bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, pharmacokinetics, and activity of EZN‐2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies
Authors: Kurzrock Razelle , Goel Sanjay , Wheler Jennifer , Hong David , Fu Siqing , Rezai Keyvan , Morgan‐Linnell Sonia K. , Urien Saik , Mani Sridhar , Chaudhary Imran , Ghalib Mohammed H. , Buchbinder Aby , Lokiec François , Mulcahy Mary
Published: June 2012

BACKGROUND:

EZN‐2208 is a water‐soluble, polyethylene glycol drug conjugate of SN38, which is the active moiety of irinotecan. In this study, the authors evaluated the tolerability, pharmacokinetics (PK), and activity of EZN‐2208 in adult patients with advanced solid tumors.

METHODS:

Patients in sequential cohorts (3 + 3 design) received intravenous EZN‐2208 at doses between 1.25 mg/m2 and 25 mg/m2 once every 21 days.

RESULTS:

Thirty‐nine patients received EZN‐2208. The median number of prior therapies was 2 (range, 0‐10 prior therapies). Seventeen patients received prior irinotecan. Two maximum tolerated doses (MTDs) were defined: EZN‐2208 with (16.5 mg/m2) and without (10 mg/m2) granulocyte‐colony–stimulating factor (G‐CSF). The dose‐limiting toxicity (DLT) was febrile neutropenia. Two of 19 patients who were heterozygous for a polymorphism in the uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene (UGT1A1*28) developed DLTs (dose, 25 mg/m2 with G‐CSF), and 2 patients who were homozygous for UGT1A1*28 were treated without DLTs (dose, 5 mg/m2). PK analysis indicated a mean terminal half‐life of 19.4 ± 3.4 hours. Sixteen patients (41%) achieved stable disease, including 6 of 39 patients (15%) who had stable disease that lasted ≥4 months. One patient with cholangiocarcinoma (no prior irinotecan) achieved a short‐lived 32% tumor regression. Among 6 patients who had stable disease that lasted for ≥4 months, 3 had received prior irinotecan, and 1 had KRAS‐positive colorectal cancer.

CONCLUSIONS:

EZN‐2208 was well tolerated and produced stable disease that lasted for ≥4 months/unconfirmed partial responses in 7 of 39 heavily pretreated patients (18%) with advanced solid tumors, including those who had failed prior irinotecan therapy. Cancer 2012. © 2012 American Cancer Society.
Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma
Authors: Lin Moubin , Eng Cathy , Hawk Ernest T. , Huang Maosheng , Lin Jie , Gu Jian , Ellis Lee M. , Wu Xifeng
Published: June 2012

BACKGROUND:

Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC).

METHODS:

Forty‐eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine‐based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease.

RESULTS:

Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.04‐5.52), in the replication set (HR, 3.70; 95% CI, 1.42‐9.64), and in a meta‐analysis (HR, 2.89; 95% CI, 1.54‐5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene‐gene interactions on recurrence risk.

CONCLUSIONS:

To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5‐fluorouracil–based chemotherapy. Cancer 2012. © 2012 American Cancer Society.
The quantitative Gleason score improves prostate cancer risk assessment
Authors: Reese Adam C. , Cowan Janet E. , Brajtbord Jonathan S. , Harris Catherine R. , Carroll Peter R. , Cooperberg Matthew R.
Published: June 2012

BACKGROUND:

In the current study, the authors propose the quantitative Gleason score (qGS), a modification of the current Gleason grading system for prostate cancer, based on the weighted average of Gleason patterns present in the pathology specimen. They hypothesize that the qGS can improve prostate cancer risk stratification and help prevent the overtreatment of patients with clinically indolent tumors.

METHODS:

The qGS was applied to patients in the University of California San Francisco urologic oncology database with tumors determined to have a GS of 7 on prostate biopsy or final pathology after radical prostatectomy (RP). Using multivariable logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC), and decision curve analyses, the ability of qGS to predict pathological GS and the risk of disease recurrence after RP was assessed.

RESULTS:

A total of 225 men were included in the analysis of biopsy specimens and 618 men were included in the assessment of RP specimens. Compared with traditional Gleason scoring, the qGS improved concordance between biopsy and pathological GS on decision curve and ROC analyses (area under the curve ROC curve, 0.79 vs 0.71). On regression analysis, the qGS of biopsy specimens was found to be significantly associated with pathological grade after RP (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.49‐2.12) and the qGS of RP specimens was significantly associated with the risk of biochemical disease recurrence after RP (HR, 1.13; 95% CI, 1.04‐1.24).

CONCLUSIONS:

The qGS, a simple modification of the current Gleason system, appears to improve the correlation between biopsy and pathological GS, as well as the prediction of biochemical disease recurrence after RP. This scoring system may allow more men to pursue active surveillance, thereby avoiding the morbidity of prostate cancer treatment modalities. Cancer 2012. © 2012 American Cancer Society.
Value of cytologic Papanicolaou smears and polymerase chain reaction screening for human papillomavirus DNA in detecting anal intraepithelial neoplasia
Authors: Etienney Isabelle , Vuong Sarra , Si‐Mohamed Ali , Fléjou Jean‐François , Atienza Patrick , Bauer Pierre ,   and the Cytological Diaconesses Group
Published: June 2012

BACKGROUND:

The performance of cytologic screening and its correlation with histology and polymerase chain reaction (PCR) detection of human papillomavirus (HPV) DNA have not been evaluated in populations with a low prevalence of anal intraepithelial neoplasia (AIN). The objective of the current study was to analyze the significance of abnormal smears relative to the histology and PCR detection of HPV DNA.

METHODS:

A cytologic smear and a viral sample were taken in 300 consecutive patients undergoing surgery (Milligan‐Morgan hemorrhoidectomy and/or fissurectomy) who gave their informed consent.

RESULTS:

The cytologic smear was normal in 216 of 290 patients (74.5%). Four high‐grade and 19 low‐grade intraepithelial neoplastic lesions were identified. In 5 patients, high‐grade lesions could not be excluded, 30 lesions were of undetermined significance, and there were 16 cellular modifications with a non‐neoplastic appearance. The PCR test for HPV was positive in 18.7% of patients, and a high‐risk genotype was identified in 63.6% of positive samples. Histologic examination of the surgical samples was normal in 92.3% of patients. The 23 AIN samples were distributed as follows: 13 grade 1 AIN (AIN1), 6 AIN2, and 4 AIN3. The sensitivity of cytologic smears and PCR for detecting AIN was 56% and 60.8%, respectively, and specificity was 77% and 84.5%, respectively. Combining the 2 tests increased sensitivity to 78% but decreased specificity to 68%.

CONCLUSIONS:

Compared with a large surgical sample, anal cytologic Papanicolaou smears and HPV PCR exhibited sensitivity and specificity that varied, depending on the risk of HPV infection and AIN. Positive HPV DNA screening increased with AIN grade, and high‐risk HPV testing was particularly helpful. Cancer 2012. © 2012 American Cancer Society.
Primary cancers before and after prostate cancer diagnosis
Authors: Van Hemelrijck Mieke , Drevin Linda , Holmberg Lars , Garmo Hans , Adolfsson Jan , Stattin Pär
Published: June 2012

BACKGROUND:

The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa.

METHODS:

The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa.

RESULTS:

In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7‰ (95% CI, 5.6‰‐8.5‰), 1.3‰ (0‰‐2.6‰), and 1.6‰ (0.6‰‐2.6‰) for these 3 cancers, respectively. From a uro‐oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort.

CONCLUSIONS:

Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms. Cancer 2012. © 2012 American Cancer Society.
Corrosion behavior of solid solution (Ti, Al) N as a function of Al concentration
Authors: Larijani M. M. , Manouchehrian M. , Seyedi H. , Yari M.
Published: June 2012

In this work, a series of (Ti, Al) N coatings with different Al contents were deposited on 304 stainless steel substrates by Hollow Cathode Discharge (HCD) method. The coatings were grown on 304 stainless steel substrates at 400 °C. The coatings were characterized using energy dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), atomic force microscopy (AFM), and microhardness test. The XRD confirmed the transition from TiN phase to (Ti, Al) N phase and then to AlN phase with increasing Al concentration in the solid solution. It was found that with increasing Al concentration the hardness of the coatings initially increased up to a maximum value of about 30 GPa at around 32 at.% of Al and then the coating hardness decreased rapidly with further increase of Al content (Al > 32 at.%). The potentiodynamic polarization analysis was carried out in 3.5 wt.% NaCl solutions to study the corrosion resistance of the coatings. From the corrosion test it can be inferred that the amount of Al atoms in the coatings plays an important role for reducing the corrosion.
Malaria Intervention Policies and Pharmaceutical Nanotechnology as a Potential Tool for Malaria Management
Authors: Kuntworbe Noble , Martini Nataly , Shaw John , Al‐Kassas Raida
Published: June 2012

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

In order to better understand the persistence of malaria, it is timely to reflect on the various approaches toward its eradication and to consider what is being done well and to identify what needs to be improved. This review explores currently available tools and policies designed to eradicate malaria and the potential difficulties associated with each. We have also considered pharmaceutical nanotechnology as a possible tool in the fight against malaria. Each policy, ranging from the adaption of combination drug therapy to the deployment of insecticide‐treated nets was considered to be laudable. The implementation and coverage of policies, however, exposed many gaps with persistence of the disease. Some of the challenges identified include misdiagnosis, production and distribution of fake and substandard antimalarial drugs, misapplication of insecticides, poor infrastructure, lack of sociopolitical will, and conflicts leading to displacement of people. Failure of malaria eradication has been attributed to the development of multiple drug resistance and the side effects associated with the use of conventional antimalarial chemotherapy. The review identified nanotechnology as a formulation strategy that has the potential to improve the safety and efficacy of drug therapy and help the cause of malaria eradication. In conclusion, this review is expected to provide a better understanding of the policies on malaria eradication and challenges associated with each of them. It also suggests that nanotechnology has the potential to reduce side effects of antimalarial drugs and improve their efficacy and should be given serious attention.
Triptolide‐Induced Apoptosis of Androgen‐Independent Prostatic Cancer (AIPC) via Modulation of Histone Methylation
Authors: Zhao Kailiang , Wang Weixing , Yu Xiaohui , Zhou Xing , Shi Qiao , Hu Yunfei
Published: June 2012

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

Triptolide is the principal active ingredient in extracts from the Chinese herb, Tripterygium wilfordii Hook.F (TwHF) and has various biological functions including immunosuppression, anti‐inflammatory, antiviral, and antitumor properties. Triptolide has antitumor activity in a variety of tumors, and numerous studies have attempted to elucidate the potential antitumor mechanism. Triptolide can modulate histone methylation, suggesting that epigenetic mechanisms may play an important role in its antitumor activity. The present study assessed the association between the antitumor effects of triptolide in androgen‐independent prostatic cancer and the regulation of histone methylation. Triptolide inhibited the proliferation of the androgen‐independent prostatic cancer cell line, Du145 and induced apoptosis in a time‐ and dose‐dependent manner. Triptolide decreased histone H3K27me3 methylation via downregulation of histone methyltransferase enhancer of zeste 2, which may represent the antitumor mechanism of triptolide.
Germ cell survival in C. elegans and C. remanei is affected when the dead box rna helicases Vbh‐1 or Cre‐VBH‐1 are silenced
Authors: Salinas Laura S. , Franco‐Cea Ari , Láscarez‐Lagunas Laura I. , Villanueva‐Chimal Emmanuel , Maldonado Ernesto , Navarro Rosa E.
Published: June 2012

The Vasa family of proteins comprises several conserved DEAD box RNA helicases important for mRNA regulation whose exact function in the germline is still unknown. In Caenorhabditis elegans, there are six known members of the Vasa family, and all of them are associated with P granules. One of these proteins, VBH‐1, is important for oogenesis, spermatogenesis, embryo development, and the oocyte/sperm switch in this nematode. We decided to extend our previous work in C. elegans to sibling species Caenorhabditis remanei to understand what is the function of the VBH‐1 homolog in this gonochoristic species. We found that Cre‐VBH‐1 is present in the cytoplasm of germ cells and it remains associated with P granules throughout the life cycle of C. remanei. Several aspects between VBH‐1 and Cre‐VBH‐1 function are conserved like their role during oogenesis, spermatogenesis, and embryonic development. However, Cre‐vbh‐1 silencing in C. remanei had a stronger effect on spermatogenesis and spermatid activation than in C. elegans. An unexpected finding was that silencing of vbh‐1 in the C. elegans caused a decrease in germ cell apoptosis in the hermaphrodite gonad, while silencing of Cre‐vbh‐1 in C. remanei elicited germ cell apoptosis in the male gonad. These data suggest that VBH‐1 might play a role in germ cell survival in both species albeit it appears to have an opposite role in each one. genesis 1–18 2012. © 2012 Wiley Periodicals, Inc.
The role of water quality in large mammal migratory behaviour in the Serengeti
Authors: Strauch Ayron M.
Published: June 2012

Surface water resources are important components of savanna landscapes, supplying large populations of wildlife with drinking water critical for thermoregulation and digestion. However, little is known about the behavioural or physiological influence of water quality on wildlife health. East African savannas are well known for their migrating populations of ungulates coinciding with seasonal and spatial patterns of forage. In the Serengeti ecosystem, seasonal rainfall, high wildlife abundance and spatially variable soil composition result in temporal and spatial differences in surface water quality. Furthermore, nutrient enrichment from dissolved minerals and animal waste transported in runoff drive bacterial and algal blooms. Previous studies have suggested that water quality may be a factor in the migratory behaviour of wildebeest as poor quality water can have significant health consequences for ungulates, including depressed milk production and reduced food conversion. This paper examines the hypothesis that water quality in the southern Serengeti plains exceeds expected maximum tolerance limits at the end of the wet season – when migratory wildlife move northward, away from this region. Data collected during the migration's movement over 3 years are examined to determine if regional differences in water quality are physiologically meaningful and how the consumption of poor quality water may influence wildebeest nutrient intake. With increased demand for surface water resources from human populations, growing climatic uncertainty and significant changes in land cover outside of protected areas, the influence of water quality on animal behaviour needs to be considered for future management strategies. Copyright © 2012 John Wiley & Sons, Ltd.
Contrasting water‐uptake and growth responses to drought in co‐occurring riparian tree species
Authors: Singer Michael Bliss , Stella John C. , Dufour Simon , Piégay Hervé , Wilson Rob J.S. , Johnstone Laura
Published: June 2012

Growth responses of riparian trees to changes in water availability are poorly understood, thereby limiting understanding of regional drought implications in river corridors. We used dendrochronological methods to develop growth series and analysed oxygen isotopic ratios (δ18O) in α‐cellulose from individual tree rings for two co‐occurring riparian species, Fraxinus excelsior and Populus nigra. Trees were sampled along the Ain River (France) to assess growth and annual source water availability, inferred from tree‐ring δ18O, compared with variations in streamflow and precipitation. Both species exhibited decreased growth during drought years, but F. excelsior demonstrated less variation in annual growth across sites compared with P. nigra. The latter species expressed a smaller range of δ18O among individuals and years, but greater δ18O sensitivity to river discharge, indicating a more consistent hyporheic water source. P. nigra also suffered more growth inhibition than F. excelsior in dry years when water tables were suppressed. These differences suggest contrasting patterns of water use, wherein F. excelsior uses primarily water from the vadose zone to maintain moderate growth rates, and P. nigra demonstrates more consistent phreatic water usage and suffers in drought years when water tables are suppressed. These observations are consistent with data on floodplain rooting depths, which show that F. excelsior maintains its roots above the gravel layer, whereas P. nigra generally roots deeply into phreatic zone gravels. These results indicate that surprisingly, poplars may be more sensitive to drought than ash trees and may be vulnerable to climate changes affecting water availability in riparian corridors. Copyright © 2012 John Wiley & Sons, Ltd.
Electronic Structures of the Electron Transfer Series [M(bpy)3]n, [M(tpy)2]n, and [Fe(tbpy)3]n (M = Fe, Ru; n = 3+, 2+, 1+, 0, 1–): A Mössbauer Spectroscopic and DFT Study
Authors: England Jason , Scarborough Christopher C. , Weyhermüller Thomas , Sproules Stephen , Wieghardt Karl
Published: June 2012

The five‐membered electron‐transfer series [M(bpy)3]n and [M(tpy)2]n (M = Fe, Ru; bpy = 2,2′‐bipyridine, tpy = 2,2′:6′,2″‐terpyridine) and [Fe(tbpy)3]n (tbpy = 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine; n = 3+, 2+, 1+, 0, 1–) have been investigated and the electronic structure of the so called “low‐valent” complexes (n = 1+, 0, 1–) have been established by a combination of electro‐ and magnetochemistry, electron paramagnetic resonance (EPR) and Mössbauer spectroscopy, X‐ray crystallography, and DFT calculations. These complexes are accessed by reduction of the d6 S = 0 dicationic starting materials [M(bpy)3]2+ and [M(tpy)2]2+ (M = Fe, Ru) and [Fe(tbpy)3]2+. The monocations [M(bpy·)(bpy0)2]1+ (S = 1/2) and [M(tpy·)(tpy0)]1+ (S = 1/2) (M = FeII, RuII) also contain a low‐spin (t2g)6 divalent metal center, plus a single radical monoanion (bpy·)1– or (tpy·)1–, and two or one neutral (bpy0) or (tpy0) ligands, respectively. The unpaired electron resides in a ligand π* orbital. The neutral complexes [FeII(bpy·)2(bpy0)]0 and [RuII(tpy·)2]0 were found, by DFT calculations, to possess an S = 1 ground state that is attained by weak intramolecular ferromagnetic coupling between two ligand radical anions and a singlet excited state (S = 0). In contrast, the neutral species [RuII(bpy·)2(bpy0)]0 possesses an S = 0 ground state. The metal centers of these neutral complexes retain a low‐spin (t2g)6 configuration. Remarkably, the corresponding neutral complex [FeII(tpy·)2]0 contains high‐spin FeII (SFe = 2). Strong intramolecular antiferromagnetic metal–radical coupling yields an experimentally observed S = 1 ground state. The monoanions [MII(bpy·)3]1– (M = Fe, Ru) are composed of a low‐spin metal ion [Fe, Ru; (t2g)6; SM = 0] and three (bpy·)1– radical anions.
Synthetic Methodologies for the Preparation of β‐Amino Thiols
Authors: Mercey Guillaume , Reboul Vincent , Gulea Mihaela , Levillain Jocelyne , Gaumont Annie‐Claude
Published: June 2012

β‐Amino thiols are an important class of bifunctional compounds that have found various applications in many areas of chemistry. This microreview highlights the synthetic methods judged to be the most efficient and general for their preparation.
Revision of the Structure and Total Synthesis of Altenuisol
Authors: Nemecek Gregor , Cudaj Judith , Podlech Joachim
Published: June 2012

A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds – a structure originally proposed as the structure of altertenuol – matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23 % yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided.
Biases and Errors on Allele Frequency Estimation and Disease Association Tests of Next‐Generation Sequencing of Pooled Samples
Authors: Chen Xiaowei , Listman Jennifer B. , Slack Frank J. , Gelernter Joel , Zhao Hongyu
Published: June 2012

Next‐generation sequencing is widely used to study complex diseases because of its ability to identify both common and rare variants without prior single nucleotide polymorphism (SNP) information. Pooled sequencing of implicated target regions can lower costs and allow more samples to be analyzed, thus improving statistical power for disease‐associated variant detection. Several methods for disease association tests of pooled data and for optimal pooling designs have been developed under certain assumptions of the pooling process, for example, equal/unequal contributions to the pool, sequencing depth variation, and error rate. However, these simplified assumptions may not portray the many factors affecting pooled sequencing data quality, such as PCR amplification during target capture and sequencing, reference allele preferential bias, and others. As a result, the properties of the observed data may differ substantially from those expected under the simplified assumptions. Here, we use real datasets from targeted sequencing of pooled samples, together with microarray SNP genotypes of the same subjects, to identify and quantify factors (biases and errors) affecting the observed sequencing data. Through simulations, we find that these factors have a significant impact on the accuracy of allele frequency estimation and the power of association tests. Furthermore, we develop a workflow protocol to incorporate these factors in data analysis to reduce the potential biases and errors in pooled sequencing data and to gain better estimation of allele frequencies. The workflow, Psafe, is available at http://bioinformatics.med.yale.edu/group/.
INCOME‐RELATED INEQUITY IN HEALTHCARE UTILISATION AMONG INDIVIDUALS WITH CARDIOVASCULAR DISEASE IN ENGLAND—ACCOUNTING FOR VERTICAL INEQUITY
Authors: Vallejo‐Torres Laura , Morris Stephen
Published: June 2012

Economic analyses of equity which focus solely on horizontal inequity offer a partial assessment of socioeconomic inequity in healthcare use. We analyse income‐related inequity in cardiovascular disease‐related healthcare utilisation by individuals reporting cardiovascular disease in England, including both horizontal and vertical aspects. For the analysis of vertical inequity, we use target groups to estimate the appropriate relationship between healthcare needs and use. We find that including vertical inequity considerations may lead us to draw different conclusions about the nature and extent of income‐related inequity. After accounting for vertical inequity in addition to horizontal inequity, there is no longer evidence of inequity favouring the poor for nurse visits, whereas there is some evidence that doctor visits and inpatient stays are concentrated among richer individuals. The estimates of income‐related inequity for outpatient visits, electrocardiography tests and heart surgery become even more pro‐rich when accounting for vertical inequity. Copyright © 2012 John Wiley & Sons, Ltd.
Development of a support‐vector‐machine‐based model for daily pan evaporation estimation
Authors: Lin Gwo‐Fong , Lin Hsuan‐Yu , Wu Ming‐Chang
Published: June 2012

Evaporation estimation is an important issue in water resources management. In this article, a four‐season model with optimal input combination is proposed to estimate the daily evaporation. First, the model based on support vector machine (SVM) coupled with an input determination process is used to determine the optimal combination of input variables. Second, a comparison of the SVM‐based model with the model based on back‐propagation network (BPN) is made to demonstrate the superiority of the SVM‐based model. In addition, season data are used to construct the SVM‐based four‐season model to further improve the daily evaporation estimation. An application is conducted to demonstrate the performance of the proposed model. Results show that the SVM‐based model can select the optimal input combination with physical mechanism. The SVM‐based model is more appropriate than the BPN‐based model because of its higher accuracy, robustness and efficiency. Moreover, the improvement due to the use of the four‐season model increases from 3.22% to 15.30% for RMSE and from 4.84% to 91.16% for CE, respectively. In conclusion, the SVM‐based model coupled with the proposed input determination process should be used to select input variables. The proposed four‐season SVM‐based model with optimal input combination is recommended as an alternative to the existing models. The proposed modelling technique is expected to be useful to improve the daily evaporation estimation. Copyright © 2012 John Wiley & Sons, Ltd.
Work Stressors, Social Support, and Burnout in Junior Doctors: Exploring Direct and Indirect Pathways
Authors: Sochos Antigonos , Bowers Alexis , Kinman Gail
Published: June 2012

The study tested a pathway model linking different occupational stressors, different sources of social support, and burnout. A sample of 184 junior medical doctors was used. Pathway analysis suggested that doctors who experienced increased time demands, organizational constraints, and a lack of personal confidence perceived their consultants as less supportive, whereas those who experienced greater clinical responsibility perceived their supervisors as more supportive. A lack of support from coworkers was linked with a lack of support from consultants, top management, and family. The perception of consultant support was linked with lower burnout, whereas the perception of coworker support was linked with higher burnout. The present findings may inform interventions aimed to support junior doctors experiencing burnout.
Impact of cell division on intracellular uptake and nuclear targeting with fluorescent SiC‐based nanoparticles
Authors: Serdiuk Tetiana , Lysenko Vladimir , Mognetti Barbara , Skryshevsky Valery , Géloën Alain
Published: June 2012

Semiconductor nanoparticles (NPs) became important and wide‐used tool for cell imaging because of their unique remarkable properties. Nevertheless, all previous investigations in this area were done on proliferating cells. For the first time, this work demonstrates strong influence of cell active proliferation/contact inhibition of proliferation on uptake of NPs. In addition, we show that cell division plays key‐role in penetration of silicon carbide based NPs (SiC NPs) inside the cell nucleus. This may very likely concern other types of NPs able to reach the cell nuclei. In particular, observed effect of cell division gives perspectives for future selective cancer treatment with NPs. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A quantum chemical calculation on Fe(CO)5 revealing the operation of the Dewar–Chatt–Duncanson model
Authors: Bachler Vinzenz
Published: June 2012

A nonstandard computational scheme has been applied to calculate Fe(CO)5 with the aim to illustrate the operation of the Dewar–Chatt–Duncanson model by computation. A full configuration interaction (CI) calculation in an active space has been performed. The active space is built from naturally localized molecular orbitals (NLMOs) localized in bond regions or forming lone pairs. For selecting this active space, Weinhold's perturbation theory formulated in the natural bond orbital (NBO) space has been applied. Bonding, lone pair, and antibond NBOs exhibiting large interaction energies serve to define the active space. The actually applied active space, however, comprises NLMOs that are close in shape to the NBOs indicated by perturbation theory. Thus, a CI calculation with localized orbitals has been performed meeting the classical reasoning of chemists that is often based on local bonding concepts. The computational scheme yields the Lewis structure for Fe(CO)5 whose energy is identical to the Hartree–Fock energy. The Lewis energy comprises CO → Fe σ‐electron transfer (ET) and CO ← Fe electron back donation (BD). This Lewis energy gets lowered by localized correlation energy contributions caused by ET processes where electrons are back donated from the Fe d‐lone pairs into the CO ligands. Thus, electron correlation within the selected active space is dominated by electron BD. Energies and electron populations of the NBOs support the notion that electrons are preferentially back donated into the equatorial CO ligands. Weights of local Slater determinants, determining the correlation energy, also point to a predominant BD into the equatorial CO ligands. Correlation energy increments resulting from electron BD into single antibond orbitals of the CO ligands have been calculated. These energy quantities also demonstrate that BD into the equatorial CO ligands is more energy lowering than BD into the axial CO ligands. © 2012 Wiley Periodicals, Inc.
Deciduous dental pulp stem cells are involved in osteoclastogenesis during physiologic root resorption
Authors: Zhu Yuan , Shang Linjuan , Chen Xiaoyan , Kong Xiangwei , Liu Na , Bai Yuyun , Fang Jun , Dang Jun , Wang Xiaojing , Jin Yan
Published: June 2012

Multipotent mesenchymal stem cells are derived from the dental pulps of permanent teeth and exfoliated deciduous teeth, and are known to induce bone and dentin generation. However, the role of deciduous dental pulp stem cells (DDPSCs) in physiologic root resorption remains unclear. In this study, dental pulp stem cells (DPSCs) in permanent teeth (P) were retrieved and compared to DDPSCs from deciduous incisors at different root resorption stages: stable (S), middle (M), and final (F). Decalcified teeth sections showed that osteoclasts and resorption lacunae were most prevalent in the M resorption stage. DDPSC proliferation rate was also highest in the M stage. DDPSCs in the F stage produced more calcified nodules than those in the S or M stages. Alkaline phosphatase (ALP) expression was highest in the F stage, indicating that DDPSCs promote mineralization. In addition, the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) expression was significantly higher in the M stage, indicating that DDPSCs promote resorption. Dickkopf 1 (Dkk1) expression was remarkably higher in the F and P groups, suggesting that the Wnt pathway is inhibited during the resorption process. Interestingly, despite the fact that Wnt3a down‐regulated OPG in osteogenic induction medium and up‐regulated RANKL in medium with 1,25‐dihydroxy vitamin D3 (VD3), the RANKL/OPG ratio was reduced only with VD3. Collectively, our data indicate that DDPSCs influence osteoclastogenesis during the physiologic root resorption process, and that the canonical Wnt pathway can change the RANKL/OPG expression ratio in DDPSCs. J. Cell. Physiol. 228: 207–215, 2013. © 2012 Wiley Periodicals, Inc.
Oxygen diffusivity in alginate/chitosan microcapsules
Authors: Zhao Wei , Zhang Ying , Liu Yang , Tan Mingqian , Yu Weiting , Xie Hongguo , Ma Ying , Sun Guangwei , Lv Guojun , Zhao Shan , Ma Xiaojun
Published: June 2012

BACKGROUND: Oxygen diffusion properties affect the proliferation and metabolism of cells cultured in microcapsules with a polyelectrolyte complex membrane. The effective diffusion coefficient (De) of oxygen in alginate/chitosan (AC) microcapsules under different preparation conditions was calculated, and a mathematic model was developed to investigate the effect of oxygen diffusion on cell loading in the microcapsules.

RESULTS: Oxygen De in AC microcapsules was independent of alginate solution concentration, intrinsic viscosity of alginate and different polyelectrolyte complex membranes. De decreased from 2.1 ± 0.3 × 10−9 to 0.17 ± 0.01 × 10−9 m2 s−1 as microcapsule diameter decreased from 1800 to 45 0 µm. Microcapsule density was increased from 1.013 ± 0.000 to 1.034 ± 0.003 g mL−1 as diameter decreased from 1775 to 430 µm. The mathematic model results showed that critical CHO cell loadings were 1.8 × 108 or 1.1 × 108 cells mL−1 in microcapsules with 450 or 1800 µm diameter, respectively.

CONCLUSIONS: No significant difference was found of oxygen De between calcium alginate beads and AC microcapsules. The decrease of De with diameter was attributed to the increasing density and compact degree on the surface. The model results indicated that risk on necrosis rose with the increasing diameter. Microcapsules with smaller diameters may have more advantages on cell culture. © 2012 Society of Chemical Industry
Efficiency of a new strategy involving a new class of natural hetero‐ligand iron(III) chelates (Fe(III)‐NHL) to improve fruit tree growth in alkaline/calcareous soils
Authors: Fuentes Marta , Ortuño María F , Pérez‐Sarmiento Francisco , Bacaicoa Eva , Baigorri Roberto , Conejero Wenceslao , Torrecillas Arturo , García‐Mina José M
Published: June 2012

BACKGROUND: Iron (Fe) chlorosis is a serious problem affecting the yield and quality of numerous crops and fruit trees cultivated in alkaline/calcareous soils. This paper describes the efficiency of a new class of natural hetero‐ligand Fe(III) chelates (Fe‐NHL) to provide available Fe for chlorotic lemon trees grown in alkaline/calcareous soils. These chelates involve the participation in the reaction system of a partially humified lignin‐based natural polymer and citric acid.

RESULTS: First results showed that Fe‐NHL was adsorbed on the soil matrix while maintaining available Fe for plants in alkaline/calcareous solution. The effects of using three different sources as Fe fertilisers were also compared: two Fe‐NHL formulations (NHL1, containing 100% of Fe as Fe‐NHL, and NHL2, containing 80% of Fe as Fe‐NHL and 20% of Fe as Fe‐ethylenediamine‐N,N′‐bis‐(o‐hydroxyphenylacetic) acid (Fe‐EDDHA)) and Fe‐EDDHA. Both Fe‐NHL formulations increased fruit yield without negative effects on fruit quality in comparison with Fe‐EDDHA. In the absence of the Fe‐starter fraction (NHL1), trees seemed to optimise Fe assimilation and translocation from Fe‐NHL, directing it to those parts of the plant more involved in development.

CONCLUSION: The field assays confirmed that Fe‐NHL‐based fertilisers are able to provide Fe to chlorotic trees, with results comparable to Fe‐EDDHA. Besides, this would imply a more sustainable and less expensive remediation than synthetic chelates. Copyright © 2012 Society of Chemical Industry
Physicochemical properties and emulsion stabilization of rice dreg glutelin conjugated with κ‐carrageenan through Maillard reaction
Authors: Du Yanxue , Shi Suhua , Jiang Yan , Xiong Hua , Woo Meng Wai , Zhao Qiang , Bai Chunqing , Zhou Qiang , Sun Wenjing
Published: June 2012

BACKGROUND: Rice dreg is an underutilized source of cereal protein with good potential for application in the food industry. Glutelin represents about 850 g kg−1 of total storage protein in rice dreg. The objective of this study was to characterize the physicochemical properties and emulsion stabilization of the Maillard type conjugate formed with rice dreg glutelin (RDG) and κ‐carrageenan (1:2 weight ratio) dry‐heated at 60 °C and 79% relative humidity for 24 h.

RESULTS: Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and Fourier transform‐infrared analysis provided evidence on the formation of the Maillard type conjugation. Amino acid analysis suggested that the major locus during the Maillard reaction were lysine and arginine. Circular dichroism spectra showed decreasing amounts of α‐helix and β‐strand in the products with increment in the amount of turns and random coil. Conjugation with κ‐carrageenan could significantly improve solubility of RDG (P < 0.05). Measurements of mean droplet size and creaming stability in oil‐in‐water emulsions showed that the conjugate was more effective at stabilizing emulsions at low pH or in the presence of high ionic strength.

CONCLUSION: The Maillard reaction can be successfully used as a coupling method for RDG and κ‐carrageenan to form the conjugate with improved solubility and emulsion stabilization. Copyright © 2012 Society of Chemical Industry
Process Sensor Systems for Laser Beam Welding
Authors: Dorsch Friedhelm , Braun Holger , Keßler Steffen , Magg Winfried , Pfitzner Dieter , Plaßwich Sven
Published: June 2012

The use of lasers in materials processing is increasing, and in particular with the availability of more brilliant laser sources, like disk and fiber lasers, new processes and applications in laser beam welding become of interest. To take full advantage of these new capabilities the accurate tool of a high‐brilliant laser beam requires precise handling and process control. Process sensor systems are cornerstones for advanced laser welding stations that are suitable for integration in automated mass production.
Study on the Morphologies of Covalent Organic Microporous Polymers: the Role of Reaction Solvents
Authors: Tan Dazhi , Fan Wenjie , Xiong Wannan , Sun Hanxue , Cheng Yaqi , Liu Xiaoyu , Meng Changgong , Li An , Deng Wei‐Qiao
Published: June 2012

Two‐dimensional conjugated microporous polymers (CMPs) composed of alternative phenylene and ethynylene units are synthesized, by cross‐coupling polymerization of 1,3,5‐triethynylbenzene and 1,3,5‐tribromobenzene with various solvents. Our work shows that the morphology of CMPs is greatly affected by the choice of solvents used in synthesis. Sphere, tubular, and plate‐like structures are received by using the toluene, p‐xylene, and mesitylene solvents, respectively. Our results demonstrate that the morphology of CMPs affects the storage capacity for organic solvents remarkably, with the plate‐like CMP showing best performance. This work is expected to provide useful guidance to rationally design CMPs as absorbent materials for organic solvents.
The domain derivative of time‐harmonic electromagnetic waves at interfaces
Authors: Hettlich Frank
Published: June 2012

The scattering of time‐harmonic electromagnetic waves by a penetrable obstacle is considered. In view of shape optimization or inverse reconstruction problems, the domain derivative of the scattering problem is investigated. Existence of the derivative in the sense of a Fréchet derivative and a characterization by a transmission boundary value problem are shown. Copyright © 2012 John Wiley & Sons, Ltd.
Local existence and blow‐up criterion for the generalized Boussinesq equations in Besov spaces
Authors: Qiu Hua , Du Yi , Yao Zheng'an
Published: June 2012

In this paper, we consider the three‐dimensional generalized Boussinesq equations, a system of equations resulting from replacing the Laplacian − Δ in the usual Boussinesq equations by a fractional Laplacian ( − Δ)α. We prove the local existence in time and obtain a regularity criterion of solution for the generalized Boussinesq equations by means of the Littlewood–Paley theory and Bony's paradifferential calculus. The results in this paper can be regarded as an extension to the Serrin‐type criteria for Navier–Stokes equations and magnetohydrodynamics equations, respectively. Copyright © 2012 John Wiley & Sons, Ltd.
Expression of M6 and M7 lysin in Mytilus edulis is not restricted to sperm, but occurs also in oocytes and somatic tissue of males and females
Authors: Heß Anne‐Katrin , Bartel Manuela , Roth Karina , Messerschmidt Katrin , Heilmann Katja , Kenchington Ellen , Micheel Burkhard , Stuckas Heiko
Published: June 2012

Sperm proteins of marine sessile invertebrates have been extensively studied to understand the molecular basis of reproductive isolation. Apart from molecules such as bindin of sea urchins or lysin of abalone species, the acrosomal protein M7 lysin of Mytilus edulis has been analyzed. M7 lysin was found to be under positive selection, but mechanisms driving the evolution of this protein are not fully understood. To explore functional aspects, this study investigated the protein expression pattern of M7 and M6 lysin in gametes and somatic tissue of male and female M. edulis. The study employs a previously published monoclonal antibody (G26‐AG8) to investigate M6 and M7 lysin protein expression, and explores expression of both genes. It is shown that these proteins and their encoding genes are expressed in gametes and somatic tissue of both sexes. This is in contrast to sea urchin bindin and abalone lysin, in which gene expression is strictly limited to males. Although future studies need to clarify the functional importance of both acrosomal proteins in male and female somatic tissue, new insights into the evolution of sperm proteins in marine sessile invertebrates are possible. This is because proteins with male‐specific expression (bindin, lysin) might evolve differently than proteins with expression in both sexes (M6/M7 lysin), and the putative function of both proteins in females opens the possibility that the evolution of M6/M7 lysin is under sexual antagonistic selection, for example, mutations beneficial to the acrosomal function that are less beneficial the function in somatic tissue of females.Mol. Reprod. Dev. 79: 517‐524, 2012. © 2012 Wiley Periodicals, Inc.
Developmental expression of the cellular prion protein (PrPC) in bovine embryos
Authors: Peralta Oscar A. , Huckle William R. , Eyestone Willard H.
Published: June 2012

The mammalian cellular prion protein (PrPC) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or PrPSc), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (TSEs). Although much is known about PrPSc conversion and its role in TSEs, the normal function of PrPC has not been elucidated. In adult mammals, PrPC is most abundant in the central nervous tissue, with intermediate levels in the intestine and heart, and lower levels in the pancreas and liver. PrPC is expressed during neurogenesis throughout development, and it has recently been proposed that PrPC participates in neural cell differentiation during embryogenesis. In order to establish the developmental timing and to address the cell‐specific expression of PrPC during mammalian development, we examined PrPC expression in bovine gametes and embryos through gestation Day 39. Our data revealed differential levels of Prnp mRNA at Days 4 and 18 in pre‐attachment embryos. PrPC was detected in the developing central and peripheral nervous systems in Day‐27, 32‐, and ‐39 embryos. PrPC was particularly expressed in differentiated neural cells located in the marginal regions of the central nervous system, but was absent from mitotically active, periventricular areas. Moreover, a PrPC cell‐specific pattern of expression was detected in non‐nervous tissues, including liver and mesonephros, during these stages. The potential participation of PrPC in neural cell differentiation is supported by its specific expression in differentiated states of neurogenesis. Mol. Reprod. Dev. 79:488–498, 2012. © Wiley Periodicals, Inc.