bluuebunny/crossref_metadata_2025 huggingface dataset:
What We Know About Environmental Policy: An Inductive Typology of the Research
Authors: Albertini Elisabeth
Published: December 2015

Environmental performance is a multidimensional concept that is difficult to measure since it concerns the pollution generated by companies, their energy consumption and their different environmental policies. Academic research has used objective and/or non‐objective indicators to measure this performance, dealing with both its managerial and measurement dimensions. This paper provides an inductive typology of the academic work concerning environmental policy through a computerized content analysis of 151 articles from 1992 to 2014 related to the management and measurement of environmental performance. The results highlight four major themes around which the academic research is organized: the relationship between environmental and financial performance, environmental performance under stakeholder engagement and institutional pressures, the strategic management of environmental performance, and increasing awareness of the sustainable development issue. Environmental performance research has evolved from a quantitative towards a more managerial dimension, highlighting the integration of performance within the management of a corporate business strategy. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Mus81 knockdown improves chemosensitivity of hepatocellular carcinoma cells by inducing S‐phase arrest and promoting apoptosis through CHK1 pathway
Authors: Wu Fan , Chen Wei‐Jia , Yan Lun , Tan Guo‐Qian , Li Wei‐Tao , Zhu Xuan‐Jin , Ge Xiao‐Chuan , Liu Jian‐Wei , Wang Bai‐Lin
Published: December 2015

As a critical endonuclease in DNA repair, Mus81 is traditionally regarded as a tumor suppressor, but recently correlated with the sensitivity of mitomycin C and 5‐fluorouracil in colon cancer and breast cancer cells. However, its role in chemosensitivity of other human malignancies still remains unknown. This study therefore aims to investigate the effects of Mus81 knockdown on the chemosensitivity of hepatocellular carcinoma (HCC), a usually chemorefractory tumor, and explore the underlying mechanisms. Mus81 expression in HepG2 and Bel‐7402 HCC cell lines was depleted by lentivirus‐mediated short hairpin RNA and the elevated sensitivity of these Mus81‐inhibited HCC cells to therapeutic agents, especially to epirubicin (EPI), was evidenced by MTT assay and an HCC chemotherapy mouse model. Flow cytometric analysis also showed that Mus81 knockdown lead to an obvious S‐phase arrest and an elevated apoptosis in EPI‐treated HepG2 and Bel‐7402 cells, which could be rescued by CHK1 inhibition. The activation of CHK1/CDC25A/CDK2 pathway was also demonstrated in Mus81‐inhibited HepG2 cells and xenograft mouse tumors under EPI treatment. Meanwhile, the apoptosis of HepG2 cells in response to EPI was remarkably promoted by Mus81 knockdown through activating p53/Bax/Caspase‐3 pathway under the controlling of CHK1. In addition, CHK2 inhibition slightly raised CHK1 activity, thereby enhancing the S‐phase arrest and apoptosis induced by EPI in Mus81‐suppressed HCC cells. In conclusion, Mus81 knockdown improves the chemosensitivity of HCC cells by inducing S‐phase arrest and promoting apoptosis through CHK1 pathway, suggesting Mus81 as a novel therapeutic target for HCC.
Targeting the PI3K signaling pathway in KRAS mutant colon cancer
Authors: Hong Suntaek , Kim SoYoung , Kim Hye Youn , Kang Myunghee , Jang Ho Hee , Lee Won‐Suk
Published: December 2015

Metastatic colorectal cancer (CRC) patients with v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide‐3‐kinase (PIK3CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations (DLD‐1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration‐dependent manner in the LoVo (PI3KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells (PIK3CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone (P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation.
KRAS mutation in lung metastases from colorectal cancer: prognostic implications
Authors: Ghidini Michele , Personeni Nicola , Bozzarelli Silvia , Baretti Marina , Basso Gianluca , Bianchi Paolo , Tronconi Maria Chiara , Pressiani Tiziana , Grizzi Fabio , Giordano Laura , Malesci Alberto , Alloisio Marco , Laghi Luigi , Santoro Armando , Rimassa Lorenza
Published: December 2015

KRAS mutant colorectal cancer (CRC) patients develop lung and brain metastases more frequently than KRAS wild‐type (WT) counterpart. We retrospectively investigated the prognostic role of KRAS, BRAF, and PIK3CA (exon 20) mutations and loss of phosphatase and tensin homolog (PTEN) in surgically resected lung metastases. Lung specimens from 75 metastatic CRC (mCRC) patients treated with one or more metastasectomies with curative intent were analyzed. Sixty‐four percent of patients had KRAS WT lung metastases. PTEN loss‐of‐function was found in 75%. BRAF and PIK3CA exon 20 mutations were not found. Seven patients subsequently developed brain metastases and 43% of them had KRAS mutation. In univariate analysis, median overall survival (OS) for KRAS WT patients was longer, compared to KRAS mutant patients (median 60.9 vs. 36.6 months, P = 0.035). In addition, both progression‐free survival (PFS) and lung disease‐free survival (LDFS) between lung surgery and relapse were not associated with KRAS and PTEN status. In multivariate analysis, the risk of death was significantly increased by KRAS mutational status (OS Hazard ratio (HR) 2.17, 95% IC 1.19–3.96, P = 0.012) and lack of adjuvant chemotherapy (OS HR 0.10, 95% IC 0.01–0.74, P = 0.024). The proportion of KRAS mutations in lung metastases was similar to the expected proportion in primary tumors. Patients harboring KRAS mutation had a poorer survival rate compared to WT group both in univariate and multivariate analysis. Moreover, administration of adjuvant chemotherapy after lung metastasectomy (LM) significantly improved both PFS and OS. KRAS mutation is a negative prognostic factor in mCRC patients undergoing LM. Further larger and prospective studies are necessary to confirm these findings.
Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies
Authors: Reed Damon R. , Mascarenhas Leo , Manning Kathleen , Hale Gregory A. , Goldberg John , Gill Jonathan , Sandler Eric , Isakoff Michael S. , Smith Tiffany , Caracciolo Jamie , Lush Richard M. , Juan Tzu‐Hua , Lee Jae K. , Neuger Anthony M. , Sullivan Daniel M.
Published: December 2015

Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose‐limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1–5 and 8–12 of each 28‐day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m2 and topotecan 1 mg/m2; (2) sorafenib 150 mg/m2 and topotecan 1.4 mg/m2; and (3) sorafenib 200 mg/m2 and topotecan 1.4 mg/m2. Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration‐time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m2 twice daily orally on days 1–28 combined with topotecan 1.4 mg/m2 once daily on days 1–5 and 8–12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied.
Challenging the Notion of Failure to Protect: Exploring the Protective Strategies of Abused Mothers Living in Urban and Remote Communities and Implications for Practice
Authors: Nixon Kendra L. , Bonnycastle Colin , Ens Stephanie
Published: December 2015

Many children are exposed to intimate partner violence against their mothers. Countering assumptions that abused women ‘fail to protect’ their children, this paper presents the results of a Canadian qualitative study that examined the protective strategies of 18 abused mothers, most of whom are Aboriginal. Half of these women were living in a large city and half were living in remote, northern communities. Despite geographic location, abused mothers engage in acts and behaviours to not only protect their children from immediate physical violence but also to mitigate the potential emotional harms of exposure to violence and to prevent their children from continuing the violence in their own future relationships. Relying on informal supports, such as family, was especially important for mothers living in northern, remote communities, and is not surprising given the few services available. Professionals must be aware of the range of strategies and approaches that mothers use, including those that do not involve formal systems (i.e. the police or shelter). Focusing on their strengths and protective capacities will help to empower abused mothers and limit unnecessary, inappropriate, or intrusive interventions. Recognising mothers' capacities will also lead to better outcomes for children, who fare best when their mothers are appropriately supported. Copyright © 2015 John Wiley & Sons, Ltd.

‘Abused mothers engage in acts and behaviours to protect their children from immediate physical violence’

Key Practitioner Messages

Abused mothers engage in acts and behaviours to protect their children from the harms of exposure to violence, and these may differ for mothers living in remote, isolated communities.

Mothers' protective acts extend beyond calling the police or going to shelter, and include informal supports.

Professionals must inquire about mothers' protective strategies and incorporate into case plans.

Professionals must support abused mothers so that they can help strengthen the mother‐child relationship and help children recover from violence.

‘Professionals must inquire about mothers' protective strategies and incorporate into case plans.’
An Adolescent Parents' Programme to Reduce Child Abuse
Authors: McHugh Margaret T. , Kvernland Alexandra , Palusci Vincent J.
Published: December 2015

Teen pregnancy is a significant social, political and economic issue, and potential adverse outcomes for children of adolescent mothers include a higher incidence of low birth weight, prematurity, developmental delays, cognitive and behavioural deficits, and school failure. These children are also at a greater risk for abuse and neglect as well as intentional injury by their adolescent mothers. We evaluated child abuse reporting and the health outcomes for infants and their adolescent parents in Bellevue Hospital's Adolescent Parenting Program to assess whether better outcomes were achieved for mother‐baby dyads in our adolescent mothers' groups compared to the general clinic and New York City populations. We found that those who completed a full year of the programme during 2011–12 had some significantly improved measures compared to those who did not, with fewer child abuse reports and more well‐baby visits, more immunisations and earlier referral for developmental delays. There were additional health benefits for the adolescent mothers noted as well. We concluded that a specialised programme for high‐risk adolescent mothers and their babies offers a number of benefits compared to standard separate care, but more research and funding are needed to tailor programmes to the unique needs of adolescent mothers in diverse social and educational contexts. Copyright © 2015 John Wiley & Sons, Ltd.

Key Practitioner Messages

Adolescent parents have increased risk for several adverse child health and development outcomes for their children, including child abuse and neglect.

An adolescent parenting programme focusing on simultaneous medical care for teen parents and their infants with multidisciplinary staff can provide important support and guidance to help teen parents improve their parenting skills.

Additional benefits of simultaneous care include improved child immunisation rates and developmental outcomes and decreased reported abuse and neglect.

‘Adolescent parents have increased risk for several adverse child health and development outcomes for their children’

‘We evaluated child abuse reporting and the health outcomes for infants and their adolescent parents in Bellevue Hospital's Adolescent Parenting Program’
Efficient Total Chemical Synthesis of 13C=18O Isotopomers of Human Insulin for Isotope‐Edited FTIR
Authors: Dhayalan Balamurugan , Fitzpatrick Ann , Mandal Kalyaneswar , Whittaker Jonathan , Weiss Michael A. , Tokmakoff Andrei , Kent Stephen B. H.
Published: December 2015

Isotope‐edited two‐dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site‐specific incorporation of stable 13C=18O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis—via a key ester insulin intermediate—of 97 % enriched [(1‐13C=18O)PheB24] human insulin: stable‐isotope labeled at a single backbone amide carbonyl. The amino acid sequence as well as the positions of the disulfide bonds and the correctly folded structure were unambiguously confirmed by the X‐ray crystal structure of the synthetic protein molecule. In vitro assays of the isotope labeled [(1‐13C=18O)PheB24] human insulin showed that it had full insulin receptor binding activity. Linear and 2 D IR spectra revealed a distinct red‐shifted amide I carbonyl band peak at 1595 cm−1 resulting from the (1‐13C=18O)PheB24 backbone label. This work illustrates the utility of chemical synthesis to enable the application of advanced physical methods for the elucidation of the molecular basis of protein function.
Primary‐like human hepatocytes genetically engineered to obtain proliferation competence display hepatic differentiation characteristics in monolayer and organotypical spheroid cultures
Authors: Herzog Natalie , Hansen Max , Miethbauer Sebastian , Schmidtke Kai‐Uwe , Anderer Ursula , Lupp Amelie , Sperling Sebastian , Seehofer Daniel , Damm Georg , Scheibner Katrin , Küpper Jan‐Heiner
Published: December 2015

Primary human hepatocytes are in great demand during drug development and in hepatology. However, both scarcity of tissue supply and donor variability of primary cells create a need for the development of alternative hepatocyte systems. By using a lentivirus vector system to transfer coding sequences of Upcyte® proliferation genes, we generated non‐transformed stable hepatocyte cultures from human liver tissue samples. Here, we show data on newly generated proliferation‐competent HepaFH3 cells investigated as conventional two‐dimensional monolayer and as organotypical three‐dimensional (3D) spheroid culture. In monolayer culture, HepaFH3 cells show typical cobblestone‐like hepatocyte morphology and anchorage‐dependent growth for at least 20 passages. Immunofluorescence staining revealed that characteristic hepatocyte marker proteins cytokeratin 8, human serum albumin, and cytochrome P450 (CYP) 3A4 were expressed. Quantitative real‐time PCR analyses showed that expression levels of analyzed phase I CYP enzymes were at similar levels compared to those of cultured primary human hepatocytes and considerably higher than in the liver carcinoma cell line HepG2. Additionally, transcripts for phase II liver enzymes and transporter proteins OATP‐C, MRP2, Oct1, and BSEP were present in HepaFH3. The cells produced urea and converted model compounds such as testosterone, diclofenac, and 7‐OH‐coumarin into phases I and II metabolites. Interestingly, phases I and II enzymes were expressed at about the same levels in convenient monolayer cultures and complex 3D spheroids. In conclusion, HepaFH3 cells and related primary‐like hepatocyte lines seem to be promising tools for in vitro research of liver functions and as test system in drug development and toxicology analysis.
Catheter interventional treatment of congenital portosystemic venous shunts in childhood
Authors: Knirsch Walter , Benz Dominik C. , Bühr Patrick , Quandt Daniel , Weber Roland , Kellenberger Christian , Braegger Christian P. , Kretschmar Oliver
Published: December 2015

Objectives

The study aimed on the catheter interventional treatment of congenital portosystemic venous shunt (CPSVS) in childhood and the impact on vascular growth of hypoplastic portal veins. Clinical course and follow up of partial or complete closure of CPSVS are described.

Background

CPSVS is a very rare vascular malformation of the portal venous drainage resulting in potentially life threatening abdominal, pulmonary, cerebral, and cardiac complications. The anatomic type, clinical course, and diagnosis must be determined for optimal management.

Methods

Single centre case series.

Results

Eight (6 female) children with extrahepatic (n = 5) and intrahepatic (n = 3) CPSVS were diagnosed invasively by catheterization, including test balloon occlusion of the shunt and simultaneous retrograde angiography, and treated by catheter interventions (n = 5) with partial (n = 2) and complete (n = 3) occlusion of CPSVS at a median age of 3.9 years (range 0.7–21). Congenital heart disease (CHD) was the most frequent associated organ manifestation (n = 5) followed by mild to severe pulmonary arterial hypertension (n = 4), hepatopulmonary syndrome (n = 2), and portosystemic encephalopathy (n = 1). CHD was simple (n = 3) or complex type (n = 2). Three patients were untreated so far, because they were in excellent clinical condition at an age <1 year, refused treatment, or planned for later treatment.

Conclusions

Accurate invasive diagnosis of CPSVS with test balloon occlusion of the shunt is mandatory to depict the anatomic situation. Catheter interventional treatment of CPSVS offers a feasible and safe approach with complete or partial closure of the vascular malformation inducing potentially significant vascular growth of a former hypoplastic portal venous system. © 2015 Wiley Periodicals, Inc.
Treatment of drug‐eluting stent restenosis: Comparison between drug‐eluting balloon versus second‐generation drug‐eluting stents from a retrospective observational study
Authors: Basavarajaiah Sandeep , Naganuma Toru , Latib Azeem , Sticchi Alessandro , Ciconte Giuseppe , Panoulas Vasilis , Chieffo Alaide , Montorfano Matteo , Carlino Mauro , Colombo Antonio
Published: December 2015

Objectives

To compare drug‐eluting balloons (DEBs) versus second‐generation DES in the treatment of drug‐eluting stent restenosis (DES‐ISR).

Background

The optimal treatment of DES‐ISR remains unclear. Several modes of treatment ranging from plain‐old balloon angioplasty to repeated use of DES have yielded disappointing results. DEBs are increasingly been used in restenotic lesions; however, their use in DES‐ISR is less established.

Methods

We evaluated all procedures between 2009 and 2011, involving DES‐ISR that were treated either with DEB or second‐generation DES. The measured end‐points during the follow‐up period were cardiac‐death, target‐vessel MI, TLR, TVR, and MACE defined as composite of cardiac‐death, TV‐MI, and TVR.

Results

Two hundred and forty‐seven patients (302 lesions) with DES‐ISR were treated with either DEB (81 patients; 104 lesions) or second‐generation DES (166 patients; 198 lesions). The mean age of patients was 66.1 ± 9.4 years. There were higher numbers of patients with diabetes in the DEB group (DEB 47% vs DES 33%; p = 0.03). The mean length of DEB was significantly longer than the DES (35.4 vs 19.8 mm; p < 0.001). During the 12‐month follow‐up, there were no significant differences in the MACE rates (12.3% vs 8.4%; p = 0.3) and TLR rates (9.9% vs 7.8%; p = 0.6) between DEB and DES, respectively. On the multivariate analysis, use of DEB or DES was not the predictor of MACE (hazard ratio: 0.84, 95% CI: 0.46–1.85; p = 0.6). There were no cases of definite or probable stent thrombosis in either group.

Conclusion

There were no significant differences in the clinical outcomes between DEB and second‐generation DES in the treatment of DES‐ISR. These results should encourage operators to consider DEB in the treatment of DES‐ISR, which offers certain advantages over DES. © 2015 Wiley Periodicals, Inc.
Incidence, treatment, and outcome of acute aortic valve regurgitation complicating percutaneous balloon aortic valvuloplasty
Authors: Dall'Ara Gianni , Saia Francesco , Moretti Carolina , Marrozzini Cinzia , Taglieri Nevio , Bordoni Barbara , Chiarabelli Matteo , Ciuca Cristina , Rapezzi Claudio , Marzocchi Antonio
Published: December 2015

Objectives

To evaluate the incidence, treatment, and outcomes of acute aortic regurgitation (ARR) complicating BAV.

Background

In the transcatheter aortic valve implantation (TAVI) era, there is an increase of percutaneous balloon aortic valvuloplasty (BAV) procedures with different indications.

Methods

From the prospective BAV registry of the University of Bologna, which has enrolled patients between the year 2000 and the present, we selected those who suffered intraprocedural AAR with overt hemodynamic instability. Worsening of baseline aortic insufficiency without hemodynamic collapse, treatment of degenerated biological valve prosthesis, and BAV performed within a planned TAVI procedure were excluded. The main endpoints were in‐hospital and 30‐day mortality.

Results

Out of 1517 BAVs, we identified 26 cases of AAR (1.7%). This complication occurred in 80.8% of cases after one or two balloon inflations. Mean transaortic gradient decreased from 50.6 ± 19.3 to 26.0 ± 14.4 mm Hg (p < 0.01). In 8(30.8%) patients, AAR spontaneously resolved within few minutes; in 18 cases, the operators had to perform a rescue maneuver to reposition a valve leaflet got stuck in the opening position (this maneuver was successful in 13/18 of the cases, 72.2%). Out of 5 persistent AAR, 3 were managed with emergency TAVI or surgery, while 2 were unresolved. In‐hospital mortality was 15.4% (n = 4), whereas no more deaths occurred up to 30 days.

Conclusions

AAR is a fearsome complication of BAV and portends a grim prognosis. In some cases, it can be resolved with appropriate technical maneuvers; in others, a rescue TAVI or surgical valve replacement may be necessary. © 2015 Wiley Periodicals, Inc.
The Origin of Catalytic Activity of Nickel Phosphate for Oxygen Evolution in Alkaline Solution and its Further Enhancement by Iron Substitution
Authors: Zhan Yi , Lu Meihua , Yang Shiliu , Liu Zhaolin , Lee Jim Yang
Published: December 2015

Nickel(II) phosphate (NPO) can be an effective catalyst for oxygen evolution reaction (OER) in alkaline solution. Unlike other transition metal phosphates, the OER is preceded by a prominent reversible redox reaction. The current study is aimed at understanding the origin of NPO‐catalyzed OER, in particular the role of the pre‐OER redox reaction. We detected the progressive formation of Ni(OH)2/NiOOH on the NPO surface during potential cycling in the anodic region similar to previous observations from Ni oxides, and found that it is associated with the change in the Ni/phosphate stoichiometry from 1.5 to 1.0, resulting in the loss of phosphate to the alkaline solution. Despite the conversion, NPO still has a good and sustained OER performance due to the activity similarity between NiPO4 (and possibly NPO) and NiOOH (the activated form of Ni oxide and hydroxide catalysts). NPO is however an easier catalyst to use than Ni oxides and hydroxides, which require extensive electrode conditioning to reach a stable performance. We also mixed NPO with Fe in view of recent findings that Ni–Fe double hydroxides are more active than simple Ni oxides in oxygen catalysis. The experimental results corroborate the positive outcome of this modification.
Vanadium‐Ion Redox Reactions in a Three‐Dimensional Network of Reduced Graphite Oxide
Authors: Maruyama Jun , Shinagawa Tsutomu , Hayashida Akihiro , Matsuo Yoshiaki , Nishihara Hirotomo , Kyotani Takashi
Published: December 2015

A three‐dimensional (3D) fine network structure of thin carbon microflakes inside a loosely entangled carbon‐fiber matrix was formed by applying an ice‐template method to a graphite oxide (GO) dispersion in the matrix and thermal reduction of the GO. Vanadium‐ion redox reactions were investigated in the network of reduced GO (RGO) for potential application as electrodes in vanadium redox flow batteries (VRFB). The development of the fineness, the degree of graphitization, the structural disorder, and the surface composition were characterized. The interaction between the carbon surface species and the vanadium ions was implied by the X‐ray absorption fine structure (XAFS). The structure of the 3D RGO network was clearly correlated to the activity for the VRFB positive electrode reactions, and the development of the fine network structure effectively enhanced the reactions due to increased exposure of the edge planes and sufficient dispersion of the active sites.
A Preliminary Study of Diastereoselectivity in the PdII‐Catalyzed C(sp3)‐H Alkoxylation of Cyclic Systems
Authors: Yang Xinglin , Sun Tian‐Yu , Rao Yu
Published: December 2015

Primary mechanism of a PdII‐catalyzed 8‐aminoquinoline‐directed C−H alkoxylation was investigated. It was understood that the PdII‐catalyzed C(sp3)−O bond formation proceeded through a concerted reductive elimination from the PdIV intermediate in the cyclic system. Deuteration experiments and related computational studies elucidate that intrinsic conformation determined the diastereoselectivity of the PdII‐catalyzed C−H alkoxylation of cyclic carboxylic acids.
The evolution and clinical relevance of prognostic classification systems in myelofibrosis
Authors: Bose Prithviraj , Verstovsek Srdan
Published: December 2015

Primary myelofibrosis, the most aggressive of the classic Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs), is a clonal disorder characterized by often debilitating constitutional symptoms and splenomegaly, bone marrow fibrosis and resultant cytopenias, extramedullary hematopoiesis, risk of leukemic transformation, and shortened survival. Post‐polycythemia vera and post‐essential thrombocythemia myelofibrosis represent similar entities, although some differences are being recognized. Attempts to classify patients with myelofibrosis into prognostic categories have been made since the late 1980s, and these scoring systems continue to evolve as new information becomes available. Over the last decade, the molecular pathogenesis of MPNs has been elucidated considerably, and the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is the first drug specifically approved by the US Food and Drug Administration to treat patients with intermediate‐risk and high‐risk myelofibrosis. This article reviews the evolution of prognostic criteria in myelofibrosis, emphasizing the major systems widely in use today, as well as recently described, novel systems that incorporate emerging data regarding somatic mutations. Risk factors for thrombosis and conversion to MPN blast phase also are discussed. Finally, the practical usefulness of the current prognostic classification systems in terms of clinical decision making is discussed, particularly within the context of some of their inherent weaknesses. Cancer 2016;122:681–692. © 2015 American Cancer Society.
The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy
Authors: Falchi Lorenzo , Verstovsek Srdan , Ravandi‐Kashani Farhad , Kantarjian Hagop M.
Published: December 2015

The therapeutic potential of arsenic derivatives has long been recognized and was recently rediscovered in modern literature. Early studies demonstrated impressive activity of this compound in patients with relapsed acute promyelocytic leukemia (APL). Over the last 2 decades, intravenous arsenic trioxide has been used successfully, both alone and in combination with other agents, for the treatment of APL and, with some success, of other myeloid neoplasms. Arsenic trioxide is currently part the standard of care for patients with APL. More recently, oral formulations of this compound have been developed and are entering clinical practice. In this review, the authors discuss the evolution of arsenic in the treatment of APL and other myeloid neoplasms. Cancer 2016;122:1160–8. © 2015 American Cancer Society.
Baseline dietary glutamic acid intake and the risk of colorectal cancer: The Rotterdam study
Authors: Viana Veloso Gilson G. , Franco Oscar H. , Ruiter Rikje , de Keyser Catherina E. , Hofman Albert , Stricker Bruno C. , Kiefte‐de Jong Jessica C.
Published: December 2015

BACKGROUND

Animal studies have shown that glutamine supplementation may decrease colon carcinogenesis, but any relation with glutamine or its precursors has not been studied in humans. The primary aim of this study was to assess whether dietary glutamic acid intake was associated with colorectal cancer (CRC) risk in community‐dwelling adults. A secondary aim was to evaluate whether the association could be modified by the body mass index (BMI).

METHODS

This study was embedded in the Rotterdam study, which included a prospective cohort from 1990 onward that consisted of 5362 subjects who were 55 years old or older and were free of CRC at the baseline. Glutamic acid was calculated as a percentage of the total protein intake with a validated food frequency questionnaire at the baseline. Incident cases of CRC were pathology‐based.

RESULTS

During follow‐up, 242 subjects developed CRC. Baseline dietary glutamic acid intake was significantly associated with a lower risk of developing CRC (hazard ratio [HR] per percent increase in glutamic acid of protein, 0.78; 95% confidence interval [CI], 0.62‐0.99). After stratification for BMI, the risk reduction for CRC by dietary glutamic acid was 42% for participants with a BMI ≤ 25 kg/m2 (HR per percent increase in glutamic acid of protein, 0.58; 95% CI, 0.40‐0.85), whereas no association was found in participants with a BMI > 25 kg/m2 (HR per percent increase in glutamic acid of protein, 0.97; 95% CI, 0.73‐1.31).

CONCLUSIONS

Our data suggest that baseline dietary glutamic acid intake is associated with a lower risk of developing CRC, but this association may be mainly present in nonoverweight subjects. Cancer 2016;122:899–907. © 2015 American Cancer Society.
Methane Activation Mediated by a Series of Cerium–Vanadium Bimetallic Oxide Cluster Cations: Tuning Reactivity by Doping
Authors: Ma Jia‐Bi , Meng Jing‐Heng , He Sheng‐Gui
Published: December 2015

The reactions of cerium–vanadium cluster cations CexVyOz+ with CH4 are investigated by time‐of‐flight mass spectrometry and density functional theory calculations. (CeO2)m(V2O5)n+ clusters (m=1,2, n=1–5; m=3, n=1–4) with dimensions up to nanosize can abstract one hydrogen atom from CH4. The theoretical study indicates that there are two types of active species in (CeO2)m(V2O5)n+, V[(Ot)2]. and [(Ob)2CeOt]. (Ot and Ob represent terminal and bridging oxygen atoms, respectively); the former is less reactive than the latter. The experimentally observed size‐dependent reactivities can be rationalized by considering the different active species and mechanisms. Interestingly, the reactivity of the (CeO2)m(V2O5)n+ clusters falls between those of (CeO2)2–4+ and (V2O5)1–5+ in terms of C−H bond activation, thus the nature of the active species and the cluster reactivity can be effectively tuned by doping.
Incorporating patient preferences into drug development and regulatory decision making: Results from a quantitative pilot study with cancer patients, carers, and regulators
Authors: Postmus D , Mavris M , Hillege HL , Salmonson T , Ryll B , Plate A , Moulon I , Eichler H‐G , Bere N , Pignatti F
Published: December 2015

Currently, patient preference studies are not required to be included in marketing authorization applications to regulatory authorities, and the role and methodology for such studies have not been agreed upon. The European Medicines Agency (EMA) conducted a pilot study to gain experience on how the collection of individual preferences can inform the regulatory review. Using a short online questionnaire, ordinal statements regarding the desirability of different outcomes in the treatment of advanced cancer were elicited from 139 participants (98 regulators, 29 patient or carers, and 12 healthcare professionals). This was followed by face‐to‐face meetings to gather feedback and validate the individual responses. In this article we summarize the EMA pilot study and discuss the role of patient preference studies within the regulatory review. Based on the results, we conclude that our preference elicitation instrument was easy to implement and sufficiently precise to learn about the distribution of the participants' individual preferences.
Tigroid background in cytology of hyalinizing clear cell carcinoma of the salivary gland
Authors: Yuan Chang‐Tsu , Hsieh Min‐Shu
Published: December 2015

Hyalinizing clear cell carcinoma (HCCC) is a rare and low grade salivary gland carcinoma with a unique recurrent EWSR1 gene translocation. HCCC most commonly arises from intraoral minor salivary glands and its cytological features have not been well evaluated. We report a 28‐year‐old man with palatal HCCC and emphasize the “tigroid background” and metachromatic matrix observed in scrape cytology. This “tigroid background,” usually associated with glycogen‐rich clear cell tumors, is an important cytological feature of HCCC. Awareness of this feature can do great help in pathological research and diagnosis. Diagn. Cytopathol. 2016;44:338–341. © 2015 Wiley Periodicals, Inc.
Recurrent giant mandibular ameloblastoma in young adults
Authors: Gravvanis Andreas , Koumoullis Harry D. , Anterriotis Dimitrios , Tsoutsos Dimosthenis , Katsikeris Nick
Published: December 2015

Background

The purpose of the study was to define the most appropriate management of the giant mandibular ameloblastoma (GMA) in young adults.

Methods

A retrospective study was performed on patients with GMA <30 years old. The data collected included initial treatment, tumor margins, reconstruction, and follow‐up. Patients evaluated speech, chewing, swallowing, and facial appearance after definitive treatment.

Results

Thirteen patients were identified with recurrent solid/multicystic disease requiring further treatment. Definitive treatment involved segmental mandibulectomy and reconstruction with free fibular flap in all patients. Seven patients had immediate reconstruction (group A) and 6 had secondary (group B). Mandibular resection was planned at least 2 cm beyond the radiological limit, free margins were achieved in all patients, and all flaps were transplanted successfully. In group A, functional score was 13.7 ± 0.45 and facial appearance score was 4.5 ± 0.49, whereas in group B were 11.16 ± 0.37 and 3.3 ± 0.5, respectively (both p < .05).

Conclusion

Aggressive resection of the GMA and immediate reconstruction is strongly advised. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1947–E1954, 2016
Guest Editors’ Introduction: The Role of Human Resources and Organizational Factors in Ambidexterity
Authors: Junni Paulina , Sarala Riikka M. , Tarba Shlomo Y. , Liu Yipeng , Cooper Cary L.
Published: December 2015

Ambidexterity is a growing field of management research. However, the role of human resources (HR) and organizational factors needs further exploration because of the fragmented nature of prior work and the subsequent lack of a unifying framework. Our review of 41 empirical studies identifies distinct research streams that relate to the effects of employee characteristics, leader characteristics, organizational structure, culture, social relationships, and organizational environment on ambidexterity. We discuss the most important findings within each stream, which contributes to the HR and ambidexterity literature by addressing the current state of our knowledge. To move forward research in this area, we identify important, yet underexplored areas in each stream. This contributes to the literature by highlighting specific gaps in our current knowledge that represent new avenues for future research. We also identify important interrelationships between different streams that need further clarification. We summarize our findings into an integrative model that elucidates the role of HR and organizational factors in ambidexterity. This contributes to a more comprehensive understanding of ambidexterity from the HR and organizational perspectives. © 2015 Wiley Periodicals, Inc.
FROM ME TO US: THE CONSTRUCTION OF FAMILY ALLIANCE
Authors: Galdiolo Sarah , Roskam Isabelle
Published: December 2015

This longitudinal prospective and multi‐informant study based on a three‐wave research program (pregnancy, 12 months’ postpartum, and 16 months’ postpartum) aimed to determine the process of construction of family alliance, as assessed by the Lausanne Trilogue Play (Fivaz‐Depeursinge & Corboz‐Warnery, 1999). A model using parents’ individual characteristics (i.e., personality traits and attachment orientations) as distal variables, coparenting as a mediator, child's temperament as a moderator, and family alliance as outcome was tested using structural equation modeling on 62 nonreferred families. Results showed that both parents’ conscientiousness was positively and mothers’ avoidant attachment and fathers’ anxious attachment were negatively and indirectly (via coparenting) associated with the family alliance. The discussion underlines mothers’ and fathers’ different roles and the importance of coparenting as a core mechanism in the development of family alliance.
WHEN MUM IS STRESSED, IS DAD JUST AS STRESSED? PREDICTORS OF PATERNAL STRESS IN THE FIRST SIX MONTHS OF HAVING A BABY
Authors: Seah Cheryl K.F. , Morawska Alina
Published: December 2015

The primary aim of this study was to examine predictors of paternal stress within the first 6 months of having a baby in a normative Australian sample, and to compare paternal and maternal stress. In total, 54 fathers and 71 mothers completed self‐report measures of postnatal depressive symptoms, parenting stress, efficacy, responsiveness, attachment, and family and social support. Paired sample t test revealed a significant relationship within couples in their level of parenting stress. Fathers reported lower levels of postnatal depression, responsiveness, and attachment than did mothers. Fathers rated their level of social support to be higher than did mothers. Regression analyses indicated that responsiveness and efficacy significantly predicted paternal stress whereas responsiveness and attachment predicted maternal stress when history of psychological diagnosis and financial stability were controlled for. Results have implications for early preventive parenting programs.
MATERNAL MIND‐MINDEDNESS: RELATIONS WITH MATERNAL–FETAL ATTACHMENT AND STABILITY IN THE FIRST TWO YEARS OF LIFE: FINDINGS FROM AN AUSTRALIAN PROSPECTIVE STUDY
Authors: McMahon Catherine , Camberis Anna‐Lisa , Berry Sinead , Gibson Frances
Published: December 2015

Mind‐mindedness captures a caregiver's attunement to his or her infant's mental states, and the tendency to interpret behavior as resulting from these mental states. The construct is assessed through analysis of maternal language during interaction or from mothers’ use of mental state words when invited to describe their child. This study examined whether maternal–fetal attachment predicted maternal mind‐mindedness, whether there was continuity in mind‐mindedness over the first 2 postnatal years, and concordance for the two approaches to measurement. One hundred fifty women completed a questionnaire measure of maternal–fetal attachment in the third trimester of pregnancy and participated in home visits to assess maternal mind‐mindedness when their infants were 7 months and 19 months of age. Path analysis showed that maternal–fetal attachment predicted indices of maternal mind‐mindedness at 7 and 19 months; mothers who made more mind‐related comments during play at 7 months also did so at 19 months, and mothers who made more mind‐related comments during play at 19 months also used more mental state words when describing their child. Results suggest that a proclivity to mind‐mindedness may be a caregiver characteristic that is present prior to birth and stable over time.
miR‐4299 mediates the invasive properties and tumorigenicity of human follicular thyroid carcinoma by targeting ST6GALNAC4
Authors: Miao Xiaolong , Jia Li , Zhou Huimin , Song Xiaobo , Zhou Ming , Xu Jinchao , Zhao Lifen , Feng Xiaobin , Zhao Yongfu
Published: December 2015

Altered sialylation is closely associated with tumor progression and invasiveness. Micro‐RNAs endogenous regulators of gene expression have been implicated in human thyroid carcinoma invasiveness. The objective of this study is to examine the alterations of miR‐4299 and ST6GALNAC family in human follicular thyroid carcinoma during metastatic process. qRT‐PCR showed the differential expressional profiles of miR‐4299 and ST6GALNAC family in three kinds of thyroid cell lines (FTC‐133,FTC‐238, Nthy‐ori 3‐1) and clinical tissue specimens(malignant and borderline). The altered expression levels of ST6GALNAC4 were corresponding to invasive phenotypes of FTC‐133 and FTC‐238 cells both in vitro and in vivo. Further date indicated that miR‐4299 regulated tumor progression and invasiveness by directly targeting ST6GALNAC4. This study implies the potential therapeutic application of miR‐4299 and ST6GALNAC4 in modulating the invasion and tumorigenicity of follicular thyroid carcinoma cell. © 2015 IUBMB Life, 68(2):136–144, 2016
Cytocompatibility studies of a biomimetic copolymer with simplified structure and high‐strength adhesion
Authors: Brennan M. Jane , Meredith Heather J. , Jenkins Courtney L. , Wilker Jonathan J. , Liu Julie C.
Published: December 2015

The development of adhesives suitable for biomedical applications has been challenging given that these materials must exhibit sufficient adhesion strengths and biocompatibility. Biomimetic materials inspired by mussel adhesive proteins appear to contain many of the necessary characteristics for biomedical adhesives. In particular, poly[(3,4‐dihydroxystyrene)‐co‐styrene] has been shown to be a high strength adhesive material with bonding comparable to or even greater than several commercial glues. Herein, a thorough study on the cytocompatibility of this copolymer provides insights on the suitability of a mussel‐mimicking adhesive for applications development. The cytotoxicity of poly[(3,4‐dihydroxystyrene)‐co‐styrene] was evaluated through assessment of the viability, proliferation rate, and morphology of NIH/3T3 fibroblasts when cultured with copolymer extracts or directly in contact with the adhesive. After 1 and 3 days of culture, both the copolymer alone and copolymer cross‐linked with periodate exhibited minimal effects on cell viability. Likewise, cells cultured on the copolymer displayed proliferation rates and morphologies similar to cells on the poly‐l‐lysine control. These results indicate that poly[(3,4‐dihydroxystyrene)‐co‐styrene] is highly cytocompatible and therefore a promising material for use where biological contact is important. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 983–990, 2016.
A mixed DFT‐MD methodology for the in silico development of drug releasing macrocycles. Calix and thia‐calix[N]arenes as carriers for Bosutinib and Sorafenib
Authors: Galindo‐Murillo Rodrigo , Aguilar‐Suárez Luis Enrique , Barroso‐Flores Joaquín
Published: December 2015

Interaction energies between a family of 36 calix[n]arenes, their corresponding thia‐ analogues, and two commercially available second generation tyrosine kinase III inhibitors—Bosutinib and Sorafenib—were calculated through DFT methods at the B97D/6‐31G(d,p) level of theory, based on Natural Population Analysis, for the in silico development of suitable drug carriers based on the aforementioned macrocycles which can increase their bioavailability and in turn their pharmaceutical efficiency. Molecular Dynamics simulations (production runs: +500 ns) using the General Amber Force Field were also carried out in order to assess the releasing process of these drugs in an explicit aqueous environment. In total, 144 host–guest complexes are examined. According to our results, five‐membered SO3H and i–Pr functionalized‐calixarenes are the best candidates for Sorafenib‐carriers while six‐membered ones SO3H and C2H4NH2 functionalized– are the lead candidates for Bosutinib‐carriers. © 2015 Wiley Periodicals, Inc.
Vascular nursing experience, practice knowledge, and beliefs: Results from the michigan PICC1 survey
Authors: Chopra Vineet , Kuhn Latoya , Ratz David , Flanders Scott A. , Krein Sarah L.
Published: December 2015

BACKGROUND

Peripherally inserted central catheters (PICCs) are increasingly used in hospitalized patients. Yet, little is known about the vascular access nurses who often place them.

METHODS

We conducted a Web‐based survey to assess vascular access nursing experience, practice, knowledge, and beliefs related to PICC insertion and care in 47 Michigan hospitals.

RESULTS

The response rate was 81% (172 received invitations, 140 completed the survey). More than half of all respondents (58%) reported placing PICCs for ≥5 years, and 23% had obtained dedicated vascular access certification. The most common reported indications for PICC insertion included intravenous antibiotics, difficult venous access, and chemotherapy. Many respondents (46%) reported placing a PICC in a patient receiving dialysis; however, 91% of these respondents reported receiving approval from nephrology prior to insertion. Almost all respondents (91%) used ultrasound to find a suitable vein for PICC insertion, and 76% used electrocardiography guidance to place PICCs. PICC occlusion was reported as the most frequently encountered complication, followed by device migration and deep vein thrombosis. Although 94% of respondents noted that their hospitals tracked the number of PICCs placed, only 40% reported tracking duration of PICC use. Relatedly, 30% of nurses reported that their hospitals had a written policy to evaluate PICC necessity or appropriateness.

CONCLUSION

This survey of vascular nursing experiences highlights opportunities to improve practices such as avoiding PICC use in dialysis, better tracking of PICC dwell times, and necessity. Hospitalists may use these data to inform clinical practice, appropriateness, and safety of PICCs in hospitalized patients. Journal of Hospital Medicine 2016;11:269–275. 2015 Society of Hospital Medicine