bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B102: Releasing oxygen-restricted CTL function: Insights from live intratumoral imaging
Authors: Feferman Tali , Manaster Yoav , Gruper Yael , Shipony Zohar , Shakhar Guy
Published: May 2016

Poor tumor vascularization is an obstacle to immunotherapy by CTLs. It impairs tumor infiltration but also introduces hypoxia, known to interfere with T cell migration. It is yet unknown how suboptimal vascularization affects CTL migration and function within tumors. To study this question, we combined immunohistochemistry of human melanoma samples with two-photon imaging in live mice. Orthotopically implanted B16-OVA tumors were studied after adoptive transfer of in-vitro matured antigen-specific OT-I CTLs. In patients, CD8 T cells concentrated around peripheral vessels in the tumor and sparsely infiltrated avascular areas. This pattern was clearest in poorly-infiltrated tumors. In mice, OT-I CTLs, as well as polyclonal CTLs, entered tumors through inflamed intratumoral vessels, and crawled only in oxygenated areas within 50 µm of flowing blood vessels. Gradually, CTLs formed dense perivascular swarms, which eliminated nearby target cells leading to patchy tumor clearance around blood vessels. Occluding intratumoral blood vessels triggered immediate arrest of CTL motility, which was quickly reversed when flow was resumed. Immunohistology indicated that CTLs avoided hypoxic tumor areas. Live CTL imaging in vitro showed deceleration under hypoxic conditions and when oxidative phosphorylation was blocked. To circumvent intratumoral CTL dysfunction we attempted to increase vascular density by implanting tumors in matrices containing bFGF. bFGF-laced tumors were more easily rejected after transfer of CTLs and displayed delayed growth in untreated mice but were not affected in mice deficient in CD8 T-cells. CTLs infiltrated such tumors in normal numbers, but displayed enhanced motility in highly-vascular tumors, suggesting that enhanced rejection resulted from improved intratumoral CTL migration. Taken together, the results suggest that hypoxia limits CTL function away from blood vessels, and that alleviating it may synergize with immunotherapy.

Citation Format: Tali Feferman, Yoav Manaster, Yael Gruper, Zohar Shipony, Guy Shakhar. Releasing oxygen-restricted CTL function: Insights from live intratumoral imaging. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B102.
Abstract B107: In vivo mouse breast cancers-xenograft imaging with radiolabeled recombinant Flagellin
Authors: Hou Guihua
Published: May 2016

Recently it was noted that Toll-like receptor 5 (TLR5), the only protein recognition receptor of TLRs, high expressed in breast cancers and closely related to tumor development. In this study, we aimed to evaluate whether TLR5 could serve as a molecular target for breast cancer monitoring.

BALB/c mice were implanted with breast cancer line MCF-7 to establish a tumor-bearing mice model. Dynamic whole-body phosphor-autoradiography in vivo and ex vivo biodistribution studies were performed after 131I-recombinant Flagellin (rFliC, a specific ligand of TLR5) injection through the tail vein.

131I- rFliC was successfully prepared with Iodogen method. The uptake of MCF-7 to 131I-rFliC was quickly, and reached the highest point at 6h. Dynamic phosphor-autoradiography imaging showed clear tumor localization of tracer from 1 h onward. At 6 h after injection, tumor uptake was the highest. Pre-treatment with anti-TLR5 mAb obviously blocked tumor uptake of tracer. Biodistribution study reflected the same tendency, and obviously 131I- rFliC uptake of tumor was obtained at 3h after tracer injection, and reached a maximum of T/NT ratio(tumor to muscle,7.09 ± 1.86 %ID/g (percent injected dose per gram) at 24 h compared with naïve mice. Immunohistochemistry staining showed higher expression of TLR5 in tumor tissue, supported the results of phosphor-autoradiographagy and ex vivo biodistrbution studies.

These data suggested that radiolabeled rFliC could quickly localise in tumor tissue, which may be as a new tracer for non-invasive in vivo imaging of TLR5 in breast cancer.

Citation Format: Guihua Hou. In vivo mouse breast cancers-xenograft imaging with radiolabeled recombinant Flagellin. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B107.
Abstract B121: Low dose, metronomic cyclophosphamide therapy sensitizes tumors to CpG-1826 immunotherapy in a preclinical glioma model
Authors: Jordan Marie , Waxman David J.
Published: May 2016

Metronomic chemotherapy, in which cytotoxic drugs are delivered at low doses at regular, intermittent intervals, has shown promising clinical results in several cancers and offers the benefit of reduced patient toxicity compared to conventional maximum tolerated dose chemotherapy. We previously showed that cyclophosphamide (CPA) treatment on a 6-day repeating metronomic schedule regresses implanted gliomas by an immune-mediated mechanism. Here, we examine whether this immune-stimulatory metronomic chemotherapy can be enhanced by combination with TLR9-stimulating CpG-1826 immunotherapy in GL261 gliomas implanted in immunocompetent BL6 mice. CpG-1826 treatment activated an anti-tumor immune response in ~50% of mice, associated with a strong increase in tumor-associated macrophages. CpG-1826 was ineffective against GL261 tumors implanted in T cell- and B cell-deficient scid mice, suggesting that adaptive immunity is essential. Combination of CpG-1826 with metronomic CPA sensitized GL261 gliomas in both CpG-1826-responsive and CpG-1826-non-responsive mice, increasing infiltration of tumor-associated macrophages, dendritic cells, and T cells and increasing anti-tumor activity. Further, the combination treatment elicited long-term regression and immune memory in a subset of glioma-bearing mice. To identify potential mechanisms for this enhanced response to the combination therapy, we assayed a number of immune-related genes in the treated tumors, including feedback inhibitory immunosuppressive T cell factors that are induced by metronomic CPA treatment. Combination of CpG-1826 with metronomic CPA failed to induce several of these factors, suggesting that TLR9-based immunotherapy can enhance the anti-tumor activity of metronomic CPA by interdicting feedback immune inhibition mechanisms. Grant support: CA49248 (to DJW).

Citation Format: Marie Jordan, David J. Waxman. Low dose, metronomic cyclophosphamide therapy sensitizes tumors to CpG-1826 immunotherapy in a preclinical glioma model. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B121.
Abstract B122: A preclinical mouse model to assess antitumor efficacy and development of immune related adverse events (irAEs) following combination immunotherapies
Authors: Liu Jing , Blake Stephten J. , Fairfax Kirsten A. , Yong Michelle C.R. , Allen Stacey , Smyth Mark J. , Teng Michele W.L.
Published: May 2016

Given that new immunotherapies in combination are displaying both efficacy and immune related adverse events (irAEs) in humans, there is a need to promptly develop a pre-clinical mouse model that can evaluate the therapeutic index (efficacy versus safety) of current and novel immunotherapies. We demonstrated that transient or prolonged T regulatory cell (Treg) depletion in tumor bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of anti-tumor responses and severity of irAEs that can occur in ipilimumab/nivolumab treated patients. We showed that transient Treg depletion with DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies (mAbs) had a high therapeutic index compared to DT plus anti-CD137. While all three mAbs suppressed tumor growth, tumor rejection was more frequently observed in the DT plus anti-PD-1 or DT plus anti-TIM-3 combinations, depending on the tumor type, and these mice developed only mild irAEs. In contrast, mice treated with DT plus anti-CD137 developed severe irAEs characterized by infiltration of activated T cells into peripheral organs, liver toxicities and elevated levels of inflammatory cytokines, similar to grade 3/4 clinical symptoms. These irAEs appeared due to an infiltration of activated proliferating effector T cells in the tissues producing IFNγ and TNF, however, TNF blockade decreased the severity of irAEs in these mice without impacting on tumor growth. This model may now be used to pre-clinically assess the therapeutic indices of novel immunotherapy combinations to understand their mechanism of action and safety.

Citation Format: Jing Liu, Stephten J. Blake, Kirsten A. Fairfax, Michelle C.R. Yong, Stacey Allen, Mark J. Smyth, Michele W.L. Teng. A preclinical mouse model to assess antitumor efficacy and development of immune related adverse events (irAEs) following combination immunotherapies. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B122.
Abstract B130: Evaluation of novel metronomic chemotherapy and cancer vaccine combinatorial strategy
Authors: Tagliamonte Maria , Petrizzo Annacarmen , Tornesello Maria Lina , Luciano Antonio , Rea Domenica , Barbieri Antonio , Arra Claudio , Napolitano Maria , Ciliberto Gennaro , Aurisicchio Luigi , Coscia Claudio , Baechle Tobias , Buonaguro Franco M. , Buonaguro Luigi
Published: May 2016

The efficacy of cancer immunotherapy approaches can be significantly hampered by the tumor immune suppressive microenvironment. In the present study, a novel combinatorial strategy (i.e. metronomic chemotherapy plus vaccine) is evaluated in a mouse model in an aggressive therapeutic setting based on sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy is a multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The vaccine is a multi-peptide cocktail of universal tumor antigen hTERT epitopes adjuvanted in Montanide.

Immunizations have been performed comparing a standard sub-cutaneous delivery with a laser-assisted epidermal immunogen delivery by P.L.E.A.S.E.™ Professional (Pantec Biosolutions). The latter, indeed, creates evenly distributed micropores through to the epidermis and provides a great opportunity to efficiently deliver vaccine antigens to Langerhans cells (LC) in the epidermis.

An interim analysis shows that the immunogenicity as well as the therapeutic effect on tumor growth of the vaccine is significantly increased by the combination with metronomic chemotherapy, and the laser-assisted epidermal immunogen delivery appears to be a very effective strategy as vaccine delivery. Complete description of both immunogenicity and therapeutic effects on tumor growth will be described.

Citation Format: Maria Tagliamonte, Annacarmen Petrizzo, Maria Lina Tornesello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Maria Napolitano, Gennaro Ciliberto, Luigi Aurisicchio, Claudio Coscia, Tobias Baechle, Franco M. Buonaguro, Luigi Buonaguro. Evaluation of novel metronomic chemotherapy and cancer vaccine combinatorial strategy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B130.
Abstract B150: Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network
Authors: Lu Haihui , Tam Wai Leong , Donnenberg Vera , Ye Xin , Bhargava Rohit , Weinberg Robert
Published: May 2016

The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. In addition, EMT upregulates the expression of cell surface receptors that enable CSCs to interact with their surrounding microenvironment in order to sustain their stem cell state. We discovered that EphA4 and CD90, two cell surface proteins upregulated in the carcinoma cells by the EMT, mediate juxtacrine signalling between the CSCs and tumor-associated monocytes and macrophages (TAMs). When engaged with its counter-receptor on TAMs, EphA4 on the CSCs activates Src and PLCγ1, the latter resulting in the translocation of NF-κB into the nucleus, which cooperates with Twist to drive the rapid induction of a variety of cytokines in the CSCs. Among the secreted cytokines IL-8 and IL-6 maintain the CSC-state by reinforcing the expression of the EMT-inducing transcription factors, whereas other cytokines GM-CSF, M-CSF and IL-10 recruit monocytes and induce their differentiation into M2-like macrophages. Together these cytokines perpetuate the CSC-promoting interactions between CSCs and TAMs. Indeed, admixed TAMs promote the tumor-initiating ability of CSCs whereas ablation of endogenous macrophages substantially diminished tumor initiation. Importantly, the juxtaposition of TAMs with the mesenchymal-like CD90high CSCs can be observed at the invading edge in primary human breast tumor sections and xenograft tumors. On the contrary, we rarely find TAMS infiltrating beyond the edge of tumors into the regions where the CD90neg non-stem carcinoma cells reside. These findings underscore the importance of TAMs as critical components of the CSC niche and highlight their potential as therapeutics targets.

Citation Format: Haihui Lu, Wai Leong Tam, Vera Donnenberg, Xin Ye, Rohit Bhargava, Robert Weinberg. Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B150.
Abstract IA03: Antitumor activity of immunomodulatory antibodies
Authors: Korman Alan J.
Published: May 2016

Immunomodulatory antibodies activate antitumor responses through multiple mechanisms. These include activation of T cells through the inhibition of negative T cell regulators (known as checkpoint blockade), as well as through the engagement of T cell costimulatory receptors with agonistic antibodies. Antibodies which block CTLA-4 function through inhibition of ligand binding were observed to derive much of their anti-tumor activity through the engagement of activating Fc receptors (Selby et al. Cancer Imm Res 2013; Simpson et al. J Exp Med 2013). This activity was due to the depletion of CTLA-4-positive regulatory T cells uniquely at the tumor site. Related observations for agonistic antibodies to GITR and OX40 (Bulliard et al. J Exp Med 2013, Bulliard et al. Immunol Cell Biol 2014) have led to the reevaluation of the mechanism of action of many immunomodulatory antibodies. We have extended the study of the role of immunoglobulin isotype on the mechanism of action of antibodies to a variety of negative regulators, including PD-1 and PD-L1, and multiple costimulatory molecules, including CD137. In addition, the role of human IgG2 hinge variants on the properties of immunomodulatory antibodies has also been studied. These results have significant impact on the design of therapeutic antibodies. The development of antibodies in which specific T cell functions are targeted will lead to superior choices in considerations for combination cancer immunotherapy.

Citation Format: Alan J. Korman. Antitumor activity of immunomodulatory antibodies. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA03.
Abstract IA06: Targeting the mutanome for individualized cancer immunotherapy
Authors: Sahin Ugur
Published: May 2016

Mutations are regarded as ideal targets for cancer immunotherapy. As neo-epitopes with strict lack of expression in any healthy tissue, they are expected to be safe. The systematic use of mutations for vaccine approaches, however, is hampered by the uniqueness of the repertoire of mutations (the mutanome) in every patient's tumor. We have recently proposed a personalized immunotherapy approach targeting the spectrum of individual mutations. Preclinically we could show in three independent murine tumor models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that unexpectedly the immunogenic mutanome is pre-dominantly recognized by CD4+ T cells (the CD4+ immunome). Vaccination with such CD4+ immunogenic mutations confers strong antitumor activity. Encouraged by these findings we set up a process comprising mutation detection by exome sequencing, selection of vaccine targets by solely bioinformatical prioritization of mutated epitopes predicted to be abundantly expressed and good MHC class II binders and rapid production of synthetic mRNA vaccines encoding multiple of these mutated epitopes. We show that vaccination with such poly-neo-epitopic mRNA vaccines induces potent tumor control and complete rejection of established aggressively growing tumors in mice.

End of 2013 this approach has been translated from bench to bedside when a first in human clinical study started demonstrating the clinical feasibility of the approach (NCT02035956). This tailored immunotherapy approach may be regarded as a universally applicable blueprint for comprehensive exploitation of the huge neo-epitope target repertoire of cancers enabling the treatment of patients by targeting every patient's tumor with individual just in time produced vaccines.

Citation Format: Ugur Sahin. Targeting the mutanome for individualized cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA06.
Abstract IA24: Immune checkpoint therapy: Immune monitoring on presurgical and tissue-based clinical trials
Authors: Sharma Padmanee
Published: May 2016

Immune checkpoint therapies, including anti-CTLA-4, anti-PD-1 and anti-PD-L1, have led to significant clinical responses in cancer patients. To investigate immunologic changes and mechanistic pathways that are elicited by these therapies, we conducted pre-surgical clinical trials, which permit access to sufficient tumor tissues for laboratory studies. The first pre-surgical trial was conducted with anti-CTLA-4 (ipilimumab) in a cohort of patients with localized bladder cancer. This trial provided access to sufficient tumor-infiltrating lymphocytes to conduct phenotypic and functional studies on these cells, which indicated the ICOS/ICOSL pathway as relevant for anti-tumor immune responses in the setting of anti-CTLA-4 therapy. In addition, since standard agents that enable tumor cell death may allow for priming of a T cell immune response that can be augmented by combination with CTLA-4 blockade, we conducted a pre-surgical clinical trial with androgen deprivation (hormonal) therapy ADT+ anti-CTLA-4 (ipilimumab), in the setting of patients with regional, high-risk prostate cancer. These pre-surgical clinical trials, and other tissue-based clinical trials, led to the identification of biomarkers and additional targets. These data, which are being used to design future immunotherapy trials, will be discussed in greater details.

Citation Format: Padmanee Sharma. Immune checkpoint therapy: Immune monitoring on presurgical and tissue-based clinical trials. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA24.
Abstract IA38: Engineered T cell-receptor based therapy of pancreatic ductal adenocarcinoma
Authors: Stromnes Ingunn M. , Schmitt Thomas M. , Brockenbrough Scott J. , Nguyen Hieu , Cuevas Carlos , Hulbert Ayaka , Hotes Jennifer , Dotson Ashley , Hingorani Sunil R. , Greenberg Philip D.
Published: May 2016

Pancreatic ductal adenocarcinoma (PDA) presents a formidable challenge for effective therapies given the robust desmoplasia, immunosuppressive elements and relatively few coding mutations characteristic of this disease. We demonstrate the safety and therapeutic activity of T cells engineered to express an affinity-enhanced T cell receptor (TCR) targeting the naturally overexpressed self/tumor antigen Mesothelin in an autochthonous, genetically engineered mouse model of PDA (KPC). Notably, despite the hostile tumor microenvironment surrounding PDA, the engineered T cells readily infiltrate the desmoplastic tumor, induce tumor cell lysis and remodel the tumor extracellular matrix without causing detectable toxicity in normal tissues. The transferred T cells persist in PDA, but antitumor activity is transient, as the tumor-infiltrating donor T cells upregulate a panel of inhibitory receptors and become progressively dysfunctional specifically in PDA that is due to both TCR-dependent and independent mechanisms of inhibition. This obstacle to sustained therapeutic activity can be overcome by serial T cell infusions, which mediate objective responses and a near doubling of KPC survival without overt toxicities. Similarly engineered human T cells recognize and lyse PDA cells in vitro, further supporting the clinical advancement of this TCR-based strategy for the treatment of human PDA.

Citation Format: Ingunn M. Stromnes, Thomas M. Schmitt, Scott J. Brockenbrough, Hieu Nguyen, Carlos Cuevas, Ayaka Hulbert, Jennifer Hotes, Ashley Dotson, Sunil R. Hingorani, Philip D. Greenberg. Engineered T cell-receptor based therapy of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA38.
Genetics of Common Antipsychotic-Induced Adverse Effects
Authors: MacNeil Raymond R. , Müller Daniel J.
Published: May 2016

The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted.
Temperatura ambiente e concentrações séricas de cortisol em suínos em crescimento-terminação
Authors: Fagundes Antonio César Alves , Negrão João Alberto , Silva Roberto Gomes da , Gomes Jacinta Diva Ferrugem , Souza Luiz Waldemar de Oliveira , Fukushima Romualdo Shigueo
Published: May 2016

Trinta e seis suínos Landrace x Large-White machos castrados e fêmeas (74 a 149 dias de idade) foram distribuídos em duas condições de temperatura ambiente: temperatura alta em câmara climática (HT; 22,2-32,8 ºC) e temperatura de conforto em galpão convencional (CT; 17,6-26,6 ºC), em variação diuturna. Semanalmente foram obtidas amostras de sangue dos animais de ambos os tratamentos para determinação das concentrações séricas de cortisol. Os níveis de cortisol não foram significativamente diferentes entre os sexos, assim como não se observou interação entre sexo e temperatura ambiente. Os suínos do grupo HT apresentaram concentrações médias de cortisol significativamente mais altos (P<0,01) que os do grupo CT (7,06 e 4,82 mg/dL, respectivamente). Este aumento foi contínuo e linear (P<0,05) durante o período experimental, sugerindo que, para suínos em crescimento-terminação, o cortisol pode ser um indicador da condição de estresse calórico.
Microlicia candolleana (Melastomataceae): a new endemic species to the Espinhaço range, Minas Gerais, Brazil
Authors: ROMERO ROSANA , VERSIANE ANA FLAVIA ALVES
Published: May 2016

A new species of Microlicia from Serra do Cipó (southern Espinhaço range, Brazil) is described and illustrated. Microlicia candolleana has branches, leaves, pedicels, hypanthium and sepals covered by spherical, golden glands, sessile leaves with evident nerves on both surfaces and subulate sepals, longer or with the same length as the hypanthium.
Determinants of Public Support for Marijuana Legalization in Uruguay, the United States, and El Salvador
Authors: Cruz José Miguel , Queirolo Rosario , Boidi María Fernanda
Published: May 2016

What are the determinants of public support for marijuana legalization? In the last 3 years, Uruguay and the states of Colorado and Washington have legalized the production, sale, and consumption of recreational marijuana. Although Uruguay and the United States have followed different paths toward legalization, these cases provide an excellent opportunity to explore the relationship between drug policy implementation and public opinion in different political contexts. Using logistic regressions on data from the 2014 AmericasBarometer cross-national surveys conducted in Uruguay, the United States, and El Salvador, this article examines citizen views toward marijuana regulation and the individual determinants of support for legalization in a comparative fashion. Results underline the role of political socialization variables in those countries in which legalization is being debated. Across countries, some of the most important factors for predicting positive attitudes toward marijuana regulation are related to political tolerance, ideology, and the views toward the government.
Multidimensional Computerized Adaptive Testing for Classifying Examinees With Within-Dimensionality
Authors: van Groen Maaike M. , Eggen Theo J. H. M. , Veldkamp Bernard P.
Published: May 2016

A classification method is presented for adaptive classification testing with a multidimensional item response theory (IRT) model in which items are intended to measure multiple traits, that is, within-dimensionality. The reference composite is used with the sequential probability ratio test (SPRT) to make decisions and decide whether testing can be stopped before reaching the maximum test length. Item-selection methods are provided that maximize the determinant of the information matrix at the cutoff point or at the projected ability estimate. A simulation study illustrates the efficiency and effectiveness of the classification method. Simulations were run with the new item-selection methods, random item selection, and maximization of the determinant of the information matrix at the ability estimate. The study also showed that the SPRT with multidimensional IRT has the same characteristics as the SPRT with unidimensional IRT and results in more accurate classifications than the latter when used for multidimensional data.
Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank
Authors: Escuder-Vieco Diana , Garcia-Algar Óscar , Joya Xavier , Marchei Emilia , Pichini Simona , Pacifici Roberta , Pallás-Alonso Carmen Rosa
Published: May 2016

Background:

The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances.

Objective:

The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it.

Methods:

Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom.

Results:

No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881.

Conclusion:

Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine.
Precise pointing and stabilization performance for the balloon-borne imaging testbed: 2015 test flight
Authors: Romualdez L Javier , Damaren Chris J , Li Lun , Galloway Mathew N , Hartley John W , Netterfield C Barth , Clark Paul , Massey Richard J
Published: May 2016

Balloon-borne astronomy offers an attractive option for experiments that require precise pointing and attitude stabilization, due to a large reduction in the atmospheric interference observed by ground-based systems as well as the low-cost and short development time-scale compared to space-borne systems. The Balloon-borne Imaging Testbed (BIT) is an instrument designed to meet the technological requirements of high-precision astronomical missions, and is a precursor to the development of a facility-class instrument with capabilities similar to the Hubble Space Telescope. The attitude determination and control systems (ADCS) for BIT, the design, implementation, and analysis of which are the focus of this paper, compensate for compound pendulation effects and other sub-orbital disturbances in the stratosphere to within 1–2′′ (rms), while back-end optics provide further image stabilization down to 0.05′′ (not discussed here). During the inaugural test flight from Timmins, Canada in September 2015, BIT ADCS pointing and stabilization performed exceptionally, with coarse pointing and target acquisition to within <0.1° and fine stabilization to 0.68′′ (rms) over long (10–30 min) integrations. This level of performance was maintained during flight for several tracking runs that demonstrated pointing stability on the sky for more than an hour at a time. To refurbish and improve the system for the three-month flight from New Zealand in 2018, certain modifications to the ADCS need to be made to smooth pointing mode transitions and to correct for internal biases observed during the test flight. Furthermore, the level of autonomy must be increased for future missions to improve system reliability and robustness.
Adaptive robust attitude control and active vibration suppression of flexible spacecraft
Authors: Yu Z , Guo Y , Wang L , Wu L
Published: May 2016

This paper presents the large angle attitude manoeuvre control design of a single-axis flexible spacecraft system that consists of a central rigid body and a cantilever beam with bonded piezoelectric sensor/actuator pairs as a flexible appendage. The proposed control strategy combines the attitude controller designed by the adaptive robust control technique with the active vibration controller designed by the positive position feedback control method. The desired angular position of the spacecraft is planned and an adaptive robust attitude control approach based on a projection type adaptation law is proposed to track the planned path and to achieve precise attitude manoeuvre control. Meanwhile, the positive position feedback control method is applied to actively increase the damping of the flexible appendage and to suppress the residual vibration induced by manoeuvre. Improved transient and steady state performance during and after large angle attitude manoeuvre can be both achieved by integration of the technical merits of all these control methods. Analytical and numerical results illustrate the effectiveness of this approach.
Changing Socio-economic Structures and the Challenge of Secondary Schooling
Authors: Chakraborty Suchita
Published: May 2016

Secondary education has been a relatively neglected area in India, both at the level of policy and research. Statistical data at the secondary level of education reveals a bleak picture in terms of enrolment and completion rates. This article explores the underlying reasons for the dismal scenario at the secondary level of education by situating it within the larger political economy and livelihood patterns in a rural region. The research is based on an ethnographic study of parents and children from labouring households in a village in Odisha in 2008–2009.
Anti-plane time-harmonic Green’s functions for a coated circular inhomogeneity in a piezoelectric medium with spring- or membrane-type imperfect interfaces
Authors: Shi Yin , Wan Yongping , Zhong Zheng
Published: May 2016

Two-dimensional anti-plane time-harmonic dynamic Green’s functions for a coated circular inhomogeneity in an infinitely extended matrix with spring- or membrane-type imperfect interfaces are presented. The inhomogeneity, coating and matrix are all assumed to be piezoelectric and transversely isotropic. By using the Bessel function expansions, explicit solutions for the electromechanical fields induced by a time-harmonic anti-plane line force and line charge located in the unbounded matrix, the annular coating and the circular inhomogeneity are derived. The present solutions can recover the anti-plane Green’s functions for some special cases, such as the dynamic or quasi-static Green’s functions of piezoelectricity with perfect interfaces, as well as the dynamic or quasi-static Green’s functions for a two-phase composite with perfect or imperfect interfaces. By means of detailed discussions, selected calculated results are graphically shown to demonstrate the dependence of the electromechanical fields on the circular frequency and the interface properties as well as the coating and size of the inclusion.
Development of a Brief Pre-Implementation Screening Tool to Identify Teachers Who Are at Risk for Not Implementing Intervention Curriculum and High-Implementing Teachers
Authors: Wang Bo , Stanton Bonita , Lunn Sonja , Patel Pooja , Koci Veronica , Deveaux Lynette
Published: May 2016

Few questionnaires have been developed to screen for potentially poor implementers of school-based interventions. This study combines teacher characteristics, perceptions, and teaching/training experiences to develop a short screening tool that can identify potential “low-performing” or “high-performing” teachers pre-implementation. Data were gathered from 208 teachers and 4,411 students who participated in the national implementation of an evidence-based HIV intervention in The Bahamas. Sensitivity and specificity were evaluated for the detection of “low-performing” and “high-performing” teachers. The validity of the screening tool was assessed using receiver operating characteristics analysis. The School Pre-implementation Screening Tool consists of seven predictive factors: duration as teacher, working site, attendance at training workshops, training in interactive teaching, perceived importance of the intervention, comfort in teaching the curriculum, and program priority. The sensitivity and specificity were 74% and 57% in identifying “low-performing” teachers and 81% and 65% with “high-performing” teachers. The screening tool demonstrated an acceptable/good validity (area under the receiver operating characteristics curve was 0.68 for “low-performing teachers” and 0.78 for “high-performing” teachers). Our brief screening tool can facilitate teacher training and recruitment of engaged teachers in implementation of school-based interventions.
Personality traits, autobiographical memory and knowledge of self and others: A comparative study in young people with autism spectrum disorder
Authors: Robinson Sally , Howlin Patricia , Russell Ailsa
Published: May 2016

The relationship between dissociable components of autobiographical memory (e.g. semantic personality traits and episodic memory retrieval) and other cognitive skills that are proposed to enable one to develop a sense of self (e.g. introspection) have not previously been explored for children with autism spectrum disorder. This study compared autobiographical memory (semantic and episodic) and knowledge of self (internal/external self-knowledge and introspection/mentalising abilities) in children (aged 11–18 years) with high-functioning autism spectrum disorder and typically developing controls (total N = 48). Novel and standard tasks were employed. Compared to typically developing controls, young people with autism spectrum disorder had autobiographical memory difficulties that were characterised by a reduction in the retrieval of semantic personality traits, with more initial prompts required to facilitate episodic memory retrieval and fewer episodic memories containing emotional and sensory information. Knowledge of the self and others was also impaired, with reduced introspection and poorer mentalising abilities. Young people with autism spectrum disorder were also identified as presenting with an atypical relationship between autobiographical memory and self-knowledge, which was significantly different from typically developing controls. Test performance is discussed in relation to the functions of autobiographical memory, with consideration of how these cognitive difficulties may contribute to clinical practices and the social and behavioural characteristics of autism spectrum disorder.
Convincing the crowd: Entrepreneurial storytelling in crowdfunding campaigns
Authors: Manning Stephan , Bejarano Thomas A
Published: May 2016

This study examines the structure of entrepreneurial stories in pursuit of mobilizing resources from crowds. Based on a comparative analysis of Kickstarter crowdfunding campaigns, we examine in particular how, across different project types, project histories and potential futures are framed and interlinked in narratives to appeal to funders. We find that projects are narrated in different styles—as “ongoing journeys” or “results-in-progress”—to convey project value. The former style narrates projects as longer-term endeavors powered by creative initial ideas and a bold vision, inviting audiences to “join the journey”; the latter narrates projects more narrowly as a progression of accomplishments, engaging the audience instrumentally to support next steps. We find that styles are used and combined in different ways, reflecting the tangibility of project outcomes, the sophistication of technology, and the social orientation of projects. Also, successful differ from unsuccessful campaigns in using narratives more coherently. Findings inform research on narrative processes in entrepreneurship and innovation, and research on the mobilization of crowds.
Gender Transformative Approaches to Engaging Men in Gender-Based Violence Prevention: A Review and Conceptual Model
Authors: Casey Erin , Carlson Juliana , Two Bulls Sierra , Yager Aurora
Published: May 2016

Engaging men and boys as participants and stakeholders in gender-based violence (GBV) prevention initiatives is an increasingly institutionalized component of global efforts to end GBV. Accordingly, evidence of the impact of men’s engagement endeavors is beginning to emerge, particularly regarding interventions aimed at fostering gender equitable and nonviolent attitudes and behaviors among men. This developing evidence base suggests that prevention programs with a “gender transformative” approach, or an explicit focus on questioning gender norms and expectations, show particular promise in achieving GBV prevention outcomes. Interventions targeting attitude and behavior change, however, represent just one kind of approach within a heterogeneous collection of prevention efforts around the globe, which can also include community mobilization, policy change, and social activism. The degree to which gender transformative principles inform this broader spectrum of men’s engagement work is unclear. The goals of this article are twofold. First, we offer a conceptual model that captures and organizes a broader array of men’s antiviolence activities in three distinct but interrelated domains: (1) initial outreach and recruitment of previously unengaged males, (2) interventions intended to promote gender-equitable attitudes and behavior among men, and (3) gender equity-related social action aimed at eradicating GBV, inclusive of all genders’ contributions. Second, we review empirical literature in each of these domains. Across these two goals, we critically assess the degree to which gender transformative principles inform efforts within each domain, and we offer implications for the continuing conceptualization and assessment of efforts to increase men’s participation in ending GBV.
Diabetes Diagnosis and Screen-Based Sedentary Behavior Among US Adults
Authors: An Ruopeng , Yang Yan
Published: May 2016

Diabetes threatens a patient’s health and quality of life, whereas disease diagnosis itself could potentially serve as a teachable moment for initiating behavior change. This study assessed diabetes diagnosis as a possible teachable moment for screen-based sedentary behavior among US adults. The nationally representative sample (n = 3690) came from the 2005-2006 and 2011-2012 National Health and Nutrition Examination Survey. Self-reported hours spent on screen-based sedentary behavior (television/video watching, computer/digital device use) were measured by the Global Physical Activity Questionnaire. Diabetes/prediabetes was identified by fasting plasma glucose and the glycated hemoglobin test. Logistic regressions were conducted to examine the relationship between diabetes diagnosis and screen-based sedentary behavior, adjusting for individual characteristics and sampling design. Compared with those with undiagnosed diabetes, the adjusted values for prevalence of daily television/video watching ≥2 hours (77.45% vs 65.14%), computer/digital device use ≥1 hour (43.20% vs 36.52%), and total screen time (ie, television/video watching plus computer/digital device use) ≥3 hours (66.75% vs 45.78%) were all noticeably higher among adults with diagnosed diabetes, although only the difference in the prevalence of daily total screen time was significant at P < .05. No evidence was found regarding diabetes diagnosis as a teachable moment in reducing screen-based sedentary behavior in US adults.
A unified modeling and control design for precision transmission system with friction and backlash
Authors: Bao Xiulan , Mao Jincheng , Luo Xin
Published: May 2016

The structural flexibility, nonlinear friction, and backlash are the major factors limiting the control performance of precision transmission systems. If uncompensated, these factors compromise the positioning and tracking accuracy of precision transmission systems and even cause limit cycles and oscillation. In this article, a framework for integrated design from dynamic modeling to controller design is proposed. A multi-state dynamic model is presented, which can unify the modeling for a multi-state, discontinuous system including the motor state, the motion state, the mechanical contact state, and the friction state. Then, a control design method related to the dynamic modeling using perturbation separation of the model parameters is presented. Using the proposed modeling method, a continuous dynamic model is established to include all different partition models. The model comprehensively describes the mechanical and electrical characteristics of the precision transmission system. A robust controller is designed using the proposed control method. Experimental results demonstrate that the proposed modeling method is accurate and the proposed control method significantly improves accuracy and robustness of the controller compared to traditional control methods.
Buckling analysis of thin-walled members via semi-analytical finite strip transfer matrix method
Authors: Zhang Yu , He Bin , Yao Li-Ke , Long Jin
Published: May 2016

Slender thin-walled members are main components of modern engineering structures, whose buckling behavior has been studied widely. In this article, thin-walled members with simply supported loaded edges can be discretized in the cross-section by semi-analytical finite strip technology. Then, the control equations of the strip elements will be rewritten as the transfer equations by transfer matrix method. This new method, named as semi-analytical finite strip transfer matrix method, expands the advantages of semi-analytical finite strip method and transfer matrix method. This method requires no global stiffness matrix, reduces the size of matrix, and improves the computational efficiency. Compared with finite element method’s results of three different cross-sections under axial force, the method is proved to be reliable and effective.
Qualifications Frameworks Between Global and European Pressures and Local Responses
Authors: Mikulec Borut , Ermenc Klara Skubic
Published: May 2016

The article considers the Europeanization of education, a process that is taking place in the European Union (EU) as a result of the establishment of a common education policy and that is playing a part in determining the development of education policies in EU member states and candidate countries. The concept of Europeanization serves as a methodological tool with which to analyze one of the fundamental political instruments of European education policy, namely, the European Qualifications Framework (EQF), and also the national qualifications frameworks (NQFs) that are emerging under its influence. In the case of our analysis of the NQF that has been prepared by Slovenia, we demonstrate that the formulation of the EQF and NQFs in the EU is influenced by two factors: by the Anglo-Saxon countries, which were the first to establish a qualifications framework of the modern type, and by global neoliberal policy, with its tendency toward the deregulation, marketization, and commodification of education. At the same time, we tried to show that NQFs in continental Europe have resulted, by virtue of their local specificities, in frameworks that differ considerably from qualifications in the Anglo-Saxon countries. It appears that the effects of globalization and Europeanization on education are unpredictable, because policies are never simply copied into national systems.