bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of high‐risk human papillomaviruses in fresh breast cancer samples using the hybrid capture 2 assay
Authors: Liang Weili , Wang Jianli , Wang Chongjie , Lv Yanrong , Gao Haidong , Zhang Kai , Liu Huantao , Feng Jinbo , Wang Leiyi , Ma Rong
Published: August 2013

The etiology of breast cancer remains unknown and the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. This study investigated the prevalence of high‐risk HPV infections in Chinese women with breast cancer and the possible relationship between high‐risk HPV infection and the clinicopathological characteristics of breast cancer. Tumor cells from 224 fresh breast cancer samples and 37 fresh breast fibroadenomas were collected for hybrid capture 2 (HC2) assay. HC2 was the only technique approved by the United States Food and Drug Administration for screening for high‐risk HPV infection in 2008. The prevalence of high‐risk HPV infection in breast cancer samples was 21.4%, which was slightly higher than the 16.2% observed in breast fibroadenomas. Age and menopausal status were not risk factors for high‐risk HPV infection among breast cancer patients. The clinical and pathological characteristics of breast cancer showed no significant correlation with high‐risk HPV infection. Although the prevalence of 13 subtypes of high‐risk HPV infections was similar in breast cancer and nonmalignant breast samples, the presence of high‐risk HPVs in both malignant and benign breast samples implies that a possible causal role in breast cancer carcinogenesis could not be ruled out. Clarifying the possible link between high‐risk HPVs and breast cancer might benefit women vaccinated against HPV and could decrease the incidence of HPV‐related breast cancer. J. Med. Virol. 85:2087–2092, 2013. © 2013 Wiley Periodicals, Inc.
Torque teno virus (TTV) in multiple sclerosis patients with different patterns of disease
Authors: Mancuso Roberta , Saresella Marina , Hernis Ambra , Agostini Simone , Piancone Federica , Caputo Domenico , Maggi Fabrizio , Clerici Mario
Published: August 2013

Torque teno virus (TTV) is highly prevalent in the general population worldwide. The relationship that TTV establishes with the central nervous system (CNS) of infected hosts is not clear but it is suspected that TTV infection of the CNS lead to increased local expression of inflammatory mediators that may play a role in the pathogenesis of multiple sclerosis (MS). The prevalence and load of TTV in serum and cerebrospinal fluid (CSF) of 207 MS patients and 93 age‐ and sex‐matched healthy controls by qPCR designed on the untranslated region were analyzed. TTV DNA was not detected in CSF, TTV prevalence in serum was similar in MS patients (76.8%) compared to healthy controls (76.3%). Sub analyses performed in MS patients stratified on the basis of clinical phenotypes indicated that TTV viremia was significantly lower in individuals with relapsing remitting compared to chronic progressive disease. Notably, viremia was increased in primary progressive, compared to secondary progressive MS patients, and in relapsing remitting MS patients during quiescent compared to relapsing phases of disease. Since TTV interacts with toll‐like receptor (TLR) stimulating the production of inflammatory cytokines, TLR9 expression were examined, showing that it was augmented on monocytes of chronic progressive MS patients, in whom higher TTV viremia was present, but this did not correlate with a distinct pattern of cytokine production. Overall these findings suggest that, although TTV infects the same proportion of MS patients and healthy controls, the levels of replication of the virus differ among patients, being correlated with the clinical phenotype of disease. J. Med. Virol. 85:2176–2183, 2013. © 2013 Wiley Periodicals, Inc.
Initial viral load in cases of single human papillomavirus 16 or 52 persistent infection is associated with progression of later cytopathological findings in the uterine cervix
Authors: Hamaguchi Daisuke , Miura Kiyonori , Abe Shuhei , Kinoshita Akira , Miura Shoko , Yamasaki Kentaro , Yoshiura Koh‐ichiro , Masuzaki Hideaki
Published: August 2013

The aim of this study was to investigate the relationship between viral load in single human papillomavirus (HPV) 16 or 52 persistent infection and the progression of later cytopathological findings in the uterine cervix. Cervical cytology and HPV genotyping tests were repeated within 3–6 months in 305 women with oncogenic HPV. Twenty‐four cases of single HPV 52 persistent infection and 24 cases of single HPV 16 persistent infection were identified. Cases with later cytopathological findings showing progression were defined as the progression group, while those with no change or regression were the non‐progression group. Relative HPV DNA loads were determined by quantitative real‐time polymerase chain reaction and expressed relative to human albumin (ALB) DNA. Differences between the two groups were evaluated. The median relative HPV 52 DNA load was 2.211 in the progression group and 0.022 in the non‐progression group (Mann–Whitney U‐test, P = 0.003). The median relative HPV 16 DNA load was 4.206 in the progression group and 0.103 in the non‐progression group (P = 0.001). HPV 52 and 16 DNA loads assessed by quantitative real‐time methods may be useful short‐term markers for identifying women at high risk for progression of cervical cytological pathology. J. Med. Virol. 85:2093–2100, 2013. © 2013 Wiley Periodicals, Inc.
Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome
Authors: Montoya Jose G. , Kogelnik Andreas M. , Bhangoo Munveer , Lunn Mitchell R. , Flamand Louis , Merrihew Lindsey E. , Watt Tessa , Kubo Jessica T. , Paik Jane , Desai Manisha
Published: August 2013

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1‐profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013. © 2013 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.
Quantitative methods for estimating foliar uptake of zinc from suspension‐based Zn chemicals
Authors: T Vu Dang , Huang Longbin , V Nguyen Anh , Du Yumei , Xu Zhiping , A Hampton Marc , Li Peng , Rudolph Victor
Published: August 2013

The present study developed methods for quantifying foliar Zn uptake from suspension‐based Zn chemicals of low solubility, which were ZnO (particle size: 0.15–1.34 μm) and a newly synthesized Zn hydroxide nitrate crystal (Zn‐HNC) (50–100 nm thickness and 0.2–1 μm lateral dimension). Recently matured leaves of citrus (Citrus aurantium L. cv. Valencia), capsicum (Capsicum annume L. cv. Giant Bell), and/or tomato (Solanum lycopersicum L. cv. Roma) were in vitro–treated with microdroplets (5 μL per droplet) of Zn‐HNC‐ and ZnO‐suspension solutions on the adaxial surface and incubated under controlled conditions for up to 72 h. Leaf‐washing protocols were compared, including: dilute ethanol (3%), dilute nitric acid (2%), and their combination. The methods for quantifying Zn uptake were: (1) whole‐leaf loading by which droplets of the Zn suspension solutions were loaded onto central regions of both left and right sides of leaf blades and (2) half‐leaf loading by which soluble‐Zn (ZnSO4) droplets were loaded onto only one side of leaf blades while the other was used as the background Zn control. Foliar‐surface characteristics of the plant species affected the effectiveness of the washing methods. The dilute nitric acid (2%; ± 3% ethanol) was required to remove residue particles of the ZnO and Zn‐HNC suspensions from foliar surfaces of capsicum and tomato (highly trichomatic), but the residue Zn chemicals on citrus leaves (nontrichomatic and highly waxy) were similarly and effectively removed by the three washing methods. For quantifying Zn uptake by the leaves, the half‐leaf loading method showed its advantages over the whole‐leaf loading method, because it did not stringently require similar background Zn concentrations in the control and treated leaves at the start and had little risks of secondary absorption of soluble Zn in the washing solution.
Lessons Learned from Lessons Learned
Authors: Rhodes Lucy , Dawson Ray
Published: August 2013

This paper describes a case study, examining the problems of capturing, disseminating and benefiting from lessons learned from projects within the project management department of a large, information‐intensive organisation. A set of recommendations to improve the organisation's involvement with ‘lessons learned’ is derived, and how these recommendations are relevant to a wider range of organisations is considered. The literature associated with lessons learned was used to direct research into the project management department of the selected organisation through the use of focus groups and questionnaires to determine why their lessons learned process is not as effective as required. The key barriers to lessons learned were found to be culture, motivation and a lack of process. Furthermore, a large percentage of the project management community was found to be unaware of any lessons learned system and found it hard to access and share lessons with other project managers. The paper therefore provides a set of recommendations to overcome these barriers concerning immediate actions and strategies for the future. The recommendations have received very positive feedback from the employees of the organisation. The paper concludes that the provided recommendations are adaptable to a wide range of organisations. Copyright © 2013 John Wiley & Sons, Ltd.
Detecting field cancerization using a hyperspectral imaging system
Authors: Neittaanmäki‐Perttu Noora , Grönroos Mari , Tani Taneli , Pölönen Ilkka , Ranki Annamari , Saksela Olli , Snellman Erna
Published: August 2013

Background

Field cancerization denotes subclinical abnormalities in a tissue chronically exposed to UV radiation. These abnormalities can be found surrounding the clinically visible actinic keratoses.

Objectives

The aim of this study was to test the feasibility of a hyperspectral imaging system in the detection of multiple clinical and subclinical AKs for early treatment of the affected areas.

Materials and Methods

Altogether 52 clinical AKs in 12 patients were included in this study. In six patients digital photos were taken of the naive AKs, and again after methylaminolevulinate(MAL)‐fluorescence diagnosis which was used to teach HIS to find subclinical lesions. After 2–3 days when the MAL had vanished, the hyperspectral images were taken. Biopsies were taken from clinical AKs, healthy‐looking skin and several suspected subclinical AKs. In the other six patients digital and hyperspectral images were taken of the naive AKs followed by one biopsy per patient.

Results

HIS detected all clinically visible 52 AKs and numerous subclinical lesions. The histopathology of the 33 biopsied lesions were concordant with the HIS results showing either AK (n = 28) or photodamage (n = 5). Of the 28 histopathologically confirmed AKs, 16 were subclinical. A specific diffuse reflectance spectrum of an AK and healthy skin was defined.

Conclusion

The hyperspectral imaging system offers a new, non‐invasive method for early detection of field cancerization. Lasers Surg. Med. 45:410–417, 2013. © 2013 Wiley Periodicals, Inc.
Thermosensitive Macroporous Cryogels Functionalized With Bioactive Chitosan/Bemiparin Nanoparticles
Authors: Peniche Hazel , Reyes‐Ortega Felisa , Aguilar María R. , Rodríguez Gema , Abradelo Cristina , García‐Fernández Luis , Peniche Carlos , Román Julio San
Published: August 2013

Thermosensitive macroporous scaffolds of poly(N‐isopropylacrylamide) (polyNIPA) loaded with chitosan/bemiparin nanoparticles are prepared by the free radical polymerization in cryogenic conditions. Chitosan/bemiparin nanoparticles of 102 ± 6.5 nm diameter are prepared by complex coacervation and loaded into polyNIPA cryogels. SEM image reveal the highly porous structure of cryogels and the integration of nanoparticles into the macroporous system. Volume phase transition temperature (VPT) and total freezing water content of cryogels are established by differential scanning calorimetry, and their porosity is determined by image‐NMR. Swelling of cryogels (above and below the VPT) is highly dependent on nanoparticles concentration. In vitro release profile of bemiparin from cryogel is highly modulated by the presence of chitosan. Bemiparin released from nanoparticles preserves its biological activity, as shown by the BaF32 cell proliferation assay. Cryogels are not cytotoxic for the human fibroblast cells and present excellent properties for application on tissue engineering and controlled release of heparin.
Passivation of HAZs of API‐X100 pipeline steel in bicarbonate‐carbonate solutions at 298 K
Authors: Eliyan F. F. , Icre F. , Alfantazi A.
Published: August 2013

This research explores electrochemical correlations between heat‐affected zones (HAZs), produced by Gleeble© thermal simulation cycles, and their passivation behavior in bicarbonate–carbonate solutions. The investigations were carried out in comparison with the base API‐X100 steel in naturally aerated 0.5 g/L chloride solutions, containing a matrix of bicarbonate and carbonate concentrations at 298 K. The slow 0.05 mV/s potentiodynamic scans revealed that the passivation onsets earlier in proportion with the bicarbonate concentrations, possessing accordingly greater immunity against chloride ions on HAZs cooled at 10 and 60 K/s from 1223 K peak temperature. The HAZs cooled at 10 K/s, particularly in concentrated carbonate solutions, showed the most stable passivation, and the HAZs cooled at 60 K/s showed the lowest cathodic activity regardless of the chemical conditions. −0.1 V, versus saturated calomel electrode, potentiostatic currents and the open‐circuit potentials decreased and increased, respectively, with the carbonate concentration, confirming with the main potentiodynamic polarization results, and a corresponding passivation behavior of the HAZs, regardless of a bicarbonate–carbonate condition, was relatively similar. In contrary to the 60 K/s HAZs, the 10 K/s HAZs showed evidence of growing passive films with time and high charge‐transfer resistance, as measured by the EIS tests.
Numerical analysis of high temperature internal corrosion mechanisms by the cellular automata approach
Authors: Jahns K. , Landwehr M. , Wübbelmann J. , Krupp U.
Published: August 2013

Aim of the study is to develop a simulation software which allows to predict the diffusion‐controlled transformation processes during oxidation and nitridation of metals and alloys. Internal oxidation and nitridation often results in a deep penetration of coarse and sometimes needle‐shaped precipitates that act as crack initiation sites, i.e., giving rise to an embrittlement of the surface layer. The method of cellular automata according to Chopard and Droz has been applied to simulate internal nitridation processes. The approach allows implementing, e.g., the diffusion‐blocking effect of the internal precipitates, and the mechanisms of nucleation and growth. As an example, TiN formation in Ni‐base alloys was simulated by treating nitrogen diffusion and precipitation separately and simultaneously. The progress of internal nitridation follows a parabolic rate law in agreement with Wagner's theory of internal oxidation and experimental results. Furthermore, the cellular automata approach is capable to predict the transition from internal precipitation to external scale formation and to implement the process of nucleation and growth of nitride and oxide precipitates.
Development of a ta‐C diamond‐like carbon (DLC) coating by magnetron sputtering for use in precision glass molding
Authors: Bernhardt F. , Georgiadis K. , Dolle L. , Dambon O. , Klocke F.
Published: August 2013

Diamond‐like carbon (DLC) coatings have become the most versatile class of coatings in various applications. However, most methods are not practical for industrial fabrication chains. The work presented here the deposition of ta‐C (tetrahedral amorphous carbon = ta‐C) coatings on molding tools for use in precision glass molding by Magnetron Sputtering Ion Plating (MSIP). The coating properties are analyzed by Scanning Electron Microscopy (SEM), Raman spectroscopy and molding tests. By using ion plating, carbon bonds can be induced to change towards the sp3 form by increasing the internal coating stress. Using this technique, it was possible to increase the sp3 ratio to about 60%, whereas 40% or less is often reported for conventional sputtering.
Development and qualification of a MSIP PVD iridium coating for precision glass moulding
Authors: Bobzin K. , Bagcivan N. , Brögelmann T. , Münstermann T.
Published: August 2013

The replicative production technology precision glass moulding becomes more important due to the increasing demand on complex optical lenses. A noble metal coating system deposited by MSIP‐PVD is used to protect the functional surface of the moulding die to increase tool lifetime and surface quality. The objective of this report is to characterise and qualify a pure iridium coating for the suitability as protection coating against glass sticking and wear in contact with different glasses. The coating was developed concerning mechanical properties and tested in a heating experiment in contact with six glasses. It was possible to deposit a metallic iridium coating with a hardness of (26.5 ± 3.6) GPa by verifying deposition temperature and gas contribution. It could be proved, that no visible interaction between coating and different low‐Tg glasses happened. Because of the high mechanical hardness and low reactivity with different low‐Tg glasses an iridium coating is a promising protection coating for precision glass moulding application.
Nano‐impact test on PVD‐coatings with graded mechanical properties for assessing their brittleness
Authors: Bouzakis K.‐D. , Skordaris G. , Gerardis S. , Bouzakis E.
Published: August 2013

In the described investigations, nano‐impact tests were conducted on PVD films with graded mechanical properties. The properties gradation was induced by micro‐blasting at different pressures for constant duration. Micro‐blasting improves the film mechanical properties due to the induced residual compressive stresses into the coating structure. The film mechanical properties as well as the ratio of the film yield to rupture stress (SY/SM) grow up to a certain micro‐blasting pressure. The augmentation of SY/SM ratio increases simultaneously the film brittleness. For analyzing the effect of the SY/SM ratio on the film brittleness, a multi‐layer 3D‐FEM model simulating the nano‐impact test was developed employing the LS‐DYNA software package. The FEM calculated results converge sufficiently with the attained experimental ones. Based on these results, the film's failure initiation and evolution can be predicted depending on the SY/SM ratio of the individual film layers.
Coated tools wear prediction in milling explained by the strain rate affected film fatigue failure
Authors: Bouzakis K.‐D. , Paraskevopoulou R. , Makrimallakis S. , Katirtzoglou G. , Bouzakis E. , Efstathiou K.
Published: August 2013

The knowledge of coated tool wear mechanisms in milling is central for explaining the film failure and selecting the appropriate cutting strategy and conditions. The described tool wear investigations in up and down milling were carried out at various cutting conditions, by coated cemented carbide inserts fixed on tool holders of different diameters. The variable stress, strain and strain rate fields developed in the tool during cutting affect the film‐substrate deformation and in this way the resulting coating's loads and its fatigue failure. The effective tool life, up to a certain flank wear width was experimentally determined and correlated to the cutting edge entry impact duration (CEEID) into the workpiece material. Using a commercial CAD/CAM system, the geometry of the chip and of the contact between the cutting edge and workpiece was calculated in various milling cases and the corresponding tool wear evolution predicted. The latter converges with cutting edge entry impact duration and with the associated film fatigue critical force, affected by the coating strain rate.
Transmission electron microscope (TEM) study of annealed gamma alumina coatings for cutting tools and of gamma alumina‐coated cutting tools after the use in cutting tests
Authors: Müller M. G. J. , Mayer J.
Published: August 2013

Among the transition phases of alumina, the gamma alumina‐phase has a high potential for the use as hard coating in many technological applications, because it exhibits excellent properties e. g. high hot hardness and high thermal stability. In the present work, transmission electron microscopic (TEM) studies are used to investigate the phase stability of nanocrystalline gamma alumina‐coatings. These coatings were deposited by means of magnetron sputter ion plating (MSIP) on cutting inserts with a titanium‐aluminum‐nitride‐interlayer or directly onto silicon‐wafers. Before transmission electron microscope‐investigation, the samples were annealed or used in cutting tests.
Microstructured surfaces in highly loaded elastohydrodynamic (EHD)‐contacts – manufacturing and tribological performance
Authors: Schrader T. , Weschta M. , Engel U. , Tremmel S. , Merklein M. , Wartzack S.
Published: August 2013

In low loaded sliding contacts, as journal bearings or piston contacts, defined microstructures on surfaces were identified for friction reduction purposes and are well established in industrial applications. It is stated that microstructures act as lubricant reservoirs and support lubricant film development. Within the scope of these investigations microstructures are specifically adapted for the tribological load collective of cam follower systems as a representative of highly loaded contacts. For those contacts, the effects of microstructures are still subject of investigations. In this paper a method for efficient microstructuring by micro laser ablation is described. The investigations focus on the determination of the geometric and mechanical properties of the microstructures as well as on the tribological behavior of the microstructured surfaces by two tribological tests.
Tribological comparison of different surface topographies coated with chromium aluminum nitride
Authors: Tillmann W. , Herper J. , Laemmerhirt I.‐A.
Published: August 2013

The reduction of friction and wear is one important goal for the extension of the tool life in many industrial applications. The forming and cutting industries in particular, are very interested in new techniques and surface coating characteristics that will improve the tribological behavior of the tools. Biomimetics is a very promising approach using biological surfaces or phenomena to optimize the properties of engineering components. The “Lotus Effect” is the most famous example, whereby surfaces are made water‐ and dirt‐repellent. Taking a closer look at nature, it can be noticed that many different natural surfaces have perfectly adapted to their environment in order to meet the respective requirements. Extending the use of natural and biological effects to improve the material performance, it was discovered that the skin of many insects has an excellent frictional behavior and thus the potential to be transferred onto technical surfaces. In this paper, the surface structure of a dung beetle (db) was investigated. The main objective was to combine nature‐adapted surface patterns with wear‐resistant near‐netshape PVD‐coatings (PVD=physical vapour deposition), in order to improve the tribological properties of a tool surface. The shell of the beetle served as a pattern for the structure of the surfaces. A substrate, composed of high speed steel material, was structured by means of milling prior to the deposition of a chromium aluminum nitride multilayer coating system, using a magnetron sputtering process. The mechanical and tribological properties of the structured and coated surfaces were compared by means of nanoindentation, ball‐on‐disc‐testing, and scanning electron microscopy.
Energy substrate influences the effect of the timing of the first embryonic cleavage on the development of in vitro‐produced porcine embryos in a sex‐related manner
Authors: Torner Eva , Bussalleu Eva , Briz Maria D. , Yeste Marc , Bonet Sergi
Published: August 2013

In vitro culture conditions and certain events during the earliest stages of development are linked to embryonic survival, possibly in a sex‐related manner. In vitro‐produced (IVP) porcine embryos cultured with glucose (IVC‐Glu) or pyruvate–lactate (IVC‐PL) were tested for any relationship between the timing of the first embryonic cleavage and development and sex ratio. The embryos were assigned to IVC‐Glu or IVC‐PL groups and classified depending on the timing of their first cleavage: 24, 26, 30, and 48 hr post‐insemination (hpi). They were cultured separately in vitro and evaluated for cleavage rate and pattern, blastocyst rate and stage, cell number, apoptosis, and sex ratio. Regardless of energy source, the percentage of two‐cell stage and fragmented embryos at the time of their first cleavage was, respectively, higher and lower in early‐cleaving embryos. Those embryos cleaved by 24 hpi developed to blastocysts at a higher rate (IVC‐Glu: 37.90 ± 3.06%; IVC‐PL: 38.73 ± 4.08%) than those cleaved between 30 and 48 hpi (IVC‐Glu: 5.87 ± 3.02%; IVC‐PL: 8.41 ± 3.50%). Furthermore, a shift toward males was seen among embryos first cleaved before 30 hpi, versus towards females among those cleaved later. The early‐cleaving embryos, only from the IVC‐PL group, had a higher proportion of expanded blastocysts (81.05 ± 6.54% vs. 13.33 ± 13.33%) with higher cell numbers than their late‐cleaving counterparts. Moreover, a shift toward males only appeared at the blastocyst stage in IVC‐PL embryos. These findings confirm that the timing of the first cleavage influences development of IVP porcine embryos in a sex‐related manner, and it depends on the main energy source of the in vitro culture medium. Mol. Reprod. Dev. 80: 924–935, 2013. © 2013 Wiley Periodicals, Inc.
Initial testing (stage 1) of the polo‐like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program
Authors: Gorlick Richard , Kolb E. Anders , Keir Stephen T. , Maris John M. , Reynolds C. Patrick , Kang Min H. , Carol Hernan , Lock Richard , Billups Catherine A. , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A.
Published: August 2013

Background

Volasertib (BI 6727) is a potent inhibitor of Polo‐like kinase 1 (Plk1), that is overexpressed in several childhood cancers and cell lines. Because of its novel mechanism of action, volasertib was evaluated through the PPTP.

Procedures

Volasertib was tested against the PPTP in vitro cell line panel at concentrations from 0.1 nM to 1.0 μM and against the PPTP in vivo xenograft panels administered IV at a dose of 30 mg/kg (solid tumors) or 15 mg/kg (ALL models) using a q7dx3 schedule.

Results

In vitro volasertib demonstrated cytotoxic activity, with a median relative IC50 value of 14.1 nM, (range 6.0–135 nM). Volasertib induced significant differences in EFS in 19 of 32 (59%) of the evaluable solid tumor xenografts and in 2 of 4 (50%) of the evaluable ALL xenografts. Volasertib induced tumor growth inhibition meeting criteria for intermediate EFS T/C (>2) activity in 11 of 30 (37%) evaluable solid tumor xenografts, including neuroblastoma (4 of 6) and glioblastoma (2 of 3) panels, and 2 of 4 ALL models. Objective responses (CR's) were observed for 4 of 32 solid tumor (two neuroblastoma, one glioblastoma, and one rhabdomyosarcoma) and one of four ALL xenografts.

Conclusions

Volasertib shows potent in vitro activity against the PPTP cell lines with no histotype selectivity. In vivo, volasertib induced regressions in several xenograft models. However, pharmacokinetic data suggest that mice tolerate higher systemic exposure to volasertib than humans, suggesting that the current results may over‐estimate potential clinical efficacy against the childhood cancers studied. Pediatr Blood Cancer 2014;61:158–164. © 2013 Wiley Periodicals, Inc.
Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world
Authors: Kajbaf Farshad , Arnouts Paul , de Broe Marc , Lalau Jean‐Daniel
Published: August 2013

Objective

We compared and contrasted guidelines on metformin treatment in patients with chronic kidney disease (CKD) around the world, with the aim of helping physicians to refine their analysis of the available evidence before deciding whether to continue or withdraw this drug.

Methods

We performed a systematic research for metformin contraindications in: (i) official documents from the world's 20 most populated countries and the 20 most scientifically productive countries in the field of diabetology and (ii) publications referenced in electronic databases from 1990 onwards.

Results

We identified three international guidelines, 31 national guidelines, and 20 proposals in the scientific literature. The criteria for metformin withdrawal were (i) mainly qualitative in the most populated countries; (ii) mainly quantitative in the most scientifically productive countries (with, in all cases, a suggested threshold for withdrawing metformin); and (iii) quantitative in all, but one of the literature proposals, with a threshold for withdrawal in most cases (n = 17) and/or adjustment of the metformin dose as a function of renal status (n = 8). There was a good degree of consensus on serum creatinine thresholds; whereas guidelines based on estimated glomerular filtration rate thresholds varied from 60 mL/minute/1.73 m2 up to stage 5 CKD. Only one of the proposals has been tested in a prospective study.

Conclusions

In general, proposals for continuing or stopping metformin therapy in CKD involve a threshold (whether based on serum creatinine or estimated glomerular filtration rate) rather than the dose adjustment as a function of renal status (in stable patients) performed for other drugs excreted by the kidney. Copyright © 2013 John Wiley & Sons, Ltd.
Limits to expanding the PN‐F series of polyphosphazene elastomers
Authors: Tian Zhicheng , Liu Xiao , Manseri Abdellatif , Ameduri Bruno , Allcock Harry R.
Published: August 2013

Mixed‐substituent fluoroalkoxyphosphazene polymers bearing ∼15% 1H,1H,2H,2H‐perfluorooctan‐1‐oxy or 1H,1H,2H,2H‐perfluorodecan‐1‐oxy side groups together with trifluoroethoxy cosubstituent groups were synthesized. The low reactivity of the long‐chain fluoroalkoxides and their limited solubility in organic solvents prevented higher levels of substitution. Moreover, the sodium alkoxides with two methylene residues adjacent to the oxygen proved to be unstable in solution due to elimination of NaF and precipitation of side products, and this limited the time available for chlorine replacement reactions. The resulting cosubstituent polymers were characterized by proton nuclear magnetic resonance (1H‐NMR), 31P‐NMR, 19F‐NMR, gel‐permeation chromatography, and differential scanning calorimetry. Unlike homo‐ or mixed‐substituent fluoroalkoxyphosphazene polymers, such as [NP(OCH2CF3)2]n (a microcrystalline thermoplastic, Tg ∼ −63°C, Tm ∼ 242°C) or [NP(OCH2CF3)(OCH2(CF2)xCF2H)]n (PN‐F, a rubbery elastomer, Tg ∼ −60°C, but no detectable Tm), the new polymers are gums (Tg ∼ −50°C, but no detectable Tm) with molecular weights in the 105 g/mol rather than the 106 g/mol range. POLYM. ENG. SCI., 54:1827–1832, 2014. © 2013 Society of Plastics Engineers
Poly(methacrylic acid)‐grafted clay–thermoplastic elastomer composites with water‐induced shape‐memory effects
Authors: Wu Tongfei , O'Kelly Kevin , Chen Biqiong
Published: August 2013

Composites with excellent water‐induced shape‐memory effects (SMEs) were successfully synthesized by first using clay as the SME‐activating phase and thermoplastic polyurethane (TPU) as the matrix. Naturally abundant clay was grafted with poly(methacrylic acid) (PMAA) to improve particle interactions, which allowed for the formation of strong percolation networks in the composites, determined by swelling tests and dynamic mechanical analysis in combination with theoretical modeling. This led to significant improvements of the polymer modulus and high water absorptions, causing reversible modulus changes of up to 30 times from the wet to the dry condition. The results from cyclic wetting‐drying‐stretching tests showed the TPU–clay composite containing 10.4 vol % PMAA‐grafted clay exhibited the best SMEs among the composites investigated, with the shape fixity and shape recovery ratios being 82% and 91%, respectively. Besides SMEs, these new polymer–clay composites were also pH‐sensitive and mechanically adaptive upon exposure to water. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1513–1522
Switching polarity of oxidized detonation diamond nanoparticles on substrates
Authors: Stehlik Stepan , Petit Tristan , Girard Hugues A. , Arnault Jean‐Charles , Kromka Alexander , Rezek Bohuslav
Published: August 2013

Evaluation of diamond nanoparticles (DNPs) electrical potential under ambient environment is important for their application in electronics as well as sensors and biology. Here we use a novel methodology for characterization of nanoparticles based on recording of their electrical potential as a function of their size by two‐pass Kelvin force microscopy (KFM). We study thermally oxidized detonation DNPs of 5 nm nominal size. The nanoparticles were deposited from diluted water solutions on a Si substrate half coated with Au. The KFM using conductive Si tip resolved characteristic negative potential differences of 10–60 mV on nanoparticles versus the substrate. When negative bias voltage to the KFM tip (−4 V) is applied during the topography acquisition (the first pass), subsequent potential measurement (the second pass) shows inversion of nanoparticles potential contrast. The same effects were observed also in the case of 20 nm colloidal Au nanoparticles. This effect is reversible and it is attributed to a charge retention in (or on) the nanoparticles.
Coordinated control of bone cutting for a CT‐free navigation robotic system in total knee arthroplasty
Authors: Yen Ping‐Lang , Chu Yi‐Jing , Hsu Shang‐Wei , Wang Jing‐Heng , Hung Shuo‐Suei
Published: August 2013

Background

Robots are gradually becoming intelligent tools for surgeons in computer assisted orthopedic surgery. A hands‐on robot combining CT‐free navigation software and coordinated control has been designed for total knee arthroplasty.

Methods

The hands‐on robot is under bilateral force control so that the robot not only follows the force commands from the operator but also shapes the reflected force back to the operator. The proposed coordinated control also defines three operating modes to fulfill intelligent bone cutting by tuning appropriate scaling to the admittance gains.

Results

Experimental results demonstrated assistive, resistant and emergent actions to meet various bone cutting conditions by the coordinated controller.

Conclusions

The proposed coordinated controller enables the robot to perform bone cutting more safely, rapidly and accurately compared with being performed by manual bone saw. The intelligent bone cutting has been successfully verified by a cadaver test. Copyright © 2013 John Wiley & Sons, Ltd.
Gravity‐independent Rock‐climbing Robot and a Sample Acquisition Tool with Microspine Grippers
Authors: Parness Aaron , Frost Mathew , Thatte Nitish , King Jonathan P. , Witkoe Kevin , Nevarez Moises , Garrett Michael , Aghazarian Hrand , Kennedy Brett
Published: August 2013

A rock‐climbing robot is presented that can free climb on vertical, overhanging, and inverted rock faces. This type of system has applications to extreme terrain on Mars or for sustained mobility on microgravity bodies. The robot grips the rock using hierarchical arrays of microspines. Microspines are compliant mechanisms made of sharp hooks and flexible elements that allow the hooks to move independently and opportunistically grasp roughness on the surface of a rock. This paper presents many improvements to early microspine grippers, and the application of these new grippers to a four‐limbed robotic system, LEMUR IIB. Each gripper has over 250 microspines distributed in 16 carriages. Carriages also move independently with compliance to conform to larger, cm‐scale roughness. Single gripper pull testing on a variety of rock types is presented, and on rough rocks, a single gripper can support the entire mass of the robot (10 kg) in any orientation. Several sensor combinations for the grippers were evaluated using a smaller test‐gripper. Rock‐climbing mobility experiments are also described for three characteristic gravitational orientations. Finally, a sample acquisition tool that uses one of the robot's grippers to enable rotary percussive drilling is shown.
MDMR‐IBE: efficient multiple domain multi‐receiver identity‐based encryption
Authors: Wang Hongbing , Zeng Peng , Choo Kim‐Kwang Raymond
Published: August 2013

In The International Conference on Practice and Theory in Public‐Key Cryptography (PKC)'05, Baek et al. proposed the first multi‐receiver identity‐based encryption scheme. Their scheme is highly efficient in that it only needs one pairing computation to encrypt a single message for n receivers. However, the application scenario considered by Baek et al. is merely the ideal “single domain environment,” where all the n receivers are from the same administrative domain. When used in the real‐world application scenario where the n receivers are from l different administrative domains (i.e., a multiple domain environment), their scheme becomes inefficient as it requires l pairing computations for one message. In this paper, we present an efficient multiple domain multi‐receiver identity‐based encryption scheme that only requires “one” pairing computation to encrypt a single message for n receivers from l different administrative domains. We prove the security of the new scheme under the modified decisional bilinear Diffie–Hellman assumption in the random oracle model. In addition, the new scheme can be extended to be adaptive chosen ciphertext secure under the gap modified bilinear Diffie–Hellman assumption. Copyright © 2013 John Wiley & Sons, Ltd.
The Effects of the Global Financial Crisis on Supply Chain Members in Non‐BRIC Emerging Markets
Authors: Schotter Andreas , Thi My Hao Diep
Published: August 2013

The global economic crises that began in 2008 had profound effects on the supply chains of many multinational firms across all industries including altering some fundamental supply chain characteristics. This study discusses the effects of the crises on lower‐level supply chain members in the context of the textile and garment industry in emerging markets. The fieldwork for this research and the integration of new United Nations data provide evidence for the vulnerability of those supply chain members that provide only commoditized basic services that do not depend on talent skills or resource availability. Most of these, less sophisticated supply chain members are located in non‐BRIC emerging economies, including Vietnam, Bangladesh, Pakistan, Haiti, Honduras, and so on. We present a framework that is transferable across industries. The framework is useful for managers when evaluating the feasibility and reliability of different suppliers from emerging and developing countries in particular. © 2013 Wiley Periodicals, Inc.
Boosting Language Skills of English Learners Through Dramatization and Movement
Authors: Greenfader Christa Mulker , Brouillette Liane
Published: August 2013

This article presents an arts integration program that uses drama and dance to promote foundational literacy skills, with an emphasis on the oral development of English Language Learners (ELLs). Previous research indicates that arts activities afford a beneficial opportunity for young students to practice language skills, but many teachers have received scant training in the arts. The Teaching Artist Project (TAP) is a professional development program that helps classroom teachers use dramatization and creative movement to enhance comprehension and promote verbal interaction in the classroom. Children learn to imaginatively connect the decontextualized vocabulary of the classroom with their own experiences. A mixed methods study ofTAPfound that K‐1ELLs who participated inTAPshowed improvements in early literacy skills compared with their peers. This article introduces approaches used inTAP, suggests sources of the language gains, and discusses strategies for successful implementation.
Climate change, ecosystem services, and costs of action and inaction: scoping the interface
Authors: Rodríguez‐Labajos Beatriz
Published: August 2013

Cost calculations related to climate change have accrued much intellectual effort. However, few works approach the assessment from the point of view of the effects of climate variability and change in ecosystem service provision. Failure to act plausibly leads to ecological, social, and economic damages as a result of ecosystem change. The necessary actions to cope with unavoidable damages from such change generate adaptation costs, while mitigation costs are associated with actions to tackle undesired future changes in the ecosystems. Examples of these effects and related costs, based on representative studies, are reviewed following the organizing scheme of the ecosystem services approach. The examination of case examples reveals the potential and limits of monetary versus non‐monetary estimations of impacts in human wellbeing from climate change‐related changes in the ecosystems, trade‐offs between types of ecosystem service provision and implications of timing in action. This article further discusses the necessary steps to advance in an inclusive scrutiny of the costs associated with the effects of climate change on ecosystem service provision. WIREs Clim Change 2013, 4:555–573. doi: 10.1002/wcc.247

This article is categorized under:

Climate, Ecology, and Conservation > Conservation Strategies

Climate Economics > Aggregation Techniques for Impacts and Mitigation Costs
Novel Prediction Score Including Pre‐ and Intraoperative Parameters Best Predicts Acute Kidney Injury after Liver Surgery
Authors: Slankamenac Ksenija , Beck‐Schimmer Beatrice , Breitenstein Stefan , Puhan Milo A. , Clavien Pierre‐Alain
Published: August 2013

Background

A recently published score predicts the occurrence of acute kidney injury (AKI) after liver resection based on preoperative parameters (chronic renal failure, cardiovascular disease, diabetes, and alanine‐aminotransferase levels). By inclusion of additional intraoperative parameters we aimed to develop a new prediction model.

Methods

A series of 549 consecutive patients were enrolled. The preoperative score and intraoperative parameters (blood transfusion, hepaticojejunostomy, oliguria, cirrhosis, diuretics, colloids, and catecholamine) were included in a multivariate logistic regression model. We added the strongest predictors that improved prediction of AKI compared to the existing score. An internal validation by fivefold cross validation was performed, followed by a decision curve analysis to evaluate unnecessary special care unit admissions.

Results

Blood transfusions, hepaticojejunostomy, and oliguria were the strongest intraoperative predictors of AKI after liver resection. The new score ranges from 0 to 64 points predicting postoperative AKI with a probability of 3.5–95 %. Calibration was good in both models (15 % predicted risk vs. 15 % observed risk). The fivefold cross‐validation indicated good accuracy of the new model (AUC 0.79 (95 % CI 0.73–0.84)). Discrimination was substantially higher in the new model (AUCnew 0.81 (95 % CI 0.76–0.86) versus AUCpreoperative 0.60 (95 % CI 0.52–0.69), p < 0.001). The new score could reduce up to 84 unnecessary special care unit admissions per 100 patients depending on the decision threshold.

Conclusions

By combining three intraoperative parameters with the existing preoperative risk score, a new prediction model was developed that more accurately predicts postoperative AKI. It may reduce unnecessary admissions to the special care unit and support management of patients at higher risk.
Hepatectomy in Elderly Patients: Does Age Matter?
Authors: Zhou Yanming , Zhang Xiaofeng , Zhang Zuobing , Liu Xiaobin , Wu Lupeng , Li Yumin , Li Bin
Published: August 2013

Background

With the increase in average life expectancy in recent decades, the proportion of elderly patients requiring liver surgery is rising. The aim of the meta‐analysis reported here was to evaluate the safety and efficacy of hepatectomy in elderly patients.

Methods

An extensive electronic search was performed for relevant articles that compare the outcomes of hepatectomy in patients ≥70 years of age with those in younger patients prior to October 2012. Analysis of pooled data was performed with RevMan 5.0.

Results

Twenty‐eight observational studies involving 15,480 patients were included in the analysis. Compared with the younger patients, elderly patients experienced more complications (31.8 vs 28.7 %; P = 0.002), mainly as a result of increased cardiac complications (7.5 vs 1.9 %; P < 0.001) and delirium (11.7 vs 4.5 %; P < 0.001). Postoperative major surgical complications (12.6 vs 11.3 %; P = 0.55) and mortality (3.6 vs 3.3 %; P = 0.68) were comparable between elderly and younger patients. For patients with malignancies, both the 5‐year disease‐free survival (26.5 vs 26.3 %; P = 0.60) and overall survival (39.5 vs 40.7 %; P = 0.29) did not differ significantly between the two groups.

Conclusions

Postoperative major surgical complications, mortality, and long‐term results in elderly patients seem to be comparable with those in younger patients, suggesting that age alone should not be considered a contraindication for hepatectomy.