bluuebunny/crossref_metadata_2025 huggingface dataset:
Policy entrepreneurs in policy valuation processes: The case of the Coalition for Environmentally Responsible Economies
Authors: Maor Moshe
Published: March 2017

Policy problems and solutions are frequently loaded with moral, emotional and cost-effectiveness components as well as with other ideational and symbolic elements in order to provide them with, or deprive them of, significance. Skillful policy entrepreneurs are key actors in this valuation process which results in policy problems and solutions becoming valued, overvalued or undervalued. Drawing on insights from the sociology of valuation, this article distinguishes between four types of policy entrepreneurs – defined by the particular strategies they pursue – that may be involved in this process: norm entrepreneurs, reputation entrepreneurs, meaning entrepreneurs and standards and performance metrics entrepreneurs. The article elaborates on the role of these actors in the policy valuation process and the interactive nature of their activities. It thereafter illustrates their activities by elaborating on the valuation strategies pursued by the Coalition for Environmentally Responsible Economies, which led several European governments to provide financial support for the Carbon Disclosure Project.
The Synthesis of Size-Adjustable Superparamagnetism Fe3O4 Hollow Microspheres
Authors: Xu Chao , Lu Xiaolong , Dai Honglian
Published: March 2017

One hundred fifty to 300-nm-sized monodisperse iron oxide (Fe3O4) hollow microspheres were synthesized by the one-pot hydrothermal method. The morphology and crystal structure of the as-prepared hollow microspheres was characterized by scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and high-resolution transmission electron microscopy, while the magnetic property was investigated by vibrating sample magnetometer. We found that the particle size of the hollow microspheres was related to the amount of sodium citrate, polyacrylamide (PAM), and urea. The hollow structure of Fe3O4 microspheres has high magnetization saturation values ranging in 49.10–75.41 emu/g.
Reviews
Authors: Saltus Rick , Krebes Edward S. , Taylor Patrick
Published: March 2017

Crustal permeability, edited by Tom Gleeson and Steve Ingebritsen, ISBN 978-1-11916-656-6, 2016, Wiley, 472 p., US$160 (paper), US$128.99 (eBook). Wavefronts and rays as characteristics and asymptotics: 2nd edition, Andrej Bóna and Michael A. Slawinski, ISBN 978-9-81464-478-5, 2015, World Scientific Publishing Co., 344 p., US$98. Predicting the unpredictable: The tumultuous science of earthquake prediction, by Susan Elizabeth Hough, ISBN 978-0-69117-330-6, 2016, Princeton University Press, 280 p., US$19.95.
Health-related quality of life outcomes in a phase I/II study of stereotactic hypofractionated once-weekly radiation therapy (SHORT) for nonmetastatic prostate cancer.
Authors: Mallick Indranil , Arunsingh Moses , Gupta Sujoy , Mukherjee Satyadip , Chatterjee Sanjoy , Shrimali Raj K , Achari Rimpa
Published: March 2017

126

Background: Stereotactic Radiation Therapy (SRT) for prostate cancer offers an opportunity to exploit the low alpha/beta ratio of prostate cancer. We present patient reported health-related Quality-of-life (HR-QoL) outcomes of an SRT schedule with once-weekly fractionation in an unselected cohort of non-metastatic prostate cancer. Methods: In a Phase I/II study 30 patients with non-metastatic prostate cancer (multiparametric MRI cT1-4N0, M0, Gleason 6-10, PSA < = 60 ng/ml) were treated to a dose of 35Gy in 5 fractions delivered once a week (along with simultaneous elective nodal radiotherapy at 25Gy/5Fr to patients high-risk by NCCN criteria). Androgen deprivation therapy given to intermediate and high-risk patients. Treatments were planned using volumetric intensity modulated arc therapy. Quality of life was assessed using the EORTC QLQ C30 and PR25 questionnaires. HR-QoL parameters at baseline (before start of SRT) was compared to those at treatment completion and 3 months post-SRT. The raw QoL scores were converted to a scale of 0-100 by convention. A scale difference of 10 or higher was considered clinically meaningful. Results: All of the 30 recruited patients completed treatment and HR-QoL data were available at 3 time points for all patients. The ratio of low, intermediate and high risk patients was 1:9:20. SRT was well tolerated with no acute Grade 3 GI or GU symptoms by NCI CTC v4 (separately reported). Twenty one parameters were studies within the QLQ C30 and PR25 framework. At the end of treatment, only the urinary symptom score showed a clinically meaningful worsening (mean of 20/100 at baseline vs 34/100 at end of treatment, p < 0.001). At 3 months, the urinary symptom score had returned close to baseline (26/100, p = 0.08). There was no clinically meaningful deterioration in the remaining HR-QoL parameters. Conclusions: Patient perception of function and symptoms with once-weekly SRT was good, with only a temporary worsening of the urinary symptom score, and subsequent recovery by 3 months. Compared to baseline scores, other QoL parameters did not show a clinically meaningful difference at end of treatment or at 3 months. Clinical trial information: CTRI/2016/02/006671.
Individual patient level meta-analysis of the performance of the Decipher genomic classifier in high-risk men post-prostatectomy to predict development of metastatic disease.
Authors: Spratt Daniel Eidelberg , Yousefi Kasra , Deheshi Samineh , Ross Ashley , Schaeffer Edward M. , Trock Bruce J. , Karnes Jeffrey , Glass Andrew , Den Robert B. , Dicker Adam , Freedland Stephen J. , Lam Lucia L.C. , du Plessis Marguerite , Choeurng Voleak , Haddad Zaid , Buerki Christine , Davicioni Elai , Weinmann Sheila , Klein Eric A. , Feng Felix Yi-Chung
Published: March 2017

133

Background: The genomic classifier, Decipher, has been validated to predict risk of metastasis after radical prostatectomy (RP). However, the cohort size and event rate in the previous studies did not allow for a thorough investigation into performance within individual clinicopathologic or treatment subgroups. In this study, we present the first meta-analysis of the performance of the 22-marker genomic classifier in men with prostate cancer (PCa) post-RP. Methods: MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports of men with PCa treated by RP between 2010 and 2016 where the benefit of the Decipher genomic classifier test was assessed. The primary end point was the ability of Decipher to independently improve prognostication of regional or distant metastasis over routine clinicopathologic factors. Meta-analysis was performed with random-effects modeling, and extent of heterogeneity between studies was determined with the I2 test. Results: Five studies (975 total patients, and 855 with individual patient genomic and clinicopathologic data) were eligible for analysis. The median follow-up was 8 years. All patients had clinical high-risk disease, yet 60.9%, 22.6%, and 16.5% of patients were classified as low, intermediate, and high-risk, respectively by Decipher and had 10-year cumulative incidence rates of metastases of 5.5%, 15.0% and 26.7% (p < 0.001), respectively. Adjusting for standard clinicopathologic variables, on multivariable analysis Decipher remained a statistically significant predictor of metastasis (hazard ratio [HR] 1.30 per 0.1 unit, 95% confidence interval [CI] 1.14-1.47, p < 0.001), and the summary HR for metastasis of Decipher across the 5 studies was 1.52 (95% CI 1.39-1.67) per 0.1 unit. Conclusions: The genomic classifier test, Decipher, has the ability to independently improve prognostication of men post-RP, as well as within nearly all clinicopathologic and treatment subgroups. Strong consideration should be given to incorporating the use of genomic testing in clinical decision making and clinical trials to better individualize treatment.
Effects of radium-223 (Ra-223) with docetaxel versus docetaxel alone on bone biomarkers in patients with bone-metastatic castration-resistant prostate cancer (CRPC): A phase I/IIa clinical trial.
Authors: Morris Michael J. , Loriot Yohann , Fizazi Karim , Sweeney Christopher , Ryan Charles J. , Shevrin Daniel H. , Antonarakis Emmanuel S. , Seger Monica , Lu Chengxing , Higano Celestia S.
Published: March 2017

154

Background: Interactions between metastatic prostate cancer cells, osteoblasts, osteoclasts, and other participants in bone metabolism are complex and result in pathologic bone physiology. Ra-223, a targeted alpha therapy, accumulates at sites of bone metastases and prolongs survival. Ra-223 and docetaxel (D), acting through different mechanisms of action, may have beneficial effects on bone pathophysiology and tumor microenvironment. Prior data suggest treatment with Ra-223 results in favorable alterations in bone biomarkers that are associated with survival. Methods: 53 patients with progressing CRPC and ≥ 2 bone metastases were randomized 2:1 to Ra-223 (55 kBq/kg q6wk × 5) + D (60 mg/m2 q3wk × 10) versus D (75 mg/m2 q3wk with step-down option to 60 mg/m2). Bone resorption (CTX-1, ICTP) and formation (P1NP, bALP) markers, tALP, and PSA were analyzed at wk 19 (after 3 Ra-223 injections) and 3 wk after end of treatment (EOT). Results: Mean % change at wk 19 and EOT are shown (Table). tALP, bALP, P1NP, and PSA declined early during treatment, reaching an average of > 30% decline from baseline by wk 19 in both arms. Mean % declines were greater in the Ra-223 + D versus the D-alone arm at wk 19 and EOT. Bone resorption markers CTX-1 and ICTP showed little decline at wk 19. Conclusions: Ra-223 + D patients had greater % decline in tALP and in bone formation markers bALP and P1NP. Due to small patient numbers and preliminary data, further analysis and correlation with clinical outcomes in a larger study is warranted. Clinical trial information: NCT01106352. [Table: see text]
Polymorphisms of the androgen transporting gene SLCO2B1 and response to abiraterone acetate in mCRPC patients.
Authors: Giacinti Silvana , Bassanelli Maria , Roberto Michela , Strigari Lidia , De Nunzio Cosimo , Aschelter Anna Maria , Marchetti Paolo
Published: March 2017

174

Background: Abiraterone Acetate (AA), an effective treatment for metastatic castration resistant prostate cancer (mCRPC), is highly variable in its effectiveness and it is well known that form of primary and acquired resistance to this agent, exist. This resistance may partly depend on the increased capacity of CRPC cells to synthesize testosterone and dihydrotestosterone from weak adrenal androgens (i.e. DHEA, DHEA-S) or de novo from cholesterol, in response to a chronic exposition to a low-testosterone environment. The organic anion-transporting polypeptides (OATPs) encoded by SLCO genes, mediate the cellular uptake of many compounds, including adrenal androgens. We hypothesized that germ-line variants of the androgen transporter gene SLCO2B1 (solute carrier organic anion transporter family member 2B1), altering the ability of the prostate cancer cell to stock adrenal precursors, may influence the response to AA of mCRPC patients. Methods: Three single nucleotide polymorphisms (SNPs), exonic SNP rs12422149 and intronic SNPs rs1789693 and rs1077858, were genotyped in a cohort of 21 consecutive patients with mCRPC who were treated with AA at the Sant’Andrea Hospital of Rome, Italy. The SNPs were detected in blood samples using pyrosequencing technique. The median TTBP (Time to Biochemical Progression), PFS (Progression Free Survival) and OS (Overall Survival) was estimated using the Kaplan-Meier method, with 95% CI. To test the association between SNPs and TTBP, PFS and OS the log-rank test was used. Results: The intronic polymorphism of SLCO2B1 rs1077858A > G was associated with TTBP (p = 0.03) and PFS (p = 0.04) of mCRPC patients on AA therapy. Patients carrying the SLCO2B1 rs1077858 risk genotype (GG) exhibited a TTBP that was 8 months shorter than that of patients with the major allele of SNP rs1077858 (AA or GA) (TTBP: A/A+G/A = 12 (95% CI: 12-NA) vs G/G = 4 (95% CI: NA) months). Patients carrying genotype GG of SNP rs1077858 also showed an 11 months shorter PFS on AA therapy than patients with AA or GA genotype (PFS: GG = 5.1 (95% CI:NA) vs AA+GA = 16.7 (95%CI:14.9-NA) months). Conclusions: Genetic variants of SLCO2B1 may function as pharmacogenomic determinants of resistance to AA in mCRPC.
Impact of metformin on prostate cancer (PC) outcomes in the E3805 CHAARTED trial.
Authors: Jarrard David Frazier , Chen Yu-Hui , Liu Glenn , Carducci Michael Anthony , Eisenberger Mario A. , Wong Yu-Ning , Hahn Noah M. , Kohli Manish , Cooney Matthew M. , Dreicer Robert , Vogelzang Nicholas J. , Picus Joel , Shevrin Daniel H. , Hussain Maha , Garcia Jorge A. , DiPaola Robert S. , Sweeney Christopher
Published: March 2017

181

Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]
Incidence and characterization of antiandrogen withdrawal syndrome (AAWS) after enzalutamide (ENZA) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC).
Authors: Poole Austin , Gill David Michael , Hahn Andrew W. , Johnson Eric , Carroll Emma , Batten Julia A. , Gupta Sumati , Boucher Kenneth M. , Maughan Benjamin Louis , Agarwal Neeraj
Published: March 2017

228

Background: AAWS manifested as PSA decline after discontinuation of first generation AAs, like bicalutamide, has been well characterized and reported. Objective of this study was to assess the incidence and characterize AAWS after ENZA in pts with mCRPC. Methods: From a single institution cohort, pts with mCRPC who discontinued ENZA after documented disease progression per PCWG2 criteria were included. AAWS after ENZA was defined as any degree of PSA decline after discontinuation of ENZA. Baseline pts, disease, and treatment characteristics were compared between Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ treated during the similar time period: median values were compared with the Wilcoxon rank sum test; proportions were compared with FisherÕs Exact test; and the log rank test was used to compare PFS (Table). Results: 5 pts of 72 eligible pts (~7%) experienced AAWS after discontinuation of ENZA. The levels of PSA decline were as follows: 84%, 32%, 17%, 15% and 15%, respectively. Median AAWS response time, until subsequent PSA progression, was 6 weeks. None of the pts, disease or treatment characteristics (such as prior duration of response to ENZA) were different among Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ. Conclusions: This is the largest study reporting on the incidence and characterization of AAWS after ENZA. AAWS after ENZA is infrequent (~7%), of short duration (6 weeks), and not predicted by pts, disease or treatment related characteristics. Unlike AAWS after first generation AR inhibitors, like bicalutamide, the AAWS after ENZA is not clinically meaningful and should not have any bearing on the eligibility criteria of clinical trials conducted in the post ENZA setting. [Table: see text]
Immune response results of vesigenurtacel-l (HS-410) in combination with BCG from a randomized phase II trial in patients with non-muscle invasive bladder cancer (NMIBC).
Authors: Steinberg Gary D. , Shore Neal D. , Karsh Lawrence Ivan , Bailen James L. , Bivalacqua Trinity J. , Chamie Karim , Cochran James S. , David Richard , Grubb Robert L. , Harb Wael A. , Holzbeierlein Jeffrey M. , Kamat Ashish M. , Trabulsi Edouard John , Walsh William Vincent , Williams Michael Brandon , Wolk Fredrick , Woods Michael , Price Melissa Leigh , Early Brandon , Schreiber Taylor Houghton
Published: March 2017

319

Background: Vesigenurtacel-L (HS-410) is a vaccine comprised of an allogeneic cell line, selected for high expression from a series of bladder tumor antigens, and transfected with gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens to a recipient's own antigen presenting cells, activating CD8+ cytotoxic T cells. Here we present the secondary immune outcomes from a randomized Phase 2 trial with HS-410 in combination with BCG in NMIBC. Trial ID NCT02010203. Methods: 78 patients with intermediate- (n=5) or high-risk (n=73) NMIBC who are either BCG-naïve or recurrent, with or without carcinoma in situ (CIS), were enrolled 1:1:1 to one of two doses of HS-410 (either 106 or 107cells/dose) or placebo in combination with 6 weeks of induction BCG, followed by 6 more weeks of HS-410 in the induction phase. Maintenance treatment consisted of 3-weekly treatments at the following timepoints: 3 mo., 6 mo., 12 mo. Concurrently, 16 patients (1 int. risk, 15 high-risk) were enrolled in an open-label monotherapy HS-410 arm for patients who did not receive BCG. The primary endpoint was 1-year RFS. Secondary immune evaluations include ELISPOT, tumor IHC, tumor antigen profiling, flow cytometry, urine cytokine analysis, and T cell receptor sequencing. Results: HS-410 treatment was well tolerated; AE profiles were similar across the treatment arms. HS-410 antigen expression showed prominent overlap with patient tumors. IFNγ ELISPOT assay demonstrated a high baseline response to HS-410; responses to overlapping peptide pools of HS-410 derived antigens defined immune responders (doubling of IFNγ-secreting cells). IHC demonstrated that ~60% of NMIBC patient tumor biopsies were TIL negative at baseline (n=84), but that only ~15% of tumor biopsies were TIL negative post treatment (n=40). Thus, TIL status may be further used to define a responder and non-responder population to HS-410. Conclusions: Vesigenurtacel-L is well-tolerated, and immunologic responses consistent with vaccine mechanism of action may correlate with efficacy and suggest future biomarkers. Vesigenurtacel-L warrants further investigation as a potential treatment for NMIBC. Clinical trial information: NCT02010203.
Therapy for chemopretreated metastatic urothelial cancer (mUC) with the antibody-drug conjugate (ADC) sacituzumab govitecan (IMMU-132).
Authors: Tagawa Scott T. , Ocean Allyson J. , Lam Elaine Tat , Saylor Philip James , Bardia Aditya , Hajdenberg Julio , Morgans Alicia Katherine , Kalinsky Kevin , Galsky Matthew , Faltas Bishoy , Molina Ana M. , Lim Emerson A. , Maliakal Pius , Sharkey Robert M. , Mudenda Boyd , Wegener William A. , Goldenberg David M
Published: March 2017

327

Background: Patients (pts) with mUC pre-treated with platinum-containing chemotherapy have limited therapeutic options, with checkpoint-inhibitor immunotherapy (IO) responses in a minority of pts. We present an interim update of the safety and activity of sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 ADC, as therapy for chemotherapy-pretreated mUC pts (ClinicalTrials.gov, NCT01631552). Methods: We enrolled 32 pts with mUC and ECOG PS 0-1 who failed ≥ 1 prior standard therapy (median=3; range, 1-5). IMMU-132 was administered at 8 or 10 mg/kg on days 1 and 8 every 21 days, continued until disease progression (PD) or unacceptable toxicity. Response-evaluable pts received ≥ 2 doses, and had ≥ 1 post-baseline response assessment. Results: Twenty-five pts [median age 68 yrs (range: 50-91), 24 males] are currently assessable for safety and response; 23 had prior platinum-containing therapy; 46% had >2 prior therapies; 4 also had IO agents. Sites of metastases included liver (N=4; 16%), lungs (N=7; 28%), bone (N=4; 16%), and lymph nodes (N=16; 64%). Pts received a median of 7 cycles (range, 2-23) of IMMU-132. ORR was 36% (9/25) [1 complete (CR) and 8 partial responses (PR)]; 44% (11/25) had stable disease (SD). Further, pts with 1 line of prior chemotherapy had an ORR of 53.8% (7/13), and 16.7% for those with 2 to 5 prior therapy lines. Median PFS for all patients is 7.2 mos (95% CI, 4.9-10.7); median survival is not reached yet. Of the 4 pts with progression after prior IO, there were 1 PR and 2 SDs with IMMU-132. Duration of response for CR/PR pts is currently 5.1 mos (95% CI, 4.1-12.9) and 10/11 pts (5 with ≥ 20% tumor reduction) had stable disease > 4 mos. Grade 4 neutropenia (16%) lasted < 7 days, and non-hematological grade 3 AEs included fatigue (12%) and hypophosphatemia (8%). No treatment-related deaths were observed. Analysis of Trop-2 expression revealed 1+ to 3+ positive staining in 95% of 19 archival patient specimens. Conclusions: With an ORR of 36% and a median PFS of 7.2 months in a heavily pretreated population, these interim results suggest that IMMU-132 is a promising agent as 2nd line or later therapy for platinum- or IO- pretreated mUC pts. Clinical trial information: NCT01631552.
Flavoperidol as a novel therapeutic agent for bladder cancer.
Authors: Railkar Reema , Sanford Thomas , Krane Spencer , Li Q. Quentin , Agarwal Piyush K.
Published: March 2017

357

Background: Bladder cancer (CaB) is the 4th most common cancer among men in the US but receives substantially less research resources than many other cancer types. There has been little change to the management of bladder cancer over the past 25 years. Quantitative high throughput screening (qHTS) of representative cancer lines with oncology drugs may identify new treatments or re-purpose already existing therapies for different disease. We utilized this technique to identify new therapies in three primary bladder lines (RT4, T24, and UMUC3) and their metastatic lines (T24T, SLT3 and FL3 for T24 and LUL-2 for UMUC3). Methods: We screened 8 bladder cancer cell lines (including RT4, T24, and UMUC3) against 1,912 oncology drugs using a 48 hour cell proliferation assay with an ATP−based readout to determine activity and potency of compounds in a dose response manner. One of the candidate drugs inhibitory in all cell lines tested is flavopiridol, a pan CDK inhibitor. We further characterized the mechanism of action and in vivo effects of flavopiridol using various cell based assays and mouse xenograft studies. Results: The initial screen identified 95 compounds active in 8 cell lines. The top 50 compounds were further analyzed for molecular size of >200 g/mol and TPSA<90. This identified mitomycin C and 8 novel compounds. Further testing revealed Flavopiridol to be most consistent with qHTS data having IC50 of 100-300nM in all the cell lines tested. Flavopiridol induces G2/M arrest; however, very little apoptosis was seen suggesting a cytostatic rather than a cytotoxic mechanism of flavopiridol action. Flavopiridol showed dose dependent inhibition of migration, invasion and colony formation in all cell lines tested. Xenograft studies in rapidly growing UMUC-3 cells showed slowing of tumor growth but not complete reduction indicating cytostatic mechanism of flavopiridol. Conclusions: A high throughput drug screen can identify novel compounds in bladder cancer. Flavopiridol seems to be a very effective inhibitor both in vitro and in vivo. Physical properties of Flavopiridol are most suited for intravesical use, which may lead to it being an effective inhibitor of CaB in the bladder at higher doses without any/few systemic toxicities.
Evaluation of cabazitaxel's toxicity and tolerance: AC Camargo Cancer Center experience.
Authors: Albuquerque Christiane Silveira Marinho , Rinck Jose A. , Costa Tatiana Vieira , Ferreira Camila Nassif Martins , Dettino Aldo A. , Cunha Ingrid Hariman Fonseca , Calsavara Vinicius Fernando
Published: March 2017

e566

Background: Cabazitaxel is an approved second-line treatment in metastatic castration-resistant prostate cancer therapy with a significant survival benefit compared to mitoxantrone. There are few data about cabazitaxel's toxicity in patients not selected. Objective: Evaluate the efficacy and toxicity among younger (< 70 years) and older (> 70 years) population. Methods: We selected 62 patients with metastatic castration resistant prostate cancer treated in AC Camargo Cancer Center from January 2011 to July 2015. 58 patients fulfilled the study criteria: diagnosis of adenocarcinoma prostate cancer, at least one session of cabazitaxel, with more than 18 years old. Results: We had in our sample 33 patients less than 70 years and 25 over 70 years. The initial dose of cabazitaxel was 25 mg/m2 in 75.8% of patients < 70 years and 52% in > 70 years patients. The use of granulocytics growing factor was observed in 64% of the older patients and more than 80% of this indication was in primary profilaxis. There were five deaths associated to the treatment, 4 lung infection and 1 kidney failure. The worst grade of adverse event up to 30 days after last administration was grade 2, including hematological and non-hematological events, both with no statistical significance between the groups. However, there was a greater number of febrile neutropenia in elderly people (28% versus 6%) with a statistical significance between < 70 e > 70 years (p 0.031). OS was 13,7 months (IC 9.16 – 18.2) and PFS was 4,6 months (IC 3.43 – 5.73). OS among the two groups was lower in < 70 years reaching 9,3 months (IC 2.06-16.5) versus 22.2 months (IC 4.86-39.50 ), p= 0.073. As well, PFS in < 70 years was 3.8 months (IC 3.26-4.36) versus 4.6 months (IC 2.4-14.1), p = 0.02. Conclusions: Treatment with cabazitaxel is tolerable, with manageable adverse events in a real-world patient population. In our cohort, elderly population (> 70 years) had more febrile neutropenia, suggesting dose reduction in this population, indication of granulocytic growing factor as primary profilaxis, close monitoring, and adequate patient counseling.
Prognostic factors for overall survival in patients with metastatic castration-resistant prostate cancer: Secondary analysis.
Authors: Anampa-Guzman Andrea Carolina , Sulca-Huamani Oliver , Perez-Mendez Rushmely , Mendoza-Soto Gloria , Contreras Chavez Pamela , Aliaga Rolig
Published: March 2017

e597

Background: The standard treatment for metastatic castration-resistant prostate cancer (MCRPC) is Docetaxel (DTX); however, it has serious adverse effects. It is necessary to know the prognostic factors for overall survival (OS) of patients with MCRPC treated with DTX. The aim of this study was to determine the prognostic factors for OS in patients with MCRPC treated with DTX. Methods: This study is a secondary analysis of the control arms of the clinical trials NTC00273338, NCT00519285 and NCT00988208. 1600 patients aged 18 years or older with MCPRC that received DTX and prednisone were included. Survival curves were estimated by Kaplan-Meier and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. Results: The median OS time was 14.64 months. The 1-yr-OS and 2-yrs-OS were 86.2% and 28.6%, respectively. Patients with an ECOG score greater than 0 lived significantly less than the rest of patients (p = 0.00). The patients with an alkaline phosphate level (ALP) > 200 had significantly lower OS (p = 0.00). In the multivariate analysis, the factors that influenced OS were ECOG, ALP, HB, LDH and number of metastases. Conclusions: Poor performance status, high alkaline phosphatase level, low hemoglobin level, high LDH and more than 2 metastases were the main prognostic factors in patients with metastatic castration resistant prostate cancer. [Table: see text]
Dose-dependent transduction of Hedgehog relies on phosphorylation-based feedback between the G-protein-coupled receptor Smoothened and the kinase Fused
Authors: Sanial Matthieu , Bécam Isabelle , Hofmann Line , Behague Julien , Argüelles Camilla , Gourhand Vanessa , Bruzzone Lucia , Holmgren Robert A. , Plessis Anne
Published: March 2017

Smoothened (SMO) is a G-protein-coupled receptor-related protein required for the transduction of Hedgehog (HH). The HH gradient leads to graded phosphorylation of SMO, mainly by the PKA and CKI kinases. How thresholds in HH morphogen regulate SMO to promote switch-like transcriptional responses is a central unsolved issue. Using the wing imaginal disc model in Drosophila, we identified new SMO phosphosites that enhance the effects of the PKA/CKI kinases on SMO accumulation, its localization at the plasma membrane and its activity. Surprisingly, phosphorylation at these sites is induced by the kinase Fused (FU), a known downstream effector of SMO. In turn, activation of SMO induces FU to act on its downstream targets. Overall, our data provide evidence for a SMO/FU positive regulatory loop nested within a multikinase phosphorylation cascade. We propose that this complex interplay amplifies signaling above a threshold that allows high HH signaling.
Imagining tomorrow's university: open science and its impact
Authors: Howe Adina , Howe Michael , Kaleita Amy L. , Raman D. Raj
Published: March 2017

As part of a recent workshop entitled "Imagining Tomorrow's University”, we were asked to visualize the future of universities as research becomes increasingly data- and computation-driven, and identify a set of principles characterizing pertinent opportunities and obstacles presented by this shift. In order to establish a holistic view, we take a multilevel approach and examine the impact of open science on individual scholars as well as on the university as a whole. At the university level, open science presents a double-edged sword: when well executed, open science can accelerate the rate of scientific inquiry across the institution and beyond; however, haphazard or half-hearted efforts are likely to squander valuable resources, diminish university productivity and prestige, and potentially do more harm than good. We present our perspective on the role of open science at the university.
MICROSTRUCTURE HYDRATION PRODUCTS BINDING COMPOSITION OBTAINED IN THE VORTEX JET MILL
Authors: Золотых Сергей , Zolotykh Sergey , Сумской Дмитрий , Sumskoy Dmitriy , Загороднюк Лилия , Zagorodnyuk Liliya , Канева Елена , Kaneva Elena
Published: March 2017

Zagorodnuk L.H., Sumy D.A., Golden S.V., Kaneva E.V.

MICROSTRUCTURE HYDRATION PRODUCTS BINDING COMPOSITION OBTAINED IN THE VORTEX JET MILL

By electron microscopy to study the microstructure of the cement stone made from Portland cement and activated binders of the compositions in the vortex jet mill. It was found that the open pores of the cement and cementitious compositions prepared using perlite fillers, always filled with tumors, at different stages of collective growth. The microstructure of cementitious compositions has a dense structure by rationally selected composition, effective use of mineral filler - perlite waste, creating additional support for the formation of the internal microstructure of the composite, mechanical activation raw mixture, allowing to obtain composites with desired properties.
EFFECT OF TiO2 NANOPARTICLES IN NI MATRIX ON MECHANICAL AND CORROSION RESISTANCE PROPERTIES
Authors: Saied Shahnez , Mekkaoui Amer , Belahssen Okba , Chala Abdelouahad
Published: March 2017

Nickel (Ni) is one of the most important hard coatings. Improvement in its tribological and mechanical properties would greatly enhance its use in industry. Nanocomposite coatings of metals with various reinforced nanoparticles have been developed in last few decades. Titania (TiO2) exhibit excellent mechanical properties. It is believed that TiO2 incorporation in Ni matrix will improve the properties of Ni coatings significantly. The main purpose of the current work is to investigate the mechanical and anti-corrosion properties of the electroplated Nickel nanocomposite with a different percentage of TiO2. The results showed that the content of TiO2 and the microhardness in the Ni-TiO2 coatings first increased and reached the maximum at the loading of 20 g/L, then decreased, due to agglomeration of dioxide of Titania for high concentration of TiO2. The [200] preferred orientation for Ni pure gradually evolved to [111] orientation with increasing TiO2 nanoparticle loading. At 20 g/L of titania, we obtained the minimum crystallite size (27 nm). The anti-corrosion property of nanocomposite coating was carried out in 3.5 % NaCl electrolyte, and the result also showed that the nanocomposite coatings improve the corrosion resistance significantly. This present work reveals that incorporation of TiO2 in nickel nanocomposite coating improves corrosion resistance and mechanical properties of both hardness and corrosion resistance performances, and the improvement becomes at it maximum for 20 g/L of TiO2.
Partner Selection in R&D Collaborations: Effects of Affiliations with Venture Capitalists
Authors: Reuer Jeffrey J. , Devarakonda Ramakrishna
Published: March 2017

This paper extends information economics to the literature on alliance partner selection by demonstrating how venture capitalists (VCs) can facilitate research and development (R&D) collaborations. We investigate a new role for VCs—information intermediation—that can enable R&D partnerships between entrepreneurial ventures that lack knowledge of each other’s technological resources. In contrast to the more diffuse signaling benefits entrepreneurial ventures obtain by affiliating with prominent VCs, backing by a common VC can privately and directly reduce information asymmetries between entrepreneurial ventures. We demonstrate that the effects of VC information intermediation are more pronounced when prospective collaborators are at the earliest stages of product development and when they find it difficult to judge each other’s technological resources, such as when they do not have previous partnerships together, do not draw upon each other’s knowledge bases, and have dissimilar technology portfolios. We empirically investigate the multiple ways in which VCs potentially facilitate R&D partner selection and identify specific conditions under which VCs’ information intermediation function contributes to segmentation in markets for R&D alliances.
Comparison of Viola-Jones And Kanade-Lucas-Tomasi Face Detection Algorithms
Authors: Aashish Kamath , Vijayalakshmi A.
Published: March 2017

Face detection technologies are used in a large variety of applications like advertising, entertainment, video coding, digital cameras, CCTV surveillance and even in military use. It is especially crucial in face recognition systems. You can’t recognise faces that you can’t detect, right? But a single face detection algorithm won’t work in the same way in every situation. It all comes down to how the algorithm works. For example, the Kanade-Lucas-Tomasi algorithm makes use of spatial common intensity transformation to direct the deep search for the position that shows the best match. It is much faster than other traditional techniques for checking far fewer potential matches between pictures. Similarly, another common face detection algorithm is the Viola-Jones algorithm that is the most widely used face detection algorithm. It is used in most digital cameras and mobile phones to detect faces. It uses cascades to detect edges like the nose, the ears etc. However, if there is a group of people and their faces are close to each other, the algorithm might not work that well as edges tend to overlap in a crowd. It might not detect individual faces. Therefore, in this work, we test both the Viola-Jones and the Kanade-Lucas-Tomasi algorithm for each image to find out which algorithm works best in which scenario.
A systematic review of Vancouver B2 and B3 periprosthetic femoral fractures
Authors: Khan T. , Grindlay D. , Ollivere B. J. , Scammell B. E. , Manktelow A. R. J. , Pearson R. G.
Published: March 2017

Aims

The aim of this study was to investigate the outcomes of Vancouver type B2 and B3 fractures by performing a systematic review of the methods of surgical treatment which have been reported.

Materials and Methods

A systematic search was performed in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. For inclusion, studies required a minimum of ten patients with a Vancouver type B2 and/or ten patients with a Vancouver type B3 fracture, a minimum mean follow-up of two years and outcomes which were matched to the type of fracture. Studies were also required to report the rate of re-operation as an outcome measure. The protocol was registered in the PROSPERO database.

Results

A total of 22 studies were included based on the eligibility criteria, including 343 B2 fractures and 167 B3 fractures. The mean follow-up ranged from 32 months to 74 months. Of 343 Vancouver B2 fractures, the treatment in 298 (86.8%) involved revision arthroplasty and 45 (12.6%) were treated with internal fixation alone. A total of 37 patients (12.4%) treated with revision arthroplasty and six (13.3%) treated by internal fixation only underwent further re-operation. Of 167 Vancouver B3 fractures, the treatment in 160 (95.8%) involved revision arthroplasty and eight (4.8%) were treated with internal fixation without revision. A total of 23 patients (14.4%) treated with revision arthroplasty and two (28.6%) treated only with internal fixation required re-operation.

Conclusion

A significant proportion, particularly of B2 fractures, were treated without revision of the stem. These were associated with a higher rate of re-operation. The treatment of B3 fractures without revision of the stem resulted in a high rate of re-operation. This demonstrates the importance of careful evaluation and accurate characterisation of the fracture at the time of presentation to ensure the correct management. There is a need for improvement in the reporting of data in case series recording the outcome of the surgical treatment of periprosthetic fractures. We have suggested a minimum dataset to improve the quality of data in studies dealing with these fractures. Cite this article: Bone Joint J 2017;99-B(4 Supple B):17–25.
Efficiency savings
Authors: Mortensen Neil
Published: March 2017

When management is hard to manage.
There is an alternative: homines curans and the limits of neoliberalism
Authors: Tronto Joan
Published: March 2017

Neoliberal policies around the globe have made caring more difficult. Yet, many scholars seem to have accepted neoliberalism as an inescapable reality. This article argues against this view. Instead, it suggests that care stands as a major alternative way to the neoliberal paradigm, both conceptually and historically. Formulating a conceptual account of people as homines curans (caring people) and drawing upon Polanyi’s history of market ideologies, the article argues that a democratic form of care – which makes the reallocation of care responsibilities its central concern – can provide the basis for a theoretical challenge to neoliberalism.
Family care work: a policy-relevant research agenda
Authors: Moen Phyllis , DePasquale Nicole
Published: March 2017

This article addresses the need for policy-relevant research agendas on family care in transaction with formal care and public as well as organisational norms and policies in light of the crisis in caregiving for older adults. We propose a combined institutional and life-course theoretical approach, suggesting seven ways of organising scholarly enquiry to promote understanding of the changing nature of family care in the 21st century, inform policymakers’ efforts at supporting family caregivers and improve caregivers’ and care recipients’ quality of life. These include: (1) moving beyond snapshots of individuals; (2) conducting comparative cross-cultural and crosscohort analyses; (3) documenting social heterogeneity, vulnerability and inequality; (4) capturing individuals’ and families’ adaptive strategies and cycles of control during the caregiving process; (5) investigating policy innovations and natural experiments; (6) assessing third parties as mediating institutions between regulatory environments and caregiving families; and (7) attending to the subjective meanings of care.
Perbandingan Efektivitas dan Keamanan Vaksin Pertusis Aselular dan Whole-cell
Authors: Tjahjowargo Sendy , Gunardi Hartono
Published: March 2017

Latar belakang. Imunisasi merupakan upaya pencegahan terbaik terhadap berbagai penyakit infeksi. Vaksin difteri, tetanus, pertusis whole-cell (DTwP) dapat menimbulkan kejadian ikutan pasca imunisasi (KIPI) yang mengkhawatirkan orangtua. Vaksin difteri, tetanus, pertusis aselular (DTaP) memiliki KIPI lebih ringan, tetapi diduga kurang efektif. Tujuan. Mengetahui efektivitas vaksin DTaP dibandingkan dengan vaksin DTwP.Metode. Penelusuran literatur elektronik PubMed dan Cochrane dengan kata kunci “DTaP/acellular pertussis”, “DTwP/whole-cell pertussis”, “children”, “pertussis”, “vaccine” and “safety/efficacy/effectiveness” dalam 10 tahun terakhir (2006 – 2016). Hasil. Terdapat dua studi meta-analisis yang membandingkan efektivitas pemberian imunisasi DTwP dan DTaP serta satu studi kasus terkontrol yang membandingkan efek perlindungan jangka panjang pemberian imunisasi DTaP dengan DTwP. Efektivitas vaksin pertusis aselular berkisar 74% (IK95%, 51–86%) – 97% (IK95%, 91–99%). Efektivitas vaksin pertusis whole-cell sebesar 94% (IK95%, 88–97%; p<0,0001). Estimasi effect size vaksin pertusis aseluer untuk melindungi terhadap penyakit pertusis sesuai kriteria WHO adalah sebesar 84% (IK95%, 81–87%); sedangkan untuk vaksin pertusis whole cell adalah 94% (IK95%, 88–97%). KIPI vaksin DTaP lebih ringan dan jarang dibandingkan vaksin DTwPKesimpulan. Vaksin DTaP dan DTwP mempunyai efektivitas yang sebanding. Vaksin DTwP mempunyai effect size yang lebih besar untuk melindungi terhadap penyakit pertusis dan perlindungan jangka panjang yang lebih baik dibandingkan vaksin DTaP. Vaksin DTaP mempunyai KIPI yang lebih ringan dan jarang dibandingkan vaksin DTwP.
Rosmarinus officinalis L. (rosemary) extract decreases the biofilms viability of oral health interest
Authors: De Oliveira Jonatas Rafae , Jesus Daiane de , Oliveira Luciane Dias de
Published: March 2017

Objective: This study evaluated the effect of rosemary extract on Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and Pseudomonas aeruginosa monomicrobial biofilms viability, as well as on C. albicans associated with S. aureus, E. faecalis, S. mutans or P. aeruginosa in polymicrobial biofilms. Material and Methods: In microtiter plate, mono- and polymicrobial biofilms for 48 h were formed. Then, they were exposed for 5 min to rosemary extract (200 mg/mL). Saline (0.9% NaCl) was used as control. After, washes were done with saline to remove the affected cells. Biofilm viability was checked by MTT colorimetric assay, after treatment. Absorbance of the wells was read in microplate spectrophotometer (570 nm) and data were converted to reduction percentage and statistically analyzed by ANOVA and Tukey test (p ? 0.05). Results: After application of rosemary extract, with exception of the E. faecalis biofilm, significant reductions in mono- and polymicrobial biofilms viability were observed. Conclusion: C. albicans, S. aureus, S. mutans and P. aeruginosa monomicrobial biofilms were affected by rosemary extract, as well as C. albicans associated with S. aureus, E. faecalis, S. mutans or P. aeruginosa in polymicrobial biofilms, presenting significant viability reductions.
Assessment of Rock Mass Stability in the Historic Area of Levels IV-V of the “Wieliczka” Salt Mine
Authors: d’Obyrn Kajetan , Hydzik-Wiśniewska Joanna
Published: March 2017

As a result, of more than 700 years of exploitation in the Wieliczka Salt Mine, a network of underground workings spreading over eleven levels was created. All mine workings of significant historic and natural qualities and the majority of functional mine workings designated to be preserved are located on levels I to V. The most precious of them, available to tourists, are located in the central part of the Mine on levels I-III. The Mine is not anticipating to make levels IV, Kołobrzeg and V available for a wider range of visitors, even though there are historically and naturally precious workings in those areas as well. The most valuable of the mine workings come from the eighteenth and nineteenth centuries and were exploited mainly in a bed of fore-shaft salt, Spiza salt and the oldest ones. The characteristic feature of these excavations, distinguish them from the chambers located on the levels I-III, is the room-and-pillar system that had been used there. Mine workings exploited in this system measure up to 100 metres in length, and the unsupported pillars standing between the chambers measuring 4-10 metres in width were remained. The described above levels, including levels of VI-IX are to provide a stable support for the workings located higher up. The remaining part of the mine, with the exception of the function workings, is designated for liquidation by backfilling.

The article presents an assessment of stability of the mine workings, located on levels IV-V, and their impact on the surrounding rock mass and the land surface. The analysis was based on geodetic measurements and numerical calculations for strain state of rock mass surrounding the mine workings, in actual conditions and after partial backfilling, and forecast of the rock stability factor after the end of backfilling. The assessment stability factor in the vicinity of excavations at levels IV-V was based on the results of spatial numerical analysis covering the entire central area of the mine from the surface to level V. Numerical calculations were performed using FLAC programme based on the finite difference method, allowing to observe the mechanisms and processes of destruction and deformation. The calculations were performed for the elastic-plastic medium with the Mohr-Coulomb failure criterium. The choice of this computational model was dictated by a very diverse geological structure of the Wieliczka rock mass and a complex system of excavations.
Standoff detection and classification of bacteria by multispectral laser-induced fluorescence
Authors: Duschek Frank , Fellner Lea , Gebert Florian , Grünewald Karin , Köhntopp Anja , Kraus Marian , Mahnke Peter , Pargmann Carsten , Tomaso Herbert , Walter Arne
Published: March 2017

Biological hazardous substances such as certain fungi and bacteria represent a high risk for the broad public if fallen into wrong hands. Incidents based on bio-agents are commonly considered to have unpredictable and complex consequences for first responders and people. The impact of such an event can be minimized by an early and fast detection of hazards. The presented approach is based on optical standoff detection applying laser-induced fluorescence (LIF) on bacteria. The LIF bio-detector has been designed for outdoor operation at standoff distances from 20 m up to more than 100 m. The detector acquires LIF spectral data for two different excitation wavelengths (280 and 355 nm) which can be used to classify suspicious samples. A correlation analysis and spectral classification by a decision tree is used to discriminate between the measured samples. In order to demonstrate the capabilities of the system, suspensions of the low-risk and non-pathogenic bacteria Bacillus thuringiensis, Bacillus atrophaeus, Bacillus subtilis, Brevibacillus brevis, Micrococcus luteus, Oligella urethralis, Paenibacillus polymyxa and Escherichia coli (K12) have been investigated with the system, resulting in a discrimination accuracy of about 90%.