Christians being a religious majority in the United States, relatively few pursue higher education and careers in science. Our studies show that stereotypes about Christians being less competent in science than other groups are recognized by both Christians and non-Christians and are openly endorsed by non-Christians (Study 1). Our studies further demonstrate that when these stereotypes become salient, Christians are less interested in and identified with science (Study 2) and underperform on science-relevant tasks (Studies 3–5), compared to non-Christians. Even subtle contextual cues that bear more or less relevance to science are sufficient to compromise Christians’ scientific task performance, particularly among the highly religious (Study 5). When these stereotypes are explicitly removed, however, performance differences between Christians and non-Christians disappear. These results suggest that Christians’ awareness of the negative societal stereotypes about their group’s scientific competence may be partially responsible for the underperformance and underrepresentation of Christians in scientific fields.
Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance
Authors: Longbrake Erin E , Naismith Robert T , Parks Becky J , Wu Gregory F , Cross Anne H
Published: August 2015

Background

Dimethyl fumarate (DMF), a disease-modifying therapy for multiple sclerosis (MS), causes lymphopenia in a fraction of patients. The clinical significance of this is unknown. Several cases of progressive multifocal leukoencephalopathy in lymphopenic fumarate-treated patients have raised concerns about drug safety. Since lymphocytes contribute to MS pathology, lymphopenia may also be a biomarker for response to the drug.

Objective

The objective of this manuscript is to evaluate risk factors for DMF-induced lymphopenia and drug failure in a real-world population of MS patients.

Methods

We conducted a retrospective cohort study of 221 patients prescribed DMF at a single academic medical center between March 2013 and February 2015.

Results

Grade 2–3 lymphopenia developed in 17% of the total cohort and did not resolve during DMF treatment. Older age (>55), lower baseline absolute lymphocyte count and recent natalizumab exposure increased the risk of developing moderate to severe lymphopenia while on DMF. Lymphopenia was not predictive of good clinical response or of breakthrough MS activity on DMF.

Conclusions

Lymphopenia develops in a significant minority of DMF-treated patients, and if grade 2 or worse, is unlikely to resolve while on the drug. Increased vigilance in lymphocyte monitoring and infection awareness is particularly warranted in older patients and those switching from natalizumab.
A Review Study on Punica granatum L
Authors: Shaygannia Erfaneh , Bahmani Mahmoud , Zamanzad Behnam , Rafieian-Kopaei Mahmoud
Published: August 2015

Punica granatum L (pomegranate) is a deciduous shrub, native to Iran. Nowadays, besides its use as a fruit, its medicinal properties have attracted the interest of researchers of many countries. Pomegranate fruit has medicinal properties such as anti-inflammatory and antibacterial activities. The pomegranate seed oil has inhibitory effect on skin and breast cancers. The pomegranate seed oil has phytoestrogenic compounds and the fruit is rich in phenolic compounds with strong antioxidant activity. Ellagic acid is one of the main components of pomegranate with phenolic structure and antioxidant activity. This review article presents the recently published findings on different aspects of this plant focusing on its medicinal properties
Bridging Indigenous and Western Sciences
Authors: Massey Amy , Kirk Ray
Published: August 2015

Emergent research methodologies congruent with Indigenous knowledge and worldviews are providing access to insights from traditional, complementary, and alternative medicine, including Indigenous healing systems. Tension is evident for researchers balancing representation of Indigenous realities with expectation to conform to the conventionality and rationality of “acceptable” Western science–based research protocols. Where past research pursuits have been limited by polarized views of legitimacy and validity, Western science and Indigenous science are now converging as equally valid notions of science to guide emergent research practices such as Kaupapa Māori. This narrative synthesis explores complex relations between epistemology, methodology, and practice. It aims to contribute to the transfer of knowledge between Indigenous and Western scientific paradigms.
Patient Use of Cost and Quality Data When Choosing a Joint Replacement Provider in the Context of Reference Pricing
Authors: Kandrack Ryan , Mehrotra Ateev , DeVries Andrea , Wu Sze-jung , SooHoo Nelson F. , Martsolf Grant R.
Published: August 2015

Health plans are encouraging consumerism among joint replacement patients by reporting information on hospital costs and quality. Little is known about how the proliferation of such initiatives impacts patients’ selection of a surgeon and hospital. We performed a qualitative analysis of semistructured interviews with 13 patients who recently received a hip or knee replacement surgery. Patients focused on the choice of a surgeon as opposed to a hospital, and the surgeon choice was primarily made based on reputation. Most patients had long-standing relationships with an orthopedic surgeon and tended to stay with that surgeon for their replacement. Despite growing availability of cost and quality information, patients almost never used such information to make a decision.
Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages
Authors: Gibbings Sophie L. , Goyal Rajni , Desch A. Nicole , Leach Sonia M. , Prabagar Miglena , Atif Shaikh M. , Bratton Donna L. , Janssen William , Jakubzick Claudia V.
Published: August 2015

Key Points

Of the 30 000 genes, there are ∼0.1% genes whose expression is linked to the origin of the cell rather than the environment. Marco was most conserved by embryonic origin and not altered by the environment, whereas C1qb and Plbd1 were most conserved by adult origin.
A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children
Authors: Brousseau David C. , Scott J. Paul , Badaki-Makun Oluwakemi , Darbari Deepika S. , Chumpitazi Corrie E. , Airewele Gladstone E. , Ellison Angela M. , Smith-Whitley Kim , Mahajan Prashant , Sarnaik Sharada A. , Casper T. Charles , Cook Lawrence J. , Dean J. Michael , Leonard Julie , Hulbert Monica L. , Powell Elizabeth C. , Liem Robert I. , Hickey Robert , Krishnamurti Lakshmanan , Hillery Cheryl A. , Nimmer Mark , Panepinto Julie A.
Published: August 2015

Key Points

Intravenous magnesium did not shorten length of stay for pain crisis in children with sickle cell anemia. Collaboration between pediatric emergency medicine and hematology allowed for successful enrollment in a sickle cell acute management trial.
Redesigning a General Education Science Course to Promote Critical Thinking
Authors: Rowe Matthew P. , Gillespie B. Marcus , Harris Kevin R. , Koether Steven D. , Shannon Li-Jen Y. , Rose Lori A.
Published: August 2015

Recent studies question the effectiveness of a traditional university curriculum in helping students improve their critical thinking and scientific literacy. We developed an introductory, general education (gen ed) science course to overcome both deficiencies. The course, titled Foundations of Science, differs from most gen ed science offerings in that it is interdisciplinary; emphasizes the nature of science along with, rather than primarily, the findings of science; incorporates case studies, such as the vaccine-autism controversy; teaches the basics of argumentation and logical fallacies; contrasts science with pseudoscience; and addresses psychological factors that might otherwise lead students to reject scientific ideas they find uncomfortable. Using a pretest versus posttest design, we show that students who completed the experimental course significantly improved their critical-thinking skills and were more willing to engage scientific theories the general public finds controversial (e.g., evolution), while students who completed a traditional gen ed science course did not. Our results demonstrate that a gen ed science course emphasizing the process and application of science rather than just scientific facts can lead to improved critical thinking and scientific literacy.
IFNAR signaling directly modulates T lymphocyte activity, resulting in milder experimental autoimmune encephalomyelitis development
Authors: Kavrochorianou Nadia , Evangelidou Maria , Markogiannaki Melina , Tovey Michael , Thyphronitis George , Haralambous Sylva
Published: August 2015

Although interferon-β is used as first-line therapy for multiple sclerosis, the cell type-specific activity of type I interferons in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis, remains obscure. In this study, we have elucidated the in vivo immunomodulatory role of type I interferon signaling in T cells during experimental autoimmune encephalomyelitis by use of a novel transgenic mouse, carrying a cd2–ifnar1 transgene on a interferon-α/β receptor 1 null genetic background, thus allowing expression of the interferon-α/β receptor 1 and hence, a functional type I interferon receptor exclusively on T cells. These transgenic mice exhibited milder experimental autoimmune encephalomyelitis with reduced T cell infiltration, demyelination, and axonal damage in the central nervous system. It is noteworthy that interferon-β administration in transgenic mice generated a more pronounced, protective effect against experimental autoimmune encephalomyelitis compared with untreated littermates. In vivo studies demonstrated that before experimental autoimmune encephalomyelitis onset, endogenous type I interferon receptor signaling in T cells led to impaired T-helper 17 responses, with a reduced fraction of CCR6+ CD4+ T cells in the periphery. At the acute phase, an increased proportion of interleukin-10- and interferon-γ-producing CD4+ T cells was detected in the periphery of the transgenic mice, accompanied by up-regulation of the interferon-γ-induced gene Irgm1 in peripheral T cells. Together, these results reveal a hitherto unknown T cell-associated protective role of type I interferon in experimental autoimmune encephalomyelitis that may provide valuable clues for designing novel therapeutic strategies for multiple sclerosis.
Interleukin-10 production by myeloid-derived suppressor cells contributes to bacterial persistence during Staphylococcus aureus orthopedic biofilm infection
Authors: Heim Cortney E , Vidlak Debbie , Kielian Tammy
Published: August 2015

Staphylococcus aureus is known to establish biofilms on medical devices. We recently demonstrated that Ly6GhighLy6C+ myeloid-derived suppressor cells are critical for allowing S. aureus biofilms to subvert immune-mediated clearance; however, the mechanisms whereby myeloid-derived suppressor cells promote biofilm persistence remain unknown. Interleukin-10 expression was significantly increased in a mouse model of S. aureus orthopedic implant biofilm infection with kinetics that mirrored myeloid-derived suppressor cell recruitment. Because myeloid-derived suppressor cells produce interleukin-10, we explored whether it was involved in orchestrating the nonproductive immune response that facilitates biofilm formation. Analysis of interleukin-10–green fluorescent protein reporter mice revealed that Ly6GhighLy6C+ myeloid-derived suppressor cells were the main source of interleukin-10 during the first 2 wk of biofilm infection, whereas monocytes had negligible interleukin-10 expression until day 14. Myeloid-derived suppressor cell influx into implant-associated tissues was significantly reduced in interleukin-10 knockout mice at day 14 postinfection, concomitant with increased monocyte and macrophage infiltrates that displayed enhanced proinflammatory gene expression. Reduced myeloid-derived suppressor cell recruitment facilitated bacterial clearance, as revealed by significant decreases in S. aureus burdens in the knee joint, surrounding soft tissue, and femur of interleukin-10 knockout mice. Adoptive transfer of interleukin-10 wild-type myeloid-derived suppressor cells into S. aureus–infected interleukin-10 knockout mice restored the local biofilm-permissive environment, as evidenced by increased bacterial burdens and inhibition of monocyte proinflammatory activity. These effects were both interleukin-10-dependent and interleukin-10-independent because myeloid-derived suppressor cell–derived interleukin-10 was required for promoting biofilm growth and anti-inflammatory gene expression in monocytes but was not involved in monocyte recruitment to biofilm-infected tissues. These results demonstrate that interleukin-10 production by myeloid-derived suppressor cells contributes to the persistence of S. aureus orthopedic biofilm infections.
Senescent profile of angiogenic T cells from systemic lupus erythematosus patients
Authors: López Patricia , Rodríguez-Carrio Javier , Martínez-Zapico Aleida , Caminal-Montero Luis , Suarez Ana
Published: August 2015

The chronic inflammatory environment associated with systemic lupus erythematosus can lead to an accelerated immunosenescence responsible for the endothelial damage and increased cardiovascular risk observed in these patients. The present study analyzed two populations with opposite effects on vascular endothelium, angiogenic T cells and the senescent CD4+CD28null subset, in 84 systemic lupus erythematosus patients and 46 healthy controls. Also, 48 rheumatoid arthritis patients and 72 individuals with traditional cardiovascular risk factors participated as disease controls. Phenotypic characterization of CD28+ and CD28null cells was performed by analyzing markers of senescence (CCR7, CD27, CD57) and cytotoxicity (CD56, perforin, granzyme B, IFN-γ). IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-α, IFN-γ, TNF-α, B lymphocyte stimulator, and GM-CSF serum levels were analyzed in systemic lupus erythematosus patients and healthy controls. CD4+CD28null cells were notably increased in the systemic lupus erythematosus patients and disease controls compared with healthy controls. In contrast, angiogenic T cells were only reduced in the disease controls (those with rheumatoid arthritis or traditional cardiovascular risk factors). Nevertheless, an anomalous presence of CD28null-angiogenic T cells, with cytotoxic and senescent characteristics, was noted in systemic lupus erythematosus patients in association with anti-dsDNA titer, anti-SSA/Ro antibodies and circulating TNF-α, IL-8, IFN-α, and B lymphocyte stimulator amounts. This subset was also detected in those with traditional cardiovascular risk factors but not in the rheumatoid arthritis patients. In contrast, CD28+-angiogenic T cells were reduced in the systemic lupus erythematosus patients with cardiovascular disorders. In conclusion, CD28 expression must be used to redefine the angiogenic T cell population, because in pathologic conditions, a senescent CD28null-angiogenic T cell subset with inflammatory, rather than protective, effects could be present.
Immune deficiency vs. immune excess in inflammatory bowel diseases—STAT3 as a rheo-STAT of intestinal homeostasis
Authors: Leppkes Moritz , Neurath Markus F , Herrmann Martin , Becker Christoph
Published: August 2015

Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory “rheo-STAT”.
Structure and signaling at hydroid polyp-stolon junctions, revisited
Authors: Harmata Katherine L. , Somova Emily L. , Parrin Austin P. , Bross Lori S. , Glockling Sally L. , Blackstone Neil W.
Published: August 2015

The gastrovascular system of colonial hydroids is central to homeostasis, yet its functional biology remains poorly understood. A probe (2′,7′-dichlorodihydrofluorescein diacetate) for reactive oxygen species (ROS) identified fluorescent objects at polyp-stolon junctions that emit high levels of ROS. A nuclear probe (Hoechst 33342) does not co-localize with these objects, while a mitochondrial probe (rhodamine 123) does. We interpret these objects as mitochondrion-rich cells. Confocal microscopy showed that this fluorescence is situated in large columnar cells. Treatment with an uncoupler (2,4-dinitrophenol) diminished the ROS levels of these cells relative to background fluorescence, as did removing the stolons connecting to a polyp-stolon junction. These observations support the hypothesis that the ROS emanate from mitochondrion-rich cells, which function by pulling open a valve at the base of the polyp. The open valve allows gastrovascular fluid from the polyp to enter the stolons and vice versa. The uncoupler shifts the mitochondrial redox state in the direction of oxidation, lowering ROS levels. By removing the stolons, the valve is not pulled open, metabolic demand is lowered, and the mitochondrion-rich cells slowly regress. Transmission electron microscopy identified mitochondrion-rich cells adjacent to a thick layer of mesoglea at polyp-stolon junctions. The myonemes of these myoepithelial cells extend from the thickened mesoglea to the rigid perisarc on the outside of the colony. The perisarc thus anchors the myoepithelial cells and allows them to pull against the mesoglea and open the lumen of the polyp-stolon junction, while relaxation of these cells closes the lumen.
Local motion detectors are required for the computation of expansion flow-fields
Authors: Schilling Tabea , Borst Alexander
Published: August 2015

Avoidance of predators or impending collisions is important for survival. Approaching objects can be mimicked by expanding flow-fields. Tethered flying fruit flies, when confronted with an expansion flow-field, reliably turn away from the pole of expansion when presented laterally, or perform a landing response when presented frontally. Here, we show that the response to an expansion flow-field is independent of the overall luminance change and edge acceleration. As we demonstrate by blocking local motion-sensing neurons T4 and T5, the response depends crucially on the neural computation of appropriately aligned local motion vectors, using the same hardware that also controls the optomotor response to rotational flow-fields.
Differences in scaling and morphology between lumbricid earthworm ecotypes
Authors: Kurth Jessica A. , Kier William M.
Published: August 2015

Many soft-bodied invertebrates use a flexible, fluid-filled hydrostatic skeleton for burrowing. The aim of our study was to compare the scaling and morphology between surface-dwelling and burrowing earthworm ecotypes to explore the specializations of non-rigid musculoskeletal systems for burrowing locomotion. We compared the scaling of adult lumbricid earthworms across species and ecotypes to determine if linear dimensions were significantly associated with ecotype. We also compared the ontogenetic scaling of a burrowing species, Lumbricus terrestris, and a surface-dwelling species, Eisenia fetida, using glycol methacrylate histology. We found that burrowing species were longer, thinner, and had higher length-to-diameter ratios than non-burrowers, and that L. terrestris was thinner for any given body mass compared to E. fetida. We also found differences in the size of the musculature between the two species that may correlate with surface crawling or burrowing. Our results suggest that adaptations to burrowing for soft-bodied animals include a disproportionately thin body and strong longitudinal muscles.
A visual horizon affects steering responses during flight in fruit flies
Authors: Caballero Jorge , Mazo Chantell , Rodriguez-Pinto Ivan , Theobald Jamie
Published: August 2015

To navigate well through three dimensional environments, animals must in some way gauge the distances to objects and features around them. Humans use a variety of visual cues to do this, but insects, with their small size and rigid eyes, are constrained to a more limited range of possible depth cues. For example, insects attend to relative image motion when they move, but cannot change the optical power of their eyes to estimate distance. On clear days, the horizon is one of the most salient visual features in nature, offering clues about orientation, altitude, and for humans, distance to objects. We set out to determine if flying fruit flies treat moving features as farther off when they are near the horizon. Tethered flies respond strongly to moving images they perceive as close. We measured the strength of steering responses while independently varying the elevation of moving stimuli and the elevation of a virtual horizon. We found responses to vertical bars are increased by negative elevations of their bases relative to the horizon, closely correlated with inverse of apparent distance. In other words, a bar that dips far below the horizon elicits a strong response, consistent with using the horizon as a depth cue. Wide-field motion also had an enhanced effect below the horizon, but this was only prevalent when flies were additionally motivated with hunger. These responses may help flies tune behaviors to nearby objects and features when they are too far off for motion parallax.
Timing matters: tuning the mechanics of a muscle-tendon unit by adjusting stimulation phase during cyclic contractions
Authors: Sawicki Gregory S. , Robertson Benjamin D. , Azizi Emanuel , Roberts Thomas J.
Published: August 2015

A growing body of research on the mechanics and energetics of terrestrial locomotion has demonstrated that elastic elements acting in series with contracting muscle are critical components of sustained, stable, and efficient gait. Far fewer studies have examined how the nervous system modulates muscle-tendon interaction dynamics to optimize ‘tuning’ or meet varying locomotor demands. To explore the fundamental neuromechanical rules that govern the interactions between series elastic (SEE) and contractile (CE) elements within a compliant muscle-tendon unit (MTU), we used a novel work loop approach that included implanted sonomicrometry crystals along muscle fascicles. This enabled us to de-couple CE and SEE length trajectories when cyclic strain patterns were applied to an isolated plantaris MTU from the bullfrog (Lithobates catesbeianus). Using this approach, we demonstrate that the onset timing of muscle stimulation (i.e., stimulation phase) that involves a symmetrical MTU stretch-shorten cycle during active force production, results in net zero mechanical power output, and maximal decoupling of CE and MTU length trajectories. We found it difficult to ‘tune’ the muscle-tendon system for strut-like isometric force production by adjusting stimulation phase only, as the zero power output condition involved significant positive and negative mechanical work by the CE. A simple neural mechanism- adjusting muscle stimulation phase- could shift a MTU from performing net zero to net positive (energy producing) or net negative (energy absorbing) mechanical work under conditions of changing locomotor demand. Finally, we show that modifications to the classical work loop paradigm better represent in vivo muscle-tendon function during locomotion.
Body temperature changes during simulated bacterial infection in a songbird: fever at night and hypothermia at day
Authors: Sköld-Chiriac Sandra , Nord Andreas , Tobler Michael , Nilsson Jan-Åke , Hasselquist Dennis
Published: August 2015

Although fever (a closely regulated increase in body temperature in response to infection) typically is beneficial, it is energetically costly and may induce detrimentally high body temperatures. This can increase the susceptibility to energetic bottlenecks and risks of overheating in some organisms. Accordingly, it could be particularly interesting to study fever in small birds, which have comparatively high metabolic rates and high, variable body temperatures. We therefore investigated two aspects of fever and other sickness behaviours (circadian variation, dose-dependence) in a small songbird, the zebra finch. We injected lipopolysaccharide (LPS) at the beginning of the day and night, respectively, and subsequently monitored body temperature, body mass change and food intake for the duration of the response. We found pronounced circadian variation in body temperature response to LPS-injection, manifested by (dose-dependent) hypothermia at day but fever at night. This resulted in body temperature during the peak response being relatively similar at day and at night. Day-to-night differences might be explained in the context of circadian variation in body temperature: songbirds have a high daytime body temperature that is augmented by substantial heat production peaks during activity. This might require a trade-off between the benefit of fever and the risk of overheating. In contrast, at night when body temperature is typically lower and less variable, fever can be used to mitigate infection. We suggest that the change in body temperature during infection in small songbirds is context-dependent and regulated to promote survival according to individual demands at the time of infection.
Recent advances in external fixation
Authors: Nicol S. , Jackson M. , Monsell F.
Published: August 2015

This review explores recent advances in fixator design and used in contemporary orthopaedic practice including the management of bone loss, complex deformity and severe isolated limb injury.
Constructing the need for retrenchment: disability benefits in the United States and Great Britain
Authors: Morris Zachary
Published: August 2015

Why are some welfare state programmes more susceptible to retrenchment than others? This article examines why the major disability benefit programme in the United States has proved resistant to austerity measures while the comparable disability benefit programme in Great Britain has been repeatedly scaled back. Using a most similar systems research design, it is argued that structural differences mattered a great deal, as did the portrayal of beneficiaries in Britain as undeserving, which proved critical for constructing the need for retrenchment. The article thus identifies the interaction between institutional and ideational factors as a driving force behind programmatic retrenchments.
Cellular Factor XIIIA Transglutaminase Localizes in Caveolae and Regulates Caveolin-1 Phosphorylation, Homo-oligomerization and c-Src Signaling in Osteoblasts
Authors: Wang Shuai , Kaartinen Mari T.
Published: August 2015

Transglutaminases (TGs) are a family of widely distributed enzymes that catalyze protein crosslinking by forming a covalent isopeptide bond between the substrate proteins. We have shown that MC3T3-E1 osteoblasts express Factor XIII-A (FXIII-A), and that the extracellular crosslinking activity of FXIII-A is involved in regulating matrix secretion and deposition. In this study, we have investigated the localization and potential role of intracellular FXIII-A. Conventional immunofluorescence microscopy and TIRF microscopy analyses showed that FXIII-A co-localizes with caveolin-1 in specialized membrane structures, caveolae, in differentiating osteoblasts. The caveolae-disrupting agent methyl-β-cyclodextrin abolished FXIII-A staining and co-localization with caveolin-1 from the osteoblast plasma membrane. The presence of FXIII-A in caveolae was confirmed by preparing caveolae-enriched cellular fractions using sucrose density gradient ultracentrifugation followed by western blotting. Despite this association of FXIII-A with caveolae, there was no detectable transglutaminase activity in caveolae, as measured by monodansylcadaverine incorporation. TG inhibitor NC9—which can alter TG enzyme conformation—localized to caveolae and displaced FXIII-A from these structures when added to the osteoblast cultures. The decreased FXIII-A levels in caveolae after NC9 treatment increased c-Src activation, which resulted in caveolin-1 phosphorylation, homo-oligomerization and Akt phosphorylation, suggesting cellular FXIII-A has a role in regulating c-Src signaling in osteoblasts.