bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B74: PTEN-deficiency in myeloid cells alters tumor immune surveillance in a murine model of inflammation driven colon cancer
Authors: Kuttke Mario , Pisoni Julia , Sahin Emine , Percig Sophie , Vogel Andrea , Kraemmer Daniel , Hanzl Leslie , Schmid Johannes , Schabbauer Gernot
Published: October 2015

Macrophages and antigen-presenting cells are important parts of the innate immune system as they fend off invading microbes, produce cytokines, activate other leukocytes and are implicated in the resolution of inflammatory processes and tissue remodeling. They have been found to contribute to tumor progression as they undergo phenotypic conversion from a ‘classical’ inflammatory state (M1) into an ‘alternatively’ activated, tumor tolerating state (M2). In our previous work we could show that the PI3K/PTEN signaling pathway plays a role in this fate decision process. Deletion of PTEN in myeloid cells leading to sustained PI3K activation results in an M2-like phenotype characterized by an increased release of anti-inflammatory factors.

Alternative activation of myeloid cells is beneficial in acute models of infection and inflammation, but a diminished innate immune response could be detrimental in tumor development since tumor-associated macrophages show an immune-suppressive, M2-like phenotype. To address the question whether myeloid PTEN plays a role in tumor immune surveillance, we applied a model of colitis associated colon cancer (CAC) in myeloid cell specific PTEN-deficient mice.

PTENfl/fl LysM cre conditional knock-out (KO) mice showed an increased tumor burden and increased mortality in this model of inflammation driven CAC. Isolated myeloid cells from these mice exhibited an up-regulation of M2-marker genes and a down-regulation of pro-inflammatory cytokines. Moreover we found an increase in immune-regulatory innate cells of the secondary lymphoid organs. T-cells isolated from PTEN KO-mice had decreased cytokine production as well as a reduced proliferative potential ex vivo. Therefore we suggest that myeloid PTEN deficiency leads to reduced T-cell stimulation thereby promoting intestinal tumor growth.

Taken together this study highlights the importance of the PI3K/PTEN signaling axis in myeloid cells to control tumor immune surveillance and supports the idea that PI3K inhibitors currently used in clinical settings may have additional functions beyond tumor cell targeting.

Citation Format: Mario Kuttke, Julia Pisoni, Emine Sahin, Sophie Percig, Andrea Vogel, Daniel Kraemmer, Leslie Hanzl, Johannes Schmid, Gernot Schabbauer. PTEN-deficiency in myeloid cells alters tumor immune surveillance in a murine model of inflammation driven colon cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B74.
Abstract B77: Targeted nano-immune conjugates to melanoma: Preclinical testing of bevacizumab targeted nab-paclitaxel
Authors: Nevala Wendy K. , Markovic Svetomir N.
Published: October 2015

Background: Phase 3 clinical results demonstrate that nab-paclitaxel (ABX) exhibits single agent activity in patients with metastatic melanoma relative to dacarbazine. Additionally, phase 2 clinical data suggest that ABX combined with bevacizumab (BEV) with/without carboplatin exhibits greater clinical efficacy than ABX alone. We hypothesized that the latter may be due to a pharmacokinetic, non-covalent interaction between bevacizumab (BEV) and nab-paclitaxel (ABX) allowing for greater localization of ABX to sites of VEGF overproduction (metastases). Herein we present pre-clinical data describing the utility of experimentally created ABX/BEV complex nanoparticles used to deliver ABX to VEGF producing cancer targets.

Methods and Results: To test whether BEV binds to ABX we employed flow cytometry and discovered that the BEV does bind to ABX while preserving the ability of BEV to bind its ligand, VEGF. To measure binding affinity we used Biolayer Interferometry (BLItz) to measure association and dissociation constants. Results of BLItz experiments demonstrate that the binding affinity of BEV to ABX is pH and temperature dependent. The size and stability of the nanoparticle formed by binding BEV and ABX was determined using light refraction (Mastersizer) and Brownian motion (Nanosight). Results of these experiments suggest that a range of nanoparticles can be produced and stability of the BEV particle is increased relative to ABX particles alone. Finally the tumor efficacy of the BEV/ABX complex relative to ABX and BEV as well as sequential administration of the two drugs was tested in a xenograft model of A375 human melanoma cell line. Pharmacokinetic studies in these mice suggest that more ABX is deposited in the tumor site when treated with the complexes relative to ABX alone.

Conclusions: The therapeutic antibody BEV has the capability to bind to the chemotherapy drug ABX while still binding its ligand, VEGF. The resulting nanoparticle is more stable than the original ABX particle. In a preclinical model of human A375 xenografts in nude mice, AB160 treatment offers significantly improved antitumor activity beyond that of ABX, BEV or ABX+BEV with no additional toxicity. Initial results indicate that the improved efficacy of the ABX/BEV nanoparticle relative to ABX alone is primarily due to the ability of the anti-VEGF antibody (BEV) to target the chemotherapy agent to the tumor where local VEGF concentration is very high. Clinical translation of the safety of a 160nm AB particle (AB160) in patients with metastatic melanoma is in progress.

Citation Format: Wendy K. Nevala, Svetomir N. Markovic. Targeted nano-immune conjugates to melanoma: Preclinical testing of bevacizumab targeted nab-paclitaxel. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B77.
Abstract IA16: Designing cancer vaccines that mimic viral infections
Authors: Celis Esteban
Published: October 2015

Numerous CD8 T cell epitopes have been identified allowing the development of epitope-based cancer immunotherapy such as the use of synthetic peptide-based vaccines. However, peptide vaccines have been notoriously poorly immunogenic and provide suboptimal therapeutic effects. In contrast, as a response to viral and bacterial infections, the immune system has the capacity to produce huge numbers of antigen-specific T cells that eliminate disease and provide memory responses to prevent future infections. Our strategy to optimize peptide vaccines is to design immunization strategies that mimic these infections by providing the necessary immune activation signals together with the appropriate immunogenic peptide. Furthermore, it has been proposed that minimal peptide epitopes are poorly immunogenic because they are presented to T cells by non-professional APCs. Therefore, it is suggested that using long peptides vaccines will improve immunogenicity by forcing antigen presentation by professional APCs. Using several mouse tumor models, we observe that peptide composition (hydrophobicity, amphipathicity), adjuvant and route of vaccine administration are more critical than peptide size for generating strong CD8 T cell responses that limit tumor growth. Two separate events are required for peptides to generate massive CD8 T cell responses, similar to those observed during acute viral infections: 1) Peptide priming mediated professional APCs, where CD40 activation and TLR signals are critical; 2) T cell expansion, which can be mediated by either professional and non-professional APCs and where type-I interferon induced by retinoic acid-inducible (RIG-I)-like receptor stimulation by poly-IC plays a critical role. Effective anti-tumor CD8 T cell responses were accomplished by 2 systemic injections (iv or im 5-7 days apart) of peptide/poly-IC.

Citation Format: Esteban Celis. Designing cancer vaccines that mimic viral infections. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA16.
Abstract IA26: Vaccines: The igniters of antitumor immunity
Authors: Zheng Lei
Published: October 2015

Pancreatic cancer is one of a number of malignancies that typically lack tumor infiltrating effector lymphocytes and are considered “non-immunogenic” neoplasms. This situation has drastically slowed the development and application of immune-based therapies for these cancers. In this study, we tested the hypothesis that vaccine based immunotherapy can convert pancreatic cancer, a “non-immunogenic” tumor, into an “immunogenic” tumor with infiltrating effector lymphocytes. We recently completed a novel neo-adjuvant and adjuvant study designed to evaluate post-immunotherapy changes within the tumor microenvironment (TME) of primary pancreatic tumors following treatment with the GM-CSF-secreting pancreatic cancer vaccine, given either alone or with immune modulating doses of cyclophosphamide to deplete regulatory T cells. Pathological examination of tumor tissue resected just two weeks following vaccination identified the formation of novel immunotherapy-induced tertiary lymphoid aggregates, organized lymphoid structures that are not observed in tumors resected from unvaccinated patients. This study shows for the first time that treatment with a vaccine-based immunotherapy directly alters the pancreatic cancer TME, allowing infiltration of organized and functional immune structures that convert an immunologically quiescent tumor into an immunologically active tumor. This study also demonstrates that the formation of these immune regulatory structures within the TME is just the first step toward establishing optimal anticancer immune responses within the TME since these lymphoid aggregates can express both effector activating and effector down-regulatory immune signatures. These data support combination immunotherapies that include vaccines that induce T cells and facilitate T cell trafficking into the TME given together with agents that modulate vaccine induced regulatory signals. In addition, these data suggest a new model for developing more effective immunotherapy for traditionally “non-immunogenic” tumors like pancreatic cancer. Finally, the intratumoral signatures identified in this study provide potential targets for developing strategies for modulating the TME and promoting more robust antitumor immune responses in future studies.

Citation Format: Lei Zheng. Vaccines: The igniters of antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA26.
Sensor-Based Interactive Balance Training with Visual Joint Movement Feedback for Improving Postural Stability in Diabetics with Peripheral Neuropathy: A Randomized Controlled Trial
Authors: Grewal Gurtej Singh , Schwenk Michael , Lee-Eng Jacqueline , Parvaneh Saman , Bharara Manish , Menzies Robert A. , Talal Talal K. , Armstrong David G. , Najafi Bijan
Published: October 2015

Background: Individuals with diabetic peripheral neuropathy (DPN) have deficits in sensory and motor skills leading to inadequate proprioceptive feedback, impaired postural balance and higher fall risk. Objective: This study investigated the effect of sensor-based interactive balance training on postural stability and daily physical activity in older adults with diabetes. Methods: Thirty-nine older adults with DPN were enrolled (age 63.7 ± 8.2 years, BMI 30.6 ± 6, 54% females) and randomized to either an intervention (IG) or a control (CG) group. The IG received sensor-based interactive exercise training tailored for people with diabetes (twice a week for 4 weeks). The exercises focused on shifting weight and crossing virtual obstacles. Body-worn sensors were implemented to acquire kinematic data and provide real-time joint visual feedback during the training. Outcome measurements included changes in center of mass (CoM) sway, ankle and hip joint sway measured during a balance test while the eyes were open and closed at baseline and after the intervention. Daily physical activities were also measured during a 48-hour period at baseline and at follow-up. Analysis of covariance was performed for the post-training outcome comparison. Results: Compared with the CG, the patients in the IG showed a significantly reduced CoM sway (58.31%; p = 0.009), ankle sway (62.7%; p = 0.008) and hip joint sway (72.4%; p = 0.017) during the balance test with open eyes. The ankle sway was also significantly reduced in the IG group (58.8%; p = 0.037) during measurements while the eyes were closed. The number of steps walked showed a substantial but nonsignificant increase (+27.68%; p = 0.064) in the IG following training. Conclusion: The results of this randomized controlled trial demonstrate that people with DPN can significantly improve their postural balance with diabetes-specific, tailored, sensor-based exercise training. The results promote the use of wearable technology in exercise training; however, future studies comparing this technology with commercially available systems are required to evaluate the benefit of interactive visual joint movement feedback.
The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia
Authors: Elamin Marwa , Holloway Guy , Bak Thomas H. , Pal Suvankar
Published: October 2015

Background/Aims: Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrooke's Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD. Methods: ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI). Results: The study included 71 EOD patients (Alzheimer's disease, n = 31; primary progressive aphasia, n = 11; behavioural-variant frontotemporal dementia, n = 18, and posterior cortical atrophy, n = 11); there were 28 HC and 15 individuals with SMI. At a cut-off score of 88/100, the ACE-III displayed high sensitivity and specificity in distinguishing EOD from HC (91.5 and 96.4%) and SMI (91.5 and 86.7%). Conclusions: The ACE-III is a reliable cognitive screening tool in EOD.
Noncorticosteroid Combination Shampoo versus 1% Ketoconazole Shampoo for the Management of Mild-to-Moderate Seborrheic Dermatitis of the Scalp: Results from a Randomized, Investigator-Single-Blind Trial Using Clinical and Trichoscopic Evaluation
Authors: Dall''Oglio Federica , Lacarrubba Francesco , Verzì Anna Elisa , Micali Giuseppe
Published: October 2015

Purpose: The aim of this study was to assess the efficacy and tolerability of a combination noncorticosteroid, antiinflammatory/antifungal shampoo versus 1% ketoconazole shampoo in the treatment of mild-to-moderate scalp seborrheic dermatitis (SD). Procedures: Twenty patients were randomized to using the combination shampoo (group A, 10 patients) or the 1% ketoconazole shampoo (group B, 10 patients) 3 times a week every other day for 8 weeks. Efficacy was evaluated by measuring the degree of scaling and pruritus by clinical and trichoscopic examination using a 4-point scale. Additionally, a physician global assessment (PGA) was assessed at the end of the study. Results: At 4 weeks, there was a significant reduction of scaling from baseline for both groups, while pruritus showed a significant reduction only for group A. After 8 weeks, there was a significant reduction of scaling and pruritus for both groups. PGA showed a complete response in 90% of the cases in both groups. Conclusions: The results of our study demonstrate that the combination noncorticosteroid, antiinflammatory/antifungal shampoo represents an alternative approach to standard topical treatment for scalp SD. A noncorticosteroid shampoo may be equally safe and effective as ketoconazole shampoo for scalp SD, and trichoscopy provides accurate and reliable quantifiable data to assist in therapeutic monitoring.
Urethral Reconstruction with Small Intestinal Submucosa Seeded with Oral Keratinocytes and TIMP-1 siRNA Transfected Fibroblasts in a Rabbit Model
Authors: Guo Hailin , Sa Yinglong , Huang Jianwen , Wang Zhou , Wang Lin , Xie Minkai , Lv Xiangguo
Published: October 2015

Background: To evaluate the effect of tissue inhibitor of metalloproteinase-1 small interfering RNA (TIMP-1 siRNA) transfected fibroblasts (FB) for urethral reconstruction. Materials and Methods: A ventral urethral mucosal defect was created. Substitution urethroplasty was performed with small intestinal submucosa (SIS) alone (8 rabbits, group 1), autogenic oral keratinocytes (OK)-seeded SIS (8 rabbits, group 2) or autogenic OK and TIMP-1 siRNA transfected FB-seeded SIS (8 rabbits, group 3). At 1 and 6 months after surgery (4 rabbits at each time point), retrograde urethrogram and histologic analysis were performed to evaluate the outcomes of urethroplasty. Results: TIMP-1 siRNA transfected FB decreased the secretion of type I collagen. Under retrograde urethrography, 5 rabbits in group 1, 6 in group 2 and 7 in group 3 maintained a wide urethral caliber. Histologically, inflammation and fibrosis were observed at 6 months in group 1. The speed of urothelium, smooth muscle and vessel regeneration in group 3 was faster than that in group 2. Comparison of smooth muscle-to-collagen ratio, epithelial layers, smooth muscle content and microvessel density among three groups revealed a significant increase (p < 0.05). Conclusions: TIMP-1 siRNA transfected FB could be used as a source of seed cell for urethral tissue engineering and could prevent the proliferation of urethral scar tissue.
Synthetic Biology: Rational Pathway Design for Regenerative Medicine
Authors: Davies Jamie A.
Published: October 2015

Rational pathway design is the invention of an optimally efficient route from one state (e.g. chemical structure, state of differentiation, physiological state) to another, based on knowledge of biological processes: it contrasts with the use of natural pathways that have evolved by natural selection. Synthetic biology is a hybrid discipline of biology and engineering that offers a means for rationally designed pathways to be realized in living cells. Several areas of regenerative medicine could benefit from rational pathway design, including derivation of patient-specific stem cells, directed differentiation of stem cells, replicating physiological function in an alternative cell type, construction of custom interface tissues and building fail-safe systems into transplanted tissues. Synthetic biological approaches offer the potential for construction of these, for example controllable ex vivo stem cell niches, genetic networks for direct transdifferentiation from adult fibroblast to restricted stem cell without going via induced pluripotent stem cells, signalling pathways for realizing physiological regulation in alternative cell types, morphological modules for producing self-constructing novel ‘tissues' and ‘kill-switches' for therapeutically applied stem cells. Given the potential of this approach, a closer convergence of the regenerative medicine and synthetic biology research fields seems timely.
Impact of Imaging and Cerebrospinal Fluid Biomarkers on Behavioral Variant Frontotemporal Dementia Diagnosis within a Late-Onset Frontal Lobe Syndrome Cohort
Authors: Krudop Welmoed A. , Dols Annemiek , Kerssens Cora J. , Prins Niels D. , Möller Christiane , Schouws Sigfried , Barkhof Frederik , van Berckel Bart N.M. , Teunissen Charlotte E. , van der Flier Wiesje M. , Scheltens Philip , Sikkes Sietske A.M. , Stek Max L. , Pijnenburg Yolande A.L.
Published: October 2015

Background: The criteria for behavioral variant frontotemporal dementia (bvFTD) incorporate MRI and [18F]-FDG-PET. Cerebrospinal fluid (CSF) analysis is merely advised for excluding Alzheimer's disease. Aims: We aimed to assess the impact of biomarkers on diagnostic certainty and contingent changes of bvFTD diagnosis within the clinically relevant neuropsychiatric differential diagnosis of subjects with a late-onset frontal lobe syndrome (LOF). Methods: We included 137 patients with LOF, aged 45-75 years, 72% males. Biomarker disclosure was considered contributing after any substantial difference in diagnostic certainty or a diagnostic change. Percentages of contributing biomarkers were compared between three major diagnostic groups (bvFTD, psychiatry, other neurological disorders). Certainty levels in stable diagnostic groups were compared to those with a diagnostic change. Results: Biomarkers contributed in 53, 60 and 41% of the LOF patients for MRI, [18F]-FDG-PET and CSF, respectively. Biomarkers changed the diagnosis in 14% of cases towards bvFTD and in 13% from bvFTD into an alternative. Those that changed had a lower level of a priori diagnostic certainty compared to stable diagnoses. Conclusion: Our study not only supports the widely accepted use of MRI and [18F]-FDG-PET in diagnosing or excluding bvFTD, but also shows that CSF biomarkers aid clinicians in the diagnostic process.
Endoscopic Therapy of Early Carcinoma of the Oesophagus
Authors: Knabe Mate , May Andrea , Ell Christian
Published: October 2015

Background: Oesophageal cancer is a comparatively rare disease in the Western world. Prognosis is highly dependent on the choice of treatment. Early stages can be treated by endoscopic resection, whereas surgery needs to be performed in the case of advanced carcinomas. Technical progress has enabled high-definition endoscopes and technical add-ons which help the endoscopist in finding fine irregularities in the oesophageal mucosa, though interpretation still remains challenging. Methods: In this review, we discuss both novel and old diagnostic procedures and their value, as well as the current recommendations for the diagnosis and treatment of early oesophageal carcinomas. The database of PubMed and Medline was searched and analysed to provide all relevant literature for this review. Results and Conclusion: Endoscopic resection is the therapy of choice in early oesophageal cancer. In case of adenocarcinoma it is mandatory to perform subsequent ablation of all residual Barrett's mucosa to avoid metachronous lesions.
Paisagens urbanas: imaginário na fase atual da globalização
Authors: Magnoli Miranda Martinelli
Published: October 2015

Este ensaio descreve, por meio de anotações muito sintéticas, o tema muito complexo e abrangente da interação, no espaço e no tempo, entre a globalização com urbanização e o meio ambiente. Discorre-se por meio de três abordagens para cada um dos dois aspectos. A inter-relação entre a globalização com urbanização e o patrimônio ambiental é o cerne das reflexões. A compressão do espaço-tempo com a conectividade universal, associada às mudanças na compreensão mundial do ambiente, fizeram emergir as mudanças na percepção,no imaginário, na diversidade da cultura urbana, no espaço construído de nosso ambiente, no cotidiano das paisagens urbanas. O contexto da época contemporânea levanta desafios na construção do conhecimento, nas pesquisas e no ensino no campo da paisagem.
Parques lineares do Tremembé: o uso de infraestruturas verdes na criação de um sistema de espaços livres
Authors: Lima Gerson Amaral , Pellegrino Paulo Renato Mesquita
Published: October 2015

Este trabalho consiste na elaboração de uma proposta de intervenção paisagística numa porção da Subprefeitura Jaçanã/Tremembé no município de São Paulo. A região compõe a zona de amortecimento do Parque Estadual da Cantareira, e o adensamento construtivo do bairro constitui uma ameaça à preservação do meio ambiente local. O projeto toma como diretriz o tratamento das águas urbanas, especialmente na requalificação dos fundos de vales, introduzindo novos conceitos de manejo das águas urbanas que se baseiam na ideia de Desenvolvimento de Baixo Impacto (Low Impact Development – LID). A proposta deste trabalho busca, também, estabelecer novas relações entre a cidade e os seus recursos naturais, tecendo novas costuras entre a floresta e a cidade.
Os córregos ocultos e seus resquícios nos espaços livres urbanos: os afluentes do córrego Mandaqui
Authors: Cabral Arthur Simões Caetano
Published: October 2015

O presente artigo visa a contextualizar, enquanto testemunhos das características geomorfológicas originais do sítio, cursos d’água da bacia do córrego Mandaqui, canalizados e tamponados no decorrer da consolidação urbana da zona norte paulistana. Tal contextualização, no entanto, mostra-se reveladora não apenas de elementos naturais historicamente negados enquanto paisagem, mas também de relações afetivas diversas estabelecidas entre o homem e as águas. A experiência dos espaços associados aos afluentes do Mandaqui demonstra a possibilidade de retomar a consciência sobre a existência de pequenos córregos tamponados em São Paulo. Por meio de vestígios, os córregos ocultos insinuam-se à superfície. Pouco a pouco, o olhar de quem se encontra em tais espaços é inevitavelmente conduzido, entre becos e vielas, a percorrer o trajeto esculpido pelas águas. Estas, ainda que apartadas da superfície, por meio de seus vestígios demonstram a impossibilidade do fazer humano em apagar por completo certos traços da natureza primitiva. O trabalho do qual resulta o presente artigo integra os estudos de caso da margem direita do Tietê, realizados no âmbito da pesquisa acerca dos Córregos Ocultos, coordenada pelo Prof. Dr. Vladimir Bartalini junto ao Laboratório da Paisagem, Arte e Cultura da Faculdade de Arquitetura e Urbanismo da Universidade de São Paulo.
Tissue-Specific Cell Cycle Indicator Reveals Unexpected Findings for Cardiac Myocyte Proliferation
Authors: Hirai Maretoshi , Chen Ju , Evans Sylvia M.
Published: October 2015

Rationale
:

Discerning cardiac myocyte cell cycle behavior is challenging owing to commingled cell types with higher proliferative activity.

Objective
:

To investigate cardiac myocyte cell cycle activity in development and the early postnatal period.

Methods and Results
:

To facilitate studies of cell type–specific proliferation, we have generated tissue-specific cell cycle indicator BAC transgenic mouse lines. Experiments using embryonic fibroblasts from CyclinA2-LacZ-floxed-EGFP, or CyclinA2-EGFP mice, demonstrated that CyclinA2-βgal and CyclinA2-EGFP were expressed from mid-G1 to mid-M phase. Using Troponin T-Cre;CyclinA2-LacZ-EGFP mice, we examined cardiac myocyte cell cycle activity during embryogenesis and in the early postnatal period. Our data demonstrated that right ventricular cardiac myocytes exhibited reduced cell cycle activity relative to left ventricular cardiac myocytes in the immediate perinatal period. Additionally, in contrast to a recent report, we could find no evidence to support a burst of cardiac myocyte cell cycle activity at postnatal day 15.

Conclusions
:

Our data highlight advantages of a cardiac myocyte–specific cell cycle reporter for studies of cardiac myocyte cell cycle regulation.
Ensemble Prediction of the Dispersion of Volcanic Ash from the 13 February 2014 Eruption of Kelut, Indonesia
Authors: Dare Richard A. , Smith David H. , Naughton Michael J.
Published: October 2015

A meteorological ensemble prediction system that represents uncertainties in both initial conditions and model formulations is coupled with a modified version of the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model. This coupled dispersion ensemble prediction system (DEPS) is used to generate a 24-member ensemble forecast of the dispersion of the volcanic ash cloud produced by the 13 February 2014 eruption of Kelut, Indonesia. Uncertainties in the volcanic ash source are not represented. For predictions up to 12 h from the start of the eruption, forecasts from the deterministic control member and from the DEPS both show very good qualitative agreement with satellite observations. By 18–24 h the DEPS forecast shows better qualitative agreement with observations than does the deterministic forecast. Although composited fields such as the ensemble mean and probability present information concisely, experiments here show that it is very important to also consider results from individual member forecasts in order to identify features that may be underrepresented. For example, an area of relatively high ash concentration that was forecast by most of the members was not particularly evident in the composited fields because the location of this feature was highly variable between member forecasts. To fully understand a DEPS forecast, it is necessary to consider both atmospheric column load and concentration fields, individual member forecasts, and a range of thresholds in computing and interpreting probabilities.
Nearest Neighbor–Genetic Algorithm for Downscaling of Climate Change Data from GCMs
Authors: Kim Soojun , Kwak Jaewon , Kim Hung Soo , Jung Younghun , Kim Gilho
Published: October 2015

The spatial and temporal resolution of readily available climate change projections from general circulation models (GCM) has limited applicability. Consequently, several downscaling methods have been developed. These methods predominantly focus on a single meteorological series at specific sites. Spatial and temporal correlation of the precipitation and temperature fields is important for hydrologic applications. This research uses a nearest neighbor–genetic algorithm (NN–GA) method to analyze the Namhan River basin in the Korean Peninsula. Using the simulation results of the CNRM-CM for the RCP 8.5 climate change scenario, archived in the fifth phase of the Coupled Model Intercomparison Project (CMIP5), the GCM projections are downscaled through the NN–GA. The NN–GA simulations reproduce the features of the observed series in terms of site statistics as well as across variables and sites.
Career Funneling
Authors: Binder Amy J. , Davis Daniel B. , Bloom Nick
Published: October 2015

Elite universities are credited as launch points for the widest variety of meaningful careers. Yet, year after year at the most selective universities, nearly half the graduating seniors head to a surprisingly narrow band of professional options. Over the past few decades, this has largely been into the finance and consulting sectors, but increasingly it also includes high-tech firms. This study uses a cultural-organizational lens to show how student cultures and campus structures steer large portions of anxious and uncertain students into high-wealth, high-status occupational sectors. Interviewing 56 students and recent alumni at Harvard and Stanford Universities, we found that the majority of our respondents experienced confusion about career paths when first arriving at college but quickly learned what were considered to be the most prestigious options. On-campus corporate recruitment for finance, consulting, and high-tech jobs functioned as a significant driver of student perceptions of status; career prestige systems built up among peers exacerbated the funneling effect into these jobs. From these processes, students learned to draw boundaries between ‘‘high-status’’ and ‘‘ordinary’’ jobs. Our findings demonstrate how status processes on college campuses are central in generating preferences for the uppermost positions in the occupational structure and that elite campus environments have a large, independent role in the production and reproduction of social inequality.
Supplemental Parenteral Vitamin E Into Conventional Soybean Lipid Emulsion Does Not Prevent Parenteral Nutrition–Associated Liver Disease in Full‐Term Neonatal Piglets
Authors: Muto Mitsuru , Lim David , Soukvilay Amanda , Field Catherine , Wizzard Pamela R. , Goruk Susan , Ball Ronald O. , Pencharz Paul B. , Mi Si , Curtis Jonathan , Wales Paul W. , Turner Justine M.
Published: October 2015

Background: Parenteral nutrition–associated liver disease (PNALD) continues to cause morbidity and mortality for neonates with intestinal failure. Lipid peroxidation is one potential etiological factor. This study was designed to test if supplementing vitamin E into conventional soy‐based lipid would reduce the risk of PNALD. Methods: Sixteen piglets, aged 2–5 days and weighing 1.8–2.5 kg, were randomized to parenteral nutrition (PN) with soy lipid (SO, n = 8) or the same lipid plus α‐tocopherol, the most bioactive form of vitamin E (SO+E, n = 8). After 17 days, bile flow, liver chemistry, gene expression associated with bile acid metabolism, and bile acid composition were assessed. C‐reactive protein (CRP) and oxidative stress markers, including plasma 8‐isoprostane, were measured. All results were compared with a sow‐reared control group (CON). Results: Comparing PN‐treated groups, SO vs SO+E mean bile flow (5.91 vs 5.54 µL/g liver; P = .83), serum bile acid concentration (39.2 vs 26.6 µmol/L; P = .12), and total bilirubin (35.2 vs 26.9 µmol/L; P = .56) were not different. Gene expression related to bile acid metabolism and bile composition was not different between PN groups. There was no difference in CRP (41.8 vs 36.8 µg/mL; P = .22) or in plasma 8‐isoprostane (27.9 vs 26.1 pg/mL; P = .77). Conclusions: In term neonatal piglets, supplemental vitamin E did not prevent cholestasis. Additional vitamin E was not associated with reduced inflammation or oxidative stress. The benefit of supplementing vitamin E into conventional lipid, vs adding fish oil, to prevent early onset of PNALD requires further clarification.
Urban fringe belts: evidence from China
Authors: Whitehand JWR , Gu Kai
Published: October 2015

Research on the fringe-belt concept has grown significantly in the past decade. This is particularly evident in parts of the world in which interest in urban morphology has been slight until recently. The main emphasis continues to be the light that this concept can shed on the historico-geographical grain of urban areas. This paper reports a morphogenetic investigation into fringe belts that gives particular attention to the fixation lines associated with Chinese city walls. Discussion is concentrated on a fringe belt related to one of the world’s longest and most massive city walls, that of Nanjing. The formation, consolidation and, in places, alienation of the Ming fringe belt of Nanjing has been influenced by natural and artificial fixation lines and the political economy of an authoritarian society. Understanding the changing spatial structure of fringe-belt landscapes has implications for the management of urban form in ways sensitive to its historico-geographical development.
Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations
Authors: Oh Joo Han , Kim Woo , Park Kyoung Un , Roh Young Hak
Published: October 2015

Background:

Variations in formulations used to prepare platelet-rich plasmas (PRPs) result in differences in the cellular composition and biomolecular characteristics.

Purpose:

To evaluate the cellular composition and the cytokine-release kinetics of PRP according to differences in the preparation protocols.

Study Design:

Controlled laboratory study.

Methods:

Five preparation procedures were performed for 14 healthy subjects, including 2 manual procedures (single-spin [SS] at 900 g for 5 minutes; double-spin [DS] at 900 g for 5 minutes and then 1500 g for 15 minutes) and 3 methods with commercial kits (Arthrex ACP, Biomet GPS, and Prodizen Prosys). After evaluation of cellular composition, each preparation was divided into 4 aliquots and incubated for 1 hour, 24 hours, 72 hours, and 7 days for the assessment of cytokine release over time. The cytokine-release kinetics were evaluated by assessing platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-1 (IL-1), and matrix metalloproteinase–9 (MMP-9) concentrations of each aliquot with bead-based sandwich immunoassay.

Results:

The DS PRP had a higher concentration of platelets and leukocytes than did the SS PRP. Every PRP preparation exhibited an increase in PDGF, TGF, VEGF, and FGF release when compared with whole blood samples. The FGF and TGF release occurred quickly and decreased over time, while the PDGF and VEGF release was constant and sustained over 7 days. The PDGF and VEGF concentrations were higher in the DS PRP than in the SS PRP, whereas the TGF and FGF concentrations were higher in the SS PRP than in the DS PRP. Biomet GPS had the highest VEGF and MMP-9 concentrations but the lowest TGF concentration. Arthrex ACP had the highest FGF concentration but the lowest PDGF concentration. Prodizen Prosys had the highest IL-1 concentration and higher PDGF concentration than Arthrex ACP.

Conclusion:

The DS method generally led to a higher concentration of platelet relative to the SS method. However, the cytokine content was not necessarily proportional to the cellular composition of the PRPs, as the greater content could be different between the SS or DS method depending on the type of cytokine.

Clinical Relevance:

Physicians should select proper PRP preparations after considering their biomolecular characteristics and patient indications.
Trends in Global Nutrition Policy and Implications for Japanese Development Policy
Authors: Nomura Marika , Takahashi Kenzo , Reich Michael R.
Published: October 2015

Background:

Although the issue of nutrition was long underrepresented in the global health agenda, it regained international attention with the introduction of the Scaling Up Nutrition (SUN) framework. A historical review of global nutrition policies over 4 decades illustrates the evolution of nutrition policy themes and the challenges confronted by SUN.

Objective:

This study reviews major events in global nutrition policy from the 1970s to the SUN movement around 2010 to illustrate the dynamics of global agenda setting for nutrition policy along with implications for the government of Japan.

Methods:

The events are categorized according to each decade’s nutrition paradigm: nutrition and its socioeconomic features in the 1970s, nutrition and community programs in the 1980s, nutrition as a political issue in the 1990s, and nutrition and evidence in the 2000s.

Results:

This study identified 2 findings: First, the arguments that led to a global consensus on nutrition policy generated paradigm shifts in core ideas, and second, in response to these paradigm shifts, global nutrition policies have changed significantly over time. With regard to Japan, this analysis concludes that the government of Japan can take a greater initiative in the global health community as supporter of SUN by strategically developing a combination of financial, political, and practical approaches to improve global nutrition policy through the concepts of Universal Health Coverage and Human Security.
Food Justice, Direct Action, and the Human Rights Enterprise
Authors: Shannon Deric
Published: October 2015

Scholars developing a concept they call the ‘human rights enterprise’ suggest a theory of human rights guaranteed, in some cases, by social movements from below and often against the wishes of the state. This article draws on data from an ethnography conducted in a small Food Not Bombs collective to critically assess the radical potential and pitfalls of the claims made by scholars promoting the human rights enterprise and the social movement organizations using the language of ‘rights’ to frame their direct action-oriented praxis.
Precariat – What it Is and Isn’t – Towards an Understanding of What it Does
Authors: Jørgensen Martin Bak
Published: October 2015

Guy Standing’s description of the precariat in his 2011 book has revitalized the debate on what the precariat is, and what it is not. Although the book faced criticism from labour studies, Marxist approaches and others, it opened up a new discussion of precarity under neoliberal capitalism. This article draws on understandings that link the notion of the precariat (and processes of precarization) to practices and investigates links between immigration and precarity. It argues that the analysis of what precarity is should be supplemented by an inquiry into what it does. Precarity is here understood as a mode for analysing economy and for rethinking heterogeneous identities and group formations. The article uses two cases, Lampedusa in Hamburg 2013–2015 and the “Freedom Not Frontex” action in June 2014, to illustrate how processes of precarization play out in everyday life situations and the economic, legal and social system for immigrants.
Development of an immunochromatographic strip for antibody detection of pseudorabies virus in swine
Authors: Li Xiujie , Sun Yaning , Yang Suzhen , Wang Yinbiao , Yang Jifei , Liu Yunchao , Jin Qianyue , Li Xuewu , Guo Chengliu , Zhang Gaiping
Published: October 2015

An immunochromatographic strip was developed for the serological detection of pseudorabies virus (PRV) in swine. In the strip, the expressed protein of gB, one of the glycoproteins of PRV, labeled with colloidal gold, was used as the detector; staphylococcal protein A and swine anti–pseudorabies virus antibody were blotted on nitrocellulose membrane for the test and control lines, respectively. The specificity of the strip was 98.1%, and the sensitivity of the strip with reference anti-PRV serum was 96.0%. Swine serum samples (296) were collected to evaluate the characteristics of the strip in comparison with an existing commercial kit. The agreement was 93.6%. Furthermore, the dipstick assay based on the strip is rapid (5 min) and easy to perform with no requirement of professional skills, reagents, or equipment. This suggests that the immunochromatographic strip is an acceptable alternative for use in clinical laboratories lacking specialized equipment and for field diagnosis.
Positive Mental Well-Being
Authors: Houghton Stephen , Wood Lisa , Marais Ida , Rosenberg Michael , Ferguson Renee , Pettigrew Simone
Published: October 2015

This study presents a Rasch-derived short form of the Warwick-Edinburgh Mental Well-Being Scale for use as a screening tool in the general population. Data from 2,005 18- to 69-year-olds revealed problematic discrimination at specific thresholds. Estimation of model fit also deviated from Rasch model expectations. Following deletion of 4 items, the 10 remaining items indicated the data fitted the model. No items showed differential item functioning, thereby making comparisons of overall positive mental well-being for the different age, gender, and income groups valid and accurate. Cronbach’s alpha and Rasch Person Separation Index indicated a strong degree of reliability. Overall, the 10-item scale challenges researchers and clinicians to reconsider the assessment of positive mental well-being.
Natural frequency analyses of segmented Timoshenko–Euler beams using the Rayleigh–Ritz method
Authors: Mazanoglu Kemal
Published: October 2015

This paper proposes part by part usage of Timoshenko and Euler–Bernoulli beam theories for obtaining natural frequencies of the non-uniform beam that has partially thick and thin beam vibration characteristics. The paper also presents convergence tests to determine proper function among the simple admissible shape functions taken into consideration. By doing so, closer approximation of the Rayleigh–Ritz method is achieved. The method is applied using a simple computation technique. In the analyses of the Timoshenko beams, an additional function is employed to identify shear deformation and rotational inertia effects. Modified angular displacement functions are defined to improve convergence capability of the method. Furthermore, optimal numbers of lateral and angular displacement terms are investigated for suggested function couple of the Timoshenko beams. Efficiencies of part by part modelling and advantages of novel approaches suggested for the Rayleigh–Ritz approximation are introduced by the comparative studies performed on tapered, stepped and continuously segmented beams under some classical end conditions. All of the computational outcomes for the beams with rectangular cross-section are validated by the results given in current literature and also those obtained by the finite element analyses.
Successful use of high-dose cytarabine in a patient with acute myeloid leukemia and severe hepatic dysfunction
Authors: Barker Jacob A , Marini Bernard L , Bixby Dale , Perissinotti Anthony J
Published: October 2015

Acute myeloid leukemia is a hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and other tissues. Prognosis is poor with 5-year survival rates ranging from 5–65% depending on demographic and clinical features. Outcomes are worse for patients that have an antecedent myeloproliferative neoplasm that evolves to acute myeloid leukemia, with a survival rate of <10%. Treatment for acute myeloid leukemia has remained cytarabine and an anthracycline given in the standard 3 + 7 regimen. However, for patients with liver dysfunction this regimen, among many others, cannot be given safely. There is currently a lack of data regarding the use of cytarabine in patients with severe hepatic dysfunction. In this case report, we present a patient with secondary acute myeloid leukemia who successfully received a modified regimen of high-dose cytarabine while in severe hepatic dysfunction (bilirubin >15 mg/dL).
Setting and within-class ability grouping
Authors: Wilkinson Shaun , Penney Dawn , Allin Linda
Published: October 2015

Within the United Kingdom and internationally, the practice of separating pupils by ability endures as a characteristic feature of mathematics and science classrooms. Although there is extensive international research literature on ability grouping within classroom-based subjects, limited research exists in the context of physical education (PE). The purpose of this paper is to explore ability grouping in PE in North East of England schools. Specifically, the paper examined the prevalence of setting and within-class ability grouping in PE, the contexts of its use, how sets and within-class ability grouping were established, and the rationales used to justify decisions about setting and within-class ability grouping in the subject. Data were collected via a web-based survey. The electronic survey was sent to 194 PE Heads of Department from North East of England schools catering for pupils in Key Stage 3 (ages 11–14) and/or Key Stage 4 (ages 14–16). The results indicated that setting is embedded in the organisational and pedagogical practices of PE in many secondary schools. Ability also served as a basis upon which to organise pupils within mixed-ability and setted PE lessons. A variety of other factors, including friendship and behaviour, were also reported as factors influencing grouping of pupils in PE lessons. Our discussion directs attention to issues arising for policy and practice in PE and points to the merits of further exploration and analysis of between-class and within-class grouping practices in the subject.
The public health response to ‘do-it-yourself’ urbanism
Authors: Sibbald Shannon L. , Graham Ross , Gilliland Jason
Published: October 2015

Greater understanding of the important and complex relationship between the built environment and human health has made ‘healthy places’ a focus of public health and health promotion. While current literature concentrates on creating healthy places through traditional decision-making pathways (namely, municipal land use planning and urban design processes), this paper explores do-it-yourself (DIY) urbanism: a movement circumventing traditional pathways to, arguably, create healthy places and advance social justice. Despite being aligned with several health promotion goals, DIY urbanism interventions are typically illegal and have been categorized as a type of civil disobedience. This is challenging for public health officials who may value DIY urbanism outcomes, but do not necessarily support the means by which it is achieved. Based on the literature, we present a preliminary approach to health promotion decision-making in this area. Public health officials can voice support for DIY urbanism interventions in some instances, but should proceed cautiously.