bluuebunny/crossref_metadata_2025 huggingface dataset:
Volume–outcome associations in head and neck cancer treatment: A systematic review and meta‐analysis
Authors: Eskander Antoine , Merdad Mazin , Irish Jonathan C. , Hall Stephen F. , Groome Patti A. , Freeman Jeremy L. , Urbach David R. , Goldstein David P.
Published: October 2013

Background

Because of the relative rarity of head and neck malignancies and their complex treatment, some groups have advocated for regionalized care. Studies comparing high‐ and low‐volume centers have demonstrated mixed results.

Methods

We conducted a systematic review using MEDLINE and EMBASE including all studies examining a volume–outcome relationship in the treatment of patients with head and neck cancer with meta‐analysis for long‐term survival results.

Results

Seventeen studies were identified. Meta‐analysis was performed for studies that assessed long‐term survival. High‐volume hospitals (5 studies; hazard ratio [HR], 0.886; 95% confidence interval [CI], 0.820–0.956) and high‐volume surgeons (2 studies; HR, 0.767; 95% CI, 0.641–0.919) have better overall survival than low‐volume hospitals and surgeons, respectively.

Conclusion

Volume–outcome associations exist for head and neck oncologic procedures, although this has not been fully investigated for salivary gland malignancies. Future quality of care studies in head and neck oncology should focus on processes of care, which may explain this relationship. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1820–1834, 2014
Temporal characterization of lymphatic metastasis in an orthotopic mouse model of oral cancer
Authors: Szaniszlo Peter , Fennewald Susan M. , Qiu Suimin , Kantara Carla , Shilagard Tuya , Vargas Gracie , Resto Vicente A.
Published: October 2013

Background

The overall mortality rate in cases of head and neck squamous cell carcinoma (HNSCC) has not improved over the past 30 years, mostly because of the high treatment failure rate among patients with regionally metastatic disease. To better understand the pathobiologic processes leading to lymphatic metastasis development, there is an urgent need for relevant animal models.

Methods

HNSCC cell lines were implanted into the tongues of athymic nude mice. Histology, immunohistochemistry, and ex vivo 2‐photon microscopy were used to evaluate tumor progress and spread.

Results

Orthotopic xenografts of different HNSCC cell lines produced distinct patterns of survival, tumor histology, disease progression rate, and lymph node metastasis development. Remarkably, all injected cell types reached the lymph nodes within 24 hours after injection, but not all developed metastasis.

Conclusion

This orthotopic xenograft model closely mimics several characteristics of human cancer and could be extremely valuable for translational studies focusing on lymphatic metastasis development and pathobiology. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1638–1647, 2014
Proliferative verrucous leukoplakia: Recognition and differentiation from conventional leukoplakia and mimics
Authors: Gillenwater Ann M. , Vigneswaran Nadarajah , Fatani Hanadi , Saintigny Pierre , El‐Naggar Adel K.
Published: October 2013

The majority of conventional leukoplakia remains constant and only a subset progress to high‐grade dysplasia or invasive carcinoma. A less recognized form known as proliferative verrucous leukoplakia (PVL) represents a unique progressive and elusive variant. Identifying patients with this form can only be achieved through the keen clinical observation of the temporal gross and histologic progression in individual patients with squamous cell carcinoma. The difficulty in the early diagnosis of PVL stems from the overlapping clinical and pathologic features with conventional multifocal leukoplakia with dysplasia. We present the current view on the clinicopathologic and biological characteristics of PVL and discuss their diagnosis, differential diagnosis, and management. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1662–1668, 2014
Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer
Authors: Tennant Paul A. , Cash Elizabeth , Bumpous Jeffrey M. , Potts Kevin L.
Published: October 2013

Background

Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ‐preservation therapy have persistent tracheostomy requirement after completion of treatment.

Methods

Patients who received primary chemoradiation for advanced laryngeal or hypopharyngeal cancer in a 3‐year interval were identified. Rate of persistent posttreatment tracheostomy requirement was evaluated. The 12‐month overall mortality rate was compared between patients who did and did not receive a tracheostomy before treatment.

Results

In 60 patients identified for this study, T3/T4 status and hemilarynx fixation at the time of presentation were associated with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022; p < .001; and p = .032; p = .0495, respectively). Twelve‐month mortality was higher in T3/T4 patients who received pretreatment tracheostomy (p = .034).

Conclusion

Patients with advanced laryngeal or hypopharyngeal cancer who require tracheostomy before treatment have low rates of decannulation and higher short‐term mortality than those who do not require tracheostomy before organ‐preservation therapy. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1628–1633, 2014
Histopathological features of clinical perineural invasion of cutaneous squamous cell carcinoma of the head and neck and the potential implications for treatment
Authors: Panizza Benedict , Warren Timothy A. , Solares C. Arturo , Boyle Glen M. , Lambie Duncan , Brown Ian
Published: October 2013

Background

Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem.

Methods

The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections.

Results

No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion.

Conclusion

Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1611–1618, 2014
Comparison of complications in free flap reconstruction for osteoradionecrosis in patients with or without hyperbaric oxygen therapy
Authors: Nolen David , Cannady Steven B. , Wax Mark K. , Scharpf Joseph , Puscas Liana , Esclamado Ramon M. , Fritz Michael , Freiberger John , Lee Walter T
Published: October 2013

Background

Hyperbaric oxygen (HBO) therapy induces native tissue oxygenation. The hypothesis was patients with mandibular osteoradionecrosis (ORN) and a history of HBO therapy would have less free flap reconstruction complications than patients without HBO therapy.

Methods

We conducted a multisite retrospective review involving radical debridement and free flap reconstruction for ORN between January 1, 1995 and June 30, 2011. Patients were stratified based on receiving prior HBO therapy or not.

Results

Thirty‐nine of 89 patients (43.8%) had HBO therapy whereas 50 of 89 (56.2%) did not. The HBO therapy group had significantly less patients with diabetes. There was no statistical difference in overall complication in patients between groups (p = .5478). However, there was marginal significance of increased infections in the patients with a history of HBO therapy (p = .0545).

Conclusion

Although no significant differences in free flap reconstruction complication rates were observed between these 2 patient cohorts, there was marginal significance of increased infections in the patients with a history of HBO therapy. A prospective multi‐institutional randomized study examining issues of infection would address issues inherent in this retrospective study. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1701–1704, 2014
Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH
Authors: Sutti Salvatore , Jindal Aastha , Locatelli Irene , Vacchiano Marco , Gigliotti Luca , Bozzola Cristina , Albano Emanuele
Published: October 2013

Previous studies have shown that human nonalcoholic steatohepatitis (NASH) is often associated with the presence of circulating antibodies against protein adducted by lipid peroxidation products. Here we used the methionine-choline deficient (MCD) model of NASH to characterize the possible involvement of adaptive immunity in NASH. In mice fed up to 8 weeks with the MCD diet the extension of liver injury and lobular inflammation paralleled the development of immunoglobulin G (IgG) against malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-derived antigens as well as with the hepatic recruitment of CD4+ and CD8+ T-lymphocytes responsive to the same antigens. Moreover, in these animals the individual IgG reactivity against MDA-adducts positively correlated with transaminase release and hepatic tumor necrosis factor alpha (TNF-α) expression. To substantiate the role of immune responses triggered by oxidative stress in the progression of NASH, mice were immunized with MDA-adducted bovine serum albumin (MDA-BSA) before feeding the MCD diet. MDA-BSA immunization did not affect control mice livers, but further stimulated transaminase release, lobular inflammation, and the hepatic expression of proinflammatory cytokine in MCD-fed mice. The increased severity of NASH in immunized MCD-fed mice involved liver recruitment and the T helper (Th)-1 activation of CD4+ T cells that, in turn, further stimulated macrophage M1 responses. Moreover, hepatic fibrosis was also evident in these animals in relation with an IL-15-mediated increase of natural killer T-cells (NKT) and the up-regulation in liver production of osteopontin by NKT cells and hepatic macrophages. Conclusion: These results indicate that oxidative stress can contribute to the progression of NASH by stimulating both humoral and cellular immune responses, pointing to the possible role of adaptive immunity in the pathogenesis of the disease. (HEPATOLOGY 2014;59:886–897)
Macrophage Plasticity and Polarization in Liver Homeostasis and Pathology
Authors: Sica Antonio , Invernizzi Pietro , Mantovani Alberto
Published: October 2013

Resident and recruited macrophages are key players in the homeostatic function of the liver and in its response to tissue damage. In response to environmental signals, macrophages undergo polarized activation to M1 or M2 or M2-like activation states. These are extremes of a spectrum in a universe of activation states. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of mononuclear phagocytes. Resident and recruited macrophages are a key component of diverse homeostatic and pathological responses of hepatic tissue. Polarized macrophages interact with hepatic progenitor cells, integrate metabolic adaptation, mediate responses to infectious agents, orchestrate fibrosis in a yin-yang interaction with hepatic stellate cells, and are a key component of tumor-promoting inflammation.

Conclusion :

A better understanding of macrophage diversity and plasticity in liver homeostasis and pathology may pave the way to innovative diagnostic and therapeutic approaches. (Hepatology 2014;59:2034–2042)
Endothelin-1 receptor A blocker darusentan decreases hepatic changes and improves liver repopulation after cell transplantation in rats
Authors: Bahde Ralf , Kapoor Sorabh , Viswanathan Preeti , Spiegel Hans-Ullrich , Gupta Sanjeev
Published: October 2013

Cell transplantation-induced hepatic ischemia and recruitment of vasoconstrictors (e.g., endothelin-1; Edn1) leads to clearance of transplanted cells and poses problems for liver repopulation. Therefore, we determined whether darusentan (DAR), which potently blocks Edn1 receptor type A, could benefit cell engraftment. We transplanted primary F344 rat hepatocytes with or without DAR in dipeptidyl peptidase IV–deficient rats. Analysis of microcirculatory events included hepatic ischemia, endothelial injury, including with gene expression arrays, and activations of Kupffer cells (KCs), neutrophils, or hepatic stellate cells (HSCs). The retrorsine-partial hepatectomy model was used for liver repopulation studies. Whether DAR was directly cytoprotective was examined in cultured rat hepatocytes or CFSC-8B rat HSCs. We found that DAR induced hepatic sinusoidal vasodilation, caused more transplanted cells to be deposited in liver parenchyma, and decreased hepatic ischemia and endothelial injury. This lessened perturbations in expression of endothelial biology genes, including regulators of vessel tone, inflammation, cell adhesion, or cell damage, versus drug-untreated controls. Moreover, in DAR-treated animals, cell transplantation-induced activation of KCs, albeit not of neutrophils, decreased, and fewer HSCs expressed desmin. In DAR-treated rats, improvements in cell engraftment led to greater extent of liver repopulation, compared to drug-untreated controls. In cell-culture assays, DAR did not stimulate release of cytoprotective factors, such as vascular endothelial growth factor, from HSCs. Moreover, DAR did not protect hepatocytes from tumor necrosis factor alpha– or oxidative stress–induced toxicity. Endothelin receptor A blockade in vitro did not improve engraftment of subsequently transplanted hepatocytes. Conclusion: Systemic administration of DAR decreases hepatic ischemia-related events and thus indirectly improves cell engraftment and liver repopulation. This vascular mechanism may permit the development of combinatorial drug-based regimens to help optimize cell therapy. (HEPATOLOGY 2014;59:1107–1117)
Ascites and Serum Sodium Are Markers of Increased Waiting List Mortality in Children With Chronic Liver Failure
Authors: Pugliese Renata , Fonseca Eduardo A. , Porta Gilda , Danesi Vera , Guimaraes Teresa , Porta Adriana , Miura Irene K. , Borges Cristian , Candido Helry , Benavides Marcel , Feier Flavia H. , Godoy Andre , Cardoso Rita Antonelli , Kondo Mario , Chapchap Paulo , Neto Joao Seda
Published: October 2013

Ascites is the most common complication of cirrhosis and in adults it is associated with 50% mortality at 5 years if patients do not receive a liver transplant. The occurrence of hyponatremia in these patients has been associated with increased mortality on the waiting list. The importance of serum sodium levels and the presence of ascites in the pediatric setting remain to be clarified. A retrospective analysis of pediatric patients with cirrhosis on the transplant list was carried out between October 2000 and February 2012. The primary objective of this study was to evaluate the association of pretransplant variables with mortality within 90 days following the inclusion of patients on the waiting list. In all, 522 patients were included in the study; 345 (66%) patients were under 1 year of age; 208 (40%) of the children presented ascites. A multivariate Cox proportional hazards analysis was conducted and total bilirubin (

P

< 0.001, hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.35-3.21), international normalized ratio (INR) (

P

< 0.001, HR = 9.83, 95% CI = 4.51-21.45), serum sodium levels (

P

= 0.03, HR = 0.96, 95% CI = 0.92-0.99), ascites (

P

= 0.001, HR = 2.59, 95% CI = 1.44-4.64), and categorized age (0-1 versus ≥1 year old) (

P

= 0.025, HR = 2.33, 95% CI = 1.11-4.86) were independently associated with risk of death in 90 days. Malnutrition (Z score height/age, weight/age) and serum albumin (pediatric endstage liver disease [PELD] formula) were not included in the final model.

Conclusion :

The presence of ascites and serum sodium levels are important variables associated with decreased patient survival while candidates wait for a liver graft. Multicenter studies are necessary to validate these findings in order to improve current allocation policies based on the PELD score. (Hepatology 2014;59:1964–1971)
Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma
Authors: Arai Yasuhito , Totoki Yasushi , Hosoda Fumie , Shirota Tomoki , Hama Natsuko , Nakamura Hiromi , Ojima Hidenori , Furuta Koh , Shimada Kazuaki , Okusaka Takuji , Kosuge Tomoo , Shibata Tatsuhiro
Published: October 2013

Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in which the molecular mechanisms underlying tumor development remain poorly understood. Identification of a novel driver oncogene and applying it to targeted therapies for molecularly defined cancers might lead to improvements in the outcome of patients. We performed massively parallel whole transcriptome sequencing in eight specimens from cholangiocarcinoma patients without KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1 and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR) screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous transplanted cells in immune-compromised mice. This transforming ability was attributable to its kinase activity. Treatment with the fibroblast growth factor receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed transformation. Conclusion: FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease. (HEPATOLOGY 2014;59:1427-1434)
Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma
Authors: Hong Yuan , Peng Yibing , Guo Sheng Z. , Guevara-Patino Jose , Pang Junfeng , Butterfield Lisa H. , Mivechi Nahid F. , Munn David H. , Bartlett David L. , He Yukai
Published: October 2013

Immunization with effective cancer vaccines can offer a much needed adjuvant therapy to fill the treatment gap after liver resection to prevent relapse of hepatocellular carcinoma (HCC). However, current HCC cancer vaccines are mostly based on native shared-self/tumor antigens that are only able to induce weak immune responses. In this study we investigated whether the HCC-associated self/tumor antigen of alpha-fetoprotein (AFP) could be engineered to create an effective vaccine to break immune tolerance and potently activate CD8 T cells to prevent clinically relevant carcinogen-induced autochthonous HCC in mice. We found that the approach of computer-guided methodical epitope-optimization created a highly immunogenic AFP and that immunization with lentivector expressing the epitope-optimized AFP, but not wild-type AFP, potently activated CD8 T cells. Critically, the activated CD8 T cells not only cross-recognized short synthetic wild-type AFP peptides, but also recognized and killed tumor cells expressing wild-type AFP protein. Immunization with lentivector expressing optimized AFP, but not native AFP, completely protected mice from tumor challenge and reduced the incidence of carcinogen-induced autochthonous HCC. In addition, prime-boost immunization with the optimized AFP significantly increased the frequency of AFP-specific memory CD8 T cells in the liver that were highly effective against emerging HCC tumor cells, further enhancing the tumor prevention of carcinogen-induced autochthonous HCC. Conclusions: Epitope-optimization is required to break immune tolerance and potently activate AFP-specific CD8 T cells, generating effective antitumor effect to prevent clinically relevant carcinogen-induced autochthonous HCC in mice. Our study provides a practical roadmap to develop effective human HCC vaccines that may result in an improved outcome compared to the current HCC vaccines based on wild-type AFP. (HEPATOLOGY 2014;59:1448-1458)
Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion
Authors: Ghonem Nisanne S. , Ananthanarayanan Meenakshisundaram , Soroka Carol J. , Boyer James L.
Published: October 2013

Multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 (MDR3/ABCB4) is a critical determinant of biliary phosphatidylcholine (PC) secretion. Clinically, mutations and partial deficiencies in MDR3 result in cholestatic liver injury. Thus, MDR3 is a potential therapeutic target for cholestatic liver disease. Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) α ligand that has antiinflammatory actions and regulates bile acid detoxification. Here we examined the mechanism by which fenofibrate regulates MDR3 gene expression. Fenofibrate significantly up-regulated MDR3 messenger RNA (mRNA) and protein expression in primary cultured human hepatocytes, and stimulated MDR3 promoter activity in HepG2 cells. In silico analysis of 5′-upstream region of human MDR3 gene revealed a number of PPARα response elements (PPRE). Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated specific binding of PPARα to the human MDR3 promoter. Targeted mutagenesis of three novel PPREs reduced inducibility of the MDR3 promoter by fenofibrate. In collagen sandwich cultured rat hepatocytes, treatment with fenofibrate increased secretion of fluorescent PC into bile canaliculi. Conclusion: Fenofibrate transactivates MDR3 gene transcription by way of the binding of PPARα to three novel and functionally critical PPREs in the MDR3 promoter. Fenofibrate treatment further stimulates biliary phosphatidylcholine secretion in rat hepatocytes, thereby providing a functional correlate. We have established a molecular mechanism that may contribute to the beneficial use of fenofibrate therapy in human cholestatic liver disease. (HEPATOLOGY 2014;59:1030–1042)
Validation of Western common recurrent chromosomal aberrations in Korean chronic lymphocytic leukaemia patients with very low incidence
Authors: Yoon Jae‐Ho , Kim Yoonjoo , Yahng Seung‐Ah , Shin Seung‐Hwan , Lee Sung‐Eun , Cho Byung‐Sik , Eom Ki‐Seong , Kim Yoo‐Jin , Lee Seok , Kim Hee‐Je , Min Chang‐Ki , Kim Dong‐Wook , Lee Jong‐Wook , Min Woo‐Sung , Park Chong‐Won , Lim Jihyang , Kim Yonggoo , Han Kyungja , Kim Myungshin , Cho Seok‐Goo
Published: October 2013

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long‐term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3–4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients. Copyright © 2013 John Wiley & Sons, Ltd.
Modeling and CFD Simulation of a Mixed‐Convection Flow of Regular Fluids and Nanofluids in Vertical Porous and Regular Channels
Authors: Hashemi Aref , Dehkordi Asghar Molaei
Published: October 2013

In this article, the problem of combined forced and free convection in vertical porous and regular channels for both regular fluids and nanofluids has been solved using the CFD technique in the entrance regions of momentum and heat transfer taking into account the influences of viscous heating and inertial force. In this regard, various types of viscous dissipation models reported in the literature such as the Darcy model, the power of the drag force model, and the clear fluid‐compatible model were applied. In the case of nanofluid flow, both the Brownian and thermophoresis molecular transfer mechanisms were considered. The dimensionless distributions of velocity, temperature, and the volume fraction of nanoparticles were determined in terms of corresponding dimensionless numbers such as the Grashof, Reynolds, Forchheimer, Brinkman, and Darcy numbers. The predicted results were validated using fully‐developed distributions of velocity and temperature. In addition, the influences of the Grashof number value on the temperature and velocity distributions in the entrance and fully‐developed regions were examined carefully. In addition, temperature and velocity distributions of nanofluids and regular fluids in porous and regular channels were compared. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(3): 243–269, 2014; Published online 30 September 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21079
Thermodynamic and Economic Optimization of Plate Fin Heat Exchangers Using the Bees Algorithm
Authors: Banooni Salem , Zarea Hossein , Molana Maysam
Published: October 2013

This study presents the successful application of the bees algorithm (BA) for optimal design of a cross‐flow plate fin heat exchanger by offset strip fins. The ε – NTU method is used to approximate the heat exchanger effectiveness and pressure drop. Two different objective functions including the minimization of total annual cost (sum of investment and operational costs) and total number of entropy generation units for certain heat duty required under given space constraints are considered as targets of optimization separately. Based on the applications, seven design parameters (heat exchanger length at hot and cold sides, fin height, fin frequency, fin thickness, fin‐strip length, and number of hot side layers) are selected as optimization variables. Two examples from the literature are presented to illustrate the efficiency and accuracy of the proposed algorithm. Results showed that the BA can detect an optimum configuration with higher speed (short computational time) and accuracy compared to the imperialist competitive algorithm (ICA) and the genetic algorithm (GA). © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(5): 427–446, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21087
CFD Simulation of Heat Transfer Augmentation in a Circular Tube Fitted with Alternative Axis Twisted Tape in Laminar Flow under a Constant Heat Flux
Authors: Salman Sami D. , Kadhum Abdul Amir H. , Takriff Mohd S. , Mohamad Abu Bakar
Published: October 2013

CFD simulation of heat transfer and friction factor characteristics in a circular tube fitted with twisted tape inserts in laminar flow and constant heat flux is conducted using FLUENT version 6.3.26. Plain and alternate axis twisted tape inserts with twist ratios (y = 2.93, 3.91, 4.89) and alternative angles (β = 30°, 60°, 90°) have been used for the simulation. The simulated results are matched with the literature correlations for a plain tube with a discrepancy of less than ±8% for Nusselt number and ±6.25% for friction factor. The results also revealed that the heat transfer in terms of the Nusselt number increased with increases of Reynolds number, alternative angles, and decreases of twist ratio. Among the various twist ratios and alternative angles, the twist ratio of y = 2.93 and alternative angle β = 90° offered a maximum heat transfer enhancement. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(4): 384–396, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21089
Theoretical Evaluation of a 10‐Watt Cooling Power Thermoacoustic Refrigerator
Authors: Prashantha B.G. , Govinde Gowda M.S. , Seetharamu S. , Narasimham G.S.V.L.
Published: October 2013

This article deals with the design, simulation, and analysis of a 10‐watt capacity thermoacoustic refrigerator using short‐stack boundary layer approximation assumptions and dimensional normalization technique. The variation of stack diameter with average gas pressure and cooling power is studied. The theoretical evaluation of quarter‐wavelength and one‐fifth‐wavelength resonator using helium gas is discussed for an operating frequency ranging from 300–500 Hz in the steps of 50 Hz. For the optimized stack, a 38.5% improvement in the stack performance for a 10‐watt cooling power quarter‐wavelength hemispherical‐ended resonator operating at 350 Hz frequency resulted in a 13.5% improvement in the coefficient of performance (COP) compared to published results. The resonator design is tested with DeltaEC software with 2% and 3% drive ratios using helium, hydrogen, neon, air, and carbon dioxide as working gases and the results are discussed. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(7): 577–591, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21094
Secondary nonmotor negative symptoms in healthy volunteers after single doses of haloperidol and risperidone: a double‐blind, crossover, placebo‐controlled trial
Authors: Mas Sergi , Gassó Patricia , Fernández de Bobadilla Ramón , Arnaiz Joan Albert , Bernardo Miquel , Lafuente Amalia
Published: October 2013

Objective

The effect of antipsychotics (APs) on negative symptoms is controversial. The present study assessed negative symptoms in healthy volunteers without any source of primary negative symptoms after single doses of haloperidol and risperidone.

Methods

Twenty‐five healthy subjects were included in this randomized, placebo‐controlled, single‐dose (haloperidol 5 mg and risperidone 2.5 mg) crossover and double‐blind clinical trial. Negative symptoms were assessed by observer‐rated scales and with a self‐report scale. Possible confounding effects considered were extrapyramidal symptoms (EPS) and sedative effects. The occupation of striatal dopamine D2 receptors was also determined.

Results

Risperidone induced a wide range of negative symptoms such as alogia, blunted affect, avolition/apathy, and attention impairment, whereas haloperidol only induced the avolition/apathy subdomain. Most of the effects of risperidone in healthy volunteers, with the exception of its effects on avolition/apathy, were attributable to AP‐induced EPS. Haloperidol did not cause significant EPS after administration. No effect of sedation or psychomotor performance was observed on negative symptoms.

Conclusions

Single doses of both haloperidol and risperidone induced nonmotor secondary negative symptoms in healthy volunteers. The clinical findings are especially relevant in view of the impact of negative symptoms on poor functioning. They may help to guide clinicians in their choice of APs (http://clinicaltrials.gov/ct2/show/NCT01259973). Copyright © 2013 John Wiley & Sons, Ltd.
Abnormal maximal finger tapping in abstinent cannabis users
Authors: Flavel Stanley C. , White Jason M. , Todd Gabrielle
Published: October 2013

Objective

To investigate movement speed and rhythmicity in abstinent cannabis users, we hypothesized that abstinent cannabis users exhibit decreased maximal finger tapping frequency and increased variability of tapping compared with non‐drug users.

Methods

The study involved 10 healthy adult cannabis users and 10 age‐matched and gender‐matched controls with no history of illicit drug use. Subjects underwent a series of screening tests prior to participation. Subjects were then asked to tap a strain gauge as fast as possible with the index finger of their dominant hand (duration 5 s).

Results

The average intertap interval did not significantly differ between groups, but the coefficient of variation of the intertap interval was significantly greater in the cannabis group than in controls (p = 0.011). The cannabis group also exhibited a slow tapping frequency at the beginning of the task.

Conclusions

Rhythmicity of finger tapping is abnormal in individuals with a history of cannabis use. The abnormality appears to be long lasting and adds to the list of functional changes present in abstinent cannabis users. Copyright © 2013 John Wiley & Sons, Ltd.
Eddy covariance‐based evapotranspiration for a subtropical wetland
Authors: Wu Chin‐Lung , Shukla Sanjay
Published: October 2013

The eddy covariance (EC) method was used in a 30‐month study to quantify evapotranspiration (ET) and vegetation coefficient (KCW) for a wetland on a ranch in subtropical south Florida. To evaluate the errors in ET estimates, the EC‐based ET (ETC‐EC) and the Food and Agricultural Organization (FAO) Penman–Monteith (PM) based ET (ETC‐PM) estimates (with literature crop coefficient, KC) were compared with each other. The ETC‐EC and FAO‐PM reference ET were used to develop KCW. Regression models were developed to estimate KCW using climatic and hydrologic variables. Annual and daily ETC‐EC values were 1152 and 3.27 mm, respectively. The FAO‐PM model underestimated ET by 25% with ETC‐EC being statistically higher than ETC‐PM. The KCW varied from 0.79 (December) to 1.06 (November). The mean KCW for the dry (November–April) season (0.95) was much higher than values reported for wetlands in literature; whereas for the wet (May–October) season, KCW (0.97) was closer to literature values. Higher than expected KCW values during the dry season were due to higher temperature, lower humidity and perennial wetland vegetation. Regression analyses showed that factors affecting the KCW were different during the dry (soil moisture, temperature and relative humidity) and wet (net radiation, inundation and wind speed) seasons. Separate regression models for the dry and wet seasons were developed. Evapotranspiration and KCW from this study, one of the first for the agricultural wetlands in subtropical environment, will help improve the ET estimates for similar wetlands. Copyright © 2013 John Wiley & Sons, Ltd.
Should the Three Gorges Dam be blamed for the extremely low water levels in the middle–lower Yangtze River?
Authors: Lai Xijun , Jiang Jiahu , Yang Guishan , Lu X. X.
Published: October 2013

Extremely low water level events have frequently occurred in the middle–lower Yangtze River (MLYR) in recent years (2006–2011). Most of these drought events coincided with the initial operation of the Three Gorges Dam (TGD). The TGD was therefore the focus of controversy about the causes of the hydrological droughts of the rivers and lakes of the region. We quantified the effects of the TGD's operation on water levels from 2006 to 2011 using a newly developed hydrodynamic model. The operation of the TGD significantly exacerbated the severe hydrological droughts that occurred in late September to November because of water impoundment, but it increased water levels from April to early June in the MLYR because of the drawdown of TGD water levels. Evidence suggests that the recent extremely low water levels were mainly because of the remarkable decline in inflows to the MLYR resulting from precipitation changes and possible human activities. Nevertheless, it should be noted that the effects of the TGD on downstream rivers and lakes will be intensified in the foreseeable future. Copyright © 2013 John Wiley & Sons, Ltd.
Short‐term flood inundation prediction using hydrologic‐hydraulic models forced with downscaled rainfall from global NWP
Authors: Nam Do Hoai , Mai Dang Thanh , Udo Keiko , Mano Akira
Published: October 2013

A short‐term flood inundation prediction model has been formulated based on the combination of the super‐tank model, forced with downscaled rainfall from a global numerical weather prediction model, and a one‐dimensional (1D) hydraulic model. Different statistical methods for downscaled rainfall have been explored, taking into account the availability of historical data. It has been found that the full implementation of a statistical downscaling model considering physically‐based corrections to the numerical weather prediction model output for rainfall prediction performs better compared with an altitudinal correction method. The integration of the super‐tank model into the 1D hydraulic model demonstrates a minimal requirement for the calibration of rainfall–runoff and flood propagation models. Updating the model with antecedent rainfall and regular forecast renewal has enhanced the model's capabilities as a result of the data assimilation processes of the runoff and numerical weather prediction models. The results show that the predicted water levels demonstrate acceptable agreement with those measured by stream gauges and comparable to those reproduced using the actual rainfall. Moreover, the predicted flood inundation depth and extent exhibit reasonably similar tendencies to those observed in the field. However, large uncertainties are observed in the prediction results in lower, flat portions of the river basin where the hydraulic conditions are not properly analysed by the 1D flood propagation model. Copyright © 2013 John Wiley & Sons, Ltd.
Human pre‐B cell receptor signal transduction: evidence for distinct roles of PI3kinase and MAP‐kinase signalling pathways
Authors: Anbazhagan Kolandaswamy , Rabbind Singh Amrathlal , Isabelle Piec , Stella Ibata , Céline Alleaume‐De Martel , Bissac Eliane , Bertrand Brassart , Rémy Nyga , Naomi Taylor , Vincent Fuentes , Rochette Jacques , Lassoued Kaïss
Published: October 2013

Pre‐BCR acts as a critical checkpoint in B cell development. However, its signalling cascade still remains indistinctly characterised in human. We investigated pre‐BCR signalling pathway to examine its regulation in normal primary pre‐B lymphocytes and pre‐B cell lines. In cell lines, early signalling events occurring after pre‐BCR stimulation include phosphorylation of Lyn, Blk and Syk together with ZAP70, Btk, Vav, PLC‐γ2 and various adaptor proteins, such as BLNK, LAB, LAT and SLP‐76. Further downstream, these molecules induced activation of the PI3K/AKT and MAP‐kinase resulting in an augmentation of canonical NF‐κB pathways and cFos/AP1 activation. PI3K and MAPK exerted opposing effects on the pre‐BCR‐induced activation of the canonical NF‐κB and c‐Fos/AP1 pathways. Immediate nuclear export of FoxO3A and delayed import of IRF4 were additional events observed after pre‐BCR crosslinking in primary cells. Pre‐BCR‐induced down‐regulation of Rag1, Rag2, E2A and Pax5 transcripts occurred in a PI3K‐dependent manner. Finally we bring evidence that pre‐BCR stimulation or co stimulation with CD19 enhances cell cycle signal.
Anthropometric, medical history and lifestyle risk factors for myeloproliferative neoplasms in The Iowa Women's Health Study cohort
Authors: Leal Alexis D. , Thompson Carrie A. , Wang Alice H. , Vierkant Robert A. , Habermann Thomas M. , Ross Julie A. , Mesa Ruben A. , Virnig Beth A. , Cerhan James R.
Published: October 2013

Classical myeloproliferative neoplasms (MPNs) are composed of essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), the etiology of which is largely unknown. We investigated the role of anthropometric, medical and lifestyle factors with risk of MPN in a prospective cohort of 27,370 women aged 55–69 years at enrollment. After >250,000 person‐years of follow‐up, 257 cases of MPN were identified (172 ET, 64 PV, 21 MF). Risk factor profiles were mostly unique for the two most common types, ET and PV. ET was associated with energy balance factors including body mass index (RR = 1.52 for >29.3vs. <23.4 kg/m2;p‐trend = 0.042), physical activity (RR = 0.66 for highvs. low;p‐trend = 0.04) and adult onset diabetes (RR = 1.82;p = 0.009), while PV was not. PV was associated with current smoking (RR = 2.83;p‐trend = 0.016), while ET was not. Regular use of aspirin was associated with lower risk of ET (RR = 0.68;p = 0.017). These results broadly held in multivariate models. Our results suggest distinct etiologies for these MPN subtypes and raise mechanistic hypotheses related to obesity‐related inflammatory pathways for ET and smoking‐related carcinogenic pathways for PV. Regular aspirin use may lower risk for ET.
Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer?
Authors: Muller I. , Giani C. , Zhang L. , Grennan‐Jones F.A. , Fiore E. , Belardi V. , Rosellini V. , Funel N. , Campani D. , Giustarini E. , Lewis M.D. , Bakhsh A.D. , Roncella M. , Ghilli M. , Vitti P. , Dayan C.M. , Ludgate M.E.
Published: October 2013

Women with breast cancer (BC) and antithyroid peroxidase (TPO) autoantibodies (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that provides a target for humoral or cell‐mediated immune activity; candidates include the sodium/iodide symporter (expressed in thyroid and BC), cross‐reacting epitopes in TPO and lactoperoxidase (LPO) or TPO itself. As the association is with TPOAb, we investigated TPO expression in BC, breast peritumoral tissue (PT), other tissues (tumoral and not) and thyroid as positive control. Transcripts for known and novel TPO isoforms were detected in BC (n = 8) and PT (n = 8) but at approximately 104‐fold lower than in thyroid while in non‐BC tumors (n = 5) they were at the limit of detection. TPO was expressed also in adipose tissue (n = 17), 103‐fold lower than in thyroid. Full length TPO (Mr 105–110 kDa) was detected in Western blots in the majority of examined tissues; preabsorption of the TPO antibody with recombinant TPO (but not LPO) reduced the signal, indicating specificity. The same occurred with some lower molecular weight bands, which could correspond to smaller TPO transcript isoforms, present in all samples. In conclusion, TPO is weakly expressed in BC and other tissues; this could partly explain the high frequency and protective role of TPOAb in BC patients. Further studies will investigate tissue specificity, function and immunogenicity of the novel TPO variants (some BC‐specific) identified.
COUP‐TFII in pancreatic adenocarcinoma: Clinical implication for patient survival and tumor progression
Authors: Polvani Simone , Tarocchi Mirko , Tempesti Sara , Mello Tommaso , Ceni Elisabetta , Buccoliero Francesca , D'Amico Massimo , Boddi Vieri , Farsi Marco , Nesi Silvia , Nesi Gabriella , Milani Stefano , Galli Andrea
Published: October 2013

Despite the accumulating knowledge of alterations in pancreatic cancer molecular pathways, no substantial improvements in the clinical prognosis have been made and this malignancy continues to be a leading cause of cancer death in the Western World. The orphan nuclear receptor COUP‐TFII is a regulator of a wide range of biological processes and it may exert a pro‐oncogenic role in cancer cells; interestingly, indirect evidences suggest that the receptor could be involved in pancreatic cancer. The aim of this study was to evaluate the expression of COUP‐TFII in human pancreatic tumors and to unveil its role in the regulation of pancreatic tumor growth. We evaluated COUP‐TFII expression by immunohistochemistry on primary samples. We analyzed the effect of the nuclear receptor silencing in human pancreatic cancer cells by means of shRNA expressing cell lines. We finally confirmed the in vitro results by in vivo experiments on nude mice. COUP‐TFII is expressed in 69% of tested primary samples and correlates with the N1 and M1 status and clinical stage; Kaplan–Meier and Cox regression analysis show that it may be an independent prognostic factor of worst outcome. In vitro silencing of COUP‐TFII reduces the cell growth and invasiveness and it strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF‐C. In nude mice, COUP‐TFII silencing reduces tumor growth by 40%. Our results suggest that COUP‐TFII might be an important regulator of the behavior of pancreatic adenocarcinoma, thus representing a possible new target for pancreatic cancer therapy.
Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR‐TKIs and mTOR inhibitor
Authors: Santoni Matteo , Berardi Rossana , Amantini Consuelo , Burattini Luciano , Santini Daniele , Santoni Giorgio , Cascinu Stefano
Published: October 2013

Angiogenesis and immunosuppression work hand‐in‐hand in the renal cell carcinoma (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune response in RCC, which involves T cells, natural killer cells, dendritic cells (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both antiangiogenic and immunomodulatory functions. Indeed, these agents affect neutrophil migration, as well as T lymphocyte‐DC cross‐talk, DC maturation and immune cell metabolism and reactivity. In this review, we overview the essential role of innate and adaptive immune response in RCC proliferation, invasion and metastasis and the relationship between tumor‐associated immune cells and the response to targeted agents approved for the treatment of metastatic RCC.
A DESCRIPTION OF THE MODIFIED ALARM DISTRESS BABY SCALE (m‐ADBB): AN INSTRUMENT TO ASSESS FOR INFANT SOCIAL WITHDRAWAL
Authors: Matthey Stephen , Črnčec Rudi , Hales Alison , Guedeney Antoine
Published: October 2013

This article introduces the m‐ADBB, a modified version of the Alarm Distress Baby Scale (ADBB; A. Guedeney & J. Fermanian, ) used to screen for infant social withdrawal. Social withdrawal can be an indicator of several factors, including infant depression. A brief description is given of various studies that have shown that infants’ behavior, as rated on the ADBB, is associated with poor maternal and paternal mental health as well as with later cognitive development. The original ADBB comprised eight items that clinicians rated on a 5‐point scale. Following work in Australia, this scale was modified to a five‐item checklist, with each item being rated on a 3‐category scale to improve interrater reliability. The m‐ADBB is described, together with data relating to psychometric properties, available training programs, and current studies.