bluuebunny/crossref_metadata_2025 huggingface dataset:
An open-label phase 1/2a study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TRC253, an androgen receptor antagonist, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rathkopf Dana E. , Saleh Mansoor N. , Tsai Frank Yung-Chin , Rosen Lee S. , Adams Bonne J. , Liu Lilian , Theuer Charles P. , Freddo James L. , Agarwal Neeraj
Published: February 2018

TPS403

Background: Resistance to AR-targeted therapy is a challenge in the treatment of mCRPC. Single amino acid mutations of the AR ligand binding domain may mediate resistance to second generation AR inhibitors, including enzalutamide (Rathkopf, Annals of Oncology 2017). Development of potent antagonists of wild-type (WT) AR as well as mutated AR is a priority. TRC253 is an orally available, high-affinity, small molecule antagonist of AR with inhibitory activity against WT AR as well as mutated variants. TRC253 blocks AR nuclear translocation and AR binding to DNA and antagonizes transcription. TRC253 does not have agonist activity toward WT or mutated ARs. Methods: This phase 1/2a study of TRC253 in patients with mCRPC will be conducted in two parts: dose-escalation (part 1) and dose-expansion (part 2). Objectives include assessment of safety, selection of a phase 2 dose, and to evaluate PSA response at week 12. Secondary objectives include the evaluation of the extent of receptor occupancy (FDHT PET) and anti-tumor effects of TRC253. Toxicity and efficacy assessments will be determined using NCI-CTCAE and PCWG3 criteria. Dose escalation will begin with single-patient cohorts. Cohorts will be expanded to 3 patients when pre-defined grades of drug-related toxicity occur. TRC253 doses in part 1 are 40 mg, 80 mg, 160 mg, 240 mg, 320 mg, and 400 mg. The DLT evaluation period will be the first 28 days of continuous daily dosing. Six patients have been enrolled to Part 1 to date. Part 2 will consist of two cohorts of up to 30 patients each. Cohort 1 (AR F876L mutation positive) and cohort 2 (AR F876L mutation negative) will receive TRC253 at the RP2D. Circulating tumor DNA will be analyzed in plasma samples to test for AR mutations. In Part 1 patients must have received ≥ 2 prior therapies. Part 2 patients must have demonstrated acquired resistance to enzalutamide or apalutamide. Descriptive statistics will be used to summarize patient characteristics, safety, efficacy, PK, and immunologic biomarkers. Clinical trial information: NCT02987829.
EV-103 study: A phase 1b dose-escalation and dose-expansion study of enfortumab vedotin in combination with immune checkpoint inhibitor (CPI) therapy for treatment of patients with locally advanced or metastatic urothelial cancer.
Authors: Hoimes Christopher J. , Petrylak Daniel Peter , Flaig Thomas W. , Carret Anne-Sophie , Melhem-Bertrandt Amal , Rosenberg Jonathan E.
Published: February 2018

TPS532

Background: Immune checkpoint inhibitors (CPIs) are approved for patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) who progress on prior platinum or are ineligible for first line cisplatin. However, only a minority of pts respond to CPI monotherapy and a combination approach may be beneficial. Enfortumab vedotin (EV), an antibody-drug conjugate (ADC), delivers the microtubule-disrupting agent monomethyl auristatin E (MMAE) to tumors expressing Nectin-4, which is overexpressed in mUC. Preliminary results from an ongoing phase 1 study of EV monotherapy in pts with mUC (Petrylak ASCO 2017) showed that EV was well tolerated in pts with mUC. EV showed a 41% (29 out of 71 pts) objective response rate (ORR) across all doses (24 wks median response duration). In pts with liver metastasis the ORR was 47% (9 out 19 pts) across all doses. Preclinical data show that an MMAE ADC, but not the unconjugated antibody, increases tumor immunogenicity by inducing immunogenic cell death, antigen presentation and tumor immune infiltration (Gardai 2015). Based on encouraging phase 1 study results and potential enhanced immune response, combining EV with a CPI may result in improved response rates with longer durability. Methods: This phase 1b study (NCT03288545) evaluates the safety/activity of EV + CPI in pts with la/mUC who have not previously received a CPI. The study has 2 parts: dose escalation (EV + pembrolizumab) and dose expansion (EV + CPI [pembrolizumab or atezolizumab]). Pts must have la/m transitional cell carcinoma of the urothelium, be eligible for treatment with a CPI, and be either ineligible for first-line cisplatin-based chemotherapy or have disease progression during or following treatment with ≥1 platinum-containing regimen. The primary objective is to assess the safety/tolerability of EV + CPI. Secondary objectives include determining a recommended dose of EV + CPI in pts with la/mUC, antitumor activity as measured by ORR, disease control rate, duration of response, PFS, and OS. Response is assessed per RECIST v1.1 and iRECIST. Study enrollment began in Oct 2017. Clinical trial information: NCT03288545.
Cabozantinib (CABO) plus durvalumab (DURVA) in patients with advanced and chemotherapy-treated bladder carcinoma of urothelial and non-urothelial histology: An open-label, single-arm, phase 2 trial.
Authors: Necchi Andrea , Giannatempo Patrizia , Raggi Daniele , Anichini Andrea , Calareso Giuseppina , Crippa Flavio , Mariani Luigi
Published: February 2018

TPS536

Background: DURVA and CABO have shown single-agent activity in patients (pts) with urothelial carcinoma (UC). Their combination may result in prolonging overall survival (OS) in pts who have failed prior platinum-based chemotherapy (CT). Additionally, DURVA+CABO may be an effective combination for treating subgroup of pts like those with bone metastases only (not having RECIST-measurable disease) or with non-UC histology. Methods: In an open-label, single-arm, multicenter, phase 2 trial, pts will assume CABO 40 mg daily, orally, and will be administered DURVA 1500 mg, intravenously, q28 days, until disease progression (PD, RECIST 1.1) or onset of unacceptable toxicity. Treatment beyond PD is not allowed. Key inclusion criteria: ECOG-PS 0-1, bladder or upper tract primary tumor, UC and non-UC histology, failure of 1 or 2 platinum-based CT for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred ≤6 months (m) of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 q2 cycles. The primary endpoint of the study is OS. The target is to detect an improvement in median OS from ≤6m (H0) to ≥9m(H1). To achieve 90% power with a one-sided non-parametric test at 5% significance, 122 pts must will be accrued over 36m and follow-up may be closed 12m after the end of accrual. PD-L1 expression will be assessed using with the Ventana SP142 assay, and categorized as high (≥25% of tumor cells [TC] or immune cells [IC]) or low/negative ( < 25% TC or IC). The decision on whether or not to undertake PD-L1+ cohort expansion will be based on predictive power (PP) calculation: a PP ≥30% will be regarded as promising and necessary to continue. An interim analysis is planned after 24m (50% expected events). This analysis will be based on PP. The criterion for stopping the trial because of futility will be a PP < 20%. Analyses on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). FDG-PET response in bone metastases will represent another translational endpoint (EudraCT number 2017-000580-32). Clinical trial information: 2017-000580-32.
A phase 3, open-label, randomized study of nivolumab plus ipilimumab or standard of care (SOC) versus SOC alone in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC; CheckMate 901).
Authors: Galsky Matt D. , Powles Thomas , Li Shengting , Hennicken Delphine , Sonpavde Guru
Published: February 2018

TPS539

Background: Cisplatin-containing regimens have been SOC for mUC for nearly 40 years, but durable responses are rare with such treatments. Furthermore, a large proportion of pts with unresectable/mUC are ineligible for cisplatin therapy. Treatment approaches conferring longer-term disease control and extending to broader mUC pt populations are urgently needed. Recently, the programmed death-1 (PD-1) inhibitor, nivolumab, induced durable responses in pts with unresectable/mUC progressing despite platinum-based chemotherapy, and nivolumab combined with ipilimumab (a CTLA-4 inhibitor) demonstrated acceptable safety and clinical activity. This phase 3 study will evaluate nivolumab + ipilimumab and nivolumab + SOC vs SOC in previously untreated pts with unresectable/mUC (NCT03036098). Methods: Key inclusion criteria: cisplatin-eligible and -ineligible pts with measurable disease, no prior systemic chemotherapy for unresectable/mUC, and evaluable tumor biopsy. Key exclusion criteria: active brain metastases, autoimmune disease, and prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways. Cisplatin-eligible and -ineligible pts will be randomized 1:1 to arm A (nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks up to 4 doses, followed by nivolumab 480 mg every 4 weeks until disease progression or unacceptable toxicity) or arm B (gemcitabine-cisplatin or gemcitabine-carboplatin for up to 6 cycles). Additional cisplatin-eligible pts will be randomized to arm C (nivolumab 360 mg + gemcitabine-cisplatin every 3 weeks for up to 6 cycles, followed by nivolumab 480 mg) or arm D (gemcitabine-cisplatin for up to 6 cycles). Stratification factors: PD-1 ligand 1 status, cisplatin eligibility, and liver metastasis. Co-primary endpoints: overall and progression-free survival (OS and PFS) by blinded independent review committee (BIRC) in cisplatin-ineligible pts receiving nivolumab + ipilimumab vs SOC, and PFS by BIRC in cisplatin-eligible pts receiving nivolumab + SOC vs SOC. Enrollment began March 2017 with a target of 897 pts. Clinical trial information: NCT03036098.
A phase 3 trial to compare efficacy and safety of lenvatinib in combination with everolimus or pembrolizumab versus sunitinib alone in first-line treatment of patients with metastatic renal cell carcinoma.
Authors: Motzer Robert J. , Grünwald Viktor , Hutson Thomas E. , Porta Camillo , Powles Thomas , Eto Masatoshi , Dutcus Corina E. , Baig Mahadi Ali , Dutta Lea , Li Di , Choueiri Toni K.
Published: February 2018

TPS706

Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, and RET and KIT. Based on a phase 2 study (Motzer et al. Lancet Oncol. 2015), LEN was approved in combination with everolimus (EVE) for the treatment of metastatic renal cell carcinoma (RCC) following 1 prior VEGF-targeted therapy. A phase 1b/2 study of LEN in combination with pembrolizumab (PEM) in patients (pts) with RCC LEN is also underway. We report the design of a multicenter, open-label, phase 3 trial of LEN plus EVE or PEM vs sunitinib (SUN; a standard therapy for RCC) as first-line treatment for advanced RCC. Methods: Pts aged ≥ 18 years with confirmed advanced RCC diagnosis, ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Karnofsky Performance Status ≥ 70, controlled blood pressure, and adequate blood coagulation, renal, hepatic, and bone marrow function are eligible. Pts will be randomized 1:1:1 to receive LEN 18 mg/d + EVE 5 mg/d, LEN 20 mg/d + PEM 200 mg every 3 wks, or SUN 50 mg/d (on a schedule of 4 wks on treatment followed by 2 wks off) until disease progression, unacceptable toxicity, withdrawal of consent, or study end. The primary endpoint is to show superiority of LEN+EVE or LEN+PEM over single-agent SUN as first-line treatment for advanced RCC in improving progression-free survival (PFS). Secondary endpoints include comparison of objective response rate, overall survival, PFS on next-line therapy, health-related quality of life, and safety and tolerability in pts receiving LEN+EVE or LEN+PEM vs SUN. Exploratory endpoints include PFS in the LEN+PEM arm using immune-related RECIST, comparison of duration of response, disease control rate, and clinical benefit rate in pts treated with LEN+EVE or LEN+PEM vs SUN, and analysis of the relationship between blood biomarkers and outcome. No interim analysis is planned for efficacy or futility. Enrollment of 735 pts is planned to achieve 90% power at 2-sided α = 0.05 to detect a difference in ≥ 1 of the primary comparisons. Clinical trial information: NCT02811861.
A phase III randomized study comparing perioperative nivolumab vs. observation in patients with localized renal cell carcinoma undergoing nephrectomy (PROSPER RCC).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T , Bhatt Rupal Satish , Van Allen Eliezer Mendel , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Shuch Brian M. , Jewett Michael A.S. , George Daniel J. , Michaelson M. Dror , Carducci Michael Anthony ,   On Behalf of the EA8143 PROSPER RCC Investigators
Published: February 2018

TPS710

Background: The anti-PD-1 antibody nivolumab (nivo) improves overall survival (OS) in metastatic treatment refractory RCC and is generally tolerable. In 2017, there is no standard adjuvant therapy proven to increase OS over surgery alone in non-metastatic (M0) disease. Mouse solid tumor models have revealed an OS benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivo in RCC patients (pts) are showing preliminary feasibility and safety with no surgical delays/complications. PROSPER RCC will examine if the addition of perioperative nivo to radical or partial nephrectomy can improve clinical outcomes in pts with locally advanced RCC. We are implementing a three-pronged, multidisciplinary approach of presurgical priming with nivo followed by resection and adjuvant PD-1 blockade with the goal of increasing cure and recurrence-free survival (RFS) rates in M0 RCC. Methods: Tumor biopsy prior to randomization is mandatory to ensure RCC diagnosis but will also permit unparalleled correlative science in this global, unblinded, phase 3 National Clinical Trials Network randomized study. 766 pts with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivo 240mg IV for 2 doses prior to surgery followed by adjuvant dosing for 9 mo (q2 wks x 3 mo followed by q4 wks x 6 mo). The control arm will undergo the current standard of care: surgical resection followed by observation. Pts are stratified by clinical T stage, node positivity, and histology. There is 84.2% power to detect a 14.4% absolute increase in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70). The study is also powered to detect a significant OS benefit (HR 0.67). Safety, feasibility, and quality of life are key secondary endpoints. PROSPER RCC exemplifies team science and incorporates a host of correlative work to examine the significance of the baseline immune milieu and changes induced by neoadjuvant priming and to identify predictive gene expression patterns. New collaborations welcomed. Clinical trial information: NCT03055013.
Yvan Goll – Ε. Χ. Γονατάς: Προς μια συγκριτική ποιητική
Authors: Γαλανάκης Αθανάσιος Β.
Published: February 2018

This study aims to explore the relationship between the works of Yvan Goll and E. Ch. Gonatas. More specifically, the main purpose of the study is to highlight the role played by the Expressionist Movement (in which Yvan Goll was an active member) in the literary works of E. Ch. Gonatas. The methodological tools of Comparative Literature and Hermeneutics are used to prove the close relationship between the two authors and the expressionistic texture of their art. In the first part, the study is concerned with the expressionistic imagery, the poetics of landscape, the use of colors and the symbolization of nature (especially through the motif of the humanization of animals). The second part deals with the influence of Expressionism on the mutability of the literary genres, the generic hybridization in the work of E. Ch. Gonatas and the small literary form.The main objectives of the study are: i) A heuristic report of the presence of Expressionism in Modern Greek Literature (especially in the post-surrealistic movement), ii) the clarification of certain aspects in Gonatas' poetics and iii) the acquaintance with the work of the major poet but unknown to the Greek general public, Yvan Goll.
Η εικονολογία του Θανάτου: μια αντιπαραβολή
Authors: Ρασιδάκη Αλεξάνδρα
Published: February 2018

Η παρούσα συγκριτολογική μελέτη προσπαθεί να συσχετίσει την μακάβρια παράδοση του δυτικού μεσαίωνα με την προσωποποίηση του θανάτου στα ελληνικά δημοτικά μοιρολόγια.Το πρώτο μέρος του άρθρου παρακολουθεί την εξέλιξη της σύλληψης του θανάτου κατά τον ευρωπαϊκό μεσαίωνα εστιάζοντας στην προσωποποίησή του ως αυτόνομης,  βίαιης και ύπουλης μορφής και τους τρόπους αναπαράστασής αυτού. Ειδικότερα παρουσιάζονται, με τη βοήθεια κειμενικών και εικονικών παραδειγμάτων, τα νοερά σχήματα του «Θριάμβου του θανάτου» και του «Χορού των νεκρών» τα οποία χαρακτηρίζουν την λεγόμενη μακάβρια περίοδο του υψηλού και ύστερου μεσαίωνα και εκφράζουν την οικειότητα του ανθρώπου της εποχής εκείνης προς την ιδέα του θανάτου.Η υπόθεση εργασίας στην μελέτη αυτή είναι ότι μια ανάλογη οικειότητα εκφράζεται και στην ελληνική δημοτική παράδοση και ειδικότερα στα τόσο εντυπωσιακά τραγούδια του θανάτου, τα μοιρολόγια. Το δεύτερο μέρος επικεντρώνεται στα ελληνικά μοιρολόγια και ειδικότερα στα «μοιρολόγια του Χάρου» και στα «μοιρολόγια του κάτω κόσμου», καθώς αυτά κυρίως, πέρα από έκφραση θλίψης και πένθους, λειτουργούν ως θεματοποιηση του αναπόφευκτου της ανθρώπινης μοίρας, ως αναστοχασμός πάνω στο θέμα του θανάτου. Παρουσιάζονται τα βασικά μοτίβα των μοιρολογιών αυτών και αντιπαραβάλλονται με την δυτική εικονολογία περί θανάτου. Ειδικότερα εστιάζω στην προσωποποίηση του θανάτου στην μορφή του Χάρου και στα χαρακτηριστικά που του αποδίδονται, συγκρίνοντάς την με τις ποικίλες εκδοχές της δράσης του θανάτου της δυτικής μακάβριας παράδοσης. Με τον τρόπο αυτό φιλοδοξώ να συμπληρώσω με μια άλλη οπτική γωνία τη μελέτη των μοιρολογιών.
Hommage à Yourcenar : Une réflexion écologique d’avant-garde
Authors: Chehab May
Published: February 2018

Our attention in this study focuses on Marguerite Yourcenar’s (1903-1987) ecological reflection. Firmly engraved in her literary work, it is also to be found in various speeches, contributions to collective works, and in an early activism that goes beyond a purely intellectual environmentalism. In a word, the ecological issue haunts Yourcenar to the highest point, until the last year of her life ‒and even beyond.
Developing WHO guidelines: Time to formally include evidence from mathematical modelling studies
Authors: Egger Matthias , Johnson Leigh , Althaus Christian , Schöni Anna , Salanti Georgia , Low Nicola , Norris Susan L.
Published: February 2018

In recent years, the number of mathematical modelling studies has increased steeply. Many of the questions addressed in these studies are relevant to the development of World Health Organization (WHO) guidelines, but modelling studies are rarely formally included as part of the body of evidence. An expert consultation hosted by WHO, a survey of modellers and users of modelling studies, and literature reviews informed the development of recommendations on when and how to incorporate the results of modelling studies into WHO guidelines. In this article, we argue that modelling studies should routinely be considered in the process of developing WHO guidelines, but particularly in the evaluation of public health programmes, long-term effectiveness or comparative effectiveness.  There should be a systematic and transparent approach to identifying relevant published models, and to commissioning new models.  We believe that the inclusion of evidence from modelling studies into the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process is possible and desirable, with relatively few adaptations.  No single “one-size-fits-all” approach is appropriate to assess the quality of modelling studies. The concept of the ‘credibility’ of the model, which takes the conceptualization of the problem, model structure, input data, different dimensions of uncertainty, as well as transparency and validation into account, is more appropriate than ‘risk of bias’.
An oxidation-resistant peptide mimic of surfactant protein B (B-YL) forms an amphipathic helix-hairpin in liposomes with high surface activity
Authors: Walther Frans J. , Gupta Monik , Gordon Larry M. , Waring Alan J.
Published: February 2018

Background: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B. Here, we studied ‘B-YL’, a 41-residue oxidation-resistant SMB variant that has its four Cys and two Met residues replaced by Tyr and Leu, respectively, to test whether these hydrophobic substitutions produce a surface-active, α-helix hairpin.

Methods:Structure and function of B-YL and SMB in surfactant lipids were compared with CD and FTIR spectroscopy and molecular dynamic (MD) simulations, and surface activity with captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits.

Results:CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to SMB in lipids. MD simulations confirmed that B-YL maintained its α-helix hairpin in a lipid bilayer, matching the hairpin obtained from MD of SMB. Unlike the disulfide-reinforced helix-turn of SMB, the B-YL fold was stabilized by a core of clustered Tyr linking the N- and C-helices through noncovalent interactions involving aromatic rings. B-YL in surfactant lipids demonstrated excellentin vitrosurface activity and good oxygenation and dynamic compliance in lavaged, surfactant-deficient adult rabbits.

Conclusions:‘Sulfur-free’ and ‘oxidation-resistant’ B-YL forms an amphipathic helix-hairpin in surfactant liposomes with high surface activity and is functionally similar to SMB and native SP-B. B-YL’s resistance against free oxygen radical damage provides an extra edge over oxidized SMB in the treatment of respiratory failure in preterm infants with RDS and children and adults with acute lung injury.
Interpretation of literary text: Russian-Spanish dialogue
Authors: Чеснокова Ольга , Chesnokova Ol'ga
Published: February 2018

The monograph is devoted to the interpretation of a literary text on the principles of consistency of language and culture, semiotics, intertextuality, theories of discourse, linguopragmatic.
Through the prism of the linguistic and cultural consciousness of Russian and Spanish-speaking, philological traditions of Russia and Spanish-speaking countries, the author analyzes and interprets the literary texts of Spanish and Latin American literature, translations of Russian classical literature into Spanish and displays the parameters of their Russian-Spanish dialogue.
The book is addressed to a wide range of linguists, culturologists, teachers of Spanish and Russian languages, postgraduates and students of philological faculties.
Transient processes in linear electric circuits (examples)
Authors: Мякишев Владимир , Myakishev Vladimir , Жеваев Максим , Zhevaev Maksim
Published: February 2018

In the tutorial on specific examples of typical algorithms for calculating transients in linear circuits by classical and operator methods, as well as several examples of the application of the Duhamel integral and the method of state variables using the program MathCAD.
A distinctive feature of the textbook is a detailed methodological analysis of all the examples, a versatile approach to solving problems and comparative analysis of the solutions.
It is intended for students of higher technical educational institutions of electrotechnical and electric power specialties, can be used by students of colleges of this direction, conforms to the standard of fgos VPO of the third generation, can be recommended at two-level system of education at preparation of bachelors as the additional source of information.
Theory and politics of identity
Authors: Капицын Владимир , Kapitsyn Vladimir
Published: February 2018

Modern societies are undergoing significant changes. Dynamic processes of globalization are accompanied by fragmentation of society, strengthening of ethnic identities, destroying national identities and integrity of States. The study of problems of social and identity attracts more and more attention of political scientists. The textbook is intended for undergraduates, graduate students, teachers, political scientists, as well as can be used by sociologists, psychologists, specialists of state and municipal administration.
Protection of human rights in States ' policies: a comparative analysis
Authors: Капицын Владимир , Kapitsyn Vladimir
Published: February 2018

The textbook discusses mechanisms for the protection of human rights, directly or indirectly included in policy, including mechanisms of state bodies, public organizations, both international and national and regional. Human rights and the institutions for their protection are examined in historical, theoretical and political aspects, accompanied by facts and analysis. Study guide recommended for students studying in areas of training 030200.62 — political Science (bachelor); it will also be useful for students and specialists in international relations, public administration, lawyers, journalists, sociologists, anyone interested in human rights policy
Kelly Betting on Horse Races with Uncertainty in Probability Estimates
Authors: Metel Michael R.
Published: February 2018

We investigate the problem of gambling with uncertainty in outcome probabilities. Stochastic optimization models are proposed for optimal investing on events with mutually exclusive outcomes when probabilities are estimated using multinomial logistic regression. Special attention is given to the case of there being two outcomes and the general case of many outcomes. An empirical study using simulated data was conducted where the loss of return from probability estimation error was observed, and superior returns were achieved taking it into consideration.
Reducing Medicare Spending Through Electronic Health Information Exchange: The Role of Incentives and Exchange Maturity
Authors: Adjerid Idris , Adler-Milstein Julia , Angst Corey
Published: February 2018

Health information exchanges (HIEs) are entities that have emerged in healthcare delivery markets across the United States. By providing an interorganizational information system (IOIS) and governance over use of this system and the information exchanged through it, HIEs enable more routine and efficient electronic sharing of patient information between disparate and fragmented healthcare providers. This should result in improved quality and efficiency of care. However, significant questions persist about the extent to which HIEs produce these benefits in practice, particularly in terms of reducing healthcare spending. We use transaction cost economics (TCE) to theorize that HIEs establish a quasi-hierarchy that decreases frictions associated with information sharing in ways that reduce healthcare spending, and that the magnitude of reductions is greater when (1) insurer and provider incentives align, and (2) HIE capabilities mature. We can test these conjectures because HIEs, unlike other efforts that provide IOIS, are typically confined to regional markets and develop heterogeneously between these markets, introducing variation in insurer-provider incentive alignment and HIE maturity. Leveraging a unique national panel data set, we evaluate whether HIEs reduce spending for the largest insurer in the United States, i.e., Medicare, and whether incentives and HIE maturity modify the magnitude of reductions. We find significant spending reductions in healthcare markets that have established operational HIEs, with an average reduction of $139 per Medicare beneficiary per year (1.4% decrease) or a $3.12 billion annual reduction in spending if HIEs were nationally implemented in 2015. We also find that these reductions occur disproportionately in healthcare markets where providers have financial incentives to use an HIE to reduce spending and when HIEs are more mature. Our results inform an important open empirical question in the healthcare domain related to the value of HIEs, while also joining perspectives from TCE with the IOIS literature to understand the factors that may be relevant to IOIS value creation more generally.
Evaluation of Phenol-Formaldehyde Resins Modified and Blended with Pyrolysis Bio-Oil for Plywood
Authors: Mao An , Xu Weitao , Xi Enhua , Li Qi , Wan Hui
Published: February 2018

The objective of this study was to compare the characteristics and bonding performance of phenol-formaldehyde (PF) resins modified and blended with crude bio-oil. For modified PF resins, crude bio-oil from the pyrolysis of pinewood was synthesized with phenol and formaldehyde at 10, 25, 50, and 75 percent phenol substitution percentages, respectively. For blended PF resins, crude bio-oil was physically blended with PF resin at 4, 13, 23, and 38 percent addition percentages, respectively. The physical properties of crude bio-oil and PF resins, such as viscosity, pH value, gel time, water content, and solid content, were measured. The bond strength of plywood was evaluated. The results indicated that incorporating crude bio-oil into PF resin either by synthesis or by blending at certain amounts could improve the bonding performance of PF resins. For blended PF resins, the best crude bio-oil addition percentage was 13 percent, while for synthesized (modified) PF resins, the best phenol substitution percentage was 25 percent. Further increment of the crude bio-oil content level decreased the bond performance of both modified and blended PF resins. This was mainly due to the increased viscosity and the acidity of blended PF resins at a high crude bio-oil addition percentage and a shortage of reactive phenolic compounds in modified PF resins at a high phenol substitution percentage. Plywood bonded with the resins could generally meet the requirement of Chinese National Standard GB/T 17657‐2013 and be suitable for outdoor applications.
Using Structural Analysis to Inform Peer Support Arrangements for High School Students With Severe Disabilities
Authors: Huber Heartley B. , Carter Erik W. , Lopano Sarah E. , Stankiewicz Kristen C.
Published: February 2018

We examined the effects of peer support arrangements as an alternative to exclusive direct support from paraprofessionals for three high school students with severe disabilities in general education classrooms. We also explored the use of structural analysis as a data-based approach for further refining the interventions to enhance their impact in particular classrooms. Peer support arrangements were associated with substantial increases in social outcomes; academic engagement maintained or improved modestly for all participants. Moreover, structural analyses yielded findings used to adapt peer support arrangements to address students' individual needs. Although the effects of structural analysis-based adaptations resulted in increases in social responses for only one participant, levels of social interactions maintained, and improvements in academic engagement occurred for two participants.
Individual and Contextual Correlates of Frequently Involved Special Olympics Athletes
Authors: Robinson Suzanne , Fraser-Thomas Jessica L. , Balogh Robert , Lunsky Yona , Weiss Jonathan A.
Published: February 2018

It is important to understand factors associated with sport participation for youth with intellectual and developmental disabilities (IDD). With a sample of 414 Special Olympics (SO) athletes, this study examined how frequently involved athletes differ from other youth who are less involved in SO. Results showed that frequently involved athletes are older, have more sport-specific parental support, stronger athlete-coach relationships, and more positive SO experiences than other athletes. These factors were predictive of SO involvement, even after controlling for athlete characteristics, including behavior problems and adaptive behavior. Athletes with IDD have the potential to be highly involved in sports when external supports (i.e., coaches and parents) are strong.
Qualidade físico-química da água para abastecimento humano em municípios do sertão da Bahia: um estudo considerando diversas fontes de suprimento
Authors: Lordelo Lidiane Mendes Kruschewsky , Porsani José Milton , Borja Patrícia Campos
Published: February 2018

O abastecimento de água nas áreas rurais do sertão brasileiro é dificultado devido à escassez de água e adoção de políticas e tecnologias inapropriadas que envolvem desde a captação até a distribuição ao consumidor. Atualmente, diversas são as fontes utilizadas para o suprimento de água, tais como: águas subterrâneas (poços), água de chuva (cisterna), e águas superficiais, o que inclui água do carro-pipa. Diante da necessidade de se garantir o acesso à água em face da sua importância para a promoção da saúde, o presente estudo visou analisar a qualidade das águas disponíveis para consumo humano, quanto aos parâmetros físico-químicos, provenientes das fontes citadas em cinco municípios do semiárido baiano. Os resultados evidenciaram que as condições áridas do solo influenciam na qualidade da água dos poços da região estudada tornando-as mais salobras. Por outro lado, as águas provenientes de carro-pipa que abastecem as cisternas do P1MC em face da seca prolongada estavam vulneráveis devido ao uso do cloro sem o devido controle podendo estar acima do permitido. As águas de chuva apresentaram condições adequadas quanto às características físico-químicas. Os resultados indicam a necessidade de políticas públicas que garantam o acesso à água de qualidade na região estudada.
Eksistensi dan Pengembangan Kurikulum Madrasah Aliyah Program Keagamaan (MAPK) MAN 1 Surakarta
Authors: Rohmah Munif Rofi’atur , Arifin Zainal
Published: February 2018

Abstract
This article discusses the existence and curriculum development of MAPK MAN 1 Surakarta. This research is qualitative research. Research data through observation, in-depth interviews and documentation. The result of this research shows, first, MAPK MAN 1 Surakarta still exist until now (1) support from various parties such as madrasah leaders, MAPK managers and dormitories as well as alumni support, (2) the developed curriculum has successfully delivered quality Islamic Education, (3) the name of MAPK is still used as marketing, (4) the desire to exist, (5) the opening of international class, (6) still needed the graduates who master of Islamic Studies, (7) successful student achievement, (8) the spirit of student have ability to speak Arabic and English. Second, the curriculum development of MAPK MAN 1 Surakarta includes: diagnostic needs, educational objectives, curriculum 2013, tutorial and boarding school activities, learning experiences, and evaluation.
Temporal and Spatial Patterns of Ship Traffic in the Canadian Arctic from 1990 to 2015 + Supplementary Appendix 1: Figs. S1–S7 (See Article Tools)
Authors: Dawson Jackie , Pizzolato Larissa , Howell Stephen E.L. , Copland Luke , Johnston Margaret E.
Published: February 2018

The limited availability of consistent, longitudinal data sources for marine traffic in Arctic Canada has presented significant challenges for researchers, policy makers, and planners. Temporally and spatially accurate shipping data that reveal historical and current traffic trends are vital to plan safe shipping corridors, develop infrastructure, plan and manage protected areas, and understand the potential environmental and cultural impacts of change, as well as for sovereignty and safety considerations. This study uses a recently developed geospatial database of ship traffic to provide the first synthesized overview of the spatial and temporal variability of different vessel types in Arctic Canada during the 26-year period from 1990 to 2015. This examination shows that, overall, the distance traveled by ships in Arctic Canada nearly tripled (from 364 179 km in 1990 to 918 266 km in 2015), that the largest proportion of ship traffic in the region is from general cargo vessels and government icebreakers (including research ships), and that the fastest growing vessel type by far is pleasure craft (private yachts). Spatial shifts in vessel activity over the last quarter century have favoured areas with active mine sites, as well as the southern route of the Northwest Passage. As a result, some communities, including Baker Lake, Chesterfield Inlet, Pond Inlet, and Cambridge Bay, are experiencing greater increases in ship traffic.
Mobilizing Inuit Qaujimajatuqangit in Narwhal Management through Community Empowerment: A Case Study in Naujaat, Nunavut
Authors: Keenan Erin , Fanning Lucia M. , Milley Chris
Published: February 2018

This research examines the relationship between government wildlife management and the use of Inuit knowledge or Inuit Qaujimajatuqangit (IQ) through a case study focusing on narwhal (Monodon monoceros) harvesting in the community of Naujaat, Nunavut. Since Fisheries and Oceans Canada (DFO) introduced a community quota system in 1971, the ultimate responsibility for decision making has shifted from hunting communities to government. This shift corresponds with changes in the use of IQ within the community. Interviews with hunters, elders, and representatives of the hunters and trappers organization in Naujaat provide insight into the nature of these changes. Key factors influencing the role of IQ in narwhal management decision making included the imposed quota system, the perception of the ongoing role of IQ, communication challenges, modern-day drivers of change, and the lack of decision-making authority at the community level.
Metaphor, Verstehen or Neither: A Reflection on Hypnotic Analgesia and Active Ingredients in Psychotherapy
Authors: Karlin Robert A.
Published: February 2018

Hamburg, an experienced and expert therapist, presents two successful psychotherapy cases. In both cases he viewed success as being the product of his use of metaphor, the patients' successful surmounting of a high difficulty task, hypnosis, and nonspecific factors. One of the cases involves a medically unexplained chronic and disabling pain. With a couple of brief vignettes of my own, I suggest careful screening, as using hypnosis to control medically unexplained, chronic pain may cause problems for some patients with major psychopathology (e.g., paranoid schizophrenia). Next, I note that clinical data will reflect back to us the a priori assumptions and interests we bring to it. As an example of how often and misleadingly this can happen, I discuss the autobiographical nature of clinical personality theories. Finally, I agree with Hamburg about the importance of ubiquitous nonspecific effects and note my difficulty accepting that they may be more important than the specific things we do deliberately in psychotherapy.
Pesticide Formulation and Delivery Systems: 37th Volume, Formulations with Ingredients on the EPA's List of Minimal Concern
Authors: Edlund Renee K.
Published: February 2018

Description

Get detailed research on formulations with ingredients on the EPA list of minimal concern, including list 4 ingredients. This book includes 11 peer-reviewed papers that address a wide range of topics in the field of agrochemical inerts.

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The featured papers were presented at the 37th Symposium on Pesticide Formulation and Delivery Systems: “Formulations with Ingredients on the EPA’s List of Minimal Concern,” held October 25-27, 2016, in Washington, D.C._x000D_
Determining Water-Sensitive Card Spread Factors for Real-World Tank Mixes
Authors: Hoffman W. Clint , Fritz Bradley K. , Gizotti-de-Moraes Jesaelen , Guerrerio Marcella , Kruger Greg R.
Published: February 2018

The use of water-sensitive cards provides a quick and easy method for sampling the coverage and deposition from spray applications. This measure is typically limited to percentage coverage because measures of droplet size, and thus deposition rate, are highly influenced by the stain diameter that results from the droplet deposition and spread on the card. To determine the diameter of the droplets from the resulting stain, spread factor relations are used. Complicating this process is the fact that the stain diameter, and thus the spread factor, are affected by the physical properties of the spray solution, meaning different spray solutions require unique spread factor relations to accurately estimate the droplet size and deposition on water-sensitive cards. We evaluated several active product tank mixes with a variety of typical adjuvants to determine the unique spread factors for each. Discrete droplets ranging from 200 to 1,000 μm were generated and deposited on water-sensitive cards, after which the resulting stain diameters were compared to the droplet diameters to develop appropriate spread factor relations.
Structure-Performance Relationships among Aromatic Polyetheramide Comb Polymer Dispersants
Authors: Stern Alan J.
Published: February 2018

A three-dimensional experimental design was used to probe the structure/function relationships among aromatic comb polymer dispersants created by the reaction of styrene maleic anhydride resins with polyetheramines. The relationships were probed by preparing model suspension concentrate formulations and measuring formulation physical properties, including suspensibility, viscosity, and Ostwald ripening. It was found that optimum dispersant performance occurred with a high degree of “backbone” aromaticity and high water solubility but low-molecular-weight polyether “comb teeth.”
Factors Affecting Growth-Regulator Herbicide Volatility
Authors: Penner Donald , Michael Jan
Published: February 2018

Numerous factors can affect the volatility of growth-regulator herbicides. At the time of herbicide application a percentage of the spray may be deposited on soil and a percentage on plant foliage. Herbicide volatility was evaluated with a tomato bioassay in which the herbicide was applied to bare soil or to wheat. Maximum tomato injury from dicamba volatility was observed 14 days after initial exposure. Adjuvants in the spray solution could increase or decrease herbicide volatility. The diglycolamine salt of dicamba was applied to two different soils in greenhouse studies. Volatility differences from the soil types tested were not observed. Foliarly applied adjuvants that increased dicamba activity in the field, when applied to bare soil, appeared to increase dicamba volatility.
Characterization of a Novel Polymeric Drift Control Agent in a Vertically Oriented Low-Speed Wind Tunnel
Authors: Dempsey Logan P. , Sun J. Susan , Lindner Gregory J.
Published: February 2018

Novel drift reduction technologies (DRTs) that can work under a wide variety of conditions are needed to address the increasing complexity of spray tank mixtures. Conventionally, large molecular weight polymer-based DRTs are thought to work by altering the rheological properties of agricultural spray solutions. Specifically, DRT polymers increase the extensional viscosity of the spray solution, which becomes significant under high-shear spraying conditions. In this paper, a novel polymeric drift control agent, AL-3412, is introduced. AL-3412 works through means other than altering the rheological properties of the solution, similar to oil-emulsion-based DRTs. Spray patterns of solutions with and without DRTs are characterized in a vertically oriented low-speed wind tunnel. Measurements reveal how AL-3412 affects the droplet size distributions of active spray solutions and how it may be used in conjunction with oil-emulsion-based DRTs.
A Review of Methods for Estimating Ballast Degradation Using Ground-Penetrating Radar
Authors: Scanlan Kirk M. , Hendry Michael T. , Martin C. Derek , Schmitt Douglas R.
Published: February 2018

Significant research has been conducted over the last two decades applying nondestructive ground-penetrating radar (GPR) measurements to evaluate the amounts of both fine-grained particles (fines) and moisture present in railway ballast. This has led to the development of a variety of quantitative as well as qualitative GPR signal interpretation techniques as variations in the amount of ballast fines and moisture result in detectable changes in recorded GPR signals. The accumulation of fines within the void spaces among the ballast particles decreases the size of the air voids while also altering the bulk dielectric permittivity and electrical conductivity of the ballast layer. Changes to the bulk ballast electromagnetic (EM) properties in turn affect GPR wave travel times, reflection strengths, and signal attenuation, while changes in air void size can directly impact the scattering behavior of GPR waves as they propagate through the ballast. Measurements from low-frequency (< 1 GHz) GPR systems are predominately affected by the changes in bulk EM properties, whereas high-frequency (> 1 GHz) GPR measurements, while affected by changes in signal attenuation, also respond directly to changes in air void size. The majority of GPR-based detection methods infer ballast degradation based on the resulting effects on the bulk EM properties; however, direct approaches, which do not rely on these intermediary properties, also exist. This paper presents a review of how ballast degradation, characterized by the accumulation of fines and increased moisture retention, affects the EM properties critical for GPR and contrasts the current methods used to estimate ballast conditions from GPR measurements.
Two Decades of Advancement in Process Simulation Testing of Ballast Strength, Deformation, and Degradation
Authors: Indraratna Buddhima , Ngo Ngoc Trung , Nimbalkar Sanjay , Rujikiatkamjorn Cholachat
Published: February 2018

This paper describes salient features of a set of large-scale ballast testing equipment developed at the University of Wollongong, Australia, and how the test results and research outcomes have contributed to transforming tracks in the Australian heavy haul and commuter networks, particularly with regards to the strength, deformation, and degradation of ballast. Ideally, ballast assemblies should be tested in prototype scale under actual loading conditions. This is because a reduction in particle sizes for testing in smaller equipment can reduce the internal angle of friction (shearing resistance) of the granular assembly in a macro sense, and the angularity of the particles in a micro sense, and hence the volumetric changes during the shearing process. In response to the worldwide lack of proper test facilities for ballast, the University of Wollongong has, since the early 1990s, designed and built a number of large-scale process simulation triaxial testing rigs. They are all custom made to minimize any boundary effects and also to evaluate the deformation and degradation of ballast, particularly the size, shape, and origin of aggregates used as ballast in Australian tracks. This triaxial process simulation equipment was originally used to characterize the behavior of coarse aggregate used for state railway standards for monotonic loading, but since then it has been fitted with dynamic actuators to simulate actual track conditions involving the true cyclic loading nature while also capturing the wheel-rail dynamics that correspond to high-speed commuter rail and fast heavy-haul operations. These tests invariably demonstrated completely different stress–strain and volumetric characteristics of ballast compared to conventional static or monotonic testing of the same test specimens.