bluuebunny/crossref_metadata_2025 huggingface dataset:
S1605: Phase II trial of atezolizumab in BCG-unresponsive nonmuscle invasive bladder cancer.
Authors: Black Peter C. , Catherine Tangen , Lerner Seth P. , McConkey David James , Lucia M. Scott , Woods Michael , Bivalacqua Trinity , Kassouf Wassim , Bangs Richard Carlton , Plets Melissa , Thompson Ian Murchie , Singh Parminder
Published: February 2018

TPS527

Background: Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific, and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC. Funding: NIH/NCI grants: CA180888, CA180819, CA180820, CA180821, and CA180863. Clinical trial registry: NCT02844816 Clinical trial information: NCT02844816.
Phase II trial of neoadjuvant nivolumab with cisplatin and gemcitabine in muscle-invasive bladder cancer patients undergoing radical cystectomy.
Authors: Gupta Shilpa , Agarwal Neeraj , Konety Badrinath R. , Weight Christopher J. , Thyagarajan Bharat , Murugan Paari J , Koopmeiners Joseph S , Sonpavde Guru
Published: February 2018

TPS528

Background:
Cisplatin-based neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) improves survival outcomes. The survival benefit correlates with pathologic response (PaR) and strategies to improve pathologic response at cystectomy are urgently needed to improve outcomes in these pts. while limiting toxicity. We are exploring the efficacy and safety of N with gemcitabine-cisplatin (GC) as neoadjuvant therapy for MIBC.
Methods:
This is a single-arm, multi-center phase II study for pts with MIBC eligible for neoadjuvant GC and planned for radical cystectomy. Pts will be treated with N+ GC every 21 days for 4 treatment cycles over 12 weeks followed by radical cystectomy. The primary endpoint of PaR will be evaluated in a single stage design; 41 adult pts will be enrolled and the treatment will be worthy of further study (and the null hypothesis rejected) if paR is seen at the time of cystectomy in more than 19 pts. Key inclusion criteria are presence of MIBC (predominantly urothelial carcinoma) with clinical stage T2-T4a and N≤1 disease (solitary lymph node measuring < 2 cm) and M0 and deemed eligible for radical cystectomy, ECOG PS of 0 or 1, Cr Cl ≥ 50 ml/min, adequate organ function, eligible to receive GC and no contraindications to receiving N. Patients will receive C (70mg/m
2
) IV on D1, G (1000mg/m2) on D1,D8 and N (360 mg) IV on D8 every 21 days for 4 cycles followed by radical cystectomy within 6-8 weeks. Secondary Objectives are to determine safety of N+GC in pts with MIBC prior to radical cystectomy and PFS. The correlative objectives include: 1)Whole Exome Sequencing (WES) of the pre-treatment bladder cancer biopsy tissues will be correlated with response.2) Molecular subtypes of bladder cancer will be performed using Genomedx to evaluate whether addition of N alters the response to neoadjuvant GC. 3)PD-L1 expression in tumor tissue at baseline will be correlated with response to N+GC therapy and 4) Nanostring pancan immune panel gene expression will be studied at baseline and at cystectomy.The extensive exploratory analyses are aimed at understanding correlation between genomic and immunologic changes in tumor tissues with clinical outcomes. (NCT03294304)
Clinical trial information: NCT03294304.
A randomized phase III double-blind clinical trial (S1600) evaluating the effect of immune-enhancing nutrition on radical cystectomy outcomes.
Authors: Hamilton-Reeves Jill , Holzbeierlein Jeffrey M. , Unger Joseph M. , Lew Danika L , Fisch Michael Jordan , Henry Norah Lynn
Published: February 2018

TPS529

Background: This phase III trial will compare the impact of consuming Specialized IMmunonutrition (SIM) to oral nutritional support on postoperative complications after radical cystectomy. Specialized IMmunonutrition is fortified with nutrients (L-arginine, omega-3 fatty acids, dietary nucleotides, and vitamin A) that have immediate effects on immune and inflammatory responses, muscle sparing, and wound healing after surgery. Methods: Two hundred patients will be randomized in a 1:1 fashion to one of two arms. Subjects will be stratified by diversion type (neobladder vs. ileal conduit) and whether the patient had neoadjuvant chemotherapy (any vs. none) to balance the intervention assignment according to important prognostic factors. Nutrition drinks are given three times a day for 5 days before and 5 days after surgery. The primary endpoint is 30 day overall complication rate. Two hundred patients gives 80% power to detect an absolute reduction of 23% in the 30 day overall complication rate (from 65% down to 42%). Secondary endpoints will assess infections, muscle mass, readmissions, quality of life, recurrence, DFS, OS, immune response, cytokines, amino acids, and fatty acids. The trial is testing a high yield, low-risk, low-cost strategy to improve the outcome of patients with bladder cancer who undergo cystectomy. Funding: NIH/NCI/DCP grant award UG1CA189974. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Pembrolizumab and chemoradiotherapy for muscle invasive bladder cancer: The ANZUP 1502 PCR-MIB trial.
Authors: Weickhardt Andrew James , Foroudi Farshad , Sengupta Shomik , Galletta Laura , Herschtal Alan , Grimison Peter S. , Patanjali Nitya , Ng Siobhan , Tang Colin , Goodwin Robert , Hovey Elizabeth J. , Jarvis Tom , Chen Colin , Sandhu Shahneen Kaur , Tai Keen Hun , Lawrentschuk Nathan , Davis Ian D. ,   Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2018

TPS531

Background: Pembrolizumab leads to responses in ~20% of metastatic bladder cancer patients. Irradiation of bladder cancer cells in-vitro and in-vivo leads to upregulation of PD-L1, and in immunocompetent mouse models blockade of PD-L1 leads to delayed tumour growth following irradiation. Randomised data from PACIFIC trial in NSCLC shows the addition of PD-L1 inhibition to chemoradiation significantly prolongs PFS. A trial of chemoradiotherapy with pembrolizumab will assess safety and synergy of the combination in localised bladder cancer. Methods: This pilot study enrols patients with maximally resected non-metastatic muscle invasive bladder cancer, who either wish for bladder preservation or are ineligible for cystectomy. This study will assess the safety and feasibility of combining pembrolizumab with chemoradiotherapy in ECOG 0-1 patients without contraindications to pembrolizumab. The study has enrolled 4 of a planned 30 patients. All patients treated with 64Gy of radiation therapy in 32 fractions over 6 weeks, 2 days. Cisplatin 35mg/m2 IV concurrently weekly for 6 doses with radiation. Pembrolizumab commences concurrently with radiation and is given 200mg IV q21 days for 7 doses. Surveillance cystoscopy is performed 12 & 24 weeks after the commencement of chemoradiotherapy to assess response to therapy. Patients will enter follow up with clinical assessment, cystoscopy and CT staging performed at intervals until close of study. The primary endpoint assessed will be safety, as defined by a satisfactorily low rate of unacceptable toxicity (G3-4 adverse events or failure of completion of planned chemotherapy and radiotherapy according to defined parameters). The secondary endpoint will be efficacy, as assessed by the proportion of patients achieving a best response of complete response based on the first two 12 and 24 week post chemoradiotherapy cystoscopic assessments. Exploratory analysis will include assessment of tumour histopathological, molecular, genetic and immunological parameters. It is expected that it will take two years to accrue the 30 patients across 5 Australian centres. NCT02662062. Clinical trial information: NCT02662062.
Avelumab as neoadjuvant therapy in subjects with muscle-invasive urothelial carcinoma (AURA trial).
Authors: Martinez Chanza Nieves , Roumeguere Thierry Andre , Sideris Spyridon , Gil Thierry , Peltier Alexandre , Awada Ahmad
Published: February 2018

TPS535

Background: Avelumab, a fully human anti-PD-L1 IgG1 monoclonal antibody, is approved in monotherapy for the advanced disease. For patients with non metastatic muscle-invasive bladder cancer (MIBC) the preferred treatment nowadays consists of a multimodal approach comprising neoadjuvant cisplatin-based chemotherapy followed by surgery. However, the benefit of the neoadjuvant chemotherapy (NAC) is modest and an important proportion of patients do not benefit providing unnecessary toxicity. In addition, forty per cent of this population is ineligible for platinum-based therapies and currently no medical alternative option exist. This trial will attempt to answer several open questions: what is the role of the immunotherapy in the neoadjuvant setting? Is efficacy of immunotherapy influenced by the association with cytotoxic agents? Which agents (anthracyclins, platin or taxanes)? Do cisplatin-ineligible patients benefit from this approach? Is there any predictive biomarker for chemotherapy and/or immunotherapy? Methods: This is a randomized phase 2 study in subject candidates for a NAC followed by surgery (EudraCT Number: 2017-002758-35). The study will recruit cisplatin eligible and ineligible patients. For the group of cisplatin-eligible, chemotherapy with high dose of Metotrexate-Vinblastin-Adriamycin-Cisplatin or Cisplatin-Gemcitabine will be associated with Avelumab. For the group of cisplatin-ineligible, Avelumab as monotherapy or associated with Paclitaxel-Gemcitabine will be used. Four cycles of treatment are provided. A radiological evaluation will be performed after 2 cycles and if evidence of progressive disease exists the neoadjuvant treatment will be stopped and the surgery will be performed (Table 1 represents the study design). The primary objective is to determine the pathologic complete response as well as to assess the toxicity profile. Blood, urine and stool samples will be collected at different points to perform translational researches. Clinical trial information: 2017-002758-35.
Phase II trial of afatinib in patients with advanced/metastatic urothelial carcinoma (UC) with genetic alterations in ERBB receptors 1-3 who failed on platinum-based chemotherapy (CT).
Authors: Font Pous Albert , Puente Javier , Castellano Daniel E. , Real Francisco X. , Climent Miguel A. , Gonzalez del Alba Aranzazu Aranzazu , Oudard Stephane , Vazquez Mazon Federico Jose , Morales Barrera Rafael , Virizuela Juan Virizuela , Sala Nuria , Pérez-Valderrama Begoña , Garcia del Muro Xavier , Fernandez Pedro L. , Jares Pedro , Aldecoa Iban , Gibson Neil , Serra Josep , Rodrigo Imedio Esteban , Mellado Begona
Published: February 2018

TPS540

Background: First-line treatment of patients (pts) with advanced/metastatic UC consists of platinum-based CT, with no well-established subsequent therapy for platinum-refractory disease. Although checkpoint inhibitors have shown promising results recently, targeted agents have generally not demonstrated significant clinical activity in this setting. Around 20% of UC harbor ERBB family genetic alterations, as such it may be a suitable therapeutic target (Knowles, Nat Rev Cancer 2015;15:25–41). The irreversible ERBB family blocker, afatinib, has shown activity in a Phase II trial in a subset of pts with UC who had ERBB2/ERBB3 aberrations (Choudhury, J Clin Oncol 2016;34:2165–71). This Phase II trial will evaluate afatinib in pts with UC molecularly selected for ERBB receptor alterations. Methods: This single-arm trial will assess the efficacy and safety of afatinib in pts with UC harboring ERBB2/ERBB3 mutations or ERBB2 amplification (Cohort A), or EGFR (ERBB1) amplification (Cohort B). Eligible pts are ≥18 years of age with ECOG PS 0–1, histologically confirmed advanced/metastatic UC of the bladder, upper tract or urethra, not amenable to surgery and progressing during or after platinum-based CT, with available archival tissue samples for pre-screening biomarker analysis. Pts will receive oral afatinib 40 mg/day until disease progression or discontinuation. Cohort A is enrolling in two stages, with Stage 2 enrollment based on anti-tumor activity observed. The primary endpoint is progression-free survival (PFS) rate at 6 months; secondary endpoints include objective response rate, PFS, overall survival, disease control rate, duration of response and tumor shrinkage. Trial objectives will be analyzed separately for the two cohorts. Safety and biomarker assessments will also be performed. The trial commenced in June 2016; as of October 4, 2017, 201 samples have been analyzed, with 24.3% and 8% of pts with genetic alterations potentially eligible for inclusion in Cohort A and B, respectively. To date, 12 pts have received study treatment in Cohort A and 6 in Cohort B; recruitment is ongoing. Clinical trial information: NCT02780687.
Phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC).
Authors: Agarwal Neeraj , Vaishampayan Ulka N. , McGregor Bradley Alexander , Green Marjorie C. , Mohamed Nehal , Chang Pei-Yun , Powles Thomas , Pal Sumanta K. ,   For the XL184-021 Study Group
Published: February 2018

TPS541

Background: Cabozantinib (CABO) is an oral receptor tyrosine kinase inhibitor of MET, VEGFR, and TAM family receptors (TYRO3, AXL, and MER). It is approved for patients (pts) with RCC after prior therapy with antiangiogenic therapy, and has demonstrated clinical activity in UC. In clinical studies, CABO exposure increased circulating CD8+ T cells and reduced immune-suppressive monocytes and Tregs. In preclinical tumor models, CABO increased MHC class 1 expression on tumor cells and reduced myeloid-derived suppressor cells. CABO may facilitate an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors. Atezolizumab (ATEZO), an anti-PD-L1 mAb, is approved for: locally advanced/metastatic UC in pts who are cisplatin-ineligible or have disease progression during/following platinum-containing chemo; pts with metastatic NSCLC and disease progression during/following platinum-containing chemo. We present the study design of an ongoing phase 1b study combining CABO with ATEZO in pts with locally advanced/metastatic UC or RCC. Methods: This multicenter, phase 1b, open-label study aims to assess safety, tolerability, preliminary efficacy, and pharmacokinetics of CABO in combination with ATEZO (NCT03170960). The study will enroll pts with advanced UC (bladder, renal pelvis, ureter, urethra) or RCC. It consists of two stages: dose escalation and expansion. In the dose-escalation stage (3+3 design), a recommended CABO dose for the combination will be established. In the expansion stage, four tumor-specific cohorts will be enrolled: 1) pts with UC who have progressed on/after platinum-containing chemo; 2) chemo-naïve pts with UC who are cisplatin ineligible; 3) chemo-naïve pts with UC who are cisplatin eligible; and 4) untreated pts with RCC with clear cell histology; the primary objective is to determine the objective response rate in each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers, and changes in immune cell profiles with clinical outcome. The study has been initiated and enrollment target is 120 pts across the 4 expansion cohorts. Clinical trial information: NCT03170960.
A phase 2 trial of lenvatinib 18 mg versus 14 mg once daily (QD) in combination with everolimus (5 mg QD) in renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment.
Authors: Glen Hilary , Puente Javier , Heng Daniel Yick Chin , Rha Sun Young , Li Di , Stepan Daniel E. , Dutcus Corina E. , Pal Sumanta K.
Published: February 2018

TPS707

Background: Based on findings from a randomized phase 2 study (Study 205), lenvatinib (LEN) + everolimus (EVE) was approved in the United States and European Union for patients (pts) with advanced RCC following 1 prior anti-angiogenic therapy. In that study, LEN 18 mg QD + EVE 5 mg QD significantly prolonged progression-free survival (PFS) compared with either monotherapy. In the LEN+EVE cohort, grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 71% of pts. We report the design of an ongoing, multicenter, randomized, double-blind, phase 2 study (Study 218) to evaluate if a lower LEN starting dosage regimen provides similar efficacy with a better safety profile than LEN 18 mg + EVE 5 mg (NCT03173560). Methods: Eligible pts are aged ≥ 18 years with advanced clear cell RCC, 1 prior anti-VEGF therapy, ≥ 1 measurable target lesion per RECIST 1.1, a KPS score of ≥ 70, and prior nivolumab is allowed. Pts will receive LEN 18 mg or 14 mg QD + EVE 5 mg QD in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The LEN 14-mg dose will be escalated to 18 mg if no intolerable grade 2, or any grade ≥ 3 TEAEs requiring dose reduction occur in cycle 1. The primary endpoints are objective response rate (ORR) at week 24 (ORR24W) and the proportion of pts with intolerable grade 2 and any grade ≥ 3 TEAEs within 24 wks after randomization. Secondary endpoints include PFS and ORR. An estimated 306 pts will be randomized. Sample size is based on detecting noninferiority (NI) of ORR24W and superiority of the primary safety endpoint. Two interim analyses (IA) will be performed when 150 and 200 pts have completed 24 wks of follow-up or discontinue earlier. Each analysis will test NI and futility of the LEN 14-mg arm ORR24W vs the 18-mg arm ORR24W. An O’Brien-Fleming boundary will be used for NI. If the 1-sided P-value is ≤ 0.005 at the first IA, ≤ 0.014 at the second IA, or ≤ 0.045 at the final analysis, then NI in ORR24W will be claimed. If the futility boundary is crossed (ie, 1-sided P-value is ≥ 0.776 at the first IA or ≥ 0.207 at the second IA), then futility will be claimed. Clinical trial information: NCT03173560.
Preparation and Characterization of a µ-P2O7-µ-HPO4 Dinuclear Fe2(III, III) Complex
Authors: Miyazato Yuji , Imaizumi Kouta , Tanaka Rikako , Wada Tohru , Matsushita Nobuyuki
Published: February 2018

The [{Fe(Me3tacn)}2(µ-P2O7)(µ-HPO4)]·12H2O dinuclear Fe2(III, III) complex was prepared. The HPO42− bridge in the complex arises from hydrolysis of the pyrophosphate bound to the Fe(III) centers in the trinuclear [{Fe(Me3tacn)}3(P2O7)2]+ intermediate. Electrochemical reduction of this complex at pH <3.2 results in dissociation of the H2PO4− bridge.
The financialisation of global health
Authors: Stein Felix , Sridhar Devi
Published: February 2018

Global health is increasingly reliant on financial markets. The ongoing financialisation of global health raises new questions of governance, which we expect to affect policy makers as much as doctors, nurses and patients in the years to come. In this editorial, we will first explain what is meant by financialisation, then illustrate its nature in the field of global health via three examples, and end by highlighting some of the governance issues that the financialisation of global health raises.
Mainstreaming as rhetoric or reality? Gender and global health at the World Bank
Authors: Winters Janelle , Fernandes Genevie , McGivern Lauren , Sridhar Devi
Published: February 2018

Background:Over the past decade gender mainstreaming has gained visibility at global health organisations. The World Bank, one of the largest funders of global health activities, released twoWorld Development Reportsshowcasing its gender policies, and recently announced a $1 billion initiative for women’s entrepreneurship. However, the development of the Bank’s gender policies and its financing for gender programmes have never been systematically analysed by external researchers in the context of global health. We use the Bank as a case study of how global health organisations frame their gender policies and measure their success.

Methods:We constructed a timeline of the Bank’s governance of gender, through a review of published articles, grey literature, and Bank documents and reports. Additionally, we performed the first health-focused analysis of two publicly available Bank gender project databases, and tracked the Bank's financing of gender projects in the health sector from 1985-2017.

Results:The Bank’s gender policy developed through four major phases from 1972-2017: ‘women in development’ (WID), institutionalisation of WID, gender mainstreaming, and gender equality through ‘smart economics’. In the more inclusive of the two Bank project databases, gender projects comprised between 1.3% (1985-1989) and 6.2% (2010-2016) of all Bank commitments, which is significantly less than the Bank’s claim that 98% of its lending is gender informed. Most funding targeted middle-income countries and particular themes, including communicable diseases and health systems. Major gender-related trust funds were absent from both databases.

Conclusion:The Bank focused most of its health sector gender projects on women’s and girls’ issues. It is increasingly embracing private sector financing of its gender activities, which may impact its poverty alleviation agenda. Measuring the success of gender mainstreaming in global health will require the Bank and global health organisations to reconsider their use of gender indicators.
Efficiency of the electrochemical treatment of textile effluent using two configurations of sacrificial electrodes
Authors: Fleck Leandro , Passos Jeysa Piza Santana , Helmann Andrieli Cristina , Eyng Eduardo , Frare Laércio Mantovani , Orssatto Fábio
Published: February 2018

Textile industries have as main characteristic the generation of effluents with high color, and efficient treatment techniques are necessary. In this context, this study compared the efficiency of the electrochemical treatment for color removal from synthetic textile effluent using two configurations of sacrificial electrodes, parallel plates and array of cylindrical electrodes. For application of the electroflocculation technique, an electrochemical reactor was used, in a laboratory scale, operated in a continuous flow. The synthetic textile effluent was prepared with preset concentrations of reactive dye Blue 5G and sodium chloride. Sacrificial iron (Fe) electrodes with different configurations were used: parallel plates and cylindrical electrodes. The Hydraulic Retention Time (HRT) and electric current density (j) were controlled, and their effects on color removal were evaluated using a Central Composite Rotational Design (CCRD) composed of 12 trials. For the electrochemical treatment using parallel plates, the color removal efficiency ranged from 56.13% to 98.95% and for the electrochemical treatment using an array of cylindrical electrode, the color removal efficiency varied from 2.11% to 97.84%. The mathematical models representative of the process explained a high proportion of the total data variability, with a coefficient of variation of 99.49% and 97.21% for parallel plates and arrangement of cylindrical electrodes, respectively. The electrochemical treatment using parallel plates presents advantages over the configuration using a cylindrical electrode array, since the color removal efficiency is superior under the same operating conditions, representing economic and environmental gains.
Abordagem multicritério na seleção de alternativas de tratamento de efluentes: uma revisão sistêmica da literatura
Authors: Goffi Andreia Dos Santos , Bortoluzzi Sandro César , Trojan Flavio , Goffi Andressa
Published: February 2018

O estudo bibliográfico estruturado tem se tornado uma excelente ferramenta para avaliar tendências cientificas em diferentes campos do conhecimento. Neste sentido, este trabalho busca analisar as oportunidades de pesquisa, apresentando uma visão geral a cerca da tomada de decisão em projetos de tratamento de efluentes no cenário internacional. ProKnow-C (Knowledge Development Process - Constructivist) foi a ferramenta de intervenção utilizada, que consiste em um processo estruturado para geração de conhecimento em um tema determinado a partir dos interesses e limitações do pesquisador. Ao final do processo de busca foram identificados 16 artigos com reconhecimento científico e conteúdo alinhado ao tema de pesquisa. Os primeiros resultados da pesquisa demostraram uma acentuada tendência de crescimento a cerca do tema nos últimos 7 anos. A análise aprofundada dos trabalhos demonstrou que a construção dos modelos no cenário internacional segue padrões possíveis de serem replicados em diferentes cenários, considerando diferentes aspectos e necessidades dos decisores. De modo geral, os estudos aplicando métodos de apoio à decisão, especialmente para a seleção de tecnologias de tratamento de efluentes se demonstraram de alto impacto, e por consequência alta relevância.
Nesting of Barnacle Goose (Branta leucopsis) in the Russian Part of the Gulf of Finland
Authors: Kouzov Sergei , Zaynagutdinova Elmira , Sagitov Rustam , Rychkova Anna
Published: February 2018

Until the end of the 1980s, the Barnacle Goose (Branta leucopsis) was an extremely rare migrating species in the Russian part of the Gulf of Finland, but in recent years it has become one of the mass migrants there. The first nest of a Barnacle Goose in the region was found on Dolgy Reef Island close to the Russian-Finnish border in 1995. Barnacle Geese then started expanding onto the islands in the eastern part of the Gulf of Finland. They occupied islands mostly in the northern part of the gulf, but nests were found in its central parts and close to the southwest coast as well. Barnacle Geese nested mostly on small, rocky, forest-free islands. By 2006, the size of the breeding population of this species had increased to 31 pairs. Forty nests were found in 2014, and an explosive population growth to 76 nests was observed in 2015. In 2010, Barnacle Geese started to breed on Ladoga Lake, and in 2015 the first nest was found on Onega Lake. Until 2010 Barnacle Geese had nested in the eastern part of the Gulf of Finland almost exclusively on the islands lying at a distance of 2.4 – 10.1 km from the coast. The population growth that occurred in subsequent years was due primarily to the birds’ breeding on islands closest to the coast, no farther than 2 km away from the shore. After hatching, broods from inshore islets moved to feed on coastal meadows, but nonbreeding birds and failed breeders generally remained on offshore islands for the molting period. Further expansion of the Barnacle Goose in the eastern part of the Gulf of Finland is expected. However, expansion could ultimately be restricted by the limited food resources for broods and molting birds.
Metaphoric Tasks in Psychotherapy: Case Studies of "Margie's" Self-Image and "Amy's" Pain
Authors: Hamburg Sam R.
Published: February 2018

Metaphor exists not simply as figurative language but as a fundamental organizing principle of human thought. Given the appropriate context, anything can function metaphorically. In the presently described cases of "Margie" and "Amy," which differed in many ways, a common theme was the effective incorporation of simple tasks, assigned as homework, which were used metaphorically in successful psychotherapy. In Margie's case, the task was not self-consciously conceived as a metaphor by the therapist, but it functioned that way. The therapeutic power of that metaphoric task was confirmed by the client many years later. In the second case, the task was deliberately formulated as a metaphor. Whether this metaphoric task contributed to the case's initially positive outcome is uncertain. To provide background for understanding the integrative psychotherapy model that I bring to these two cases, a statement on my development as a psychotherapist is included as Appendix 1.
Visualization of Urea Treatments Using Micro-X-Ray Fluorescence Spectrometry
Authors: Brehm Lora , Keene Ellen C. , Ng Sze-Sze
Published: February 2018

Urea has many uses in agriculture. It is a common source of nitrogen fertilizer but is also used as an inert ingredient in solid formulations. Urea is listed on the U.S. EPA’s list of minimal concern. When used as an inert ingredient, urea can be used as a dissolution aid. Its worldwide availability, low cost, and safe-handling profile are some of the drivers of its use. Therefore, a wide variety of chemicals are coated on urea for various reasons. Having a method for detecting the deposition of various chemicals on urea is useful for understanding how uniformly a chemical has deposited on urea. Dyes and pigments have been used in fertilizer and seed treatments as an indication that a treatment has been applied. However, this method assumes that the treatment has the same mobility as the dye through the urea granule. Alternatively, chromatography techniques such as high-performance liquid chromatography and gas chromatography can indicate how much treatment has been applied, but these techniques do not provide information regarding the uniformity of treatment from granule to granule or the penetration of the treatment into the granule. An analytical technique called micro-X-ray fluorescence (MXRF) was evaluated for visualizing urea treatments. MXRF is a nondestructive form of elemental analysis capable of collecting elemental maps over a region of interest. Because urea is a simple organic molecule that contains only carbon, hydrogen, oxygen, and nitrogen (elements not typically detected by X-ray fluorescence spectrometry [XRF]), treatment that contains elements that are detectable by XRF can be differentiated from urea and visualized. This technique was used to analyze urea samples treated with zinc and N-(n-butyl)thiophosphoric triamide (NBPT). The distribution of zinc and NBPT (sulfur and phosphorus) across the granule and within the granule could be observed with MXRF. Whereas a red dye of a commercial NBPT treatment fully penetrated a urea granule, MXRF indicated that NBPT remained on its surface.
Clays in Biological Formulations
Authors: Goss G. Robert
Published: February 2018

Clays are used in commercial biological formulations for agricultural purposes. There are different types of clays, each of which has its own unique properties. As a class, clays have several useful properties that can be exploited. The most common formulation uses are as a diluent, carrier, moisture regulator, and absorbent. As a diluent, clay is used to modify the concentration (microbial count) of a biological formulation concentration. As a carrier, clay is used to provide the appropriate particle size for application. As a moisture regulator, clay can provide a suitable moisture environment for biological activity (or lack thereof) during storage. As an absorbent, clay can absorb material such as a fermentation broth. It can then be dried and used as is or as an ingredient in a downstream process. Commercial examples of clay use are with mychorrizae, pseudomads, Trichoderma, Rhizobium, and Penicillium.
Increase in Herbicide Efficacy Using High Surfactant Oil Concentrate Adjuvants
Authors: Wirth Devin , Zollinger Richard K.
Published: February 2018

High surfactant oil concentrate (HSOC) adjuvants were developed to enhance lipophilic herbicides without antagonizing hydrophilic herbicides. The oil was either a methylated seed oil (HSMOC) or petroleum oil (HSPOC). HSOC adjuvants contained a minimum of 50 % oil with 25 % to 50 % emulsifier surfactant. The purpose of this study was to screen multiple HSOC adjuvants to quantify their relative effectiveness when applied with glyphosate mixed with either dicamba or tembotrione. Reduced rates of glyphosate at 473 g ai ha−1, dicamba at 214 g ai ha−1, and tembotrione at 46 g ai ha−1 were applied with HSOC adjuvants at 1,170 mL ai ha−1. HSOC adjuvants increased the efficacy of the tank mixes glyphosate plus dicamba and glyphosate plus tembotrione. There were few statistical differences between all HSOC adjuvants and within HSMOC and HSPOC groups. In both trials, HSMOC adjuvants increased the efficacy of the tank mix more than the HSPOC adjuvants. However, the performance of an HSOC varies depending on the herbicide tank mix.
Review of Size and Loading Conditions for Large-Scale Triaxial Testing
Authors: Stark Timothy D. , Wilk Stephen T. , Swan Robert H.
Published: February 2018

The large particle size of railroad ballast and the wide range of loading conditions make it difficult to appropriately represent ballast behavior in laboratory shear testing. This paper presents an overview of the advantages and disadvantages of large-scale triaxial compression testing of ballast, how it can be used to represent field ballast conditions, and typical results. Minimum size restrictions and diameter along with appropriate confining stress, loading frequencies, and deviator stresses are discussed with examples of the range of loading conditions experienced in the field from field monitoring and numerical modeling. In triaxial compression testing, a specimen diameter of six times the maximum particle size is required. In addition, standard confining stresses can range from 0 kPa to 72 kPa, and the deviator stresses can range from 50 kPa to 360 kPa.
Large-Scale Triaxial Tests on Railway Embankment Material
Authors: Dyvik Rune , Kaynia Amir M.
Published: February 2018

Large-scale vacuum triaxial tests were performed as a part of the European project SUPERTRACK. The triaxial specimen dimensions were large enough to allow testing of large-grained railway ballast material. Two different materials were tested—ballast (two tests) and sub-ballast (one test). The confining pressure used in the triaxial tests was 40 kPa, supplied by a vacuum applied to the inside of the specimen (membrane) and normal atmospheric pressure outside the specimen. The tests thereby had drained conditions throughout. Load-controlled cycling at a frequency of 1 Hz was applied to each specimen. The two tests on ballast material had several cyclic loading stages with different stress amplitudes and numbers of cycles, with one test including more than one million cycles. The specimens were finally loaded to failure monotonically at a displacement rate of 1 mm/min. The parameters and results of these special tests are presented and compared with some results of scaled materials and general functions found in the literature.
Large Direct Shear Tests Performed with Fresh Ballast
Authors: Estaire Jose , Santana María
Published: February 2018

This study evaluates the ballast shear strength from the testing of 20 specimens, performed in a very large direct shear box that has a shearing plane of 1 m by 1 m and can hold specimens with a thickness up to 80 cm. Tests comprise two different types of ballast (mylonitic and andesitic) and two different specimen preparation techniques (with and without compaction). The normal stresses used cover a wide range from 10 kPa to 400 kPa. Geometrical and physical properties of both ballasts were obtained according to EN-13450, Aggregates for Railway Ballast, showing that both ballasts are similar, can be ranked as high-quality class ballast and fulfill the recommended limiting values set by the American Railway Engineering and Maintenance-of-Way Association. The values obtained for the Mohr–Coulomb failure criterion were: (a) for noncompacted ballast—a friction angle of 39° combined with an “apparent cohesion” of 25 kPa, and (b) for compacted ballast—a friction angle of 50° and cohesion between 10 kPa and 20 kPa. Test results were also interpreted according to a parabolic model that proved the nonlinear nature of ballast shear envelope. The results also showed the decrease of secant friction angles with an increase of normal stress. It is worth remarking that, for very low normal stress (10 kPa), secant friction angles are around 70°, while for large stresses (400 kPa), they decrease to values around 40°. Finally, the use of direct shear boxes of two different sizes (30 cm by 30 cm and 1 m by 1 m) made it possible to analyze the scale effect in these tests. Test results show that the use of the smallest direct shear boxes produces an increase in the shear strength between 40 % and 60 %. Results obtained in this study agree well with those in the literature.
Large-Scale Testing Box: A Tool to Evaluate the Structural Performance of Railway Tracks
Authors: Sol-Sánchez Miguel , Moreno-Navarro Fernando , Carmen Rubio-Gámez M.
Published: February 2018

Ballasted railway tracks are regarded as a complex infrastructure composed of very distinct elements made from various materials. It is thus essential to understand the mechanical performance of the group of components as a whole section, particularly when developing innovative components or solutions to analyze their effect on the global track. However, traditional laboratory tests commonly consider each element separately or are based on simplification, while facilities reproducing real track sections, despite their ability to simulate real conditions, provide limited versatility to study different solutions for track sections in a short time and with low costs. A large-scale testing box in a laboratory could provide a useful tool to understand, in a cost and time-efficient way, the mechanical response of the whole track section, while also evaluating the effect of each element on the behavior of the system under full-scale conditions and analyzing different configurations in the search for track optimization. In this context, the present paper set out to determine the mechanical behavior of various configurations used for global track sections using a testing box, with a particular focus on the effect of innovative elastic components. The results indicate that at least when an appropriate procedure is applied, box tests are sufficiently sensitive to evaluate the effect of various design factors on global track behavior, depending on the section configuration and properties to be analyzed.
Evaluation of Ballast Particle Movement Using SmartRocks for Track Transitions
Authors: Gao Yin , Liu Shushu , McHenry Mike
Published: February 2018

Ballast is a critical layer in the railroad track substructure that provides track drainage and supports track upper structures and railway trains. Many types of track problems, such as differential settlement, ballast migration, and track geometry degradation, are associated with ballast. Both laboratory and numerical research efforts have been undertaken to study ballast performance. These show that individual ballast particle movement can strongly affect the overall track performance. To measure the movement of an individual ballast particle, a wireless ballast-shaped device (called a “SmartRock”) equipped with a nine-degree-of-freedom inertial measurement unit was used. This device can be placed in the ballast layer to record and send back the real-time ballast particle motion through Bluetooth, such as accelerations and angular velocities. A ballast performance test/evaluation was conducted at the Transportation Technology Center in Pueblo, CO, which is a world-class railway research and testing center. The test sections include a bridge approach and an open track, both located in the same five-degree curve. The bridge approach had differential track settlement and required frequent maintenance based on a historic track maintenance log. The SmartRocks were instrumented west of the bridge approach and in the nearby open track. The second stage of this test investigates the effectiveness of under tie pads on reducing the vibration at the tie–ballast interaction. Therefore, the bridge approach was installed with a 50-tie track panel with under tie pads. The ballast performance was evaluated based on the analysis of the measured acceleration data. Detailed results and conclusions are presented in the paper.
Perceptions of HIV Self-Testing Among Men Who Have Sex With Men in the United States: A Qualitative Analysis
Authors: Freeman Arin E. , Sullivan Patrick , Higa Darrel , Sharma Akshay , MacGowan Robin , Hirshfield Sabina , Greene George J. , Gravens Laura , Chavez Pollyanna , McNaghten A. D. , Johnson Wayne D. , Mustanski Brian
Published: February 2018

HIV testing is the gateway into both prevention and treatment services. It is important to understand how men who have sex with men (MSM) perceive HIV self-tests. We conducted focus groups and individual interviews to collect feedback on two HIV self-tests, and on a dried blood spot (DBS) specimen collection kit. Perceptions and attitudes around HIV self-testing (HIVST), and willingness to distribute HIV self-tests to others were assessed. MSM reported HIVST to be complementary to facility-based testing, and liked this approach because it offers privacy and convenience, does not require counseling, and could lead to linkage to care. However, they also had concerns around the accuracy of HIV self-tests, their cost, and receiving a positive test result without immediate access to follow-up services. Despite these issues, they perceived HIVST as a positive addition to their HIV prevention toolbox.
Acceptability of an Adapted HIV Prevention Intervention for Native American Adolescents
Authors: Lee Crystal , Thompson-Robinson Melva , Dodge-Francis Carolee
Published: February 2018

Relatively few HIV evidence-based interventions (EBIs) among Native Americans have been developed, adapted, evaluated, and/or published in the scientific literature. An adolescent HIV EBI was adapted in three phases: (1) securing input from a Native American Advisory Board; (2) modifying the EBI to be more consistent with Native American culture; and (3) conducing a pilot with 14 Native American adolescents to examine acceptability and cultural congruence between the adapted intervention and the youth's culture based on Likert-scale ratings and a focus group. The adaptations included diverse Native American social and cultural stories that assisted with responsible decision-making skills. The adolescents consistently rated each intervention session as highly acceptable. A difference in knowledge from pre-survey (M = 13.93, SD = 3.08) to post-survey (M = 17.14, SD = 2.25) was statistically significant; t(13) = 4.166, p < .0005. The adapted curriculum did appear culturally responsive based on the pilot test results.
Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTRin Nociception
Authors: Sung Kijung , Ferrari Luiz F. , Yang Wanlin , Chung ChiHye , Zhao Xiaobei , Gu Yingli , Lin Suzhen , Zhang Kai , Cui Bianxiao , Pearn Matthew L. , Maloney Michael T. , Mobley William C. , Levine Jon D. , Wu Chengbiao
Published: February 2018

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGFβ sequence (NGFR100W) in patients with hereditary sensory and autonomic neuropathy type V (HSAN V) made it possible to distinguish the signaling mechanisms that lead to two functionally different outcomes of NGF: trophic versus nociceptive. We performed extensive biochemical, cellular, and live-imaging experiments to examine the binding and signaling properties of NGFR100W. Our results show that, similar to the wild-type NGF (wtNGF), the naturally occurring NGFR100Wmutant was capable of binding to and activating the TrkA receptor and its downstream signaling pathways to support neuronal survival and differentiation. However, NGFR100Wfailed to bind and stimulate the 75 kDa neurotrophic factor receptor (p75NTR)-mediated signaling cascades (i.e., the RhoA-Cofilin pathway). Intraplantar injection of NGFR100Winto adult rats induced neither TrkA-mediated thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia based on agonism for TrkA signaling. Together, our studies provide evidence that NGFR100Wretains trophic support capability through TrkA and one aspect of its nociceptive signaling, but fails to engage p75NTRsignaling pathways. Our findings suggest that wtNGF acts via TrkA to regulate the delayed priming of nociceptive responses. The integration of both TrkA and p75NTRsignaling thus appears to regulate neuroplastic effects of NGF in peripheral nociception.

SIGNIFICANCE STATEMENTIn the present study, we characterized the naturally occurring nerve growth factor NGFR100Wmutant that is associated with hereditary sensory and autonomic neuropathy type V. We have demonstrated for the first time that NGFR100Wretains trophic support capability through TrkA, but fails to engage p75NTRsignaling pathways. Furthermore, after intraplantar injection into adult rats, NGFR100Winduced neither thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia. We have also provided evidence that the integration of both TrkA- and p75NTR-mediated signaling appears to regulate neuroplastic effects of NGF in peripheral nociception. Our study with NGFR100Wsuggests that it is possible to uncouple trophic effect from nociceptive function, both induced by wild-type NGF.
When Cultures Divide
Authors: Wyndham Marivic , Read Peter
Published: February 2018

We two Australian public historians recently published a history of memorials in Santiago, Chile, to the victims of the Augusto Pinochet dictatorship, Narrow but Endlessly Deep: The Struggle for Memorialisation in Chile since the Transition to Democracy. Our different upbringings and experiences (one a migrant from Cuba, the other Anglo-Australian) produced disagreements as to how we should interpret the memorializations. In particular, the foundational narratives of Cuba and Australia in which we were raised affected our differing interpretations. The article explains these differing foundational narratives and then cites examples of textual disagreements and how we resolved them. We believe that this challenging interrogation of lifetime values improved the monograph and may offer insights for other cross-cultural collaborations.