bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Early Marriage from Married Girls’ Perspectives in Iranian Setting: A Qualitative Study
Authors: Montazeri Simin , Gharacheh Maryam , Mohammadi Nooredin , Alaghband Rad Javad , Eftekhar Ardabili Hassan
Published: March 2016

Early marriage is a worldwide problem associated with a range of health and social consequences for teenage girls. Designing effective health interventions for managing early marriage needs to apply the community-based approaches. However, it has received less attention from policymakers and health researchers in Iran. Therefore, the current study aimed to explore determinants of early marriage from married girls’ perspectives. The study was conducted from May 2013 to January 2015 in Ahvaz, Iran. A purposeful sampling method was used to select fifteen eligible participants. Data were collected through face-to-face, semistructured interviews and were analyzed using the conventional content analysis approach. Three categories emerged from the qualitative data including “family structure,” “Low autonomy in decision-making,” and “response to needs.” According to the results, although the participants were not ready to get married and intended to postpone their marriage, multiple factors such as individual and contextual factors propelled them to early marriage. Given that early marriage is a multifactorial problem, health care providers should consider a multidimensional approach to support and empower these vulnerable girls.
The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells
Authors: Wang Can , Jiang Jian-Dong , Wu Wei , Kong Wei-Jia
Published: March 2016

The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinaseα(AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα(Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.
Preparation and Characterization of Irinotecan Loaded Cross-Linked Bovine Serum Albumin Beads for Liver Cancer Chemoembolization Therapy
Authors: Yan Jin , Wang Fei , Chen Jun , Liu Tao , Zhang Tao
Published: March 2016

In this paper, a novel temporary embolization agent for transarterial chemoembolization of liver cancer was developed and tested. The Irinotecan loaded bovine serum albumin (BSA) beads were tried to be used as embolic agent of liver cancer therapy. BSA beads were prepared by a water-in-oil emulsion solvent diffusion method in soya oil and Span 85 was used as the emulsifier. The obtained BSA beads were able to swell 2.37-fold comparing to dried beads. Depending on the equilibrium swelling process, the Irinotecan was loaded with 9.8% total drug concentration and tested. In vitro drug release studies showed that a burst release of Irinotecan was achieved. Eventually BSA beads were completely degraded in a few weeks. CCK-8 assay demonstrated that BSA beads showed no cytotoxicity against human umbilical vein endothelial cells, and the Irinotecan loaded BSA beads showed comparable cytotoxicity against Hep G2, a human liver carcinoma cell line, as the traditional Irinotecan. In a rabbit model, it was found that BSA beads can successfully be transferred to liver and provide occlusion of small arteries. The present investigation suggested that the BSA beads are promising drug carriers and can potentially be used as temporary embolization agents in interventional oncology.
Three Revised Kalman Filtering Models for Short-Term Rail Transit Passenger Flow Prediction
Authors: Jiao Pengpeng , Li Ruimin , Sun Tuo , Hou Zenghao , Ibrahim Amir
Published: March 2016

Short-term prediction of passenger flow is very important for the operation and management of a rail transit system. Based on the traditional Kalman filtering method, this paper puts forward three revised models for real-time passenger flow forecasting. First, the paper introduces the historical prediction error into the measurement equation and formulates a revised Kalman filtering model based on error correction coefficient (KF-ECC). Second, this paper employs the deviation between real-time passenger flow and corresponding historical data as state variable and presents a revised Kalman filtering model based on Historical Deviation (KF-HD). Third, the paper integrates nonparametric regression forecast into the traditional Kalman filtering method using a Bayesian combined technique and puts forward a revised Kalman filtering model based on Bayesian combination and nonparametric regression (KF-BCNR). A case study is implemented using statistical passenger flow data of rail transit line 13 in Beijing during a one-month period. The reported prediction results show that KF-ECC improves the applicability to historical trend, KF-HD achieves excellent accuracy and stability, and KF-BCNR yields the best performances. Comparisons among different periods further indicate that results during peak periods outperform those during nonpeak periods. All three revised models are accurate and stable enough for on-line predictions, especially during the peak periods.
Antiobesity Effects of the Combined Plant Extracts Varying the Combination Ratio of Phyllostachys pubescens Leaf Extract and Scutellaria baicalensis Root Extract
Authors: Kim Dong-Seon , Kim Seung-Hyung , Cha Jimin
Published: March 2016

The antiobesity effects of several different combinations of extracts (BS) prepared from two plants, Phyllostachys pubescens leaf (bamboo leaf: BL) and Scutellaria baicalensis root (SB), were investigated using a high fat diet (HFD) induced obese mouse model. In order to find the most effective mixture among the mixtures of the two plant extracts, experimental preparations were made by combining BL and SB by different proportions of 3 : 1 (BS31), 2 : 1 (BS21), 1 : 1 (BS11), 1 : 2 (BS12), and 1 : 3 (BS13). Body weight, weight of adipose tissues, size of adipocytes, levels of glucose, leptin and adiponectin, and lipid profile in serum, and fat accumulation in liver were investigated. We have found that BS21 is the most effective in antiobesity among the five mixtures investigated, indicated by reduction in body weight gain, total mass of adipose tissue, and the size of adipocyte. In addition, BS21 has shown to be beneficial in serum lipid profile, levels of glucose, leptin, and adiponectin in serum, and fat accumulation in liver. By chromatographic separation of BS21, the two maker compounds, isoorientin and baicalin, were identified and quantified for the standardization of BS21.
An Epidemiological Study of Neuropathic Pain Symptoms in Canadian Adults
Authors: VanDenKerkhof Elizabeth G. , Mann Elizabeth G. , Torrance Nicola , Smith Blair H. , Johnson Ana , Gilron Ian
Published: March 2016

The reported prevalence of neuropathic pain ranges from 6.9% to 10%; however the only Canadian study reported 17.9%. The objective of this study was to describe the epidemiology of neuropathic pain in Canada. A cross-sectional survey was conducted in a random sample of Canadian adults. The response rate was 21.1% (1504/7134).Likelyorpossibleneuropathic pain was defined using a neuropathic pain-related diagnosis and a positive outcome on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) or the Douleur Neuropathique 4 (DN4) Questions. The prevalence oflikelyneuropathic pain was 1.9% (S-LANSS) and 3.4% (DN4) and that ofpossibleneuropathic pain was 5.8% (S-LANSS) and 8.1% (DN4). Neuropathic pain was highest in economically disadvantaged males. There is a significant burden of neuropathic pain in Canada. The low response rate and a slightly older and less educated sample than the Canadian population may have led to an overestimate of neuropathic pain. Population prevalence varies by screening tool used, indicating more work is needed to develop reliable measures. Population level screening targeted towards high risk groups should improve the sensitivity and specificity of screening, while clinical examination of those with positive screening results will further refine the estimate of prevalence.
KvLEA, a New Isolated Late Embryogenesis Abundant Protein Gene fromKosteletzkya virginicaResponding to Multiabiotic Stresses
Authors: Tang Xiaoli , Wang Hongyan , Chu Liye , Shao Hongbo
Published: March 2016

The LEA proteins are a kind of hydrophilic proteins, playing main functions in desiccation tolerance. However, their importance as a kind of stress proteins in abiotic stress is being clarified little by little. In this study we isolated, cloned, and identified the firstKvLEAgene inKosteletzkya virginica. Bioinformatic analysis showed that the protein encoded by this gene had common properties of LEA proteins and the multiple sequences alignment and phylogenetic analysis further showed that this protein had high homology with twoArabidopsisLEA proteins. Gene expression analysis revealed that this gene had a higher expression in root and it was induced obviously by salt stress. Moreover, the transcripts ofKvLEAwere also induced by other abiotic stresses including drought, high temperature, chilling, and ABA treatment. Among these abiotic stresses, ABA treatment brought about the biggest changes to this gene. Collectively, our research discovered a novel LEA gene and uncovered its involvement in multiabiotic stresses inK. virginica. This research not only enriched studies on LEA gene in plant but also would accelerate more studies onK. virginicain the future.
Caspase-9b Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-κB and Lung Tumorigenesis
Authors: Vu Ngoc T. , Park Margaret A. , Shultz Michael D. , Bulut Gamze B. , Ladd Amy C. , Chalfant Charles E.
Published: March 2016

Alternate RNA processing of caspase-9 generates the splice variants caspase 9a (C9a) and caspase 9b (C9b). C9b lacks a domain present in C9a, revealing a tumorigenic function that drives the phenotype of non–small cell lung cancer (NSCLC) cells. In this study, we elucidated the mechanistic underpinnings of the malignant character of this splice isoform. In NSCLC cells, C9b expression correlated with activation of the canonical arm of the NF-κB pathway, a major pathway linked to the NSCLC tumorigenesis. Mechanistic investigations revealed that C9b activates this pathway via direct interaction with cellular inhibitor of apoptosis 1 (cIAP1) and subsequent induction of the E3 ligase activity of this IAP family member. The C9b:cIAP1 interaction occurred via the BIR3 domain of cIAP1 and the IAP-binding motif of C9b, but did not require proteolytic cleavage of C9b. This protein:protein interaction was essential for C9b to promote viability and malignant growth of NSCLC cells in vitro and in vivo, broadly translating to diverse NSCLC oncogenotypes. Overall, our findings identified a novel point for therapeutic invention in NSCLC that may be tractable to small-molecule inhibitors, as a new point to broadly address this widespread deadly disease. Cancer Res; 76(10); 2977–89. ©2016 AACR.
Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3
Authors: Wang Meilin , Li Zhiqiang , Chu Haiyan , Lv Qiang , Ye Dingwei , Ding Qiang , Xu Chuanliang , Guo Jianming , Du Mulong , Chen Jianhua , Song Zhijian , Yin Changjun , Qin Chao , Gu Chengyuan , Zhu Yao , Xia Guowei , Liu Fang , Zhang Zhengsheng , Yuan Lin , Fu Guangbo , Hu Zhibin , Tong Na , Shen Jiawei , Liu Ke , Sun Jielin , Sun Yinghao , Li Jue , Li Xingwang , Shen Hongbing , Xu Jianfeng , Shi Yongyong , Zhang Zhengdong
Published: March 2016

Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27 (rs2042329), that was significantly associated with disease risk (OR = 1.40; P = 4.61 × 10−11). However, rs2042329 was not associated with bladder cancer risk in patients of European descent. The rs2042329 risk allele was also related to significantly increased expression levels of CWC27 mRNA and protein in bladder cancer tissues from Chinese patients. Additional functional analyses suggested that CWC27 played an oncogenic role in bladder cancer by inducing cell proliferation and suppressing apoptosis. In conclusion, the identification of a risk-associated locus at 5q12.3 provides new insights into the inherited susceptibility to bladder cancer in Chinese populations and may help to identify high-risk individuals. Cancer Res; 76(11); 3277–84. ©2016 AACR.
Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer
Authors: Wisinski Kari B. , Tevaarwerk Amye J. , Burkard Mark E. , Rampurwala Murtuza , Eickhoff Jens , Bell Maria C. , Kolesar Jill M. , Flynn Christopher , Liu Glenn
Published: March 2016

Purpose: Preclinical data support combining AKT inhibitors with HER2-targeted therapies to overcome resistance to treatment. This phase I study combined the investigational AKT inhibitor, MK-2206, with lapatinib to determine the MTD.

Experimental Design: The dose escalation cohort enrolled adults with advanced solid tumors, who received MK-2206 dosed 30 to 60 mg every other day and lapatinib 1,000 to 1,500 mg daily continuously, escalated using a 3+3 design. Cycles were 28 days except cycle 1 (35 days, including an initial 8 days of MK-2206 alone to evaluate pharmacokinetic interactions). The dose expansion cohort enrolled adults with advanced HER2+ breast cancer.

Results: Twenty-three participants enrolled in the dose escalation cohort. Dose-limiting toxicities were hyponatremia, fatigue, rash, hypocalcemia, and mucositis. Common toxicities included diarrhea, nausea, and rash. The MTD was reached at MK-2206 45 mg orally every other day and lapatinib 1,500 mg orally daily. Two participants maintained stable disease for >4 months, including a colorectal cancer participant with substantial carcinoembryonic antigen decrease. Of 5 participants in the dose expansion cohort, 2 maintained stable disease for >6 months, including one with prior progression on single-agent lapatinib. Plasma MK-2206 concentrations decreased after addition of lapatinib, but in vitro studies indicate lapatinib increases the intracellular levels of MK-2206.

Conclusions: MK-2206 combined with lapatinib can be tolerated with both drugs above biologically active single-agent doses. Overlapping toxicities result in significant diarrhea and rash, which can be managed medically. Antitumor activity was promising and supports evaluation of AKT inhibitors combined with HER2-targeted therapies. Clin Cancer Res; 22(11); 2659–67. ©2016 AACR.
Carfilzomib Triggers Cell Death in Chronic Lymphocytic Leukemia by Inducing Proapoptotic and Endoplasmic Reticulum Stress Responses
Authors: Lamothe Betty , Wierda William G. , Keating Michael J. , Gandhi Varsha
Published: March 2016

Purpose: Carfilzomib, while active in B-cell neoplasms, displayed heterogeneous response in chronic lymphocytic leukemia (CLL) samples from patients and showed interpatient variability to carfilzomib-induced cell death. To understand this variability and predict patients who would respond to carfilzomib, we investigated the mechanism by which carfilzomib induces CLL cell death.

Experimental Design: Using CLL patient samples and cell lines, complementary knockdown and knockout cells, and carfilzomib-resistant cell lines, we evaluated changes in intracellular networks to identify molecules responsible for carfilzomib's cytotoxic activity. Lysates from carfilzomib-treated cells were immunoblotted for molecules involved in ubiquitin, apoptotic, and endoplasmic reticulum (ER) stress response pathways and results correlated with carfilzomib cytotoxic activity. Coimmunoprecipitation and pull-down assays were performed to identify complex interactions among MCL-1, Noxa, and Bak.

Results: Carfilzomib triggered ER stress and activation of both the intrinsic and extrinsic apoptotic pathways through alteration of the ubiquitin proteasome pathway. Consequently, the transcription factor CCAAT/enhancer-binding protein homology protein (CHOP) accumulated in response to carfilzomib, and CHOP depletion conferred protection against cytotoxicity. Carfilzomib also induced accumulation of MCL-1 and Noxa, whereby MCL-1 preferentially formed a complex with Noxa and consequently relieved MCL-1′s protective effect on sequestering Bak. Accordingly, depletion of Noxa or both Bak and Bax conferred protection against carfilzomib-induced cell death.

Conclusions: Collectively, carfilzomib induced ER stress culminating in activation of intrinsic and extrinsic caspase pathways, and we identified the CHOP protein level as a biomarker that could predict sensitivity to carfilzomib in CLL. Clin Cancer Res; 22(18); 4712–26. ©2016 AACR.
DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1
Authors: Ogitani Yusuke , Aida Tetsuo , Hagihara Katsunobu , Yamaguchi Junko , Ishii Chiaki , Harada Naoya , Soma Masako , Okamoto Hiromi , Oitate Masataka , Arakawa Shingo , Hirai Takehiro , Atsumi Ryo , Nakada Takashi , Hayakawa Ichiro , Abe Yuki , Agatsuma Toshinori
Published: March 2016

Purpose: An anti-HER2 antibody–drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed.

Experimental Design: In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed.

Results: DS-8201a exhibited a HER2 expression-dependent cell growth–inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1–insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression.

Conclusions: DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1–insensitive HER2-positive cancers and low HER2–expressing cancers. Clin Cancer Res; 22(20); 5097–108. ©2016 AACR.
Irinotecan-Induced Gastrointestinal Dysfunction and Pain Are Mediated by Common TLR4-Dependent Mechanisms
Authors: Wardill Hannah R. , Gibson Rachel J. , Van Sebille Ysabella Z.A. , Secombe Kate R. , Coller Janet K. , White Imogen A. , Manavis Jim , Hutchinson Mark R. , Staikopoulos Vasiliki , Logan Richard M. , Bowen Joanne M.
Published: March 2016

Strong epidemiological data indicate that chemotherapy-induced gut toxicity and pain occur in parallel, indicating common underlying mechanisms. We have recently outlined evidence suggesting that TLR4 signaling may contribute to both side effects. We therefore aimed to determine if genetic deletion of TLR4 improves chemotherapy-induced gut toxicity and pain. Forty-two female wild-type (WT) and 42 Tlr4 null (−/−) BALB/c mice weighing between 18 and 25 g (10–13 weeks) received a single 270 mg/kg (i.p.) dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. Bacterial sequencing was conducted on cecal samples of control animals to determine the gut microbiome profile. Gut toxicity was assessed using validated clinical and histopathologic markers, permeability assays, and inflammatory markers. Chemotherapy-induced pain was assessed using the validated rodent facial grimace criteria, as well as immunologic markers of glial activation in the lumbar spinal cord. TLR4 deletion attenuated irinotecan-induced gut toxicity, with improvements in weight loss (P = 0.0003) and diarrhea (P < 0.0001). Crypt apoptosis was significantly decreased in BALB/c-Tlr4−/−billy mice (P < 0.0001), correlating with lower mucosal injury scores (P < 0.005). Intestinal permeability to FITC-dextran (4 kDa) and LPS translocation was greater in WT mice than in BALB/c-Tlr4−/−billy (P = 0.01 and P < 0.0001, respectively). GFAP staining in the lumbar spinal cord, indicative of astrocytic activation, was increased at 6 and 72 hours in WT mice compared with BALB/c-Tlr4−/−billy mice (P = 0.008, P = 0.01). These data indicate that TLR4 is uniquely positioned to mediate irinotecan-induced gut toxicity and pain, highlighting the possibility of a targetable gut/CNS axis for improved toxicity outcomes. Mol Cancer Ther; 15(6); 1376–86. ©2016 AACR.
A New Triglycyl Peptide Linker for Antibody–Drug Conjugates (ADCs) with Improved Targeted Killing of Cancer Cells
Authors: Singh Rajeeva , Setiady Yulius Y. , Ponte Jose , Kovtun Yelena V. , Lai Katharine C. , Hong E. Erica , Fishkin Nathan , Dong Ling , Jones Gregory E. , Coccia Jennifer A. , Lanieri Leanne , Veale Karen , Costoplus Juliet A. , Skaletskaya Anna , Gabriel Rabih , Salomon Paulin , Wu Rui , Qiu Qifeng , Erickson Hans K. , Lambert John M. , Chari Ravi V.J. , Widdison Wayne C.
Published: March 2016

A triglycyl peptide linker (CX) was designed for use in antibody–drug conjugates (ADC), aiming to provide efficient release and lysosomal efflux of cytotoxic catabolites within targeted cancer cells. ADCs comprising anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-EGFR antibodies with maytansinoid payloads were prepared using CX or a noncleavable SMCC linker (CX and SMCC ADCs). The in vitro cytotoxic activities of CX and SMCC ADCs were similar for several cancer cell lines; however, the CX ADC was more active (5–100-fold lower IC50) than the SMCC ADC in other cell lines, including a multidrug-resistant line. Both CX and SMCC ADCs showed comparable MTDs and pharmacokinetics in CD-1 mice. In Calu-3 tumor xenografts, antitumor efficacy was observed with the anti-EpCAM CX ADC at a 5-fold lower dose than the corresponding SMCC ADC in vivo. Similarly, the anti-EGFR CX ADC showed improved antitumor activity over the respective SMCC conjugate in HSC-2 and H1975 tumor models; however, both exhibited similar activity against FaDu xenografts. Mechanistically, in contrast with the charged lysine-linked catabolite of SMCC ADC, a significant fraction of the carboxylic acid catabolite of CX ADC could be uncharged in the acidic lysosomes, and thus diffuse out readily into the cytosol. Upon release from tumor cells, CX catabolites are charged at extracellular pH and do not penetrate and kill neighboring cells, similar to the SMCC catabolite. Overall, these data suggest that CX represents a promising linker option for the development of ADCs with improved therapeutic properties. Mol Cancer Ther; 15(6); 1311–20. ©2016 AACR.
Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes
Authors: Wang Chen-Pin , Lehman Donna M. , Lam Yui-Wing F. , Kuhn John G. , Mahalingam Devalingam , Weitman Steven , Lorenzo Carlos , Downs John R. , Stuart Elizabeth A. , Hernandez Javier , Thompson Ian M. , Ramirez Amelie G.
Published: March 2016

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779–87. ©2016 AACR.
R-Ras Inhibits VEGF-Induced p38MAPK Activation and HSP27 Phosphorylation in Endothelial Cells
Authors: Sawada Junko , Li Fangfei , Komatsu Masanobu
Published: March 2016

R-Ras is a Ras family small GTPase that is highly expressed in mature functional blood vessels in normal tissues. It inhibits pathological angiogenesis and promotes vessel maturation and stabilization. Previous studies suggest that R-Ras affects cellular signaling in endothelial cells, pericytes and smooth-muscle cells to regulate vessel formation and remodeling in adult tissues. R-Ras suppresses VEGF-induced endothelial permeability and vessel sprouting while promoting normalization of pathologically developing vessels in mice. It attenuates VEGF receptor-2 (VEGFR2) activation by inhibiting internalization of the receptor upon VEGF ligand binding, leading to significant reduction of VEGFR2 autophosphorylation. Here, we show that R-Ras strongly suppresses the VEGF-dependent activation of stress-activated protein kinase-2/p38 mitogen-activated protein kinase (SAPK2/p38MAPK) and the phosphorylation of downstream heat-shock protein 27 (HSP27), a regulator of actin cytoskeleton organization, in endothelial cells. The suppression of p38MAPK activation and HSP27 phosphorylation by R-Ras concurred with altered actin cytoskeleton architecture, reduced membrane protrusion and inhibition of endothelial cell migration toward VEGF. Silencing of endogenous R-Ras by RNA interference increased membrane protrusion and cell migration stimulated by VEGF, and these effects were offset by p38MAPK inhibitor SB203580. These results suggest that R-Ras regulates angiogenic activities of endothelial cells in part via inhibition of the p38MAPK-HSP27 axis of VEGF signaling.
Prevention of Cutaneous Penetration and CD1c+ Uptake of Pollen Allergens by a Barrier-Enhancing Formulation
Authors: Meinke Martina Claudia , Schanzer Sabine , Richter Heike , Rippke Frank , Filbry Alexander , Bohnsack Kerstin , Patzelt Alexa , Lademann Jürgen
Published: March 2016

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms.
Solving Multiple Isolated, Interleaved, and Blended Tasks through Modular Neuroevolution
Authors: Schrum Jacob , Miikkulainen Risto
Published: March 2016

Many challenging sequential decision-making problems require agents to master multiple tasks. For instance, game agents may need to gather resources, attack opponents, and defend against attacks. Learning algorithms can thus benefit from having separate policies for these tasks, and from knowing when each one is appropriate. How well this approach works depends on how tightly coupled the tasks are. Three cases are identified: Isolated tasks have distinct semantics and do not interact, interleaved tasks have distinct semantics but do interact, and blended tasks have regions where semantics from multiple tasks overlap. Learning across multiple tasks is studied in this article with Modular Multiobjective NEAT, a neuroevolution framework applied to three variants of the challenging Ms. Pac-Man video game. In the standard blended version of the game, a surprising, highly effective machine-discovered task division surpasses human-specified divisions, achieving the best scores to date in this game. In isolated and interleaved versions of the game, human-specified task divisions are also successful, though the best scores are surprisingly still achieved by machine discovery. Modular neuroevolution is thus shown to be capable of finding useful, unexpected task divisions better than those apparent to a human designer.
Sensory, Cognitive, and Sensorimotor Learning Effects in Recognition Memory for Music
Authors: Mathias Brian , Tillmann Barbara , Palmer Caroline
Published: March 2016

Recent research suggests that perception and action are strongly interrelated and that motor experience may aid memory recognition. We investigated the role of motor experience in auditory memory recognition processes by musicians using behavioral, ERP, and neural source current density measures. Skilled pianists learned one set of novel melodies by producing them and another set by perception only. Pianists then completed an auditory memory recognition test during which the previously learned melodies were presented with or without an out-of-key pitch alteration while the EEG was recorded. Pianists indicated whether each melody was altered from or identical to one of the original melodies. Altered pitches elicited a larger N2 ERP component than original pitches, and pitches within previously produced melodies elicited a larger N2 than pitches in previously perceived melodies. Cortical motor planning regions were more strongly activated within the time frame of the N2 following altered pitches in previously produced melodies compared with previously perceived melodies, and larger N2 amplitudes were associated with greater detection accuracy following production learning than perception learning. Early sensory (N1) and later cognitive (P3a) components elicited by pitch alterations correlated with predictions of sensory echoic and schematic tonality models, respectively, but only for the perception learning condition, suggesting that production experience alters the extent to which performers rely on sensory and tonal recognition cues. These findings provide evidence for distinct time courses of sensory, schematic, and motoric influences within the same recognition task and suggest that learned auditory–motor associations influence responses to out-of-key pitches.
Beat that Word: How Listeners Integrate Beat Gesture and Focus in Multimodal Speech Discourse
Authors: Dimitrova Diana , Chu Mingyuan , Wang Lin , Özyürek Asli , Hagoort Peter
Published: March 2016

Communication is facilitated when listeners allocate their attention to important information (focus) in the message, a process called “information structure.” Linguistic cues like the preceding context and pitch accent help listeners to identify focused information. In multimodal communication, relevant information can be emphasized by nonverbal cues like beat gestures, which represent rhythmic nonmeaningful hand movements. Recent studies have found that linguistic and nonverbal attention cues are integrated independently in single sentences. However, it is possible that these two cues interact when information is embedded in context, because context allows listeners to predict what information is important. In an ERP study, we tested this hypothesis and asked listeners to view videos capturing a dialogue. In the critical sentence, focused and nonfocused words were accompanied by beat gestures, grooming hand movements, or no gestures. ERP results showed that focused words are processed more attentively than nonfocused words as reflected in an N1 and P300 component. Hand movements also captured attention and elicited a P300 component. Importantly, beat gesture and focus interacted in a late time window of 600–900 msec relative to target word onset, giving rise to a late positivity when nonfocused words were accompanied by beat gestures. Our results show that listeners integrate beat gesture with the focus of the message and that integration costs arise when beat gesture falls on nonfocused information. This suggests that beat gestures fulfill a unique focusing function in multimodal discourse processing and that they have to be integrated with the information structure of the message.
Evaluation of boldness assays and associated behavioral measures in a social parrot, monk parakeet (Myiopsitta monachus)
Authors: Kerman Kaan , Sieving Kathryn E. , Mary Colette S. , Avery Michael L.
Published: March 2016

Boldness reflects consistent individual differences in risk-taking behavior across various contexts. However, evaluating this basic assumption has largely been neglected in birds. In a captive monk parakeet population (Myiopsitta monachus; ), we undertook an analysis of 7 measures across 3 commonly used boldness assays (i.e., novel object, emergence, and predator-exposure tests). Using principal component analysis, we derived 3 components (PCs). PC-2 loaded strongly with measures from emergence and predator-exposure tests; we interpreted it as the closest approximation of boldness. PC-1 and PC-3 described different aspects of feeding such as foraging activity and rate, respectively. Finally, we assessed the predictive power of each measure that loaded significantly on the boldness axis. We found that no single metric explained even %55 of the variation in PC-2, nor could more than %50 individuals at the extremes of the spectrum be predicted. Our results demonstrate the utility of an inclusive approach in personality research.
A REVISION OF PLATANTHERA (ORCHIDACEAE; ORCHIDOIDEAE; ORCHIDEAE) IN ASIA
Authors: EFIMOV PETR G.
Published: March 2016

A revision of Platanthera of Asia is presented, which recognises 78 species. Each species description is supplemented by extensive synonymy and a distribution map; all species are illustrated by line drawings. In the general chapters, special importance is given to delineating the generic limit of Platanthera, which is continuously changing. An improved taxonomic system of Platanthera on a global scale is elaborated in connection with existing phylogenetic studies and discussed in detail. The genus is subdivided into five subgenera, two of which are further divided into sections. The possible main routes of transcontinental migrations during the evolution of the genus are speculated upon in a section on ‘biogeographic considerations’. One new species (P. miniangustata), 12 new subgenera and sections, five new combinations at specific and intraspecific ranks and 20 new neo- and lectotypes are included.
Forest Degradation Associated with Logging Frontier Expansion in the Amazon: The BR-163 Region in Southwestern Pará, Brazil
Authors: Pinheiro T. F. , Escada M. I. S. , Valeriano D. M. , Hostert P. , Gollnow F. , Müller H.
Published: March 2016

Forest degradation is the long-term and gradual reduction of canopy cover due to forest fire and unsustainable logging. A critical consequence of this process is increased atmospheric carbon emissions. Although this issue is gaining attention, forest degradation in the Brazilian Amazon has not yet been properly addressed. The claim here is that this process is not constant throughout Amazonia and varies according to colonization frontiers. Moreover, the accurate characterization of degradation requires lengthy observation periods to track gradual forest changes. The forest degradation process, the associated timeframe, spatial patterns, trajectories, and extent were characterized in the context of the Amazon frontiers of the 1990s using 28 years (1984–2011) of annual Landsat images. Given the large database and the characteristic of logging and burning, this study used data mining techniques and cell approach classification to analyze the spatial patterns and to construct associated trajectories. Multitemporal analysis indicated that forest degradation in the last two decades has caused as many interannual landscape changes as have clear-cuts. In addition, selective logging, as a major aspect of forest degradation, affected a larger amount of forest land than did forest fire. Although a large proportion of logged forest was deforested in the following years, selective logging did not always precede complete deforestation. Instead, the results indicate that logged forests were abandoned for approximately 4 years before clearance. Throughout the forest degradation process, there were no recurrent forest fires, and loggers did not revisit the forest. Forest degradation mostly occurred as a result of a single selective logging event and was associated with low-intensity forest damage.
On the Impacts of Different Definitions of Maximum Dimension for Nonspherical Particles Recorded by 2D Imaging Probes
Authors: Wu Wei , McFarquhar Greg M.
Published: March 2016

Knowledge of ice crystal particle size distributions (PSDs) is critical for parameterization schemes for atmospheric models and remote sensing retrieval schemes. Two-dimensional in situ images captured by cloud imaging probes are widely used to derive PSDs in term of maximum particle dimension (). In this study, different definitions of for nonspherical particles recorded by 2D probes are compared. It is shown that the derived PSDs can differ by up to a factor of 6 for μm and mm. The large differences for μm are caused by the strong dependence of sample volume on particle size, whereas differences for mm are caused by the small number of particles detected. Derived bulk properties can also vary depending on the definitions of because of discrepancies in the definition of used to characterize the PSDs and that used to describe the properties of individual ice crystals. For example, the mass-weighted mean diameter can vary by 2 times, the ice water content (IWC) by 3 times, and the mass-weighted terminal velocity by 6 times. Therefore, a consistent definition of should be used for all data and single-particle properties. As an invariant measure with respect to the orientation of particles in the imaging plane for 2D probes, the diameter of the smallest circle enclosing the particle () is recommended as the optimal definition of . If the 3D structure of a particle is observed, then the technique can be extended to determine the minimum enclosing sphere.
Mapping access to community-developed healthy food baskets including cost and availability
Authors: Ginn Alison , Majumdar Anne , Carr Marimba , Eastwood Ginny , Menger Beth
Published: March 2016

Background:

Food security is a topical issue but one that can be difficult to measure.

Objective:

To develop a community-approved food basket tool and use this to investigate the availability and affordability of a healthy diet in a multicultural urban setting.

Design:

A 7-day healthy food basket (HFB) containing 96 foods for six household types was developed through focus groups ( n = 6) with local residents recruited via the local health service and community organisations. A total of 41 stores were surveyed against the recommendations of the HFB. The availability and price of core food groups and energy dense discretionary foods were analysed.

Setting:

A multicultural area in Central London with a high concentration of socially and economically deprived households.

Results:

Healthy food for a variety of minority ethnic diets was available in the study area, although only one supermarket and three online stores stocked the full basket. Discretionary foods were readily available and often cheaper than healthier options. The largest proportions of cost were attributed to protein foods (30%–38%) and fruit and vegetables (20%–27%). Most foods in the HFB were cheaper at larger supermarkets, although fruit and vegetables cost less at markets and local stores. Total basket price varied greatly between stores, with cost savings achieved when buying from at least three stores.

Conclusion:

Economically disadvantaged members of the community may be excluded from accessing a healthy diet rather than cheaper foods that are energy dense and low in nutrients, particularly if they are unable to shop around. These findings provide insight for the development of voluntary sector partnership programmes, community education and local policy planning.
How Financial Cutbacks Affect the Quality of Jobs and Care for the Elderly
Authors: Burns Diane J. , Hyde Paula J. , Killett Anne M.
Published: March 2016

Based on case studies in 12 nursing homes in the United Kingdom, the authors illustrate how financial cutbacks affect job quality and the quality of care. The dimensions of job quality that suffered most were those directly related to the ability of workers to provide care: reductions in staffing, longer working hours, and work intensification. Cuts to labor costs eroded the quality of workers’ jobs in all 12 homes but with two differential outcomes: in seven homes, care quality was maintained, and in five homes, it deteriorated. Care quality was maintained in homes where a patient-centered care approach and remaining job quality allowed workers to develop work-arounds to protect residents from spillover effects. Care quality declined in homes where custodial approaches to care and low job quality did not provide workers the time or resources to protect residents or to maintain prior levels of care. A tipping point was reached, leading to a spillover into impoverished care.
The Effect of Pre-Electoral Party Coordination on Vote Choice: Evidence from the Italian Regional Elections
Authors: Plescia Carolina
Published: March 2016

Although it is theoretically relevant, the effect of pre-electoral coalitions on vote choice remains a largely unexplored area in the field of party strategy. The article addresses this gap by focusing on the Italian regional elections, where the electoral rules allow parties to run alone and, at the same time, to present pre-electoral coalitions on the ballot paper. This setting allows us to investigate under what conditions citizens vote for their preferred party and the coalition that this party indicated to coalesce with. The results suggest that ideological congruence and the size of the parties entering a pre-electoral agreement are decisive factors. Findings also reveal that the time elapsed since the establishment of a coalition has no effect on vote choice.
Young people and UK labour market policy: A critique of ‘employability’ as a tool for understanding youth unemployment
Authors: Crisp Richard , Powell Ryan
Published: March 2016

This paper presents a critical analysis of the contemporary policy focus on promoting employability among young people in the UK. Drawing on analysis of UK policy approaches to tackling youth unemployment since the late 1970s, we suggest that existing critiques of employability as ‘supply-side orthodoxy’ fail to capture fully its evolving meaning and function. Under the UK Coalition Government, it became increasingly colonised as a targeted tool of urban governance to legitimise ever more punitive forms of conditional welfare. We argue that this colonisation undermines the value of the notion of employability as an academic tool for understanding the reasons why young people face difficulties in entering the labour market. The paper suggests that the notion of youth transitions offers more potential for understanding youth unemployment, and that more clearly linking this body of research to policy could provide a fruitful avenue for future research. Such a shift requires a longer term, spatially informed perspective as well as greater emphasis on the changing power relations that mediate young people’s experiences of wider social and economic transformations. The paper concludes that promoting employment among urban young people requires a marked shift to address the historically and geographically inadequate knowledge and assumptions on which policies are based.
Principles and Policies
Authors: Stelzer Harald
Published: March 2016

Even though social engineering has gained a bad reputation, due to new possibilities in the information age, it may be time to reconsider Karl Popper’s conception of “piecemeal social engineering.” Piecemeal social engineering is not only an element within Popper’s open society. It also connects his political philosophy to his philosophy of science and his evolutionary epistemology. Furthermore, it seems to fit well into the search for implementation strategies for policies and social actions in the context of nonideal theory. Nevertheless, this does not necessarily undermine the need for political ideals and first-order principles, which are inhabitants of “World 3.”
Current status of medical radiation exposure in Korea – recent efforts to develop a radiation exposure control system focussed on justification and optimisation
Authors: Do K-H. , Jung S.E.
Published: March 2016

Radiation exposure from diagnostic medical imaging has increased in Korea. Radiological societies play a key role in radiation safety issues in Korea, including guidelines, accreditation, advocacy, scientific activity, and education. Any medical radiation exposure must be justified, and examinations using ionising radiation must be optimised. Education of referring physicians and radiologists is also important for justification. Medical physicists and radiographers have an important role to play in quality management and optimisation. Regulations are essential to control medical radiation exposure. Therefore, national organisations have made a significant effort to regulate and monitor medical radiation exposure using guidelines, accreditation, and even the law. Medical radiation exposure must be controlled, and this could be achieved by continuous interest from health professionals and organisations.