bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Change
Authors: Gascoigne Toss
Published: April 2008

The Australian national election at the end of 2007 replaced a decade-long conservative government with a new, socially progressive government by a comfortable nationwide margin. This election has been widely reported as hinging on the progressive party's ability to successfully communicate about global climate change issues, and has even been heralded as the first national election campaign in recent history to turn on a scientific topic. However, analysis of the rhetoric used in the campaign cycle suggests that while climate change was the defining issue in this national campaign, in reality it served as a proxy for perceptions that the conservative government held closely to outdated ideas and ideologies in the face of new and emerging information. Climate change, which had previously not registered as a voter concern, worked as an analogy because Australia was experiencing its worst drought in 100 years.
Examining Local Government Service Delivery Arrangements Over Time
Authors: Lamothe Scott , Lamothe Meeyoung , Feiock Richard C.
Published: April 2008

While scholars of local service delivery arrangements are fully aware the process is dynamic, research has tended to take the form of cross-sectional studies that are inherently static in nature. In this article, the authors model the determinants of production mode accounting for past delivery decisions. They find, not surprisingly, that there are strong inertial effects; previous delivery mode is a strong predictor of the current service delivery arrangement. More interestingly, the impact of the transaction cost nature of services on production choice is conditioned on past decisions, such as the extent of contracting and the type of vendors used. There is also evidence that contract management capacity and the competitiveness of the contracting environment are influential.
What Does HRD Know About Organizational Crisis Management? Not Enough! Read on
Authors: Hutchins Holly M.
Published: April 2008

The problem and the solution. Organizational crises have become more complex, far-reaching, and prevalent in modern times. Disease outbreaks, investor fraud, terrorist acts, and natural disasters are but a few of the events that can morph into crisis events and have severe impacts on organization sustainability.This article introduces the area of organizational crisis management to the human resource development (HRD) community, discusses trends that contribute to organizational crisis being a relevant area for HRD inquiry, and previews the contributing perspectives included in this issue.
Basic Science Review: The Myopathy of Peripheral Arterial Occlusive Disease: Part 2. Oxidative Stress, Neuropathy, and Shift in Muscle Fiber Type
Authors: Pipinos Iraklis I. , Judge Andrew R. , Selsby Joshua T. , Zhen Zhu  , Swanson Stanley A. , Nella Aikaterini A. , Dodd Stephen L.
Published: April 2008

In recent years, an increasing number of studies have demonstrated that a myopathy is present, contributes, and, to a certain extent, determines the pathogenesis of peripheral arterial occlusive disease. These works provide evidence that a state of repetitive cycles of exercise-induced ischemia followed by reperfusion at rest operates in patients with peripheral arterial occlusive disease and mediates a large number of structural and metabolic changes in the muscle, resulting in reduced strength and function. The key players in this process appear to be defective mitochondria that, through multilevel failure in their roles as energy, oxygen radical species, and apoptosis regulators, produce and sustain a progressive decline in muscle performance. In this 2-part review, the currently available evidence that characterizes the nature and mechanisms responsible for this myopathy is highlighted. In part 1, the functional and histomorphological characteristics of the myopathy were reviewed, and the main focus was on the biochemistry and bioenergetics of its mitochondriopathy. In part 2, accumulating evidence that oxidative stress related to ischemia reperfusion is probably the major operating mechanism of peripheral arterial occlusive disease myopathy is reviewed. Important new findings of a possible neuropathy and a shift in muscle fiber type are also reviewed. Learning more about these mechanisms will enhance our understanding of the degree to which they are preventable and treatable.
Are Rape Crisis Centers Feminist Organizations?
Authors: Maier Shana L.
Published: April 2008

Although rape crisis centers began as feminist organizations, research exploring centers' current feminist identity is limited. Data from interviews with 63 staff, volunteers, interns, and directors affiliated with six rape crisis centers and programs located in four East Coast states are used to examine how they view feminism and whether they believe their rape crisis centers maintain a feminist ideology. Although most directors identified their organization as a feminist one, they also indicated that the feminist identity of rape crisis centers has changed over time as organizations increasingly collaborated with mainstream organizations and became less politically active. Because of the possible negative connotation of the word “feminism,” some directors and advocates spoke of their reluctance to advertise as a feminist organization for fear of alienating victims, potential volunteers, and/or funders.
The Violence Against Women Campaigns in Latin America
Authors: Cole Sally , Phillips Lynne
Published: April 2008

This article urges caution in reading the backlash against gender-sensitive policies as a global phenomenon. Drawing inspiration from Latin America, the authors consider how international agreements for nation-states to adopt measures to prevent violence against women have been taken up in proactive ways through the collaboration of international organizations, national governments, and expanding and evolving women's movements. The push for the development of democratic citizenship in Latin America has opened up possibilities for bringing awareness of violence against women to a public that is in the process of engaging with a range of social justice issues and collaborating on multiple fronts. The authors argue that strategic coalitions across difference have been central to the success of the efforts to combat violence against women. They show how new feminist alliances have not only helped denormalize and deprivatize gender violence but revitalized feminist issues as part of a broad front to build progressive societies.
Falling Between the Cracks of Retributive and Restorative Justice
Authors: Balfour Gillian
Published: April 2008

In 1996, the Canadian government introduced progressive sentencing law reforms that called for special consideration of the conditions in Aboriginal communities as legacies of colonialism and to limit the use of incarceration. At the same time, feminist-inspired law reforms sought compulsory criminalization and vigorous prosecution of gendered violence. Since that time, there has been a doubling of the rate of imprisonment of Aboriginal women, and gendered violence is three and a half times greater in Aboriginal communities. Using the sentencing decisions of two cases involving Aboriginal women convicted of manslaughter, the author explores the practice of law as a site of backlash and an appropriation of feminist-inspired antiviolence strategies. The author draws on feminist and critical race studies of restorative justice in the context of gendered violence to examine why the victimization–criminalization continuum has not been fully recognized in the practice of restorative justice.
Memory, history and the claims of the past
Authors: Poole Ross
Published: April 2008

This article presents an account of collective memory which explains its relationship to individual memory on the one hand and to history on the other. It argues that the role of memory, both individual and collective, is not merely cognitive; it is also normative. That is, memory does not simply transmit information from the past to the present; it also transmits responsibilities. Insofar as collective memory has a cognitive aspect, it makes claims about the past. These may be confirmed or disconfirmed by historical research. This does not mean that collective memory is just bad history. It is more like history written in the first person, and its role is to inform the present generation of its responsibilities to the past.
Local conditions, global environment and transnational discourses in memory work: The case of Bloody Sunday (1972)
Authors: Conway Brian
Published: April 2008

Within the collective memory literature, very few scholars have sought to examine commemoration through the lens of globalization theory even though it poses challenges to understandings of time and space that underpin memory studies. This article examines the local political conditions and global institutional environment influencing memory discourses. Drawing on the case of Bloody Sunday (1972), I examine the role of memory choreographers in constructing universalizing commemorative idioms and the local conditions and global setting influencing this memory work. I argue that the mid-1990s was characterized by an increasing emphasis on Bloody Sunday's globally `chic' qualities that seemed to liquidate its earlier localized meaning, and that this was achieved through drawing analogies between the Bloody Sunday experience and other global casualties of injustice and oppression. This narrative reframing of the event is explained in terms of Irish, British, European, American and global influences as well as political, economic and demographic shifts, which came together in the mid-1990s, to create a propitious environment for a global turn in Bloody Sunday memory.
Gender and collective memory: Women and representation at Auschwitz
Authors: Jacobs Janet
Published: April 2008

This research examines the representation of women at Auschwitz. Based on fieldwork at the museum/memorial at the death camp site, the study explores the complex ways in which women's experiences are recalled through gendered narratives that reify traditional representations of women as either suffering mothers and/or sexual possessions of the perpetrators. Drawing on the methods of visual sociology in ethnographic study, the imagery in photographs, sculptures and artifact installations is analyzed to reveal patterns of gendered memory that have become characteristic of Holocaust museum culture. The findings of the research raise significant questions for the social construction of gendered memories of atrocity and genocidal histories. In particular, the study suggests that, as nations and groups seek to accurately recall and remember mass violence against women, traumatized societies must be wary of creating visual and public narratives that promote voyeurism and exploit the memory of the dead.
Critical but divergent roles for CD62L and CD44 in directing blood monocyte trafficking in vivo during inflammation
Authors: Xu Heping , Manivannan Ayyakkannu , Crane Isabel , Dawson Rosemary , Liversidge Janet
Published: April 2008

Using noninvasive in vivo imaging and experimental autoimmune uveoretinitis as a model, we show for the first time that the mechanisms controlling blood monocyte recirculation through peripheral and lymphoid tissues alter during inflammation. The recirculation of monocytes in mice with ocular inflammation but not controls was found to depend on the selectin CD62-ligand (CD62L) and on CD44. Not only was rolling efficiency ablated or markedly reduced in antibody-treated mice, but most of the labeled monocytes also disappeared from the circulation within seconds, anti-CD44–treated monocytes homing to the lymph nodes and anti–CD62L-treated monocytes homing to the spleen. Our data indicate that, although PSGL-1 has a partial role in the transmigration of monocytes into the inflamed retina, CD62L has a key role in regulating recruitment of monocytes to lymphoid tissue from the blood during inflammation and that CD44 is required to maintain CD62L+ inflammatory monocytes within the circulation during inflammation. This effect was systemic, because sequestered monocytes accumulated in mesenteric as well as draining cervical lymph nodes, and inflammation dependent, because depletion of circulating blood monocytes was much reduced or absent in normal mice and accumulations of adoptively transferred monocytes in the lymphoid tissues did not occur.
A novel method of differential gene expression analysis using multiple cDNA libraries applied to the identification of tumour endothelial genes
Authors: Herbert John MJ , Stekel Dov , Sanderson Sharon , Heath Victoria L , Bicknell Roy
Published: April 2008

Background

In this study, differential gene expression analysis using complementary DNA (cDNA) libraries has been improved. Firstly by the introduction of an accurate method of assigning Expressed Sequence Tags (ESTs) to genes and secondly, by using a novel likelihood ratio statistical scoring of differential gene expression between two pools of cDNA libraries. These methods were applied to the latest available cell line and bulk tissue cDNA libraries in a two-step screen to predict novel tumour endothelial markers. Initially, endothelial cell lines were in silico subtracted from non-endothelial cell lines to identify endothelial genes. Subsequently, a second bulk tumour versus normal tissue subtraction was employed to predict tumour endothelial markers.

Results

From an endothelial cDNA library analysis, 431 genes were significantly up regulated in endothelial cells with a False Discovery Rate adjusted q-value of 0.01 or less and 104 of these were expressed only in endothelial cells. Combining the cDNA library data with the latest Serial Analysis of Gene Expression (SAGE) library data derived a complete list of 459 genes preferentially expressed in endothelium. 27 genes were predicted tumour endothelial markers in multiple tissues based on the second bulk tissue screen.

Conclusion

This approach represents a significant advance on earlier work in its ability to accurately assign an EST to a gene, statistically measure differential expression between two pools of cDNA libraries and predict putative tumour endothelial markers before entering the laboratory. These methods are of value and availablehttp://www.compbio.ox.ac.uk/data/diffex.htmlto researchers that are interested in the analysis of transcriptomic data.
Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism
Authors: Jakubowska Anna , Gronwald Jacek , Menkiszak Janusz , Górski Bohdan , Huzarski Tomasz , Byrski Tomasz , Benner Axel , Lubiński Jan , Scott Rodney J , Hamann Ute
Published: April 2008

Background

The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations.

Methods

To investigate whether the PHB 3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.

Results

A comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11).

Conclusion

Our data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.
A Korean version of the Oral Impacts on Daily Performances (OIDP) scale in elderly populations: Validity, reliability and prevalence
Authors: Jung Se-Hwan , Ryu Jae-In , Tsakos Georgios , Sheiham Aubrey
Published: April 2008

Background

This study aimed to develop a Korean version of the OIDP index for elderly people and to assess the levels of sociodental impacts in an older Korean population.

Methods

The OIDP index for elderly people was cross-culturally adapted from English into Korean and then the derived instrument was tested for reliability and validity. The study population was elderly (65+ year-old) residents of Gangneung City, South Korea. Twenty two of the 222 senior day centres were randomly selected.

Results

687 people were invited and 668 participated in the study (response rate: 97.2%). The standardized Cronbach's alpha coefficient was 0.85. The OIDP related significantly with different subjective measures of oral and general health (p < 0.001). 62.9% of the people had oral impacts relating to one or more performances, with eating food being the most frequently affected performance (47.6%). More than 70% of people with oral impacts had up to 3 performances affected by oral health conditions.

Conclusion

The Korean OIDP index showed satisfactory validity and internal consistency reliability, confirming its appropriateness for use among older Korean people. The prevalence of oral health related impacts was high. Future studies should focus on the test-retest reliability and the sensitivity to change of the Korean OIDP.
Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal
Authors: Accurso Anthony , Bernstein Richard K , Dahlqvist Annika , Draznin Boris , Feinman Richard D , Fine Eugene J , Gleed Amy , Jacobs David B , Larson Gabriel , Lustig Robert H , Manninen Anssi H , McFarlane Samy I , Morrison Katharine , Nielsen Jørgen Vesti , Ravnskov Uffe , Roth Karl S , Silvestre Ricardo , Sowers James R , Sundberg Ralf , Volek Jeff S , Westman Eric C , Wood Richard J , Wortman Jay , Vernon Mary C
Published: April 2008

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.
An improved Diagnostic PCR Assay for identification of Cryptic Heterozygosity for CGG Triplet Repeat Alleles in the Fragile X Gene (FMR1)
Authors: Khaniani Mahmoud S , Kalitsis Paul , Burgess Trent , Slater Howard R
Published: April 2008

Background

Fragile X syndrome (OMIM #300624) is the most common, recognised, heritable cause of mental retardation. Widespread testing is warranted by the relatively high frequency of the disorder, the benefits of early detection and the identification of related carriers whose offspring are at a 1 in 2 risk of inheriting the expanded pathogenic mutation. However, cost-effective screening of mentally retarded individuals has been impeded by the lack of a single, simple laboratory test. Currently, Fragile X syndrome can be excluded in males and a majority of females using a simple high-throughput PCR test. Due to the limited sensitivity of the PCR test, we find in our diagnostic service that approximately 40% of females appear homozygous and a labour intensive and expensive Southern blot test is required to distinguish these from females carrying one normal allele and an expanded allele.

Results

We describe an improved PCR test which displays a high level of precision allowing alleles differing by a single triplet to be resolved. Using the new assay, we detected 46/83 (53%) cryptic heterozygotes previously labelled as homozygotes. The assay also extended the range of repeats amplifiable, up to 170 CGG repeats in males and 130 CGG repeats in females. Combined with the high precision, the assay also improves discrimination of normal (CGG repeats < 45) from grey zone (45 < CGG repeats < 54) alleles and grey zone alleles from small premutations (55 < CGG repeats < 100).

Conclusion

Use of this PCR test provides significantly improved precision and amplification of longer alleles. The number of follow-up Southern blot tests required is reduced (up to 50%) with consequent improvement in turnaround time and cost.
Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release
Authors: Cuadrado Eloy , Ortega Laura , Hernández-Guillamon Mar , Penalba Anna , Fernández-Cadenas Israel , Rosell Anna , Montaner Joan
Published: April 2008

Recombinant tissue plasminogen activator (t-PA), the only approved stroke treatment, is used for clot lysis within the occluded brain artery. Unfortunately, matrix metalloproteinase-9 (MMP-9) concentration increases after t-PA treatment and has been related to hemorrhagic transformation after ischemic stroke. Although the exact cellular source of brain MMP-9 remains unknown, invading, inflammatory cells, such as neutrophils, release MMP-9 to cross the blood brain barrier. Therefore, we hypothesize that the most feared side effect of stroke reperfusion therapy, brain hemorrhage, is related to t-PA-induced MMP-9 release by neutrophils. We show by means of ELISA that t-PA treatment promotes MMP-9, MMP-8, and tissue inhibitor metalloproteinase-2 release from human neutrophils ex vivo within 10 and 30 min. Moreover, by zymography and Western blot, we observed that neutrophils are emptied of MMP-9 content after t-PA treatment at those times. Finally, total internal reflection fluorescent imaging allowed us to observe the t-PA effect on neutrophils, showing the promotion of degranulation on these cells in vivo. Our data suggest that neutrophils are good candidates to be the main source of MMP-9 following t-PA stroke treatment and in consequence, partially responsible for thrombolysis-related brain bleedings.
Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
Authors: DiGiovanna Michael P. , Stern David F. , Edgerton Susan , Broadwater Gloria , Dressler Lynn G. , Budman Daniel R. , Henderson I. Craig , Norton Larry , Liu Edison T. , Muss Hyman B. , Berry Donald A. , Hayes Daniel F. , Thor Ann D.
Published: April 2008

Purpose

ErbB-2 (human epidermal growth factor receptor 2) overexpression may be predictive of relative resistance and/or sensitivity to specific chemotherapeutic agents. Results from a previous study from the Cancer and Leukemia Group B (CALGB 8541) demonstrated an interaction between ErbB-2 and increasing dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) chemotherapy. Other studies have suggested that evaluation of the phosphorylated/activated form of ErbB-2 might be more precise in defining the impact of ErbB-2 in breast cancer. We have evaluated tumor tissue sections from CALGB 8541 patients to determine whether the interaction of ErbB-2 with CAF dose is dependent on ErbB-2 activation state, and whether phosphorylated ErbB-2 is an adverse prognostic factor in patients treated with CAF.

Patients and Methods

Patients were randomly assigned to one of three dosing regimens of CAF. Paraffin samples from 992 of 1,572 patients who participated in CALGB 8541 were available. Of the 570 tumors with any staining for ErbB-2, 488 had tissue available for assay for phosphorylated ErbB-2, which was performed by immunohistochemistry.

Results

Of 910 total assessable cases, 112 of 488 ErbB-2-positive cases (23%) stained positively for phosphorylated ErbB-2. The previously described interaction of dosing regimen of CAF with ErbB-2 was not dependent on phosphorylation status of ErbB-2.

Conclusion

Monitoring phosphorylation of ErbB-2 with an antiphospho-ErbB-2 antibody did not add further precision to identifying those patients most likely to benefit from increased dose of anthracycline-based adjuvant chemotherapy. Favorable outcomes are observed in ErbB-2-overexpressing patients treated with high-dose CAF regardless of ErbB-2 phosphorylation state.
Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer
Authors: Gruenberger Brigit , Tamandl Dietmar , Schueller Johannes , Scheithauer Werner , Zielinski Christoph , Herbst Friedrich , Gruenberger Thomas
Published: April 2008

Purpose

Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, but can benefit from perioperative chemotherapy and disease resection. Bevacizumab improves outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration after liver resection remains to be determined.

Patients and Methods

Fifty-six patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-center, nonrandomized phase II trial. Eligibility criteria defined patients at high risk of early recurrence. Patients received biweekly bevacizumab plus capecitabine and oxaliplatin for six cycles. The sixth cycle of therapy did not include bevacizumab, resulting in 5 weeks between the last administration of bevacizumab and surgery.

Results

Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%). Fifty-two patients underwent liver resection including 11 with synchronous primary tumor resection. No increased intraoperative bleeding events or wound-healing complications were observed and only three patients (6%) required perioperative blood transfusions. Further surgery was necessary in a single patient. Postoperative liver function and regeneration were normal in all but one patient. No postoperative mortality occurred and morbidity was encountered in 11 patients (20%). The mean length of postoperative hospitalization was 9 days (± 4.0).

Conclusion

These data suggest that bevacizumab can be safely administered until 5 weeks before liver resection in patients with metastatic CRC without increasing the rate of surgical or wound healing complications or severity of bleeding. To our knowledge, they are also the first to show that neoadjuvant bevacizumab does not affect liver regeneration after resection.
Graft-Versus-Lymphoma Effect for Aggressive T-Cell Lymphomas in Adults: A Study by the Société Française de Greffe de Moëlle et de Thérapie Cellulaire
Authors: Le Gouill Steven , Milpied Noel , Buzyn Agnès , Peffault De Latour Régis , Vernant Jean-Paul , Mohty Mohamad , Moles Marie-Pierre , Bouabdallah Krimo , Bulabois Claude-Eric , Dupuis Jehan , Rio Bernard , Gratecos Nicole , Yakoub-Agha Ibrahim , Attal Michel , Tournilhac Olivier , Decaudin Didier , Bourhis Jean-Henry , Blaise Didier , Volteau Christelle , Michallet Mauricette
Published: April 2008

Purpose

Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas.

Patients and Methods

On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT).

Results

The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic γ/δ lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04).

Conclusion

We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.
Phase I and Pharmacokinetic Study of Daily Oral AZD2171, an Inhibitor of Vascular Endothelial Growth Factor Tyrosine Kinases, in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non–Small-Cell Lung Cancer: The National Cancer Institute of Canada Clinical Trials Group
Authors: Laurie Scott A. , Gauthier Isabelle , Arnold Andrew , Shepherd Frances A. , Ellis Peter M. , Chen Eric , Goss Glenwood , Powers Jean , Walsh Wendy , Tu Dongsheng , Robertson Jane , Puchalski Thomas A. , Seymour Lesley
Published: April 2008

Purpose

AZD2171 is a potent inhibitor of vascular endothelial growth factor receptors that showed broad antitumor activity in preclinical models. Doses of up to 45 mg/d of AZD2171 are tolerable when administered alone. This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non–small-cell lung cancer.

Patients and Methods

Eligible patients received carboplatin targeted to an area under the concentration time curve of 6 mg · min/mL and paclitaxel 200 mg/m2, both on day 1 of a 3-week cycle; daily oral AZD2171 at either 30 mg or 45 mg commenced day 2 of cycle 1. Pharmacokinetics of all drugs were performed, and tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST).

Results

Twenty patients were enrolled. No dose-limiting toxicities were observed during cycle 1 at either dose. Fatigue, diarrhea, anorexia, and granulocytopenia were common; hypertension was manageable with a treatment algorithm designed for this protocol. No clinically significant drug-related bleeding was observed. At 45 mg/d, fatigue and diarrhea were increased, and headache and hoarseness were observed. Paclitaxel clearance decreased during cycle 2, but no other significant pharmacokinetic interactions were observed. After radiology review, confirmed responses were observed in nine patients (response rate, 45%; 95% CI, 23% to 68%); all but one enrolled patient showed evidence of tumor shrinkage, some with cavitation.

Conclusion

AZD2171 can be combined with standard doses of carboplatin/paclitaxel with encouraging antitumor activity. Toxicity is increased, but predictable and manageable.
Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers
Authors: Adjei Alex A. , Cohen Roger B. , Franklin Wilbur , Morris Clive , Wilson David , Molina Julian R. , Hanson Lorelei J. , Gore Lia , Chow Laura , Leong Stephen , Maloney Lara , Gordon Gilad , Simmons Heidi , Marlow Allison , Litwiler Kevin , Brown Suzy , Poch Gregory , Kane Katie , Haney Jerry , Eckhardt S. Gail
Published: April 2008

Purpose

To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer.

Patients and Methods

In part A, patients received escalating doses to determine the maximum-tolerated dose (MTD). In both parts, blood samples were collected to assess PK and PD parameters. In part B, patients were stratified by cancer type (melanoma v other) and randomly assigned to receive the MTD or 50% MTD. Biopsies were collected to determine inhibition of ERK phosphorylation, Ki-67 expression, and BRAF, KRAS, and NRAS mutations.

Results

Fifty-seven patients were enrolled. MTD in part A was 200 mg bid, but this dose was discontinued in part B because of toxicity. The 50% MTD (100 mg bid) was well tolerated. Rash was the most frequent and dose-limiting toxicity. Most other adverse events were grade 1 or 2. The PKs were less than dose proportional, with a median half-life of approximately 8 hours and inhibition of ERK phosphorylation in peripheral-blood mononuclear cells at all dose levels. Paired tumor biopsies demonstrated reduced ERK phosphorylation (geometric mean, 79%). Five of 20 patients demonstrated ≥ 50% inhibition of Ki-67 expression, and RAF or RAS mutations were detected in 10 of 26 assessable tumor samples. Nine patients had stable disease (SD) for ≥ 5 months, including two patients with SD for 19 (thyroid cancer) and 22 (uveal melanoma plus renal cancer) 28-day cycles.

Conclusion

AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing.
The influence of an upstream diffuser on a downstream wing in ground effect
Authors: Soso M D , Wilson P A
Published: April 2008

In a further effort to provide additional insight into the aerodynamic factors that may influence the creation of overtaking opportunities in open-wheeled racing categories such as Formula 1, a series of wind tunnel experiments were initiated at the University of Southampton to provide information on the effect that an upstream diffuser in ground effect may have on a downstream single-element wing in ground effect. Investigations focused on force measurements and on the extraction of wake profiles from the downstream wing and its flow field. The upstream model configuration was altered by changing the angle of the diffuser ramp and by varying the height of the diffuser above the ground. It was found that a lower diffuser angle increased the efficiency of the downstream wing and that changes to the vortex wake generated by the diffuser induced changes to the wake characteristics of the wing. It was also found that decreasing the ride height of the bluff body produced an increase in the thickness of the wake of the downstream wing.
A non-linear dynamic approach to the motion of four-wheel-steering vehicles under various operation conditions
Authors: Han Q , Dai L
Published: April 2008

This research aims to analyse systematically the non-linear dynamic behaviour of four-wheel-steering (4WS) vehicles. A practical non-linear dynamic model of multiple degrees of freedom for 4WS vehicles is established. The non-linear model presented is shown to be feasible for the vehicles under normal and the other operation manoeuvres. Compared with those of documented investigations, this model may be employed to analyse the motions of the vehicle and motions of the vehicle wheels in turning and braking processes together with the consideration of the effects of air drag and wind. Numerical simulation for the motion of the 4WS vehicles under various operation manoeuvres is performed with the model established. Comparison of the behaviours of 4WS and two-wheel-steering vehicles is also presented with respect to the inputs on the steering system, the manoeuvrability, the stability, and the relationship between the steering phase and vehicle speed.
Non-linear observer for slip estimation of tracked vehicles
Authors: Song Z-B , Zweiri Y H , Seneviratne L D , Althoefer K
Published: April 2008

Accurate estimation of slip is essential in developing autonomous navigation strategies for mobile vehicles operating in unstructured terrain. This paper presents an accurate and robust technique for the estimation of slip parameters of a tracked vehicle. The technique uses a sliding mode observer (SMO) with sprocket wheel angular velocities and vehicle trajectory as inputs and estimates slip parameters by minimizing the errors between the predicted trajectory and the measured trajectory. The error dynamics is proven to converge after a finite time from any arbitrary point in error space and remains in the neighbourhood of the sliding motion. Slip estimation schemes using an extended Kalman filter (EKF) and direct mathematical inversion of the kinematic equations are also presented for comparison purposes. It is shown that the non-linear SMO is more accurate than the other two methods. The robustness and superior performance of the SMO are demonstrated using both simulation and experimental results. A specially designed test rig is used for accurate control and measurement of track slips during the experimental validation of the proposed observer.
Study on combustion characteristics of a methanol—diesel dual-fuel compression ignition engine
Authors: Wang L-J , Song R-Z , Zou H-B , Liu S-H , Zhou L-B
Published: April 2008

There is an increasing interest in applying methanol to diesel engines so as to achieve fuel diversity and reduce engine emissions. Dual-fuel application is the most promising method, but its combustion characteristics have been less extensively studied. In this paper, with the measured cylinder pressures of the engine operated on pure diesel and on dual fuel (methanol—diesel), the engine combustion characteristics are investigated. The increase in methanol mass fraction lowers the polytropic index of compression and the temperatures at BDC and TDC, as well as the oxygen concentration in the mixture. This prolongs the ignition delay under the same engine load and speed condition by comparison with diesel operation. The combustion heat release rate changes from dual-peak mode to single-peak mode. The centre of the heat release rate curve moves near to TDC under high load conditions, which indicates a better fuel economy. The high methanol mass fraction will realize a simultaneous reduction in both smoke and NO x under all the operating conditions. Meanwhile, the NO x smoke trade-off curve disappears in combustion of the dual fuel, but CO and HC increase.
Influence of injection conditions and exhaust gas recirculation in a high-speed direct-injection diesel engine operating with a late split injection
Authors: Benajes J , Molina S , Novella R , DeRudder K
Published: April 2008

This paper describes an investigation on low-temperature combustion in a small single-cylinder high-speed direct-injection diesel engine. This engine is representative of turbocharged passenger car diesel engines equipped with a particulate trap and an oxidation catalyst.

A medium-load engine operation condition was evaluated using two fuel injection events near top dead centre and high levels of exhaust gas recirculation. The combustion was characterized by extremely low emission of nitrogen oxides (of the order of 10—15ppm) and low combustion noise.

The study was carried out by means of a design of experiments, consisting of four factors varied on three levels according to a Box—Behnken design. This Box—Behnken design was extended with validation points, allowing all factors to be studied independently in a parametric approach. Additionally, some relevant two-factor interactions have been studied. The investigated factors were the exhaust gas recirculation rate, the combustion phasing, the injection pressure, and the dwell between the split injections.

The results show how it is possible to achieve very low levels of nitrogen oxides and low combustion noise with reasonable fuel consumption, smoke emissions, hydrocarbons, and carbon monoxide emissions, with injection and combustion just after top dead centre.
Design and characterization of a novel permanent magnet synchronous motor used in a growing prosthesis for young patients with bone cancer
Authors: Meswania J M , Taylor S J G , Blunn G W
Published: April 2008

Approximately 50 child sarcomas are treated with limb salvage surgery each year in the United Kingdom. These children need an extendable implant that can be lengthened periodically to keep pace with the growth in the opposite limb. Surgically, invasive devices have been used for the past 30 years with intrinsic problems of infection and long-term recurrent trauma to the patient. To eliminate problems associated with the invasive device, a non-invasive extendable prosthesis was developed. The magnetically coupled drive technology used for this prosthesis was a synchronous motor with a gear-driven telescoping shaft. In this design the motor configuration was in two parts: a rotating magnet (rotor) that fitted inside the prosthesis where space was limited and the stator, which was an external device used to extend the prosthesis remotely as the patient grew. This compact external drive produced a focused magnetic flux that required no cooling and operated on a single-phase power supply. The extending mechanism in the implant was able to overcome up to 1300 N force, which is the tension force exerted by the soft tissues during the lengthening procedure. The device has been successfully implanted in 50 patients.
Improvement in the assessment of wear of total knee replacements using coordinate-measuring machine techniques
Authors: Blunt L A , Bills P J , Jiang X-Q , Chakrabarty G
Published: April 2008

Total joint replacement is one of the most common elective surgical procedures performed worldwide, with an estimate of 1.5×106 operations performed annually. Currently joint replacements are expected to function for 10–15 years; however, with an increase in life expectancy, and a greater call for knee replacement due to increased activity levels, there is a requirement to improve their function to offer longer-term improved quality of life for patients.

Wear analysis of total joint replacements has long been an important means in determining failure mechanisms and improving longevity of these devices. The effectiveness of the coordinate-measuring machine (CMM) technique for assessing volumetric material loss during simulated life testing of a replacement knee joint has been proved previously by the present authors. The purpose of the current work is to present an improvement to this method for situations where no pre-wear data are available.

To validate the method, simulator tests were run and gravimetric measurements taken throughout the test, such that the components measured had a known wear value. The implications of the results are then discussed in terms of assessment of joint functionality and development of standardized CMM-based product standards. The method was then expanded to allow assessment of clinically retrieved bearings so as to ascertain a measure of true clinical wear.
Sensitivity of proximal femoral stiffness and areal bone mineral density to changes in bone geometry and density
Authors: Pisharody S , Phillips R , Langton C M
Published: April 2008

Areal bone mineral density (aBMD) is the most common surrogate measurement for assessing the bone strength of the proximal femur associated with osteoporosis. Additional factors, however, contribute to the overall strength of the proximal femur, primarily the anatomical geometry. Finite element analysis (FEA) is an effective and widely used computer-based simulation technique for modelling mechanical loading of various engineering structures, providing predictions of displacement and induced stress distribution due to the applied load. FEA is therefore inherently dependent upon both density and anatomical geometry. FEA may be performed on both three-dimensional and two-dimensional models of the proximal femur derived from radiographic images, from which the mechanical stiffness may be predicted.

It is examined whether the outcome measures of two-dimensional FEA, two-dimensional, finite element analysis of X-ray images (FEXI), and three-dimensional FEA computed stiffness values of the proximal femur are more sensitive than aBMD to changes in trabecular bone density and femur geometry. It is assumed that if an outcome measure follows known trends with changes in density and geometric parameters, then an increased sensitivity will be indicative of an improved prediction of bone strength. All three outcome measures increased non-linearly with trabecular bone density, increased linearly with cortical shell thickness and neck width, decreased linearly with neck length, and were relatively insensitive to neck-shaft angle. For femoral head radius, aBMD was relatively insensitive, with two-dimensional FEXI and three-dimensional FEA demonstrating a non-linear increase and decrease in sensitivity respectively. For neck anteversion, aBMD decreased non-linearly, whereas both two-dimensional FEXI and three-dimensional FEA demonstrated a parabolic-type relationship, with the maximum stiffness being achieved at an angle of approximately 15°. Multi-parameter analysis showed that all three outcome measures demonstrated their highest sensitivity to a change in cortical thickness. When changes in all input parameters were considered simultaneously, three and two-dimensional FEA had statistically equal sensitivities (0.41 ± 0.20 and 0.42 ± 0.16 respectively, p= ns) that were significantly higher than the sensitivity of aBMD (0.24 ± 0.07; p=0.014 and 0.002 for three-dimensional and two-dimensional FEA respectively). This simulation study suggests that since mechanical integrity and FEA are inherently dependent on anatomical geometry, FEXI stiffness, being derived from conventional two-dimensional radiographic images, may provide an improvement in the prediction of bone strength of the proximal femur than currently provided by aBMD.
On the process capability of the solid free-form fabrication: A case study of scaffold moulds for tissue engineering
Authors: Liu C Z , Han Z W , Hourd P , Czernuszka J T
Published: April 2008

This study applies the methodology and procedure of process capability to investigate a solid free-form fabrication technique as a manufacturing method to produce scaffold moulds for tissue engineering. The process capability Cp k and process performance Pp k of scaffold mould manufacture using a solid free-form fabrication technique has been analysed with respect to the dimension deviations. A solid free-form fabrication machine T66 was used to fabricate scaffold moulds in this study and is able to create features that ranged from 200 μm to 1000 μm. The analysis showed that the printing process under the normal cooling conditions of the printing chamber was in statistical control but gave low process capability indices, indicating that the process was ‘inadequate’ for production of ‘dimension-consistent’ scaffold moulds. The study demonstrates that, by lowering the temperature of the cooling conditions, the capability Cp k of the printing process can be improved (about threefold) sufficiently to ensure the consistent production of scaffold moulds with dimension characteristics within their specification limits.