bluuebunny/crossref_metadata_2025 huggingface dataset:
“Official” and “practical” kin: Inferring social and community structure from dental phenotype at Neolithic Çatalhöyük, Turkey
Authors: Pilloud Marin A. , Larsen Clark Spencer
Published: May 2011

The Neolithic site of Çatalhöyük, Turkey (7400–5600 cal BC) is widely acknowledged for its role in the study of early farming communities. To better understand the social and community structure of this setting, an intracemetery biological distance analysis was conducted. Metric and nonmetric observations were recorded in both deciduous and permanent dentitions (n = 266) to explore phenotypic patterning of individuals interred within individual buildings. Specifically, this study tests the hypothesis that individuals within houses and house groupings represent family units and the social structure of Çatalhöyük was largely biological‐kin based. Multivariate and univariate statistical procedures were applied to phenotypic dental data. Results indicate that inclusion for interment within a house was only minimally related to biological affinity. Moreover, the site does not appear to be organized into larger, biologically related neighborhoods of houses. These findings suggest that Çatalhöyük may not have been a kin‐based society, largely because membership within a house cemetery was not solely defined on the basis of biological affinity, such as in a family group. Rather, it appears that social structure was centered on the house as the unifying social principle. The choice for interment location may have transcended biological lines thereby creating an alternate and more fluid definition of “kin.” These findings can be used to understand the transition to settled life and biological patterning in this Neolithic community. Am J Phys Anthropol 2011. © 2011 Wiley‐Liss, Inc.
Power system lightning transient simulation on OrCAD with corona effect consideration for educational purposes
Authors: Vahidi B. , Tabatabaei S. M. , Baharlou M. M.
Published: May 2011

This article describes an efficient method of teaching lightning transient on power system, to undergraduate students of power system groups in electrical engineering departments, as a part of a high voltage course for senior undergraduate students. The article shows how to simulate the components of power system in order to teach students the basics of lightning transient phenomena, and to practice the simulation of power system components. In the first part of the article the simulation of component is described, and in the second part a system is simulated for lightning transient study. Evaluation of the simulation over several semesters with more than 48 students is very positive in terms of their developing confidence in and understanding of lightning transient phenomena. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:266–271, 2014; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.20552
Malignant biphasic peritoneal mesothelioma in a child: Fine‐needle aspiration cytology, Histopathology, and immunohistochemical features along with review of literature
Authors: Arora Sandeep Kumar , Srinivasan Radhika , Nijhawan Raje , Bansal Deepak , Menon Prema
Published: May 2011

Peritoneal mesotheliomas in children are of rare occurrance. We herein report the clinical, radiological, and pathological findings of a rare case of malignant peritoneal mesothelioma occurring in nine‐year‐old female child. The child presented with abdominal distension and awareness of a painless mass in the abdomen which on radiology appeared as a large heterogeneous pelvic mass with peritoneal deposits at multiple sites. To the best of our knowledge, this is the first case of a peritoneal malignant mesothelioma on which fine needle aspiration (FNA) was performed as first line investigation of the primary tumor. The cytological features, major differential diagnoses, and the pitfalls therein are discussed. Histopathology revealed biphasic pattern of mesothelioma which is again a rare pattern. Immunochemistry was carried out on the cell block made from the FNA as well as the biopsy specimen essentially showed the same features. There was positivity for vimentin, EMA, and cytokeratin 5/6 while WT1, calretinin, and CEA were negative; however, D2‐40 showed diffuse membranous positivity in the epithelial areas and cytoplasmic positivity in the spindle areas confirming a mesothelioma. We emphasize the use of immunochemistry on cell block material for a confident diagnosis of mesothelioma in such cases. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla
Authors: Boerboom Derek , Lafond Jean‐François , Zheng Xiaofeng , Lapointe Evelyne , Mittaz Laureane , Boyer Alexandre , Pritchard Melanie A. , DeMayo Francesco J. , Mort John S. , Drolet Richard , Richards Joanne S.
Published: May 2011

Adamts4 encodes a widely‐expressed proteinase thought to be involved in processes ranging from cartilage metabolism to ovarian follicle development. To study its physiological roles, Adamts4‐null mice were created by gene targeting. Unexpectedly, these were found to be phenotypically normal, suggesting that other gene(s) may compensate for its loss. Adamts4−/− mice were, therefore, crossed with a strain lacking Adamts1, whose pattern of expression and substrate specificity overlap that of Adamts4. Most (>95%) Adamts1−/−;Adamts4−/− mice died within 72 hr after birth with a marked thinning of the renal medulla. The renal defect was not observed in embryonic Adamts1−/−;Adamts4−/− kidneys, but became apparent around birth. The few (<5%) Adamts1−/−;Adamts4−/− animals to reach adulthood had the same renal phenotype seen in newborns. This study is thus the first to report Adamts4 expression and function in the mammalian kidney, and to demonstrate that Adamts1 and Adamts4 play redundant and essential roles in perinatal kidney development. Developmental Dynamics 240:1806–1814, 2011. © 2011 Wiley‐Liss, Inc.
Experimental tests on full‐scale RC unretrofitted frame and retrofitted with buckling‐restrained braces
Authors: Di Sarno L. , Manfredi G.
Published: May 2011

The results of experimental tests carried out on reinforced concrete (RC) full‐scale 2‐storey 2‐bays framed buildings are presented. The unretrofitted frame was designed for gravity loads only and without seismic details; such frame was assumed as a benchmark system in this study. A similar RC frame was retrofitted with buckling‐restrained braces (BRBs). The earthquake structural performance of both prototypes was investigated experimentally using displacement‐controlled pushover static and cyclic lateral loads. Modal response properties of the prototypes were also determined before and after the occurrence of structural damage. The results of the dynamic response analyses were utilized to assess the existing design rules for the estimation of the elastic and inelastic period of vibrations. Similarly, the values of equivalent damping were compared with code‐base relationships. It was found that the existing formulations need major revisions when they are used to predict the structural response of as‐built RC framed buildings. The equivalent damping ratio ξeq was augmented by more than 50% when the BRBs was employed as bracing system. For the retrofitted frame, the overstrength Ω and the ductility µ are 1.6 and 4.1, respectively; the estimated R‐factor is 6.5. The use of BRBs is thus a viable means to enhance efficiently the lateral stiffness and strength, the energy absorption and dissipation capacity of the existing RC substandard frame buildings. The foundation systems and the existing members of the superstructure are generally not overstressed as the seismic demand imposed on them can be controlled by the axial stiffness and the yielding force of the BRBs. Copyright © 2011 John Wiley & Sons, Ltd.
Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma
Authors: Bennett Kristi L. , Campbell Rebecca , Ganapathi Shireen , Zhou Ming , Rini Brian , Ganapathi Ram , Neumann Hartmut P.H. , Eng Charis
Published: May 2011

We recently identified germline methylation of KILLIN, a novel p53‐regulated tumor suppressor proximal to PTEN, in >1/3 Cowden or Cowden syndrome‐like (CS/CSL) individuals who are PTEN mutation negative. Individuals with germline KILLIN methylation had increased risks of renal cell carcinoma (RCC) over those with PTEN mutations. Therefore, we tested the hypothesis that KILLIN may be a RCC susceptibility gene, silenced by germline methylation. We found germline hypermethylation by combined bisulfite restriction analysis in at least one of the four CpG‐rich regions in 23/41 (56%) RCC patients compared to 0/50 controls (P < 0.0001). Of the 23, 11 (48%) demonstrated methylation in the −598 to −890 bp region in respect to the KILLIN transcription start site. Furthermore, 19 of 20 advanced RCC showed somatic hypermethylation upstream of KILLIN, with the majority hypermethylated at more than one CpG island (13/19 vs. 3/23 with germline methylation, P < 0.0001). qRT‐PCR revealed that methylation significantly downregulates KILLIN expression (P = 0.05), and demethylation treatment by 5‐aza‐2′deoxycytidine significantly increased KILLIN expression in all RCC cell lines while only increasing PTEN expression in one line. Furthermore, targeted in vitro methylation revealed a significant decrease in KILLIN promoter activity only. These data reveal differential epigenetic regulation by DNA promoter methylation of this bidirectional promoter. In summary, we have identified KILLIN as a potential novel cancer predisposition gene for nonsyndromic clear‐cell RCC, and the epigenetic mechanism of KILLIN inactivation in both the germline and somatic setting suggests the potential for treatment with demethylating agents. © 2011 Wiley‐Liss, Inc.
Maffucci syndrome: A genome‐wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases
Authors: Pansuriya Twinkal C. , Oosting Jan , Verdegaal Suzan H. M. , Flanagan Adrienne M. , Sciot Raf , Kindblom Lars‐Gunnar , Hogendoorn Pancras C. W. , Szuhai Karoly , Bovée Judith V. M. G.
Published: May 2011

Ollier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co‐existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here, we report the first genome‐wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier‐related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray‐v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis. © 2011 Wiley‐Liss, Inc.
Quality of life for patients requiring surgical resection and reconstruction for mandibular osteoradionecrosis: 10‐year experience at the university of California San Francisco
Authors: Chang Edward I. , Leon Pablo , Hoffman William Y. , Schmidt Brian L.
Published: May 2011

Background

Mandibular osteoradionecrosis is the most devastating complication after radiation therapy for head and neck malignancies. Quality of life (QOL) after surgical treatment is unclear.

Methods

A retrospective cohort analysis (1997–2007) was conducted of all patients treated at our institution for stage II and III mandibular osteoradionecrosis. Nineteen of 35 patients responded to a modified University of Washington QOL questionnaire. Twenty had undergone reconstruction using free flaps, and the remainder with plates, plates and local flaps, or debridement alone.

Results

Complications included 3 infections, 5 with hardware, 5 flap‐specific, and 1 nonunion. Four patients had recurrent squamous cell carcinoma (SCC). The factors of greatest concern to patients were appearance, swallowing, and chewing. Average overall QOL was good to very good, and very good compared to preoperative.

Conclusion

Despite a 37% complication rate, a multidisciplinary team approach with adequate debridement, resection, and reconstruction can greatly improve QOL. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Primary Succession of Soil Rotifers in Clays of Brown Coal Post‐Mining Dumps
Authors: Devetter Miloslav , Frouz Jan
Published: May 2011

Changes in rotifer soil communities along a primary succession chronosequence was studied on brown coal post mining areas near Sokolov, NW part of the Czech Republic. The chronosequence of unreclaimed plots was 2, 11, 14, 20, 43 years old. The rotifers were extracted from soil samples using a modification of the Baermann funnel method with combined light and temperature gradients.

In total, 34 taxa of soil rotifers were identified throughout the study. The most common species wereEncentrum arvicola, Adineta vaga, A. steineri, Habrotrocha rosa, H. elegans, H. filum, Macrotrachela quadricorniferaandM. nana. Rotifer abundance varied from 4 ± 2 · 103to 516 ± 488 · 103individuals m–2. Species number per sample increased with age of the plot (r= 0.45,P= 0.003). The most important environmental variables which significantly affected rotifer community were wood cover, sodium concentration and age of the plot. Pioneer plant species occupied 2 and 11 year old plots, 14–20 year old plots were covered bySalix capreashrubs and a forest formed byBetula pendulaandPopulus tremuloidesdeveloped on the 43 year old plot. Some species were ubiquitous and present throughout the chronosequence (Macrotrachela quadricornifera). Among the pioneer species wereEncentrum incisum, Habrotrocha rosaandMacrotrachela papillosa, 14–20 years old plots were preferred byAdineta vaga, E. arvicola, H. filumandM. nana, while the oldest plot was dominated byAdineta steineriandEncentrum mucronatum. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Role of Cell Hydrophobicity on Colony Formation in Microcystis (Cyanobacteria)
Authors: Yang Hualin , Cai Yuanfeng , Xia Meng , Wang Xingyu , Shi Limei , Li Pengfu , Kong Fanxiang
Published: May 2011

Colony formation is highly import ant for the competitive advantage of the cyanobacterium Microcystis over other phytoplankton species. The laboratory‐grown colonial Microcystis strains isolated from Lake Taihu (China) maintained colonial forms under the low light condition (10 μE m–2 s–1). The cell surface hydrophobicities of the Microcystis colonies were measured by cyanobacterial adherence to xylene in comparison with unicellular Microcystis strains. The cells of the tested colonial strains were all hydrophobic, while the cells of the tested unicellular strains were all hydrophilic. Incubation under the higher light condition (75 μE m–2 s–1) leaded to the significant decrease in the cell hydrophobicities of the colonial Microcystis and the transition from colonial forms to unicellular forms. These findings indicated that the cell hydrophobicity of Microcystis may play a role in cell‐cell adherence and colony formation. Phosphate‐limitation, nitrate‐limitation and pH did not affect cell hydrophobicities of colonial Microcystis. Treatment with proteolytic enzymes had no effect on the cell hydrophobicity, indicating that cell surface proteins did not contribute to high cell hydrophobicity. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relationship of testosterone and osteocalcin levels during growth
Authors: Kirmani Salman , Atkinson Elizabeth J , Melton L Joseph , Riggs B Lawrence , Amin Shreyasee , Khosla Sundeep
Published: May 2011

Recent studies in mice have demonstrated that osteocalcin (OCN) regulates testosterone (T) production in males but not in females. We hypothesized that this novel bone-testis axis may be most relevant during rapid skeletal growth to help maximize bone size. Thus we measured serum T, total and undercarboxylated (UC) OCN, and periosteal circumference at the radius in 56 boys (bone age 4 to 20 years). T was correlated with OCN (bone-age-adjusted r = 0.30, p = .024), with a similar trend for UC OCN. T began to increase in the boys at bone age 11 years, and OCN peaked at bone age 14 years. Thus we divided the boys into three groups: 4 to 10 years (n = 16), 11 to 14 years (n = 18), and 15 to 20 years (n = 22). In boys of bone age 11 to 14 years (but not the other two groups), OCN was correlated with T (r = 0.57, p = .013), with a similar trend for UC OCN; T, in turn, was correlated with periosteal circumference (r = 0.75, p < .001). Collectively, these findings support the recent observations in mice of a novel bone-testis axis. Moreover, our data suggest that in human males, this axis may be most relevant during rapid skeletal growth, when T levels are rising under the influence of the hypothalamic-pituitary axis and OCN is increasing due to skeletal growth. During this phase, OCN may further stimulate testicular T production, which, in turn, contributes to an increase in bone size. © 2011 American Society for Bone and Mineral Research
Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: A 7-year longitudinal study
Authors: Xu Leiting , Wang Qin , Wang Qingju , Lyytikäinen Arja , Mikkola Tuija , Völgyi Eszter , Cheng Shumei , Wiklund Petri , Munukka Eveliina , Nicholson Patrick , Alén Markku , Cheng Sulin
Published: May 2011

A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin-like growth factor 1 (IGF-1), estradiol (E2), and testosterone (T) with peripubertal bone growth in a 7-year longitudinal study. Two-hundred and fifty-eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF-1, E2, and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF-1, E2, and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF-1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross-sectional area (mCSA). On the other hand, IGF-1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF-1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty. © 2011 American Society for Bone and Mineral Research
Simultaneous screening for osteoporosis at CT colonography: Bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard
Authors: Pickhardt Perry J , Lee Lawrence J , Muñoz del Rio Alejandro , Lauder Travis , Bruce Richard J , Summers Ron M , Pooler B Dustin , Binkley Neil
Published: May 2011

The purpose of this study was to evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening computed tomographic colonography (CTC) using central dual-energy X-ray absorptiometry (DXA) as the reference standard. Two-hundred and fifty-two adults (240 women and 12 men; mean age 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per World Health Organization as osteoporosis (DXA T-score ≤ −2.5) or osteopenia (DXA T-score between −1.0 and −2.4). Both phantomless quantitative computed tomography (QCT) and simple nonangled region-of-interest (ROI) multi-detector CT (MDCT) attenuation measurements were applied to the T12–L5 levels. The ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed. A BMD cut-off of 90 mg/mL at phantomless QCT yielded 100% sensitivity for osteoporosis (29 of 29) and a specificity of 63.8% (143 of 224); 87.2% (96 of 110) below this threshold had low BMD and 49.6% (69 of 139) above this threshold had normal BMD at DXA. At L1, a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29 of 29), with a specificity of 46.4% (104 of 224); 83.9% (125 of 149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T12–L5 levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT [95% confidence interval (CI) 0.780–0.946] and ranged from 0.825 to 0.853 using trabecular ROIs at single lumbar levels (0.864; 95% CI 0.752–0.930 at multivariate analysis). Supine-prone reproducibility was better with the simple ROI method compared with QCT. It is concluded that both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC with high sensitivity for osteoporosis, as defined by the DXA T-score. © 2011 American Society for Bone and Mineral Research
The effects of a two-year randomized, controlled trial of whey protein supplementation on bone structure, IGF-1, and urinary calcium excretion in older postmenopausal women
Authors: Zhu Kun , Meng Xingqiong , Kerr Deborah A , Devine Amanda , Solah Vicky , Binns Colin W , Prince Richard L
Published: May 2011

The effects of dietary protein on bone structure and metabolism have been controversial, with evidence for and against beneficial effects. Because no long-term randomized, controlled studies have been performed, a two-year study of protein supplementation in 219 healthy ambulant women aged 70 to 80 years was undertaken. Participants were randomized to either a high-protein drink containing 30 g of whey protein (n = 109) or a placebo drink identical in energy content, appearance, and taste containing 2.1 g of protein (n = 110). Both drinks provided 600 mg of calcium. Dual-energy X-ray absorptiometric (DXA) hip areal bone mineral density (aBMD), 24-hour urinary calcium excretion, and serum insulin-like growth factor 1 (IGF-1) were measured at baseline and at 1 and 2 years. Quantitative computed tomographic (QCT) hip volumetric bone mineral density (vBMD) and a femoral neck engineering strength analysis were undertaken at baseline and at 2 years. Baseline average protein intake was 1.1 g/kg of body weight per day. There was a significant decrease in hip DXA aBMD and QCT vBMD over 2 years with no between-group differences. Femoral neck strength was unchanged in either group over time. The 24-hour urinary calcium excretion increased significantly from baseline in both groups at 1 year but returned to baseline in the placebo group at 2 years, at which time the protein group had a marginally higher value. Compared with the placebo group, the protein group had significantly higher serum IGF-1 level at 1 and 2 years (7.3% to 8.0%, p < .05). Our study showed that in protein-replete healthy ambulant women, 30 g of extra protein increased IGF-1 but did not have beneficial or deleterious effects on bone mass or strength. The effect of protein supplementation in populations with low dietary protein intake requires urgent attention. © 2011 American Society for Bone and Mineral Research
Mediation of Rac1 activation by kindlin‐2: An essential function in osteoblast adhesion, spreading, and proliferation
Authors: Jung Gil‐Yong , Park Yoon‐Jeong , Han Jung‐Suk
Published: May 2011

Kindlins are focal adhesion proteins that regulate integrin signaling. Although integrin activation is critical for bone development, little is known about the expression and role of kindlins in osteoblasts. We therefore investigated the function of kindlin‐2 in osteoblast adhesion, spreading, and proliferation using small interfering RNA. In MC3T3‐E1 cells, only kindlin‐2 is highly expressed and localizes to focal adhesion. We found that kindlin‐2 was involved in integrin activation in MC3T3‐E1 cells and that kindlin‐2 knockdown osteoblasts resulted in diminished cell adhesion, spreading, and proliferation. In this process, kindlin‐2 knockdown impaired transient Rac1 activation, influencing Akt activation and AP‐1 activity. In agreement with these data, pharmacological inhibition of Rac1 reduced MC3T3‐E1 cell adhesion, spreading, and proliferation. Overall, these findings demonstrated that kindlin‐2 governs Rac1 activation, which controls osteoblast function. Our findings provide the first insights concerning the function of kindlin‐2 in osteoblast, and suggest that kindlin‐2 is a critical mediator for osteoblast physiology. J. Cell. Biochem. 112: 2541–2548, 2011. © 2011 Wiley‐Liss, Inc.
IL‐8 increases integrin expression and cell motility in human chondrosarcoma cells
Authors: Lee Chun‐Yi , Huang Chun‐Yin , Chen Meng‐Yi , Lin Ching‐Yuang , Hsu Horng‐Chaung , Tang Chih‐Hsin
Published: May 2011

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Over‐expression of IL‐8 has been detected in many human tumors. However, the effects of IL‐8 in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that IL‐8 increased the migration and the expression of αvβ3 integrin in human chondrosarcoma cells. Activations of phosphatidylinositol 3‐kinase (PI3K), Akt, and AP‐1 pathways after IL‐8 treatment were demonstrated, and IL‐8‐induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP‐1 cascades. Taken together, our results indicated that IL‐8 enhances the migration of chondrosarcoma cells by increasing αvβ3 integrin expression through the PI3K/Akt/AP‐1 signal transduction pathway. J. Cell. Biochem. 112: 2549–2557, 2011. © 2011 Wiley‐Liss, Inc.
Development of a successive targeting liposome with multi‐ligand for efficient targeting gene delivery
Authors: Ma Kun , Shen Haijun , Shen Song , Xie Men , Mao Chuanbin , Qiu Liyan , Jin Yi
Published: May 2011

Background

A successful gene delivery system needs to breakthrough several barriers to allow efficient transgenic expression. In the present study, successive targeting liposomes (STL) were constructed by integrating various targeting groups into a nanoparticle to address this issue.

Methods

Polyethylenimine (PEI) 1800‐triamcinolone acetonide (TA) with nuclear targeting capability was synthesized by a two‐step reaction. Lactobionic acid was connected with cholesterol to obtain a compound of [(2‐lactoylamido) ethylamino]formic acid cholesterol ester (CHEDLA) with hepatocyte‐targeting capability. The liposome was modified with PEI 1800‐TA and CHEDLA to prepare successive targeting liposome (STL). Its physicochemical properties and transfection efficiency were investigated both in vitro and in vivo.

Results

The diameter of STL was approximately 100 nm with 20 mV of potential. The confocal microscopy observation and potential assay verified that lipid bilayer of STL was decorated with PEI 1800‐TA. Cytotoxicity of STL was significantly lower than that of PEI 1800‐TA and PEI 25K. The transfection efficiency of 10% CHEDLA STL in HepG2 cells was the higher than of the latter two with serum. Its transfection efficiency was greatly reduced with excessive free galactose, indicating that STL was absorbed via galactose receptor‐mediated endocytosis. The in vivo study in mice showed that 10% CHEDLA STL had better transgenic expression in liver than the other carriers.

Conclusions

STL with multi‐ligand was able to overcome the various barriers to target nucleus and special cells and present distinctive transgenic expression. Therefore, it has a great potential for gene therapy as a nonviral carrier. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial patterns and regimes of daily precipitation in Iran in relation to large‐scale atmospheric circulation
Authors: Raziei Tayeb , Mofidi Abbas , Santos João A. , Bordi Isabella
Published: May 2011

The relationships between large‐scale atmospheric circulation types and seasonal regimes of daily precipitation over Iran are assessed using daily precipitation from a high‐resolution gridded dataset provided by the Asian Precipitation‐Highly Resolved Observational Data Integration Towards the Evaluation of Water Resources (APHRODITE) Project. Regional spatial modes of daily precipitation variability were identified by S‐mode Principal Component Analysis (PCA) with Varimax rotation, applied to the subset of days when at least 10% of all grid‐points over Iran received precipitation ≥ 5 mm. The study refers to the period 1961–2004 and is carried out for each season (excluding summer) separately. To characterize the dynamical features associated with each regional precipitation regime (PR), composites of daily atmospheric fields are computed by only averaging days with rotated PCA scores ≥ 1.5 (strong positive phase). In autumn and winter, Iran is divided into five PRs, while four PRs are identified in spring. Results suggest that the spatial distribution of precipitation over Iran is largely governed by the geographical position of both the mid‐tropospheric trough over the Middle East and the Arabian anticyclone. In fact, in almost all PRs, the trough, as a pre‐conditioning factor, leads to regional‐scale ascending motions, whereas the Arabian anticyclone induces low‐tropospheric moisture transports from southern water bodies into the cyclonic systems near Iran, triggering rain‐generating conditions. Copyright © 2011 Royal Meteorological Society
The demise of strategic groups as an influence on firm performance: lessons from the UK plastics industry
Authors: O'Regan Nicholas , Kluth Carole , Parnell John
Published: May 2011

Repositioning enables firms to shift their business efforts to profitable areas, as their size is not an all‐encompassing determinant of performance and the aggressive pursuit of market share can ultimately be destructive to their value.
Risk of surgical delivery to deep nuclei: A meta‐analysis
Authors: Kimmelman Jonathan , Duckworth Katherine , Ramsay Tim , Voss Tiffini , Ravina Bernard , Emborg Marina Elena
Published: May 2011

Many novel strategies aimed at neuroprotection or neurorestoration involve surgical delivery of agents to deep nuclei along multiple trajectories. Using intracerebral hemorrhage on a per‐trajectory basis as our primary end point, we quantified the level of surgical risk associated with agent delivery to deep nuclei. Secondarily, we quantified other event rates and examined relationships between intracerebral hemorrhage and 8 variables related to patient and practice characteristics. Meta‐analytic techniques were used to pool complication rates reported in published articles involving deep brain stimulator electrode implantation or infusion of vectors, tissues, or trophic factors. One hundred nine studies were included in our analysis, comprising 6237 patients and 9890 trajectories to deep nuclei. The estimated per‐trajectory intracerebral hemorrhage rate was 1.57% (95% confidence interval, 1.26%–1.95%). The proportion of trajectories leading to permanent or serious neurological deficits was 0.41% (0.28%–0.60%). The estimated mortality rate per trajectory was 0.14% (0.07%–0.29%). No relationship between intracerebral hemorrhage and sex, age, duration of disease, or exclusion of patients with surgical complications was observed; a significant positive relationship was observed with the use of microelectrode recording and a significant negative relationship with putamenal delivery. Our results show a significant difference in intracerebral hemorrhage rates between inoculations and electrode implantation. Our findings suggest that studies involving multiple trajectories to deep nuclei involve a high level of risk. However, inoculations may be significantly safer than electrode implantation. Our analysis has implications for the ethics of preclinical research, independent review of risk, subject selection, and adverse event reporting. © 2011 Movement Disorder Society
Body SAR study of the planar WWAN monopole slot antenna for tablet device application
Authors: Wong Kin‐Lu , Lin Wun‐Jian
Published: May 2011

A study on the body SAR of the planar WWAN (wireless wide area network) monopole slot antenna for tablet device application is presented. The monopole slot antenna covers penta‐band WWAN operation in the 824∼960/1710∼2170 MHz bands with low near‐field emission such that its body SAR (specific absorption rate) values for 1‐g tissue in the bottom face, landscape and portrait orientations to the flat phantom meet the limit of 1.6 W/kg for practical applications. Effects of the monopole slot antenna disposed at various possible locations in the tablet device on the body SAR results are also analyzed. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26094
kT‐points: Short three‐dimensional tailored RF pulses for flip‐angle homogenization over an extended volume
Authors: Cloos M. A. , Boulant N. , Luong M. , Ferrand G. , Giacomini E. , Le Bihan D. , Amadon A.
Published: May 2011

With Transmit SENSE, we demonstrate the feasibility of uniformly exciting a volume such as the human brain at 7T through the use of an original minimalist transmit k‐space coverage, referred to as “kT‐points.” Radio‐frequency energy is deposited only at a limited number of k‐space locations in the vicinity of the center to counteract transmit sensitivity inhomogeneities. The resulting nonselective pulses are short and need little energy compared to adiabatic or other B‐robust pulses available in the literature, making them good candidates for short‐repetition time 3D sequences at high field. Experimental verification was performed on three human volunteers at 7T by means of an 8‐channel transmit array system. On average, whereas the standard circularly polarized excitation resulted in a 33%‐flip angle spread (standard deviation over mean) throughout the brain, and a static radio‐frequency shim showed flip angle variations of 17% and up, application of kT‐point‐based excitations demonstrated excellent flip angle uniformity (8%) for a small target flip angle and with sub‐millisecond durations. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
The Influence of Environmental Factors on the Development of Ultra‐Orthodox Preschool Boys in Israel
Authors: Golos Anat , Sarid Miri , Weill Michal , Yochman Aviva , Weintraub Naomi
Published: May 2011

The study objectives were: (a) to compare the prevalence of children at risk and/or with developmental delay (at risk/delayed) among the Ultra‐Orthodox community with the prevalence reported in the literature and (b) to compare the performance of Ultra‐Orthodox children in kindergarten versus that of children in preschool. To this end, motor, visual–motor integration and cognitive performance of 203 Ultra‐Orthodox boys from low socio‐economic status were assessed. We found a higher percentage of children who were at risk/delayed in gross motor and motor–cognitive skills as compared with the percentage reported in the literature. However, as opposed to expected, the results did not show that there was a higher percent of at‐risk/delayed children among the kindergarten group as compared with those among the preschool group. Our findings are consistent with the research literature suggesting that children's cultural background and economic constraints can affect their motor and cognitive development. Thus, occupational therapists and other health professionals should be more culturally competent and more aware of the specific values and practices of families of children with whom they work, which can impact their development. However, in this study, it is difficult to distinguish between the influence of the cultural factors and the influence of socio‐economic factors. Therefore, it is recommended to repeat this study among children from either low socio‐economic status or other cultural backgrounds. Copyright © 2011 John Wiley & Sons, Ltd.
A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly
Authors: Weintraub Michael , Waldman Elisha , Koplewitz Benjamin , Bloom Allan I. , Gross Eitan , Freeman Arnold I. , Revel‐Vilk Shoshana
Published: May 2011

Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded prognosis and mortality approaches 30%. We report on eight patients with 4s NB and massive hepatomegaly treated with multiple modalities. One patient had spontaneous tumor regression. Three patients had progressive disease and responded to chemotherapy. Four patients progressed despite intravenous chemotherapy, of whom two died, and two were salvaged with hepatic intra‐arterial chemoembolization. Treatment of infants with stage 4s NB with massive hepatomegaly should be individualized based on disease course. A sequential approach with observation, intravenous chemotherapy, and intra‐arterial chemoembolization, may improve the outcome of these infants. Pediatr Blood Cancer 2012; 59: 182–184. © 2011 Wiley Periodicals, Inc.
Validity of claims‐based definitions of left ventricular systolic dysfunction in Medicare patients
Authors: Li Qian , Glynn Robert J. , Dreyer Nancy A. , Liu Jun , Mogun Helen , Setoguchi Soko
Published: May 2011

Purpose

Ejection fraction (EF) is crucial information when studying the use and effectiveness of therapies in patients with heart failure (HF) and myocardial infarction (MI). We aimed to assess the validity of claims data‐based definitions of systolic dysfunction (SD).

Methods

We identified 1072 patients with EF recorded for an HF/MI hospitalization in Medicare linked with pharmacy data and national HF/MI registries in 1999–2006. Thirteen claims‐based definitions for SD were developed using a single or combination of ICD‐9 diagnosis codes and cardiovascular medications use. We calculated sensitivity, specificity, and positive predictive values (PPVs) using recorded EFs as the gold standard.

Results

Using an EF cutoff of 45%, the definitions based on digoxin use and no atrial fibrillation or flutter had the highest PPVs (76% to 84%) and specificity (>97%) but low sensitivity (6%–14%). As we varied the EF cutoff between 50% and 25%, the specificity decreased by 3%, but the PPVs decreased by 52%. We observed potential differences in the PPVs by patients' characteristics. In a hypothetical study assessing implantable defibrillator effectiveness, using our definition to identify patients with SD would underestimate the effectiveness by 3% to 24%. In another hypothetical study comparing two classes of angiotensin system blockers where SD was considered confounding, our definition introduced ~43% misclassification bias.

Conclusions

Claims‐based definitions for SD had excellent specificity and good PPV but low sensitivity. The definitions with good PPV could be used for cohort identification or confounding adjustment by restriction and would result in relatively small misclassification bias albeit limited generalizability. Copyright © 2011 John Wiley & Sons, Ltd.
The national burden of E‐code‐identified adverse drug events among hospitalized children using a national discharge database
Authors: Tundia Namita L. , Heaton Pamela C. , Kelton Christina M.L.
Published: May 2011

Purpose

The purpose of this study was to provide a national‐level assessment of pediatric adverse drug events (ADEs), including types, frequencies, and burdens.

Methods

Discharge data were obtained from the 2006 Kids' Inpatient Database. ADEs were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification and supplemental E codes as adverse effects (AEs), accidental poisonings (APs), or those involving neuropathy, dermatitis, and contact dermatitis. For ADEs occurring in the hospital, visits were matched, by all patient refined diagnostic‐related group, age, and gender, to one control visit without an ADE code. Burden was measured as excess length of stay and excess cost relative to the control. Using regression analysis, we obtained estimates on the effects of over 100 predictors on excess length of stay and excess cost of cases relative to the control.

Results

Out of 7 558 812 hospital discharges in 2006, there were 84 510 ADEs identified during 69 620 visits (0.9% of the total number of discharges); 55 285 (79.4%) visits involved an AE; and 13 630 (19.6%) involved an AP; 12 151 (17.5%) were characterized by an ADE (usually an AP) at admission. The national pediatric ADE burden was estimated at 104 230 days with direct costs of $252.9 million. The most common AEs occurred with antineoplastic and immunosuppressive drugs (20.4%) and adrenal corticosteroids (12.5%). The most common APs involved aromatic analgesics (13.7%), cardiovascular drugs (9.5%), antidepressants (8.6%), and benzodiazepine tranquilizers (8.0%).

Conclusion

By identifying specific ADEs that occur most often and/or have the highest burden, physicians and hospital administrators can better target their strategies for reducing pediatric medication‐related harm. Copyright © 2011 John Wiley & Sons, Ltd.
Market withdrawal of new molecular entities approved in the United States from 1980 to 2009
Authors: Qureshi Zaina P. , Seoane‐Vazquez Enrique , Rodriguez‐Monguio Rosa , Stevenson Kurt B. , Szeinbach Sheryl L.
Published: May 2011

Purpose

Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009.

Methods

Data were obtained from the FDA, Micromedex, Medline, and Lexis‐Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal.

Results

There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo‐skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti‐infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals).

Conclusions

Approximately one in seven approved NMEs were discontinued from the market in the period of 1980–2009. Less than one‐quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society. Copyright © 2011 John Wiley & Sons, Ltd.
Filler exfoliation and dispersion in polypropylene/as‐received graphite nanocomposites via cryogenic milling
Authors: Hubert Paul J. , Kathiresan Krishna , Wakabayashi Katsuyuki
Published: May 2011

Nanocomposites from polypropylene and unmodified, as‐received graphite were fabricated via solid‐state cryogenic milling (cryomilling) process. Filler contents up to 10 wt% were studied with cryomilling cycles and postcryomill melt mixing option as processing parameters. Scanning electron microscopy and X‐ray diffraction of the cryomilled samples reveal that graphite filler particles are partially exfoliated into nanoplatelets, as well as fragmented in the lateral dimensions, when incorporated into the polymer matrix. Various physical performance, including polymer crystallization rate, thermomechanical response, oxygen barrier, and electrical conductivity, is closely dictated by the filler morphology. An increase in cryomilling time leads to a higher degree of exfoliation, resulting in an enhancement in stiffness/strength, thermal stability, and electrical conductivity. Postcryomill melt mixing disperses the partially exfoliated graphite nanoplatelets, raising stiffness/strength and thermal stability while reducing electrical conductivity and oxygen permeability. The percolation threshold occurs between 1 and 3 wt%, with an optimum content for most properties at ∼3 wt%. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
A facile pathway for the fast synthesis of colloidal crystal‐loaded hydrogels via frontal polymerization
Authors: Liu Si‐Si , Yu Zi‐Yi , Fang Yuan , Yin Su‐Na , Wang Cai‐Feng , Chen Li , Chen Su
Published: May 2011

In this work, a dually sensitive colloidal crystal (CC)‐loaded hydrogel has been synthesized via frontal polymerization (FP) in a facile and rapid way. First, a polystyrene CC film was fabricated by vertical deposition on the inner wall of a test tube. Then, a mixture of acrylic acid (AAc), 2‐hydroxyethyl methacrylate (HEMA), and glycerol along with the initiator and crosslinker was added to this test tube to carry out FP, resulting in the formation of CC‐loaded hydrogel. The influence of the mass ratios of HEMA/AAc on front velocity and temperatures were studied. The swelling behavior, the morphology, and the stimuli‐responsive behavior of the CC‐loaded hydrogels prepared via FP were thoroughly investigated on the basis of swelling measurement, scanning electron microscopy, and reflection spectra. Results show that the as‐prepared CC‐loaded hydrogels exhibit excellent dual sensitivity to both methanol concentrations and pH values with very short response time, which can be observed visually without the aid of instruments. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011