bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Case Developments in Health Law
Authors: Wang Sally
Published: September 2010

The False Claims Act (FCA), 31 U.S.C. § 3729, a post-Civil War law inspired by cases of defense contracting fraud, was revitalized in 1986. Since then it has been used to sue both manufacturers and providers of pharmaceuticals. In some cases, these suits were meant to target offlabel marketing of pharmaceuticals. In 2009, the 11th Circuit rendered a decision in Hopper v. Solvay Pharmaceuticals that dramatically limits the ability of private plaintiff whistle-blowers to bring qui tam suits under the FCA for such marketing. In June 2010, the Supreme Court denied certiorari, making the Circuit court decision final. The Solvay decision creates a significant barrier to certain kinds of qui tam suits, requiring the plaintiff to demonstrate the intent to market off-label, including by showing specific prescriptions that were written as a result of efforts to do so.
The use of bisphosphonates in cancer treatment
Authors: Coleman Robert
Published: September 2010

Bone metastases result in considerable morbidity and exert complex demands on health care resources. Additionally, for many patients, metastatic bone disease is a chronic condition affecting quality of life and independence over years rather than months. The bisphosphonates, notably zoledronic acid, have been shown to reduce skeletal morbidity in multiple myeloma, as well as a wide range of solid tumors affecting bone, by 30–50%. Quite appropriately, the bisphosphonates are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain. In addition, they are increasingly used to prevent cancer treatment–induced bone loss and show promise in the adjuvant setting to prevent metastasis from breast cancer.
Use of bisphosphonates in the management of postmenopausal osteoporosis
Authors: Papapoulos Socrates E.
Published: September 2010

Bisphosphonates are widely used in the treatment of postmenopausal osteoporosis. They decrease the rate of bone turnover, maintain or improve structural and material properties of bone, and increase bone mineral density and thereby decrease the risk of fractures. Available potent bisphosphonates can be given to patients by different dosing regimens that range from daily oral administration to yearly intravenous infusions. Controlled studies, extending to 10 years of continuous treatment, provide information about long‐term efficacy and safety and can help in the planning of long‐term treatment strategies. Selection of bisphosphonates for the treatment of individuals should be based on a careful review of efficacy data, a risk profile of the bisphosphonate, and values and preferences of the patient.
Bisphosphonate‐related osteonecrosis of the jaw: an overview
Authors: Ruggiero Salvatore L.
Published: September 2010

Bisphosphonates are widely used in the management of metastatic disease to bone and in diseases of altered bone turnover. Recently, multiple‐case series and retrospective studies have established a relationship between necrotic bone lesions localized to the jaw and the use of chronic bisphosphonate therapy. This condition has been named bisphosphonate‐related osteonecrosis of the jaw (BRONJ). To evaluate the potential risks associated with this new and emerging complication, stage‐specific management strategies and guidelines have been developed. In view of the widespread use of chronic bisphosphonate therapy, the observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized complication and to reevaluate the indications for and the duration of bisphosphonate therapy in patients with osteopenia/osteoporosis and cancer. Morbidity associated with BRONJ might be prevented or reduced by implementing prevention strategies and establishing early diagnostic procedures. The current widespread use of bisphosphonates as an inhibitor of bone resorption is directly attributable to their efficacy in improving the quality of life for patients with metastatic bone cancer, osteoporosis, and Paget's disease.
Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients
Authors: Hoff Ana O. , Toth Bela , Hu Mimi , Hortobagyi Gabriel N. , Gagel Robert F.
Published: September 2010

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high‐potency nitrogen‐containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Paget's disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.
Mendelian genetics of rare—and not so rare—cancers
Authors: Eng Charis
Published: September 2010

Mendelian genetics forms the basis for gene‐informed risk assessment and management for the patient and family, and should be at the very foundation of 21st century personalization of healthcare. Yet this is an underutilized commodity. Identification and characterization of germline mutations in the RET proto‐oncogene, encoding a receptor tyrosine kinase, as causing >90% of multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominant disorder characterized by medullary thyroid cancer, pheochromocytoma, and hyperparathyroidism, heralded the era of evidence‐based molecular diagnosis, predictive testing, genetic counseling, gene‐informed cancer risk assessment, and preventative medicine. Since then, many syndromic endocrine neoplasias have proven to fall under this clinically utile and actionable model, such as those caused by mutations in RET, VHL, or SDHB‐D. The familial risk associated with epithelial (nonmedullary) thyroid carcinoma is among the highest of all solid tumors, yet only a few highly penetrant heritable epithelial thyroid cancer syndrome exist. This is illustrated by Cowden syndrome, a difficult‐to‐recognize autosomal dominant disorder characterized by breast, thyroid, and other cancers, caused by germline mutations in PTEN, encoding a phosphatase, and minorly, SDHB/SDHD variants.
Ultraviolet‐C Irradiation for Prevention of Central Venous Catheter‐related Infections: An In Vitro Study
Authors: Dai Tianhong , Tegos George P. , St. Denis Tyler G. , Anderson Don , Sinofsky Ed , Hamblin Michael R.
Published: September 2010

Central venous catheters (CVC) are widely used in the United States and are associated with 250 000 to 500 000 CVC‐related infections in hospitals annually. We used a catheter made from ultraviolet‐C (UVC) transmissive material to test whether delivery of UVC from the lumen would allow inactivation of microorganisms on the outer surface of CVC. When the catheter was exposed to UVC irradiation from a cold cathode fluorescent lamp inside the catheter lumen at a radiant exposure of 3.6 mJ cm−2, more than 6‐log10 of drug‐resistant Gram‐positive bacteria adhered to the outer surface of the catheter were inactivated. Three to 7‐log10 of drug‐resistant Gram‐negative bacteria and 2.80‐log10 of fungi were inactivated at a radiant exposure of 11 mJ cm−2. UVC irradiation also offered a highly selective inactivation of bacteria over keratinocytes under exactly comparable conditions. After 11 mJ cm−2 UVC light had been delivered, over 6‐log10 of bacteria were inactivated while the viability loss of the keratinocytes was only about 57%.
Ultraviolet‐A Irradiation to the Eye Modulates Intestinal Mucosal Functions and Properties of Mast Cells in the Mouse
Authors: Yamate Yurika , Hiramoto Keiichi , Kasahara Emiko , Jikumaru Mika , Sato Eisuke F. , Inoue June , Inoue Masayasu
Published: September 2010

We previously reported that topical irradiation of the eye by ultraviolet‐B (UVB) activated hypothalamo‐pituitary‐adrenal axis (HPA‐A) of the mouse to increase 3, 4‐dihydroxyphenylalanine (DOPA)‐positive melanocytes in the skin by an inducible nitric oxide synthase (iNOS)‐dependent mechanism. This work demonstrates that irradiation of the eye by ultraviolet‐A (UVA) specifically increased DOPA‐positive cells in the mucosa of the jejunum and colon of C57BL/6J mice by some HPA‐ and iNOS‐independent mechanism. UVA‐induced increase in DOPA‐positive cells in the intestine was inhibited by the administration of hexamethonium or prazosin plus propranolol, blockers for the sympathetic nervous system. UVA irradiation of the eye increased DOPA‐ and histidine decarboxylase (HDC)‐positive cells in the intestinal mucosa of both C57BL/6J and WBB6F1/J mice but not in the mutant strain W/Wv of the latter that lack mast cells. UVA irradiation of the eye suppressed the intestinal peristalsis of control, hypophysectomized or iNOS−/− C57BL/6J mice by the mechanism that was inhibited by hexamethonium or prazosin plus propranolol. These observations suggest that UVA irradiation of the eye stimulated the sympathetic nervous system to increase the mucosal DOPA‐ and HDC‐positive mast cells and suppressed the peristalsis of the small intestine of the mouse.
Effect of cytotoxic T lymphocyte‐associated molecule 4 1661 gene polymorphism on its expression and transcription in ulcerative colitis
Authors: JIANG Ting , GE Liu Qing , CHEN Zhi Tao , LI Chun , ZHOU Feng , LUO Yan , XIA Bing
Published: September 2010

OBJECTIVE:  Our aim was to investigate the expression of cytotoxic T lymphocyte‐associated molecule 4 (CTLA‐4) in ulcerative colitis (UC) and to evaluate the effect of CTLA‐4 gene ‐1661A/G polymorphism on CTLA‐4 expression and transcription.

METHODS:  A total of 20 UC patients and 22 healthy controls matched by age and sex were enrolled at Zhongnan Hospital of Wuhan University in central China. The CTLA‐4 ‐1661A/G polymorphism was genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. A Western blot analysis was performed to determine the full length CTLA‐4 (flCTLA‐4) protein expression in the peripheral blood of the UC patients. Serum‐soluble CTLA‐4 (sCTLA‐4) levels were measured by enzyme‐linked immunosorbent assay. CTLA‐4‐1661G mutant promoter transcription function was analyzed by site‐directed PCR‐based mutagenesis.

RESULTS:  CTLA‐4 protein expression on CD4+ T cells in UC patients was lower than that in the healthy controls (P < 0.001) while serum sCTLA‐4 in the UC patients was significantly higher than that in the healthy controls (P < 0.001). No correlation was found between flCTLA‐4 and sCTLA‐4 expression levels and the ‐1661 A/G polymorphism of the CTLA‐4 gene. Meanwhile, CTLA‐4 ‐1661 allele A had no significant impact on the promoter activity compared with allele G (P > 0.05).

CONCLUSION:  CTLA‐4 expressions were aberrant in UC patients compared with the healthy controls. CTLA‐4 ‐1661A/G polymorphism had no significant impact on CTLA‐4 expression and transcription in the peripheral CD4 T cells of UC patients.
Quantitative expression profiling of G‐protein‐coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target
Authors: Qin Y. , Verdegaal E. M. E. , Siderius M. , Bebelman J. P. , Smit M. J. , Leurs R. , Willemze R. , Tensen C. P. , Osanto S.
Published: September 2010

G‐protein‐coupled receptors (GPCRs) have been implicated in the tumorigenesis and metastasis of human cancers and are considered amongst the most desirable targets for drug development. Utilizing a robust quantitative PCR array, we quantified expression of 94 human GPCRs, including 75 orphan GPCRs and 19 chemokine receptors, and 36 chemokine ligands, in 40 melanoma metastases from different individuals and benign nevi. Inter‐metastatic site comparison revealed that orphan GPR174 and CCL28 are statistically significantly overexpressed in subcutaneous metastases, while P2RY5 is overexpressed in brain metastases. Comparison between metastases (all three metastatic sites) and benign nevi revealed that 16 genes, including six orphan receptors (GPR18, GPR34, GPR119, GPR160, GPR183 and P2RY10) and chemokine receptors CCR5, CXCR4, and CXCR6, were statistically significantly differentially expressed. Subsequent functional experiments in yeast and melanoma cells indicate that GPR18, the most abundantly overexpressed orphan GPCR in all melanoma metastases, is constitutively active and inhibits apoptosis, indicating an important role for GPR18 in tumor cell survival. GPR18 and five other orphan GPCRs with yet unknown biological function may be considered potential novel anticancer targets in metastatic melanoma.
Comparative studies on the growth, chlorophyll, amino acids and minerals of Thesium chinense (Santalaceae) in association with different hosts
Authors: Guo Qiao‐Sheng , Luo Fu‐Lai
Published: September 2010

Thesium chinense is a root hemiparasite and the whole weed serves as a traditional medicine in China. The resource of T. chinense is sharply declining, due to unsustainable exploitation and environmental destruction. At the same time, the obligate hemiparasitic nature and the relationship of the T. chinense‐host association are not well understood. In order to protect and cultivate T. chinense, we aimed to find a superior host for T. chinense by studying the effect of different hosts (eight host species and without host) on the growth, chlorophyll and nutrient content of pot‐cultured T. chinense. The results showed that the presence of a host species significantly promoted the growth of T. chinense but considerable differences existed among different host species. Imperata cylindrica, Prunella vulgaris, Chrysanthermum indicum were more efficient in promoting the growth of T. chinense than the other hosts. Thesium chinense chlorophyll (chl) concentration and chl a:chl b ratio increased significantly when grown with a host. Asp and Glu were the most common amino acids in T. chinense. Dry weight of T. chinense per plant was significantly positively correlated to the concentration of Pro (r=0.870, p<0.01), but significantly negatively correlated to the concentration of Gly (r=−0.688, p<0.01). Thesium chinense grown with a host had a high concentration of K, P, Cu and K/Ca ratio and a low Na concentration compared with those without host plants. Dry weight of T. chinense per plant was significantly positively correlated to the concentration of K. It is concluded that Imperata cylindrica, Prunella vulgaris, Chrysanthermum indicum are superior hosts for T. chinense.
High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients
Authors: Akkarathamrongsin Srunthron , Sugiyama Masaya , Matsuura Kentaro , Kurbanov Fuat , Poovorawan Yong , Tanaka Yasuhito , Mizokami Masashi
Published: September 2010

Aim:  Recent human genome‐wide association studies (GWAS) revealed a strong association between IL28B gene variation and the pegylated interferon‐α with ribavirin (PEG‐IFN‐α/RBV) treatment response in chronic hepatitis C patients. Two single nucleotide polymorphisms (SNP), rs8103142 and rs11881222 located in the IL28B gene, were found in significant association with the viral clearance. The present study employed these SNPs to develop a new accessible screening method allowing identification of potential non‐responders before starting the therapy.

Methods:  Primer sets were designed to amplify rs8103142 and rs11881222 fragments from genomic DNA extracted from serum samples. This method was validated using microarray typing (GWAS) and applied for genotyping of 68 hepatitis C virus‐infected patients with PEG‐IFN‐α/RBV treatment at baseline.

Results:  In comparison with GWAS, the screening method showed 100% and 95.6% accuracy in typing of rs8103142 and rs11881222, respectively, indicating incomplete specificity but 100% of sensitivity in both. Genotyping by both SNP showed that 53 (77.9%), 14 (20.6%) and one (1.5%) of the patients were of major homozygous, heterozygous and minor homozygous type, respectively. The majority (85%) of homozygous patients exhibited response to therapy in contrast to heterozygous patients (29%). Among all genotyped only one case was found with the minor homozygous genotype which had late virological response to therapy before relapsing.

Conclusion:  This study described a highly sensitive assay that can be useful in determining SNP genotypes as well as in predicting the response to IFN‐based treatment.
New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma
Authors: Kawamura Yusuke , Ikeda Kenji , Hirakawa Miharu , Yatsuji Hiromi , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Kobayashi Masahiro , Saitoh Satoshi , Suzuki Fumitaka , Suzuki Yoshiyuki , Arase Yasuji , Kumada Hiromitsu
Published: September 2010

Aim:  The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic computed tomography (CT) images.

Methods:  This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial‐ and portal‐phase dynamic CT images obtained preoperatively were classified into four enhancement patterns: Type‐1 and Type‐2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type‐3, heterogeneous enhancement pattern with septum‐like structure; and Type‐4, heterogeneous enhancement pattern with irregular ring‐like structures. We also evaluated the predictive factors for poorly‐differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses.

Results:  The percentages of poorly‐differentiated HCC according to the enhancement pattern were three of 51 nodules (6%) of Type‐1 and ‐2, three of 24 (13%) of Type‐3, and eight of 11 (73%) of Type‐4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type‐1 and ‐2, 13 of 24 (54%) of Type‐3, and five of 11 (45%) of Type‐4. Multivariate analysis identified Type‐4 pattern as a significant and independent predictor of poorly‐differentiated HCC (P < 0.001) while Type‐3 pattern was a significant predictor of SNEG/CMN (P = 0.017).

Conclusion:  Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment.
Efficacy and safety of double filtration plasmapheresis in combination with interferon therapy for chronic hepatitis C
Authors: Kaneko Shuichi , Sata Michio , Ide Tatsuya , Yamashita Tatsuya , Hige Shuhei , Tomita Eiichi , Mochida Satoshi , Yamashita Yukitaka , Inui Yoshiaki , Kim Soo Ryang , Komada Naoto , Mikami Takafumi , Satoh Shinichi , Morita Sumiharu , Takaguchi Koichi , Hirashima Noboru , Nishio Yuji , Watanabe Daisuke , Kioka Kiyohide , Fujiwara Kenji
Published: September 2010

Aim:  Efficacy and safety of double filtration plasmapheresis (DFPP) for chronic hepatitis C were prospectively analyzed in Japanese clinical settings.

Methods:  All patients who received DFPP in combination with interferon (IFN) therapy for chronic hepatitis C were serially recruited at 36 institutions between April 2008 and July 2009 in Japan.

Results:  A total of 239 patients were analyzed for the safety of DFPP and 206 patients for the efficacy. Of the 206 patients, 181 patients were treated with DFPP in combination with pegylated interferon plus ribavirin (PEG‐IFN/RBV + DFPP). Among the 181 patients, 60 patients (33.1%) were treatment‐naïves, 35 (19.3%) relapsers and 62 (34.3%) non‐responders. Complete early virological response (cEVR) in patients treated with PEG‐IFN/RBV + DFPP was achieved in 57.5% overall, 70.0% in treatment‐naïves, 57.1% in relapsers and 41.9% in non‐responders. In patients with previous PEG‐IFN/RBV therapy, cEVR were found in 63.0% of relapsers and 18.9 % of non‐responders, and cEVR in patients with other than PEG‐IFN/RBV therapy as previous IFN therapy, relapsers and non‐responders was 37.5% and 76.0%, respectively. Adverse events were found in 55 patients (23.0%). Serious adverse events were found in four patients (1.7%) who showed puncture‐site injury. Adverse events were related to female sex, but not related to age, and DFPP could be performed safely.

Conclusion:  The cEVR results in this study suggest that high rates of sustained virological response can be achieved in retreated and treatment‐naïve patients using DFPP in combination with PEG‐IFN/RBV therapy. Results indicate that this therapy could be safely conducted, even in elderly patients.
Radiofrequency ablation of hepatocellular carcinoma: The feasibility of magnetic resonance imaging with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid for evaluating the ablative margin
Authors: Okubo Hironao , Kokubu Shigehiro , Komiyama Masae , Yamagata Hisafumi , Uchiyama Akira , Miyazaki Akihisa , Watanabe Sumio
Published: September 2010

Aim:  The aim of this study was to evaluate the feasibility of gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA) in magnetic resonance imaging (MRI) to assess the ablative margin of radiofrequency (RF) ablation to hepatocellular carcinoma (HCC).

Methods:  RF ablation was performed in the livers of six pigs after the i.v. administration of Gd‐EOB‐DTPA 20 min before ablation. Three pigs were killed 2 h after administration (group A), and the other pigs were killed 7 days after ablation (group B). Thereafter, correlation between pathological findings and MRI was investigated. Moreover, the Gd concentrations were examined in ablated and non‐ablated regions. An initial clinical evaluation was conducted for 28 HCC nodules. Percutaneous RF ablation was performed 20 min after administration, and T1‐weighted images were taken 2, 24 and 72 h post‐treatment.

Results:  On T1‐weighted images of the porcine liver, the RF ablated lesions showed hyperintense regions with hypointense rims, which histopathologically corresponded to sinusoidal congestion. The Gd concentrations in ablated regions in group A were significantly higher than those in non‐ablated regions, while the concentrations in both regions in group B fell to nearly undetectable levels. In 27 of the 28 HCC nodules, the treated area consisted of a hypointense region, indicative of the tumor, and a surrounding hyperintense rim 2 h after ablation. Subsequently, a thin hypointense region was observed in the outermost layer 24 and 72 h after ablation.

Conclusion:  Administration of Gd‐EOB‐DTPA in conjunction with RF ablation of HCC may be feasible for the assessment of an accurate ablative margin.
Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressin
Authors: Kalambokis George , Baltayiannis Gerasimos , Tsiouris Spyridon , Pappas Konstantinos , Kokkinou Panorea , Fotopoulos Andreas , Tsianos Epameinondas V.
Published: September 2010

Aim:  The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment.

Methods:  Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium‐99m‐labeled macroaggregated albumin (99mTc‐MAA) and calculation of brain uptake (positive value ≥6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography.

Results:  Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child–Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01).

Conclusion:  IPS fractions detected by 99mTc‐MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt.
Clinical and histopathological study of “follicular cholangitis”: Sclerosing cholangitis with prominent lymphocytic infiltration masquerading as hilar cholangiocarcinoma
Authors: Fujita Takeo , Kojima Motohiro , Kato Yuichiro , Gotohda Naoto , Takahashi Shinichiro , Konishi Masaru , Kinoshita Taira
Published: September 2010

Aim:  Sclerosing cholangitis which mimic hilar biliary carcinoma have not been fully categorized. In this study, we investigated the clinicopathological features of sclerosing cholangitis of unknown origin, so‐called “follicular cholangitis”.

Methods:  Patients who had undergone surgery of the proximal bile duct from 1993–2008 on suspicion of proximal bile carcinoma were evaluated. Of these, we investigated the cases compatible with follicular cholangitis. Then, we reviewed the previous reports of follicular cholangitis showing similar clinicopathological findings.

Results:  Among 176 patients, two who were diagnosed with benign sclerosing cholangitis of unknown origin shared the common histopathological findings compatible with follicular cholangitis. Histopathological findings showed dense fibrosis with prominent lymph follicles and germinal centers, being appropriate for neither primary sclerosing cholangitis nor immunoglobulin G4‐related sclerosing cholangitis. Review of previous published work revealed two other cases diagnosed with follicular cholangitis and showing histopathological findings similar to ours. All these cases were middle‐aged patients with no history of autoimmune disease with focal strictures mainly involved in the hilar bile duct, mimicking hilar cholangiocarcinoma.

Conclusion:  Benign sclerosing cholangitis has not been fully categorized, yet. Follicular cholangitis shows unique histopathological features and can be categorized as an independent entity.
Iron state in association with retinoid metabolism in non‐alcoholic fatty liver disease
Authors: Tsuchiya Hiroyuki , Ashla An Afida , Hoshikawa Yoshiko , Matsumi Yoshiaki , Kanki Keita , Enjoji Munechika , Momosaki Seiya , Nakamuta Makoto , Taketomi Akinobu , Maehara Yoshihiko , Shomori Kohei , Kurimasa Akihiro , Hisatome Ichiro , Ito Hisao , Shiota Goshi
Published: September 2010

Aim:  We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non‐alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders.

Methods:  Thirty‐six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism‐related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action.

Results:  In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein (CRBP1), alcohol dehydrogenase 1 (ADH1) and cytochrome P450 26A1(CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively.

Conclusion:  The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease.
Cyclooxygenase‐2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression
Authors: Sakaki Masashi , Makino Reiko , Hiroishi Kazumasa , Ueda Kumiko , Eguchi Junichi , Hiraide Ayako , Doi Hiroyoshi , Omori Risa , Imawari Michio
Published: September 2010

Aim:  Because polymorphisms of cyclooxygenase‐2 (COX‐2) and osteopontin (OPN) promoter regions and a promoter/enhancer region of forkhead box protein 3 (FOXP3) gene are known to affect immune responses, we examined whether these polymorphisms can influence susceptibility to hepatitis C virus (HCV) infection and progression of liver disease.

Methods:  Peripheral blood samples were obtained from 104 Japanese patients with chronic HCV infection and 74 healthy Japanese donors. Polymerase chain reaction single‐stranded conformational polymorphism analysis of genomic DNA was performed to determine the polymorphisms.

Results:  The risk of persistent HCV infection was decreased in subjects with –1195GG genotype of the COX‐2 promoter region. However, in patients with chronic HCV infection, the –1195GG genotype was associated with advanced‐stage liver disease. A luciferase reporter assay performed to analyze the effect of single nucleotide polymorphisms (SNP) (–1195A or –1195G) in COX‐2 gene on transcriptional activity using the HepG2, Huh7 and HeLa cell lines indicated that the –1195G genotype showed higher transcriptional activity than the –1195A genotype. SNP of OPN and FOXP3 did not differ between patients with chronic HCV infection and controls. However, the –443TT genotype of the OPN promoter region was associated with increased inflammatory activity of the liver.

Conclusion:  These results suggest that the –1195GG genotype of the COX‐2 promoter region protects against HCV infection in the Japanese. However, once chronic infection is established, the –443TT genotype of the OPN promoter region and the –1195GG genotype of the COX‐2 promoter are thought to promote inflammation and contribute to the progression of liver disease.
An Iterative Learning Control of Nonlinear Systems Using Neural Network Design
Authors: Chien Chiang‐Ju , Fu Li‐Chen
Published: September 2010

In this paper, a feedforward neural network with sigmoid hidden units is used to design a neural network based iterative learning controller for nonlinear systems with state dependent input gains. No prior offline training phase is necessary, and only a single neural network is employed. All the weights of the neurons are tuned during the iteration process in order to achieve the desired learning performance. The adaptive laws for the weights of neurons and the analysis of learning performance are determined via Lyapunov‐like analysis. A projection learning algorithm is used to prevent drifting of weights. It is shown that the tracking error vector will asymptotically converges to zero as the iteration goes to infinity, and the all adjustable parameters as well as internal signals remain bounded.
Producing Customer Happiness: The Job to Do for Brand Innovation
Authors: Norton David W. , Durgee Jeffrey F. , VanDeVelde Jeffrey
Published: September 2010

Millions of marketing dollars have been spent trying to satisfy customers, when what customers really want is to be happy. These authors categorize four types of happiness. Your job is to align what you do with at least one of them.
Living Briefs to Turn Desired Futures into Reality
Authors: Topalian Alan
Published: September 2010

Design briefs have changed over the past 20 years, in terms of both expectations and outcomes. Increasingly, designers have gotten involved in diagnosing business problems and uncovering opportunities, as well as considering user experiences. Living briefs provide a framework that can help with this process.
Glass Transition Behavior: A Generic Phenomenological Approach
Authors: Gutzow Ivan , Pascova Radost , Schmelzer Jürn W. P.
Published: September 2010

This paper surveys phenomenological and atomistic methods by which glass transition can be described. A new generic phenomenological approach to the study of glass transition as an irreversible process is then derived and fully used. This new approach describes the kinetics and thermodynamics of vitrification as a real, nonequilibrium process of structural arrest, entropy freeze, and entropy production. The temperature dependence of the thermodynamic functions is constructed as it corresponds to the principles of both classical and irreversible thermodynamics and to the experimental evidence obtained through long years of glass‐science research. The developed generic phenomenological approach complements, expands, and quantitatively corrects the approximations of F. Simon, which have been the principal method in glass science thermodynamics for over 80 years. Using the same generic phenomenological approach, new and classical models for describing the glass transition are examined in terms of past and current molecular statistical models. The methods derived in the present phenomenological approach indicate alternative ways to synthesize glasses with new properties and technical applications by changing the rates of structural arrest at vitrification, as they are determined by cooling rate, pressure increase, or alteration of the strength of electric or magnetic fields.
Kit for detection of fungal endophytes of grasses yields inconsistent results
Authors: Jensen John Beck , González Victoria T. , Guevara Diego Urrutia , Bhuvaneswari T. V. , Wäli Piippa R. , Tejesvi Mysore V. , Pirttilä Anna Maria , Bazely Dawn , Vicari Mark , Bråthen Kari Anne
Published: September 2010

1. The Agrinostics field immunoblot assay is a colour‐imprint assay originally developed for routinely and rapid detection of mycotoxin‐producing fungi Neotyphodium spp./Epichloë spp. from samples of pasture, turf, cereals and seeds of agricultural grasses.

2. In addition the Agrinostics immunoblot assay has been used and recommended for exploring the presence and ecological role of Neotyphodium and the closely related Epichloë in several cool season grasses.

3. Here we demonstrate that this method is not limited to detection of only these two species, as several other fungal endophyte genera or species also yielded positive results when mycelia were loaded onto cards. Moreover, other closely related endophyte genera or species were found to yield negative result. Thus, the assay is neither specific to isolates of Neotyphodium/Epichloë nor is it universal for fungal endophyte detection.

4. Our study underscore the fact that the Agrinostics field immunoblot assay should not be used on its own for field research into the broader ecological significance of Neotyphodium/Epichloë.

5. We suggest that the assay may be best suited for use in agricultural fields or in controlled greenhouse experiments for hyphal load estimates, and should always be accompanied by other methods (e.g. microscopic visualization, DNA‐sequencing) to confirm infection frequencies and certify that the endophyte present actually is Neotyphodium/Epichloë.
A generic structure for plant trait databases
Authors: Kattge Jens , Ogle Kiona , Bönisch Gerhard , Díaz Sandra , Lavorel Sandra , Madin Joshua , Nadrowski Karin , Nöllert Stephanie , Sartor Karla , Wirth Christian
Published: September 2010

1. Plant traits are fundamental for understanding and predicting vegetation responses to global changes, and they provide a promising basis towards a more quantitative and predictive approach to ecology. As a consequence, information on plant traits is rapidly accumulating, and there is a growing need for efficient database tools that enable the assembly and synthesis of trait data.

2. Plant traits are highly heterogeneous, exhibit a low degree of standardization and are linked and interdependent at various levels of biological organization: tissue, organ, plant and population. Therefore, they often require ancillary data for interpretation, including descriptors of the biotic and abiotic environment, methods and taxonomic relationships.

3. We introduce a generic database structure that is tailored to accommodate plant trait complexity and is consistent with current theoretical approaches to characterize the structure of observational data. The over‐arching utility of the proposed database structure is illustrated based on two independent plant trait database projects.

4. The generic database structure proposed here is meant to serve as a flexible blueprint for future plant trait databases, improving data discovery, and ensuring compatibility among them.
Laparoscopic assisted surgical removal of a congenital rectal hamartoma in a foal
Authors: Salazar T. , Caldwell F. , Joiner K. , Parra‐Sanchez A. , Stewart A. J.
Published: September 2010

In this report we describe a 3‐week‐old Paint horse filly that presented with rectal bleeding associated with a protruding mass. Rectal bleeding in neonates can be caused by infectious agents, trauma, congenital defects, rectal tears or tumours. Histopathology was performed on an avulsed piece of tissue. A second mass was identified endoscopically and was removed using a stapling instrument per rectum under endoscopic guidance and laparoscopic assistance. The mass was diagnosed as a rectal hamartoma. Recovery was uneventful.
Effect of Weld Location, Orientation, and Strain Path on Forming Behavior of AHSS Tailor Welded Blanks
Authors: Panda S. K. , Li J. , Hernandez V. H. Baltazar , Zhou Y. , Goodwin F.
Published: September 2010

Use of multiple advanced high strength steel sheets for fabrication of tailor welded blanks (TWBs) is one of the current interests for automotive and steel industries as it reduces manufacturing cost and weight of the vehicle, and also improves the quality of the component. As the varieties of TWB applications are increasing, the effects of the difference in material properties, weld, and its orientation on blank formability have become important both in deep drawing and stretch forming. In this work, high strength low alloy (HSLA) grade steels were laser welded with two different dual phase steels having 980 MPa (DP980) and 600 MPa (DP600) tensile strengths to fabricate two different material combination TWBs (DP980-HSLA and DP600-HSLA). Formability of these two types of TWBs has been studied experimentally both in biaxial and plane strain stretch forming modes by performing limiting dome height (LDH) tests using a 101.6 mm diameter hemispherical punch. Five different weld locations during biaxial-stretch forming mode, and the effect of weld orientation with respect to major principal strain in plane strain stretch forming mode, have been studied. It was found that formability LDH and failure location depended on weld location, and LDH increased when weld line was positioned at the extreme positions away from the center due to more uniform strain distribution on the deformed dome. The welded blanks had lower formability in plane strain deformation mode compared with biaxial-stretch forming mode. However, influence of weld orientation on the formability depended on material combination. Changes in the fracture mode were confirmed from fractography analysis of biaxial, transverse plane strain, and longitudinal plane strain stretch formed samples.
Strain-Rate Sensitivity of Aluminum Alloys AA1200 and AA3103
Authors: Lademo O.-G. , Engler O. , Aegerter J. , Berstad T. , Benallal A. , Hopperstad O. S.
Published: September 2010

Tensile tests are carried out for the aluminum alloys AA1200 and AA3103 at various strain-rates in the range from 10−4 s−1 to 1 s−1. Tests with constant nominal strain-rate and strain-rate jump tests are conducted, and the instantaneous rate sensitivity and the rate sensitivity of strain hardening are investigated. For both materials, the instantaneous rate sensitivity is found to be rather independent of strain, while the rate sensitivity of the strain hardening is important and the saturation stress increases with increasing strain-rate. A phenomenological constitutive model is described that comprises a kinetic equation governing the instantaneous rate sensitivity of the flow stress and a structural parameter that determines the mechanical state of the material. The evolution of the structure parameter is assumed to depend on strain-rate. The model parameters are determined for the two materials using the available experimental information. It is found that the constitutive model provides a good representation of the experimental results.
Fatigue Characterization and Modeling of Friction Stir Spot Welds in Magnesium AZ31 Alloy
Authors: Jordon J. B. , Horstemeyer M. F. , Daniewicz S. R. , Badarinarayan H. , Grantham J.
Published: September 2010

The fatigue behavior of friction stir spot welds in magnesium AZ31 alloy is experimentally investigated and modeled. The friction stir spot welds employed in this study are representative of preliminary welds made in developing the joining process for potential use in automobile manufacturing. Load control cyclic tests were conducted on single weld lap-shear coupons to determine fatigue life properties. Optical fractography of the failed fatigue coupons revealed that fatigue cracks initiated from the interfacial “hook” and eventually failed by either nugget pullout or full width separation, depending on the cyclic load amplitude. The failure modes of the magnesium AZ31 alloy were similar to the aluminum alloys of comparable friction stir spot welds. To predict the fatigue life of the lap-joint coupons, a crack growth modeling approach based on a kinked crack stress intensity solution was used. The fatigue model predictions compared well to the experimental fatigue life results, despite an approximate stress intensity factor solution for this weld geometry. The experiments and modeling conducted in this study suggest that the size of the interfacial hook, which comes about from the speed, depth of plunge, dwell time, and tool configuration of the friction stir spot weld process, is a major contributor to the fatigue life of the joint.
Creep Behavior of Copper and Cu–0.3Cr–0.1Ag Alloy
Authors: Akbari-Fakhrabadi A. , Mahmudi R. , Karsaz A. , Geranmayeh A. R.
Published: September 2010

The creep behavior of Cu–0.3Cr–0.1Ag alloy was investigated by the impression creep testing technique and compared with that of pure copper under constant punching stress in the range 80–550 MPa at temperatures in the range 688–855 K. The enhanced creep resistance of the Cr- and Ag-containing alloys was attributed to the distribution of Cr-rich phase in the copper matrix. Assuming a power-law relationship between the impression stress and velocity, the average stress exponents of 6.0–7.5 and 6.4–8.0 were obtained for pure Cu and CuCrAg, respectively. It was found that the average activation energies were 112.4 kJ mol−1 and 143.5 kJ mol−1 for the pure Cu and CuCrAg alloys, respectively. These activation energies are close to 138 kJ mol−1 for dislocation climb in Cu. This, together with the stress exponents of about 7, suggests that the operative creep mechanism is dislocation climb controlled by dislocation pipe diffusion.
Metal artifact suppression from reformatted projections in multislice helical CT using dual‐front active contours
Authors: Li Hua , Yu Lifeng , Liu Xin , Fletcher Joel G. , McCollough Cynthia H.
Published: September 2010

Purpose:

Large metallic implants, such as hip prosthesis and shoulder implants, can cause severe artifacts in CT exams. As such, there have been significant efforts on the design of various image‐ or projection‐based correction methods or iterative reconstruction methods with the hope to reconstruct artifact‐free images. Unfortunately, suppression of metal artifacts remains a very challenging problem, in which metal region segmentation is one of the most important steps in assuring the efficiency of artifact suppression. In this article, the authors propose a novel, semiautomatic metal region segmentation algorithm based on a dual‐front active contour model and a boundary mapping strategy to detect multiple large metal implants on reformatted projection data and to effectively suppress or eliminate metal artifacts on reconstructed images.

Methods:

First, the projections created from helical scan data were reformatted by combining data at the same view angle over the full longitudinal scan range. In this way, the shape, location, and number of the metal structures show up clearly on each reformatted projection, changing only slightly between adjacent projections. Second, an initial boundary on one of the reformatted projections is defined, and a boundary mapping strategy was utilized to map the metal boundary on the first reformatted projection to the next adjacent projection. Third, a novel dual‐front active contour model was used to evolve the mapped boundary from the prior projection to the actual boundary in the current projection. By iteratively performing the boundary mapping and boundary evolution procedure, the metal structures (one or multiple) on all the projections can be extracted efficiently and accurately. Finally, a Delaunay triangulation was applied to fill the metal shadows and the corrected projection data were reconstructed with a commercially available algorithm.

Results:

Experimental studies on clinical hip and shoulder CT exams and a comparison with a gradient‐based threshold method were performed. The results demonstrated that the proposed segmentation strategy was able to segment multiple metal implants more accurately than the threshold method. Soft‐tissue visibility was improved dramatically.

Conclusions:

In total, the artifacts caused by dense metal implants were suppressed dramatically with the proposed metal artifact suppression technique.
Modeling scatter‐to‐primary dose ratio for megavoltage photon beams
Authors: Wang Ken Kang‐Hsin , Zhu Timothy C.
Published: September 2010

Purpose:

A three‐parameter semiempirical model for scatter‐to‐primary dose ratio (SPR) is proposed to fit PDD (or TPR) and beam data. The SPR formula proposed in this study is more accurate than the previously published formula utilizing two parameters, especially for lower energy megavoltage photon beams, because the effect of backscattered photons is now taken into account.

Methods:

Monte Carlo (MC) calculated SPR for photon energy spectrum between and 24 MV are used to evaluate the accuracy of the models. Based on fitting the MC data, the dependence of the SPR parameters with the attenuation coefficients of the photon beams is obtained and they were incorporated into the authors’ optimization routine. The ability of the optimization routine to fit measured clinic data is examined for photon energies ranging from to 25 MV for all major cobalt and linear accelerator manufacturers.

Results:

The authors’ model successfully fits the measured photon beam data for field size, where is photon energy in MV and for clinically usable depths, to 20 cm for , to 30 cm for 4 MV, and to 40 cm for 6 MV and higher photon energies. The maximum error among these fits is better than 2% for photon energies above .

Conclusions:

The new SPR formula, along with the optimization routine, can serve as an efficient tool for performing quality control of x‐ray beam data that conforms to AAPM Radiation Therapy Committee TG40 and Therapy Physics Committee TG142 reports on beam data requirement.