bluuebunny/crossref_metadata_2025 huggingface dataset:
Nasoseptal Flap Reconstruction of Pediatric Sellar Defects
Authors: Purcell Patricia L. , Shinn Justin R. , Otto Randolph K. , Davis Greg E. , Parikh Sanjay R.
Published: February 2015

Objectives

In this study, we used computed tomography measurements to investigate the feasibility of nasoseptal flap reconstruction of sellar defects in children, and we reviewed our institutional experience with the procedure.

Study Design

Cross‐sectional and case series.

Setting

Pediatric tertiary care facility.

Methods

We obtained 10 normal maxillofacial scans for each year of age from birth to 18. Computer‐assisted nasal and skull‐base measurements were performed. Patients with incomplete pneumatization were excluded from analysis. Reconstruction was presumed feasible if the ratio of nasoseptal flap length to associated sellar defect length was greater than 1. Chart review identified surgical patients.

Results

Of 190 scans, 125 had complete pneumatization. Of these, 120 (96%) displayed a ratio of nasoseptal flap length to sellar defect length greater than 1, suggesting that reconstruction would be feasible. Mean ratio of flap length to defect length for all subjects was 1.47 (SD 0.33; 95% CI, 1.41‐1.53). Only 5 of 125 patients (4%) had a ratio less than 1; the median age for these patients was 15 years, which is older than the median age of 12 years for subjects with a ratio greater than 1 (P =. 02). An inverse relationship was identified between age and ratio of flap length to defect length (r = −0.49, P <. 001). Case series identified 6 children, ages 5 to 17; flap length was never described as a limitation.

Conclusions

Nasoseptal flap length is not a limiting factor for reconstruction of pediatric sellar defects. When compared with older patients, younger patients tend to have greater nasoseptal flap length relative to sellar defect length.
Influence of different reconstruction parameters in the visualization of intracranial stents using C-arm flat panel CT angiography: experience in an animal model
Authors: Ott Sabine , Struffert Tobias , Saake Marc , Gölitz Philipp , Adamek Edyta , Doerfler Arnd
Published: February 2015

Background

C-arm flat panel computed tomography angiography (CA-CTA) is a relatively new imaging modality. Consequently, knowledge about postprocessing parameters and their influence on image quality is still limited, especially for the visualization of implanted microstents.

Purpose

To optimize reconstruction parameters by evaluating the influence of these different parameters for CA-CTA visualization of microstents in an animal model.

Material and Methods

Eleven microstents were implanted within the left common carotid artery of 11 New Zealand white rabbits. Both CA-CTA, using intra-venous delivery of contrast material, and conventional digital subtraction angiography (DSA) was performed. CA-CTA datasets were reconstructed using three different image characteristics (normal, sharp, smooth). Two experienced neuroradiologists evaluated the image quality and performed measurements of inner and outer stent diameters as well as measurements of the lumen area.

Results

Stent deployment was performed successfully in all animals. Inter-observer correlation coefficient for all measurements was high (r = 0.87–0.92). Lumen area and inner stent diameter were significantly smaller in image characteristic “smooth” ( P < 0.01) than in “sharp” and “normal”. Outer stent diameter was larger in “smooth” than in “sharp” and “normal” ( P < 0.01). Stent strut size was significantly wider using image characteristic “smooth”. “Sharp” and “normal” compared best to DSA, with “sharp” providing the closest match to DSA measurements, with the trade-off of significantly more noise than in the “normal” reconstructions.

Conclusion

The use of different image characteristics in the postprocessing of CA-CTA datasets has an influence on the visualization of implanted stents. Image characteristic “sharp” and “normal” compared best to DSA.
On laughter and loss: Children’s views of shared time, parenting and security post-separation
Authors: Sadowski Christina , McIntosh Jennifer E
Published: February 2015

Among the research, practice and socio-legal commentary on the substantial sharing of parenting time after separation, children’s voices about their experiences remain overwhelmingly silent. This article draws on findings of a descriptive phenomenological study which investigated Australian school-aged (8- to 12-year-old) children’s descriptions of two binary phenomena: security and contentment in shared time arrangements, and the absence of security and contentment in shared time parenting. Specifically, this article focuses on exploring parental behaviours and interactions recognised by children as sources of security in shared time lifestyles, through happy and needy times. Central to this is the juxtaposition of the child’s experience of security and shared enjoyment with the present parent, against the absence of security emanating from unresolved longing for the ‘absent’ parent. The article provides an empirically derived formulation of children’s advice to parents about shared time parenting, with relevance for family law related parent education forums.
Chinese Kindergartners Learn to Read Characters Analytically
Authors: Yin Li , McBride Catherine
Published: February 2015

Do Chinese children implicitly extract information from Chinese print before they are formally taught to read? We examined Chinese kindergartners’ sensitivity to regularities in Chinese characters and the relationship between such sensitivity and later literacy ability. Eighty-five kindergartners from Beijing were given a character-learning task and assessed on word reading and word writing twice within a 1-year interval. Sensitivity to the structural and phonetic regularities in Chinese appeared in 4-year-olds, and sensitivity to the positions of radicals in Chinese characters emerged in 5-year-olds. Such sensitivities explained unique variance in Chinese word reading and writing 1 year later, with age and nonverbal IQ statistically controlled. Young children detected regularities in written Chinese before they received formal instruction in it, which underscores both the importance of early statistical learning for literacy development and the analytic properties of Chinese print.
Empagliflozin, an SGLT2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus
Authors: White John R.
Published: February 2015

Objective: To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: PubMed was searched using the search terms empagliflozin, BI 10773, and BI10773, for entries between January 1, 2000, and December 1, 2014. Reference lists from retrieved articles were searched manually for additional peer-reviewed publications. Study Selection and Data Extraction: All publications reporting clinical trials of empagliflozin were eligible for inclusion. Data Synthesis: Empagliflozin is a new once-daily oral SGLT2 inhibitor with a mechanism of action that is independent of β-cell function and the insulin pathway. Data from a comprehensive phase III clinical trial program have demonstrated its efficacy as monotherapy, as add-on to other glucose-lowering agents, and in different patient populations. In these studies, empagliflozin resulted in improvements in blood glucose levels as well as reductions in body weight and blood pressure. Empagliflozin was well tolerated and was not associated with an increased risk of hypoglycemia versus placebo. Conclusion: The oral antidiabetes agent, empagliflozin, can be used as monotherapy or alongside other glucose-lowering treatments, including insulin, to treat T2DM.
An Attachment-Based Description of the Medial Collateral and Spring Ligament Complexes
Authors: Cromeens Barrett P. , Kirchhoff Claire A. , Patterson Rita M. , Motley Travis , Stewart Donald , Fisher Cara , Reeves Rustin E.
Published: February 2015

Background:

Anatomy of the medial collateral and spring ligament complexes has been the cause of confusion. The anatomic description is highly dependent on the source studied and little agreement exists between texts. In addition, inconsistent nomenclature has been used to describe the components. This study attempted to clarify confusion through the creation of a 3D ligament map using attachment-based dissection.

Methods:

Nine fresh foot and ankle specimens were observed. The medial collateral ligament and spring ligament complexes were dissected using their attachment sites as a guide to define individual components. Each component’s perimeter and thickness was measured and each bony attachment was mapped using a microscribe 3D digitizer.

Results:

Five components were identified contributing to the ligament complexes of interest: the tibiocalcaneonavicular, superficial posterior tibiotalar, deep posterior tibiotalar, deep anterior tibiotalar, and inferoplantar longitudinal ligaments. The largest component by total attachment area was the tibiocalcaneonavicular ligament followed by the deep posterior tibiotalar ligament. The largest ligament surface area of attachment to the tibia and talus was the deep posterior tibiotalar ligament. The largest attachment to the navicular and calcaneus was the tibiocalcaneonavicular ligament, which appeared to function in holding these bones in proximity while supporting the head of the talus.

Conclusion:

By defining complex components by their attachment sites, a novel, more functional and reproducible description of the medial collateral and spring ligament complexes was created.

Clinical Relevance:

The linear measurements and 3D maps may prove useful when attempting more anatomically accurate reconstructions.
Unstable characteristics of two-dimensional parametric sloshing in various shape tanks: theoretical and experimental analyses
Authors: Li Yuchun , Wang Zhuang
Published: February 2015

The equations of two-dimensional parametric sloshing are derived for a fluid in an arbitrary shape tank. The parametric instability of the liquid free surface is reduced to the Mathieu equation. An energy-growth exponent λ (EGE) and the corresponding non-dimensional energy-growth coefficient (EGC) η are defined for measuring the instability intensity and determining the stability boundaries of the parametrically-excited fluid system. A stability criterion is proposed by using the EGE. On the basis of the numerical tests, the analytical expressions of EGE/EGC are developed for the fluid system that is governed by the Mathieu equation. Under the small excitations, the stability boundaries by using EGE/EGC agree well with those by the traditional theory. The unstable properties, including instability intensity, instability boundaries and competition of unstable patterns etc, of parametric sloshing are analyzed and discussed in details with EGE/EGC for the fluid system. The fluid system always selects such an unstable pattern that possesses a larger energy-growth exponent. A two-dimensional parametric sloshing experiment is respectively conducted for the fluid in the rectangular, circular and U-shaped tanks. The theoretical and experimental stability boundaries of the principal parametric sloshing are obtained and compared for the fluid in three different shape tanks. Some theoretical predictions of the unstable properties of parametric sloshing are verified through the experiment.
Poetic Inquiry, 2007-2012
Authors: Prendergast Monica
Published: February 2015

A found poem created from a selection of poems published in indexed peer-reviewed social science journals between 2007 and 2012 is presented. The excerpts from poems were drawn from a 595-page annotated bibliographic update of a bibliography on this poetic inquiry in the social sciences that was completed in 2007. Excerpts from poems were gathered from this updated compilation via Kurt H. Wolff’s phenomenological surrender and catch method. Surrendering to the process of engaging with the bibliography allowed me to catch phrases, lines, and verses. Excerpts were chosen based on aesthetic criteria such as imagery, metaphor, truthfulness, affective impact, and so on. These excerpts were then grouped according to various voice forms and topics covered. A found poem created from excerpts from 30 poems focuses on Vox Poetica, one of five new voices discovered that are employed in recent poetic inquiry practice.
“Hey, You Stylized Woman There”
Authors: Dosekun Simidele
Published: February 2015

This article presents an uncomfortable reflexive account of a feminist poststructuralist research project on young women in Lagos, Nigeria who dress in what I call “hyper-feminine style.” It reflects on the messy processes by which I framed the research and recruited participants, and considers how the women who did or did not eventually take part exercised agency to resist the terms of my address. The article illustrates the usefulness of Butler’s theoretical notions of “excitable discourse” and “performative interpellation” for poststructuralist reflexive practice, concerning as they do the unpredictable political and ontological effects of what one says and does.
The Learning About My Pain study protocol: Reducing disparities with literacy-adapted psychosocial treatments for chronic pain, a comparative behavioral trial
Authors: Eyer Joshua C , Thorn Beverly E
Published: February 2015

Chronic pain is a critical public health problem that affects over 100 million Americans. Medical pain treatments carry undesirable side effects, whereas low-risk psychosocial treatments offer notable benefits, in combination or in isolation. This report presents the protocol for the Learning About My Pain study, one of the first comparative-effectiveness trials funded by the Patient-Centered Outcomes Research Institute. Adhering to published standards for clinical trials (e.g. Standard Protocol Items: Recommendations for Intervention Trials), it provides an overview of the trial ( n = 294), comparing cognitive-behavioral and education pain interventions to usual care, and a detailed description of how its methodology reduces the risks from bias.
Adapting diesel large-eddy simulation spray models for direct-injection spark-ignition applications
Authors: Van Dam Noah , Rutland Christopher
Published: February 2015

Direct-injection spark-ignition engines are a promising technology to achieve high efficiency and low emissions for automotive applications. Robust operation of direct-injection spark-ignition engines requires understanding the local fuel–air mixing process. Large-eddy simulations can capture more details of the local mixing structure than traditional Reynolds-averaged Navier–Stokes methods. Presented in this work are the results of applying a large-eddy simulation spray methodology originally developed for use with diesel injections to direct-injection spark-ignition sprays. Comparisons were carried out over a wide range of ambient temperatures (400–900 K) and densities (3–9 kg/m3). To accurately simulate the large-scale vapor mixing, it was necessary to adjust spray break-up model parameters as functions of the density ratio. After this adjustment to the spray models, the large-eddy simulations matched experimental vapor penetration data and vapor images across the full range of tested ambient conditions. Liquid penetration trends with respect to changing ambient temperature were captured, but the trends with changing ambient density were not fully captured. Simulations using a Reynolds-averaged Navier–Stokes turbulence model at select conditions showed that the liquid predictions were very similar to large-eddy simulation results, but the Reynolds-averaged Navier–Stokes models were unable to accurately capture the large-scale vapor mixing and did not produce accurate vapor results.
Hannah Arendt reads Carl Schmitt’s The Nomos of the Earth: A dialogue on law and geopolitics from the margins
Authors: Jurkevics Anna
Published: February 2015

Many studies have deduced subterranean dialogues between Hannah Arendt and Carl Schmitt from indirect evidence. This article uses new evidence from marginalia in Arendt’s copy of Nomos of the Earth and finds that she formed, but never published, an incisive critique of Schmitt’s geopolitics. Through an analysis of Arendt’s comments on the topics of soil, conquest, and contract, I show that Arendt deemed Schmitt’s theory to be imperialist and in contradiction with itself. Her reading of Schmitt prompts important new questions regarding the scholarly use of Schmitt’s conception of nomos as a tool of critique against American empire in the post-9/11 era. The marginalia also suggests, against past scholarship, that Arendt thought justice should play a central role in politics. I propose that we look to Arendt’s own conception of nomos, which she developed later, in order to form an alternative geopolitics. Because of her focus on intersubjective world-building, Arendt’s nomos embraces contract and promise-making, and thus provides the foundation for a theory of geopolitics and law that is as necessarily democratic as Schmitt’s is violent.
Gastrointestinal ischemia monitoring through impedance spectroscopy as a tool for the management of the critically ill
Authors: Beltran Nohra E , Sacristan Emilio
Published: February 2015

Impedance spectroscopy (IS) has been proposed as a tool for monitoring mucosal tissue ischemia and damage in the gut of critically ill patients resulting from shock and hypoperfusion. A specific device and system have been developed and tested for this specific application over the past 12 years by our research group. This paper reviews previously published studies as well as unpublished experimental results, and puts the whole in context and perspective to help understand this technology. Results presented include summaries of gastric reactance measurement understanding, in vivo measurements in animal models, clinical significance of the measurement, and future perspectives of clinical use of this technology. All of the experimental work done to date has been designed to determine the evolving device prototypes’ performance and limitations from an instrumentation point of view. Although there are still questions to be answered with regard to the IS measurement, we conclude that we have reached enough confidence in the measurement and the device’s performance and safety to begin clinically oriented research to learn how this technology may be useful in the diagnosis and management of different populations of the critically ill.
A case of overdose via tattoo
Authors: Borg Roberta , Ashton Antony
Published: February 2015

Transdermal fentanyl patches are used frequently for the management of both acute and chronic pain. Adverse events with their use, in particular overdose, are not uncommon. We describe a case of fentanyl overdose from transdermal patch placed over a five-day old tattoo. The report will review the pharmacology of transdermal fentanyl and the physiology of tattooing, as well as the potential link between the two, which may have lead to the overdose.
Development of the Content and Quality in Briefs Instrument (CQB-I)
Authors: Elf Marie , Engström Maria Svedbo , Wijk Helle
Published: February 2015

Objective:

The Content and Quality in Briefs Instrument (CQB-I) was designed to develop a valid and reliable audit instrument to examine the content and quality of information in documents (briefs) created in the early stages of designing healthcare environments.

Background:

The importance of effective briefing has been emphasized in many research studies during the past two decades. However, there is no developed instrument for auditing the content and quality of these documents.

Methods:

The study had a methodological and developmental design based on an established methodology for instrument development and validation. The development process consisted of three main phases: (1) item generation and scale construction; (2) assessment of face and content validity, and (3) testing of the reliability. To obtain face and content validity, expert panels reviewed the CQB-I. Content validity was assessed using the Content Validity Index (I – CVI = item level, S – CVI = scale level). Reliability was tested by test-retest and inter-rater reliability.

Results:

CQB-I was found to have good content validity (I − CVI = 0.78–1.0 and S – CVI = 0.98). Inter-rater reliability was acceptable (Spearman's correlation = 0.62) and stability was considered high for both raters (83% and 88%, respectively).
Optimizing the Patient-Centered Environment
Authors: Locatelli Sara M. , Turcios Stephanie , LaVela Sherri L.
Published: February 2015

Objective:

To examine providers’ perspectives on the care environment and patient-centered care (PCC) through the eyes of the veteran patient, using guided tours qualitative methodology.

Background:

Environmental factors, such as attractiveness and function, have the potential to improve patients’ experiences. Participatory qualitative methods allow researchers to explore the environment and facilitate discussion.

Methods:

Guided tours were conducted with 25 health care providers/employees at two Veterans Affairs (VA) health care facilities. In guided tours, participants lead the researcher through an environment, commenting on their surroundings, thoughts, and feelings. The researcher walks along with the participant, asking open-ended questions as needed to foster discussion and gain an understanding of the participant’s view. Participants were asked to walk through the facility as though they were a veteran. Tours were audio recorded, with participant permission, and transcribed verbatim by research assistants. Three qualitative researchers were responsible for codebook development and coding transcripts and used data-driven coding approaches.

Results:

Participants discussed physical appearance of the environment and how that influences perceptions about care. Overall, participants highlighted the need to shed the “institutional” appearance. Differences between VA and non-VA health care facilities were discussed, including availability of private rooms and staff to assist with navigating the facility. They reviewed resources in the facility, such as the information desk to assist patients and families. Finally, they offered suggestions for future improvements, including improvements to waiting areas and quiet areas for patients to relax and “get away” from their rooms.

Conclusions:

Participants highlighted many small changes to the care environment that could enhance the patient experience. Additionally, they examined the environment from the patient's perspective, to identify elements that enhance, or detract from, the patient's care experience.
A randomized controlled study examining the effect of exercise on inflammatory cytokine levels in post-menopausal women
Authors: Tartibian Bakhtyar , FitzGerald Leah Z , Azadpour Noushin , Maleki Behzad Hajizadeh
Published: February 2015

Background

Elevated plasma levels of inflammatory cytokine are associated with body mass index, percent body fat and increased morbidity. Evidence suggests that higher levels of physical activity result in beneficial anti-inflammatory effects compared to a more sedentary lifestyle. Further, reproductive hormones are associated with inflammaotry cytokines. This study examined the effect of a 16-week low-moderate intensity exercise (EX) programme on reproductive hormones and inflammatory cytokines.

Methods

Twenty-eight healthy, sedentary post-menopausal women were randomly assigned to EX ( n = 14) or control (Con, n = 14) groups. The EX group completed low-moderate intensity treadmill training 25–30 min/day, up to 55% of HRmax, 3–4 days/week, for 16-weeks. Con maintained current physical activity level. Baseline and week-16 serum samples evaluated interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, estradiol, luteinizing hormone and follicular stimulating hormone.

Results

Post-intervention, the EX group showed a significant decrease in interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, estradiol, follicular stimulating hormone and luteinizing hormone levels compared to baseline values. No significant changes were observed in Con. Significant correlations were observed between IL-1β, IL-6, TNF-α, and reproductive hormones, both before and after the exercise intervention.

Conclusion

Findings suggest that a low-moderate intensity EX programme decreases cytokines in relation to reproductive hormones in post-menopausal women. These findings support the role of EX in reducing inflammatory markers and improved reproductive hormones in post-menopausal women.
Stress-Induced Changes in Executive Control Are Associated With Depression Symptoms
Authors: Quinn Meghan E. , Joormann Jutta
Published: February 2015

Deficits in executive control may underlie an inability to effectively respond to stressors, which has been linked to depression symptoms. Previous studies, however, have almost exclusively focused on trait executive control and have not assessed individual differences in changes in executive control when facing acute stressors. The current study examined whether changes in executive control when under stress are related to depression symptoms and whether this relation is moderated by brooding, a subtype of rumination. Ninety-two undergraduate students completed an n-back task before and immediately following a stress induction. As predicted, changes in n-back performance following the stress induction were related to depression symptoms and this relation was moderated by trait brooding. These results suggest that future studies examining the role of executive control in depression should measure executive control under conditions of stress as this may tap into a construct that is distinct from trait measures of executive control.
p53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency
Authors: Belle Jad I. , Langlais David , Petrov Jessica C. , Pardo Mercedes , Jones Russell G. , Gros Philippe , Nijnik Anastasia
Published: February 2015

Key Points

Developmental defects and impairment in lymphopoiesis in Mysm1-knockout mice are the result of p53 activation. Loss of hematopoietic stem cell function and bone marrow failure in Mysm1-knockout mice are the result of p53 activation.
Tyrosine kinase inhibitors induce mesenchymal stem cell–mediated resistance in BCR-ABL+ acute lymphoblastic leukemia
Authors: Mallampati Saradhi , Leng Xiaohong , Ma Haiqing , Zeng Jianfang , Li June , Wang Haiying , Lin Kevin , Lu Yue , Yang Yang , Sun Baohua , Gong Yun , Lee Ju-Seog , Konopleva Marina , Andreeff Michael , Arlinghaus Ralph B. , Cai Zhen , Fang Bingliang , Shen Haifa , Han Xin , Hirsch-Ginsberg Cheryl F. , Gao Xiaolian , Paranjape Anurag N. , Mani Sendurai A. , Clise-Dwyer Karen , Sun Xiaoping
Published: February 2015

Key Points

TKI resistance can be caused by the action of TKIs on MSCs. Inhibition of the IL-7R/Janus kinase pathway diminishes TKI resistance in MSC milieu.
‘Hearts and minds’: association, causation and implication of cognitive impairment in heart failure
Authors: Cannon Jane A , McMurray John JV , Quinn Terry J
Published: February 2015

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment.
Angiotensin-(1-7) improves oxygenation, while reducing cellular infiltrate and fibrosis in experimental Acute Respiratory Distress Syndrome
Authors: Zambelli Vanessa , Bellani Giacomo , Borsa Roberto , Pozzi Federico , Grassi Alice , Scanziani Margherita , Castiglioni Vittoria , Masson Serge , Decio Alessandra , Laffey John G , Latini Roberto , Pesenti Antonio
Published: February 2015

Background

The renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases.

Methods

Male Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured.

Results

In the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05).

Conclusions

Angiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS.
Δ9-Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3/S100A8
Authors: Sido Jessica Margaret , Yang Xiaoming , Nagarkatti Prakash S , Nagarkatti Mitzi
Published: February 2015

MDSCs are potent immunosuppressive cells that are induced during inflammatory responses, as well as by cancers, to evade the anti-tumor immunity. We recently demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the current study, we investigated the epigenetic mechanisms through which THC, an exogenous cannabinoid, induces MDSCs and compared such MDSCs with the nai¨ve MDSCs found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs, which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore, promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs, and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding protein associated with accumulation of MDSCs in cancer models. Neutralization of S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the suppressive function of MDSCs. Together, the current study demonstrates that THC mediates epigenetic changes to promote MDSC differentiation and function and that S100A8 plays a critical role in this process.
Store-operated calcium signaling in neutrophils
Authors: Clemens Regina A , Lowell Clifford A
Published: February 2015

Calcium signals in neutrophils are initiated by a variety of cell-surface receptors, including formyl peptide and other GPCRs, FcRs, and integrins. The predominant pathway by which calcium enters immune cells is termed SOCE, whereby plasma membrane CRAC channels allow influx of extracellular calcium into the cytoplasm when intracellular ER stores are depleted. The identification of 2 key families of SOCE regulators, STIM calcium “sensors” and ORAI calcium channels, has allowed for genetic manipulation of SOCE pathways and provided valuable insight into the molecular mechanism of calcium signaling in immune cells, including neutrophils. This review focuses on our current knowledge of the molecules involved in neutrophil SOCE and how study of these molecules has further informed our understanding of the role of calcium signaling in neutrophil activation.
Lessons From Anti–Vascular Endothelial Growth Factor and Anti–Vascular Endothelial Growth Factor Receptor Trials in Patients With Glioblastoma
Authors: Lu-Emerson Christine , Duda Dan G. , Emblem Kyrre E. , Taylor Jennie W. , Gerstner Elizabeth R. , Loeffler Jay S. , Batchelor Tracy T. , Jain Rakesh K.
Published: February 2015

Treatment of glioblastoma (GBM), the most common primary malignant brain tumor in adults, remains a significant unmet need in oncology. Historically, cytotoxic treatments provided little durable benefit, and tumors recurred within several months. This has spurred a substantial research effort to establish more effective therapies for both newly diagnosed and recurrent GBM. In this context, antiangiogenic therapy emerged as a promising treatment strategy because GBMs are highly vascular tumors. In particular, GBMs overexpress vascular endothelial growth factor (VEGF), a proangiogenic cytokine. Indeed, many studies have demonstrated promising radiographic response rates, delayed tumor progression, and a relatively safe profile for anti-VEGF agents. However, randomized phase III trials conducted to date have failed to show an overall survival benefit for antiangiogenic agents alone or in combination with chemoradiotherapy. These results indicate that antiangiogenic agents may not be beneficial in unselected populations of patients with GBM. Unfortunately, biomarker development has lagged behind in the process of drug development, and no validated biomarker exists for patient stratification. However, hypothesis-generating data from phase II trials that reveal an association between increased perfusion and/or oxygenation (ie, consequences of vascular normalization) and survival suggest that early imaging biomarkers could help identify the subset of patients who most likely will benefit from anti-VEGF agents. In this article, we discuss the lessons learned from the trials conducted to date and how we could potentially use recent advances in GBM biology and imaging to improve outcomes of patients with GBM who receive antiangiogenic therapy.
Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study
Authors: Hensley Martee L. , Miller Austin , O'Malley David M. , Mannel Robert S. , Behbakht Kian , Bakkum-Gamez Jamie N. , Michael Helen
Published: February 2015

Purpose

Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS.

Patients and Methods

In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs.

Results

In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n = 54) and gemcitabine-docetaxel plus bevacizumab (n = 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12; P = .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; P = .81). Objective responses were observed in 17 (31.5%) of 54 patients randomly assigned to gemcitabine-docetaxel plus placebo and 19 (35.8%) of 53 patients randomly assigned to gemcitabine-docetaxel plus bevacizumab. Mean duration of response was 8.6 months for gemcitabine-docetaxel plus placebo versus 8.8 months for gemcitabine-docetaxel plus bevacizumab.

Conclusion

The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS.
Economics of Malignant Gliomas: A Critical Review
Authors: Raizer Jeffrey J. , Fitzner Karen A. , Jacobs Daniel I. , Bennett Charles L. , Liebling Dustin B. , Luu Thanh Ha , Trifilio Steven M. , Grimm Sean A. , Fisher Matthew J. , Haleem Meraaj S. , Ray Paul S. , McKoy Judith M. , DeBoer Rebecca , Tulas Katrina-Marie E. , Deeb Mohammed , McKoy June M.
Published: February 2015

With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve.
Breast Cancer Stage and Treatment Among Ohio Medicaid Beneficiaries With and Without Mental Illness
Authors: Koroukian Siran M. , Bakaki Paul M. , Golchin Negar , Tyler Carl V. , Owusu Cynthia , Loue Sana
Published: February 2015

Among Ohio Medicaid beneficiaries, women with mental illness did not experience disparities in breast cancer treatment. This may reflect equalizing effects of Medicaid through improved access.
Shared Medical Appointments in Cancer Survivorship Care: A Review of the Literature
Authors: Reed Sarah C. , Partridge Ann H. , Nekhlyudov Larissa
Published: February 2015

Shared medical appointments (SMAs) may offer an innovative care model for cancer survivors and their providers. Implementation and evaluation of SMAs in the care of cancer survivors is warranted.
The origin and evolution of synaptic proteins – choanoflagellates lead the way
Authors: Burkhardt Pawel
Published: February 2015

The origin of neurons was a key event in evolution, allowing metazoans to evolve rapid behavioral responses to environmental cues. Reconstructing the origin of synaptic proteins promises to reveal their ancestral functions and might shed light on the evolution of the first neuron-like cells in metazoans. By analyzing the genomes of diverse metazoans and their closest relatives, the evolutionary history of diverse presynaptic and postsynaptic proteins has been reconstructed. These analyses revealed that choanoflagellates, the closest relatives of metazoans, possess diverse synaptic protein homologs. Recent studies have now begun to investigate their ancestral functions. A primordial neurosecretory apparatus in choanoflagellates was identified and it was found that the mechanism, by which presynaptic proteins required for secretion of neurotransmitters interact, is conserved in choanoflagellates and metazoans. Moreover, studies on the postsynaptic protein homolog Homer revealed unexpected localization patterns in choanoflagellates and new binding partners, both which are conserved in metazoans. These findings demonstrate that the study of choanoflagellates can uncover ancient and previously undescribed functions of synaptic proteins.
Trophic dynamics of scleractinian corals: A stable isotope evidence
Authors: Tremblay Pascale , Maguer Jean François , Grover Renaud , Ferrier-Pagès Christine
Published: February 2015

Reef-building corals form symbioses with dinoflagellates from the diverse genus Symbiodinium. This symbiotic association has developed adaptations to acquire and share nutrients, which are essential for its survival and growth in nutrient-poor tropical waters. The host is thus able to prey on a wide range of organic food sources (heterotrophic nutrition) while the symbionts acquire most of the inorganic nutrients (autotrophic nutrition). Nutrient fluxes between the two partners remain however unclear, especially concerning heterotrophically-acquired carbon (C) and nitrogen (N). We combined physiological measurements and pulse-chase isotopic labeling of heterotrophic C and N as well as autotrophic C to track nutrient fluxes in two coral species, Stylophora pistillata and Turbinaria reniformis, in symbiosis with Symbiodinium clades A, and C-D respectively. We showed a rapid acquisition, exchange and a long-term retention of heterotrophic nutrients within the symbiosis, whereas autotrophic nutrients were rapidly used to meet immediate metabolic needs. In addition, there was a higher retention of heterotrophic nitrogen compared to carbon, in agreement with the idea that tropical corals are nitrogen-limited. Finally, a coupling between auto- and heterotrophy was observed in the species S. pistillata, with a higher acquisition and retention of heterotrophic nutrient under low irradiance to compensate for a 50% reduction in autotrophic nutrient acquisition and translocation. Conversely, T. reniformis conserved an equivalent heterotrophic nutrient acquisition at both light levels, because this coral species did not significantly reduced its rates of gross photosynthesis and autotrophic carbon acquisition between the two irradiances. These experiments advance the current understanding of the nutrient exchanges between the two partners of a symbiotic association, providing evidence of the complexity of the host-symbiont relationship.
Thermoregulatory consequences of salt loading in the lizard, Pogona vitticeps
Authors: Scarpellini Carolina da Silveira , Bícego Kênia C. , Tattersall Glenn J.
Published: February 2015

Previous research has demonstrated that dehydration increases the threshold temperature for panting and decreases the thermal preference of lizards. Conversely, it is unknown whether thermoregulatory responses like shuttling and gaping are similarly influenced. Shuttling, as an active behavioural response, is considered one of the most effective thermoregulatory behaviours, while gaping has been proposed to be involved in preventing brain over-heating in lizards. In this study we examined the effect of salt loading, a proxy for increased plasma osmolality, on shuttling and gaping in Pogona vitticeps. Then, we determined the upper and lower escape ambient temperatures (UETa and LETa), the percentage of time spent gaping, the metabolic rate (V̇O2), the evaporative water loss (EWL) during gaping and non-gaping intervals and the evaporative effectiveness (EWL/V̇O2) of gaping. All experiments were performed under isotonic (154 mM) and hypertonic saline injections (625, 1250 or 2500 mM). Only the highest concentration of hypertonic saline altered the UETa and LETa, but this effect appeared to be the result of diminishing the animal's propensity to move, instead of any direct reduction in thermoregulatory set-points. Nevertheless, the percentage of time spent gaping was proportionally reduced according to the saline concentration; V̇O2 was also decreased after salt-loading. Thermographic images revealed lower head than body surface temperatures during gaping; however this difference was inhibited after salt loading. Our data suggest that EWL/V̇O2 is raised during gaping, possibly contributing to an increase in heat transfer away from the lizard, and playing a role in head or brain cooling.
Features of Educational Process under the Formation of Diagnostic Competences of Masters in Speech Therapy
Authors: ��������  , Logunova Elena , ��������  , Levchenko Irina
Published: February 2015

The article is devoted to the peculiarities of �Speech Pathology Education� Ph.D. program against the reforms of the education of persons with disabilities.

The work implements competency-based approach to the preparation of students for the Master?s program. Competences of the Master of

psychological-pedagogical diagnostics and one�s activities in the field of integrated studying of persons with disabilities, as well as of teaching and

research activities, are described. To assess the development of diagnostic competence authors developed and submitted tasks of different levels of

complexity, allowing to assess competence at different stages of learning. The article presents an innovative technology of application of a "Portfolio"

didactic method in the formation of diagnostic competence, describes the contents of the �Portfolio� (created by the magistrand), and provides evaluation

criteria for the performance of the proposed technology.