bluuebunny/crossref_metadata_2025 huggingface dataset:
The importance of political context: Motives to participate in a protest before and after the labor reform in Spain
Authors: Gómez-Román Cristina , Sabucedo José-Manuel
Published: October 2014

The objective of this study is to ascertain how political context and participants’ union membership affect the motivation to participate in a protest. The study compares participants of two demonstrations in Spain on different dates, organized by the same trade unions, with the same objectives (opposition to a new labor law). The design of the study compares political context (demonstrating before or after the labor reform) and union membership (unionist/non-unionist). This provides an excellent frame of analysis as to how these factors affect the variables that motivate participation in a protest: anger, efficacy, identity, satisfaction with democracy and trust in institutions. The results confirm that political context mainly affects the variables identity and efficacy, whereas the union membership factor influences trust in political institutions, identity and satisfaction with democracy. Furthermore, analysis shows how the interaction between political context and union membership affects feelings of anger, trust and satisfaction with democracy.
The Impact of Numeracy on Verbatim Knowledge of the Longitudinal Risk for Prostate Cancer Recurrence following Radiation Therapy
Authors: Hamstra Daniel A. , Johnson Skyler B. , Daignault Stephanie , Zikmund-Fisher Brian J. , Taylor Jeremy M. G. , Larkin Knoll , Wood Alexander , Fagerlin Angela
Published: October 2014

Objective. Given the long natural history of prostate cancer, we assessed differing graphical formats for imparting knowledge about the longitudinal risks of prostate cancer recurrence with or without ‘hormone’ or ‘androgen deprivation’ therapy. Methods. Male volunteers without a history of prostate cancer were randomized to 1 of 8 risk communication instruments that depicted the likelihood of prostate cancer returning or spreading over 1, 2, and 3 years. The tools differed in format (line, pie, bar, or pictograph) and whether the graph also included no numbers, 1 number (indicating the number of affected individuals), or 2 numbers (indicting both the number affected and the number unaffected). The main outcome variables evaluated were graphical preference and knowledge. Results. A total of 420 men were recruited; respondents were least familiar and experienced with pictographs ( P < 0.0001), and only 10% preferred this particular format. Overall accuracy ranged from 79% to 92%, and when assessed across all graphical subtypes, the addition of numerical information did not improve verbatim knowledge ( P = 0.1). Self-reported numeracy was a strong predictor of accuracy of responses (odds ratio [OR] = 2.6, P = 0.008), and the impact of high numeracy varied across graphical type, having a greater impact on line (OR = 5.1; 95% confidence interval [CI] = 1.6–16; P = 0.04) and pie charts (OR = 7.1; 95% CI = 2.6–19; P =0.01), without an impact on pictographs (OR = 0.4; 95% CI = 0.1–1.7; P = 0.17) or bar charts (OR = 0.5; 95% CI = 0.1–1.8; P = 0.24). Conclusion. For longitudinal presentation of risk, baseline numeracy was strongly prognostic for outcome. However, the addition of numbers to risk graphs improved only the delivery of verbatim knowledge for subjects with lower numeracy. Although subjects reported the least familiarity with pictographs, they were one of the most effective means of transferring information regardless of numeracy.
The Impact of Uncertainty in Barrett’s Esophagus Progression Rates on Hypothetical Screening and Treatment Decisions
Authors: Kroep Sonja , Lansdorp-Vogelaar Iris , van der Steen Alex , Inadomi John M. , van Ballegooijen Marjolein
Published: October 2014

Background. Estimates for the annual progression rate from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) vary widely. In this explorative study, we quantified how this uncertainty affects the estimates of effectiveness and efficiency of screening and treatment for EAC. Design. We developed 3 versions of the University of Washington / Microsimulation Screening Analysis–EAC model. The models differed with respect to the annual progression rate from BE to EAC (0.12% or 0.42%) and the possibility of spontaneous regression of dysplasia (yes or no). All versions of the model were calibrated to the observed Surveillance, Epidemiology, and End Results esophageal cancer incidence rates from 1998 to 2009. To identify the impact of natural history, we estimated the incidence and deaths prevented as well as numbers needed to screen (NNS) and treat (NNT) of a one-time perfect screening at age 65 years that detected all prevalent BE cases, followed by a perfect treatment intervention. Results. Assuming a perfect screening and treatment intervention for all patients with BE, the maximum EAC mortality reduction (64%–66%) and the NNS per death prevented (470–510) were similar across the 3 model versions. However, 3 times more people needed to be treated to prevent 1 death (24 v. 8) in the 0.12% regression model compared with the 0.42% progression model. Restricting treatment to those with dysplasia or only high-grade dysplasia resulted in smaller differences in NNT (2–3 to prevent one EAC case) but wider variation in effectiveness (mortality reduction of 15%–24%). Conclusion. The uncertainty in the natural history of the BE to EAC sequence influenced the estimates of effectiveness and efficiency of BE screening and treatment considerably. This uncertainty could seriously hamper decision making about implementing BE screening and treatment interventions.
Objectified Body Consciousness, Body Image Discomfort, and Depressive Symptoms Among Breast Cancer Survivors in Taiwan
Authors: Fang Su-Ying , Chang Hong-Tai , Shu Bih-Ching
Published: October 2014

The literature comparing the effects of breast reconstructive surgery, breast-conserving surgery, and mastectomy on body image and mental health yields conflicting results. Objectified body consciousness may be a factor that influences the psychological well-being of breast cancer survivors. Women with average time of 19 months from breast cancer surgery were approached in outpatient clinics to participate in our study. Using structural equation modeling, we tested and verified a model that included self-reported objectified body consciousness, cancer-related body image discomfort, and depression among 193 breast cancer survivors in Taiwan. Our results provided support for the hypothesized indirect relation of objectified body consciousness with depression through the mediating role of cancer-related body image discomfort. Specifically, women with higher objectified body consciousness levels reported more cancer-related body image discomfort, which in turn was related to greater depression. Additionally, the degree of this mediation relationship across surgery types was different. These findings are significant to clinicians who should be cognizant of the potential role of objectified body consciousness in promoting cancer-related body image discomfort and depression in breast cancer survivors. Encouraging women to clarify their perceptions of their new bodies and providing care combined with psychological counseling after breast cancer surgery are critical.
Chemical and biological processes for multi-metal extraction from waste printed circuit boards of computers and mobile phones
Authors: Shah Monal B , Tipre Devayani R , Dave Shailesh R
Published: October 2014

E-waste printed circuit boards (PCB) of computers, mobile-phones, televisions, LX (LongXiang) PCB in LED lights and bulbs, and tube-lights were crushed to ≥250 µm particle size and 16 different metals were analysed. A comparative study has been carried out to evaluate the extraction of Cu–Zn–Ni from computer printed circuit boards (c-PCB) and mobile-phone printed circuit boards (m-PCB) by chemical and biological methods. Chemical process showed the extraction of Cu–Zn–Ni by ferric sulphate was best among the studied chemical lixiviants. Bioleaching experiments were carried out with the iron oxidising consortium, which showed that when E-waste and inoculum were added simultaneously in the medium (one-step process); 60.33% and 87.50% Cu, 75.67% and 85.67% Zn and 71.09% and 81.87% Ni were extracted from 10 g L-1 of c-PCB and m-PCB, respectively, within 10–15 days of reaction time. Whereas, E-waste added after the complete oxidation of Fe2+ to Fe3+ iron containing medium (two-step process) showed 85.26% and 99.99% Cu, 96.75% and 99.49% Zn and 93.23% and 84.21% Ni extraction from c-PCB and m-PCB, respectively, only in 6–8 days. Influence of varying biogenerated Fe3+ and c-PCB concentrations showed that 16.5 g L-1 of Fe3+ iron was optimum up to 100 g L-1 of c-PCB. Changes in pH, acid consumed and redox potential during the process were also studied. The present study shows the ability of an eco-friendly process for the recovery of multi-metals from E-waste even at 100 g L-1 printed circuit boards concentration.
Maternal Experiences of Their Unborn Child’s Spiritual Care
Authors: Heidari Tooba , Ziaei Saeideh , Ahmadi Fazlollah , Mohammadi Eesa , Hall Jenny
Published: October 2014

Preparing for pregnancy and childbirth has significant association with spirituality. Review of the literature shows that the spirituality of the “unborn child” has not yet attracted much critical attention. This study was conducted with the aim of exploration of maternal behaviors associated with the spiritual health of the unborn child. A qualitative approach was used to investigate the research question. Twenty-seven in-depth unstructured interviews were conducted with 22 Iranian mothers in Tehran city (Iran) who were pregnant or had experienced pregnancy in 2012-2013. Data analysis was carried out using a conventional content analysis approach. “Refusing to eat forbidden food,” “Overcoming mental adversity,” “Regulating one’s social interactions,” “Preventing the effects of harmful environments on the senses,” “Avoidance of using insulting and abusive language,” “Keeping one’s mind and spirit free from evil traits,” and “Refraining from damaging behaviors” were important experiences that the mothers used for “Holistic Abstinence.” The results provide new information about the subjective experiences of Iranian women on the patterns of abstinence for the midwives, research community, policy makers, and planners of maternal and child health care services in order to contribute to holistic, culturally, and religiously competent prenatal care for Muslim pregnant women throughout the world.
Design resource management for virtual prototyping in product collaborative design
Authors: He Bin , Wang Yangang , Song Wei , Tang Wen
Published: October 2014

Designers often have some difficulties in fulfilling complex product design due to the lack of design resources. It is a crucial issue that how to help designers to produce design from enormous, isomeric, and even distributed design resources of virtual prototyping and then ally those correlative distributed design resources to collaborative design. This article is devoted to an object-oriented design resource management for virtual prototyping in collaborative design. After the design resource unit model is proposed with the representation model of virtual prototyping, the object-oriented product design resource representation framework for virtual prototyping is then put forward. The storage, usage, search, version management, and security management strategies for design resources of virtual prototyping are then discussed in detail. The framework of design resource management system for virtual prototyping is also put forward to support collaborative design. The collaborative design of cold heading machine is given as an example, which demonstrates that the methodology is helpful to distributed knowledge reuse for collaborative design.
Coastal palaeoenvironmental record of the last 7 kyr BP in NW France: Sub-millennial climatic and anthropic Holocene signals
Authors: Fernane Assia , Gandouin Emmanuel , Penaud Aurélie , Van Vliet-Lanoë Brigitte , Goslin Jérôme , Vidal Muriel , Delacourt Christophe
Published: October 2014

To date, Holocene palaeoecological signatures on the Northwestern coast of France have not been thoroughly investigated. In this study, environmental changes related to both climate processes and human disturbances were reconstructed over the last 7000 cal. yr BP, based on pollen and chironomid assemblages from four coastal cores retrieved in Western Brittany (Porsmilin beach, NW France). Pollen and chironomid records show an environmental response to both millennial- and centennial-scale climate changes. During the mid-Holocene (until around 4200 cal. yr BP), when human impact was low, Porsmilin’s landscape was characterized by a mixed oak forest dominated by Corylus trees. Comparison of our data with other palynological data from the NW French Atlantic coast shows that this dominance may be related to more humid conditions prevailing at Porsmilin. Furthermore, over the mid-Holocene, Corylus and Quercus patterns appear anti-correlated, with Quercus declines appearing synchronous with major storms revealed by data recently compiled for the Holocene in Brittany, suggesting that cold conditions probably caused the Quercus contractions, which in turn favoured the rise of the heliophile taxon Corylus. Regarding chironomids over this period, our results show variations in lotic–lentic taxa related to hydrological conditions, more specifically changes in river run off strength. Over the Late Holocene, the Porsmilin palynological record shows progressive vegetation changes mainly related to human settlement and development of agricultural activities.
The future of trade unions in Croatia – various stakeholders’ perspectives
Authors: Vokić Nina Pološki , Obadić Alka
Published: October 2014

This article explores different stakeholders’ perceptions of the future of trade unions in Croatia. Findings reveal that respondents (managers, HR experts, trade union officials, government representatives and employees) are not optimistic about the future of trade unions in Croatia, agreeing that they will face many obstacles in the near future, such as a lack of consensus between the five trade union federations, a lack of agreement among the unions within a federation, and further union disintegration. However, survey respondents believe that there are many strategies capable of revitalizing the union movement in Croatia, including networking, ‘organizing unionism’ and union modernization.
Encoding risk: Probation work and sex offenders’ narrative identities
Authors: Digard Léon
Published: October 2014

Legislation governing the management of released sex offenders in England and Wales has frequently focused on the monitoring of behaviour and the structuring of external controls. Such policies would appear to limit concern for the subject’s internal world to manual-based cognitive behavioural therapy courses. Interviews conducted in England both with paroled individuals convicted for sexual offences and their supervising (probation) officers, however, reveal the various ways in which officers attempt to direct the narrative identities of their parolees – shaping their subjectivities. Drawing upon Foucauldian descriptions of confession as a ‘technology of the self’, it is possible to see how probation officers sought to transform their clients’ self-conceptualisations. This analysis highlights the internal nature of supervisory work, offering insights into the reasons why sex offenders may engage with or resist their community management. Furthermore, the potential impact of the narratives encouraged must be considered; while explanatory discourses of public protection and risk management prevailed, there are good reasons to suggest that the work conducted may have hindered the pursuit of these aims.
Death by family: Honor violence as punishment
Authors: Cooney Mark
Published: October 2014

Occurring in a broad range of non-western and western countries, violence committed against women in the name of family honor has been viewed in several ways, including as a crime, as gendered violence, or as a violation of human rights. But from a purely explanatory point of view, family honor violence is most profitably viewed as a type of social control, specifically penal social control. As punishment, honor violence appears to obey the same principles as other forms of punishment. Drawing on the theoretical strategy of pure sociology, the present article highlights two such principles: punishment increases with the social distance and social inferiority of the offender. These twin principles help to explain a broad range of facts about when and where family honor violence will occur, and how severe – in particular, how lethal – it will be.
Noninvasive Native Fluorescence Imaging of Head and Neck Tumors
Authors: Katz A. , Savage Howard E. , Schantz Stimson P. , McCormick Steven A. , Alfano R. R.
Published: October 2014

Fluorescence images were acquired from ex vivo head and neck tumor specimens. The excitation and emission wavelength combinations were selected to image emission from native tissue fluorophores (collagen, tryptophan, elastin and nicotinamide adenine dinucleotide). Two dimensional intensity ratio maps were generated from the fluorescence images and compared to histology images. The ratio maps accurately distinguished the regions of tumor from normal tissue in the specimens. Additional features, such as collagen capsules, blood vessels, mucus glands and muscles were evident in the fluorescence images.
Three-Dimensional Computed Tomography-Guided Salvage Brachytherapy of Recurrent Large Nonresectable Familial Colo-Rectal Cancer in the Pelvis: Case Report
Authors: Koutrouvelis Panos G.
Published: October 2014

Here we present the first reported case of three-dimensional CT-guided salvage brachytherapy of recurring colorectal cancer in the pelvis after failed radiation therapy, total colectomy, and chemotherapy. Initial CEA was 67.0 ng/mL and tumor volume 93 cm3 with no metastasis outside the pelvis. A total of 333 seeds of Iodine-125 were delivered to the entire target, with dosage of 150 to 200 Gy as calculated by post-implant CT dosimetry with Varian MMS software. CEA 12 months after implant decreased to 5.7 ng/mL. Clinical and biochemical results are encouraging; however long-term data in a greater universe of patients are required.
Very High Energy Electrons (50 – 250 MeV) and Radiation Therapy
Authors: Papiez Lech , DesRosiers Colleen , Moskvin Vadim
Published: October 2014

High energy electron beams in the range 150–250 MeV are investigated to evaluate their feasibility for radiotherapy. Monte Carlo simulation results from PENELOPE code are used to determine lateral spread and penetration of these beams. It is shown that dose distribution of electron beams compare favorably with photon beams. Electromagnetic control of electron beams enables scanned intensity modulation not possible with photon beams.
Historical Technical Developments in Mammography
Authors: Haus Arthur G.
Published: October 2014

In mammography it is most important to consistently produce high-contrast, high resolution images at the lowest radiation dose consistently with high image quality. Today it is possible to obtain mammograms with higher image quality that require significantly lower radiation dose compared to mammograms dating back to the 1970's and early 1980's. Some of the technical developments due to x-ray equipment and image receptors and quality control programs that have let to todays high quality mammographic images are discussed in this article.
Breast Cancer Screening: Potential Role of Computer-Aided Detection (CAD)
Authors: Feig Stephen A.
Published: October 2014

Four separate studies conducted as blinded retrospective radiologist reviews of screening mammograms where cancer subsequently developed found lesions requiring work-up or biopsy in 25% to 41% of cases. Three non-blinded retrospective reviews by radiologists identified 57% to 75% of cancers. Among breast cancers detected by radiologists on blinded retrospective review in one study, computer aided detection (CAD) would have found 77%. These studies suggest that improved cancer detection rates could result if radiologists who interpret screening mammography were aided by computers.

One prospective study initiated on that premise found that CAD increased the screening detection rate by 19.5%. At the current state-of-the-art, CAD performs best for cancers presenting as calcifications, less well for cancers appearing as spiculated masses, and least well for cancers appearing as circumscribed masses. CAD does not seem to increase false positive call back rates for additional imaging work-up or to increase false positive biopsy rates.
Fractionated Stereotactic Radiotherapy: A Short Review
Authors: Tomé Wolfgang A. , Mehta Minesh P. , Meeks Sanford L. , Buatti John M.
Published: October 2014

Currently, optimally precise delivery of intracranial radiotherapy is possible with stereotactic radiosurgery and fractionated stereotactic radiotherapy. We present in this article a review of the underlying basic physical and radiobiological principles of fractionated stereotactic radiotherapy and review the clinical experience for ateriovenus malformations, pituitary adenomas, mengiomas, vestibular schwanomas, low grade astrocytomas, malignant gliomas, and brain metatases.
Enhanced Anatomic Visualization with Ultrasound-Assisted Intracranial Image-Guidance in Neurosurgery
Authors: Marinho Alexandre M. N. , Barua Manali , Haller John , Ryken Timothy C.
Published: October 2014

Anatomical comparisons between ultrasound images and magnetic resonance imaging (MRI)/computed tomography (CT) preoperative images were performed in four ultrasound-assisted image-guided intracranial surgeries. An ultrasound scanner connected to a surgical navigation system allowed the neurosurgeon to acquire useful views from that integration, offering an improved method for visualization. This surgical navigation device and associated ultrasound provides real-time brain shift correction. The accuracy of navigation depends on the identification of the anatomic structures. Despite some limitations of the ultrasound images, the ability to compare preoperative MRI and intraoperative ultrasound proved useful to the surgeon.
Molecular and Functional Imaging Technology for the Development of Efficient Treatment Strategies for Gliomas
Authors: Jacobs A. H. , Winkeler A. , Dittmar C. , Gossmann A. , Deckert M. , Kracht L. , Thiel A. , Garlip G. , Hilker R. , Sobesky J. , Vollmar S. , Kummer C. , Graf R. , Voges J. , Wienhard K. , Herholz K. , Heiss W. D.
Published: October 2014

Gliomas are the most common types of brain tumors, which invariably lead to death over months or years. Before new and potentially more effective treatment strategies, such as gene therapy, can be effectively introduced into clinical application the following goals must be reached: (1) the determination of localization, extent and metabolic activity of the glioma; (2) the assessment of functional changes within the surrounding brain tissue; (3) the identification of genetic changes on the molecular level leading to disease; and in addition (4) a detailed non-invasive analysis of both endogenous and exogenous gene expression in animal models and in the clinical setting. Non-invasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging techniques may reveal the assessment of the location, magnitude and duration of therapeutic gene expression and its relation to the therapeutic effect. Here, we review the main principles of PET imaging and its key roles in neurooncology research.
Computer-Aided Diagnosis of Breast Cancer in Mammography: Evidence and Potential
Authors: Jiang Yulei
Published: October 2014

Computer-aided diagnosis (CAD) methods are being developed to help radiologists improve the interpretation of mammograms for the detection of breast cancer. We review several laboratory observer performance studies of computer-aided diagnosis of malignant and benign breast lesions. These studies show that CAD can improve radiologists' diagnostic performance by increasing the number of their biopsy recommendations for actual malignant lesions while reducing the number of their biopsy recommendations for suspicious but actually benign lesions, and by reducing the variability in their interpretation of mammograms. These results indicate a potential clinical role of CAD in mammography for the detection of breast cancer.
Oncoproteomics: State-of-the-Art
Authors: Jain K. K.
Published: October 2014

Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in carcinogenesis. Proteomic technologies are now being incorporated in oncology in the post-genomic era. Cancer involves alterations in protein expression and provides a good model not only for detection of biomarkers but also their use in drug discovery. Proteomics has an impact on diagnostics as well as drug discovery. Genomics still remains an important approach but the value of proteomics lies in the fact that most of the diagnostics and drugs target proteins. The importance of application of proteomics in oncology is recognized by the publication of this special issue of TRCT.
Understanding Cancer through Proteomics
Authors: Choi Woonyoung , Song Sonya W. , Zhang Wei
Published: October 2014

Proteomics is a rapidly expanding discipline that aims to gain a comprehensive understanding of the expressions, modification, interactions, and regulation of proteins in cells. New high-throughput technologies, such as protein chips and isotope-coded affinity tag peptide labeling, coupled with classic technologies such as two-dimensional gel electrophoresis and mass spectrometry, complement genomic technologies, providing cancer researchers with powerful tools for cancer diagnosis and prognosis and for the identification of targets for therapy.
Proteomics-based Anticancer Drug Discovery and Development
Authors: Jain K. K.
Published: October 2014

Proteins are important targets for drug discovery and this applied to cancer as well because there is a defect in the protein machinery of the cell in malignancy. Proteomic technologies are now being integrated with genomic approaches for cancer drug discovery and target validation. Among the large number of proteomic technologies available for this purpose, the most important ones are 3-D protein structure determination, protein microarrays, laser capture microdissection and study of protein-protein and protein-drug interactions. Cancer biomarkers and several cell pathways are important drug targets. Several companies are involved in using proteomic technologies for drug discovery. Finally, proteomic approaches will play an important role in the discovery and development of personalized medicines.
Identification of Tumor-Associated Antigens Using Proteomics
Authors: Le Naour François , Brichory Franck , Beretta Laura , Hanash Samir M.
Published: October 2014

In the post-genomic era, the identification of tumor-associated antigens that elicit a humoral response is allowed at the protein level using proteomics. Indeed, the screening of autoantibodies using 2-D Western blot experiments with sera from cancer patients, followed by the subsequent identification of the target protein by mass spectrometry and database search has permitted the exploitation of the B-cell repertoire of patients with cancer. Applied to several types of cancer, a proteomic-based approach has revealed a high frequency of autoantibodies in sera from patients. Several of the antigenic proteins identified may constitute novel cancer markers and may have clinical utility in diagnosis or in establishing prognosis. Furthermore, the approach has allowed to distinguish isoforms that may help to define epitopes. On the other hand, the analysis of the expression levels of some of the antigenic proteins has revealed differential expression in tumors as compared with healthy tissues that might explain antigenicity.
Proteomics of Breast Cancer: Outcomes and Prospects
Authors: Yazidi-Belkoura Ikram El , Adriaenssens Eric , Vercoutter-Edouart Anne-Sophie , Lemoine Jérôme , Nurcombe Victor , Hondermarck Hubert
Published: October 2014

Breast cancer is a major public health problem. The identification of new markers to differentiate neoplastic from the normal cells, more thorough understanding of different stages of the pathology, as well as the definition of new therapeutic targets, are all of critical importance. With the completion of human genome sequencing and the introduction of mass spectrometry, combined with protein identification via advanced bioinformatics, proteomics has emerged as a valuable tool for the discovery of new molecular markers. New methods in functional proteomics have also been developed to study the intracellular signaling pathways that underline the development of breast cancer. As illustrated with the examples of fibroblast growth factor-2 and H19, an oncogenic, noncoding mRNA, proteomics have become a powerful approach for deciphering the complex signaling circuitry involved in tumor growth. Breast cancer proteomics have already identified proteins of potential clinical interest (such as the molecular chaperone 14-3-3 sigma) and technological innovations in large scale/high throughput analysis are now ushering in new prospects.
Helical Tomotherapy: An Innovative Technology and Approach to Radiation Therapy
Authors: Welsh James S. , Patel Rakesh R. , Ritter Mark A. , Harari Paul M. , Mackie T. Rockwell , Mehta Minesh P.
Published: October 2014

Helical tomotherapy represents both a novel radiation treatment device and an innovative means of delivering radiotherapy. The helical tomotherapy unit itself is essentially a hybrid between a linear accelerator and a helical CT scanner for the purpose of delivering intensity-modulated radiation therapy (IMRT). The imaging capacity conferred by the CT component allows targeted regions to be visualized prior to, during, and immediately after each treatment. The megavoltage CT (MVCT) images supplant the port-films used in conventional radiotherapy, providing unprecedented anatomical detail. Image-guidance through MVCT will allow the development and refinement of the concept of “adaptive radiotherapy”, the reconstruction of the actual daily delivered dose (as opposed to planned dose) accompanied by prescription and delivery adjustments when appropriate. In addition to this unique feature, helical tomotherapy appears capable of further improvements over 3-dimensional conformal radiation therapy and non-helical IMRT in the specific avoidance of critical normal structures, i.e. “conformal avoidance”, the counterpart of conformal radiation therapy. Based on radiobiological principles that exploit the physical advantages of helical tomotherapy, several dosimetric and clinical investigations are underway.
Overview of Electroporation
Authors: Heller Richard
Published: October 2014

This special issue of Technology in Cancer Research and Treatment focuses on the versatility of electroporation. Contributed papers report on the basic mechanisms as well as the use of this procedure ex vivo and in vivo. In addition, recent studies utilizing in vivo electroporation for plasmid DNA and drug delivery are presented.
Modification of Reference Array Attachment for Image Guided Neurosurgery: Direct Cranial Fixation
Authors: Ryken Timothy C. , Haller John W.
Published: October 2014

We have modified the cranial fixation technique of the reference array used for the Stealth (Medtronics Inc., Minneapolis, MN) image guided neurosurgical workstation to avoid rigid immobilization and to accommodate patients undergoing awake procedures. The modification allows attachment of a reference array directly to the skull prior to registration, avoiding the requirement for rigid cranial fixation. The accuracy of fiducial registration for the modified reference array was compared to the conventional reference array using a phantom system yielding similar registration results and target accuracy. The successful application of the modified system to two operative cases is described.
Challenges and Opportunities for In Vivo Imaging in Oncology
Authors: Sullivan Daniel C.
Published: October 2014

Advances in genomics, proteomics and technology are changing medicine in fundamental ways. There are increasing clinical and laboratory requirements to obtain cellular and molecular information in vivo. This is particularly true in oncology, where the behavior of tumor cells is inextricably linked to their milieu. If cancer cells are removed from their microenvironment, their pattern of gene expression changes. Therefore, non-invasive, quantitative means of detecting gene and protein activity are essential. In vivo imaging is one methodology for achieving this. Marked advances in tracer methods for PET scanning or single-photon nuclear medicine techniques have occurred in the past few years. MRI contrast agents that reflect physiologic information are also being developed, although larger mass quantities of injectable material are required. The useful concept of “activatable agents” was pioneered in MRI. Similarly, ultrasound and computed tomography are being re-engineered to reflect information at the cellular level. In vivo optical imaging technologies have matured to the point where they are indispensable laboratory tools for small animal imaging. Human applications are in the feasibility testing stage, and the future for clinical optical imaging techniques looks bright. Merging these molecular imaging techniques with minimally or non-invasive image-guided therapeutic delivery techniques is a subsequent goal in the fight against cancer.
Development and Monte Carlo Analysis of Antiscatter Grids for Mammography
Authors: Boone John M. , Makarova Olga V. , Zyryanov Vladislav N. , Tang Cha-Mei , Mancini Derrick C. , Moldovan Nikolaie , Divan Ralu
Published: October 2014

Mammography arguably demands the highest fidelity of all x-ray imaging applications, with simultaneous requirements of exceedingly high spatial and contrast resolution. Continuing technical improvements of screen-film and digital mammography systems have led to substantial improvements in image quality, and therefore improvements in the performance of anti-scatter grids are required to keep pace with the improvements in other components of the imaging chain. The development of an air-core honeycomb (cellular) grid using x-ray lithography and electroforming techniques is described, and the production of a 60 mm × 60 mm section of grid is reported. A crossed grid was constructed with 25 μm copper septa, and a period of 550 μm. Monte Carlo and numerical simulation methods were used to analyze the theoretical performance of the fabricated grid, and comparisons with other grid systems (Lorad HTC and carbon fiber interspaced grids) were made over a range of grid ratios. The results demonstrate essentially equivalent performance in terms of contrast improvement factor (CIF) and Bucky factor (BF) between Cu and Au honeycomb grids and the Lorad HTC (itself a copper honeycomb grid). Gold septa improved both CIF and BF performance in higher kVp, higher scatter geometries. The selectivity of honeycomb grids was far better than for linear grids, with a factor of ∼3.9 improvement at a grid ratio of 5.0. It is concluded that using the fabrication methods described, that practical honeycomb grid structures could be produced for use in mammographic imaging, and that a substantial improvement in scatter rejection would be achieved using these devices.
Steady-state and Dynamic Contrast MR Imaging of Human Prostate Cancer Xenograft Tumors: A Comparative Study
Authors: Kim Young Ro , Savellano Mark D. , Weissleder Ralph , Bogdanov Alexei
Published: October 2014

Understanding tumor vascular physiology is critically important for developing non-invasive, molecularly targeted diagnostic agents and therapies. In this study, using three different human prostate cancer xenografts (MDA PCa 2b, PC3, and LnCap), structural and physiological parameters of neoplastic vasculature and interstitum were explored with a widely available magnetic resonance imaging (MRI) pulse sequence (3D SPGR: spoiled gradient echo). Using dual injection technique employing two T1 contrast agents of different molecular masses (Weissleder, R., Cheng, H. C., Marecos, E., Kwong, K. K., Bogdanov, A., Jr. Eur. J. Cancer 34, 1448–1454 (1998)), steady state (SS) MRI measurements and dynamic contrast agent enhancement (DCE) MRI measurements were simultaneously acquired and analyzed using a two-compartment model for calculating parameters reflecting tumoral architecture and physiology. In particular, interstitial volume and vascular permeability were independently quantified using these two different MRI techniques. Relative vascular water exchange rate, calculated by the flip angle (FA) dependence of measured blood volume using SS technique, and vascular permeability of contrast agent, extrapolated from DCE MRI, were compared. It was found that the SS and DCE techniques were comparable and yielded similar qualitative results for extravascular compartment (interstitial volume). However, the permeability (water exchange rate and contrast agent vascular permeability) values were in disagreement. The results of MR studies are important for interpreting optical imaging results obtained using long-circulating of tumor-associated enzymatic activity.
CyberKnife Radiotherapy for Localized Prostate Cancer: Rationale and Technical Feasibility
Authors: King Christopher R. , Lehmann Joerg , Adler John R. , Hai Jenny
Published: October 2014

There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy.

Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes.

The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.
Cancer Gene Therapy
Authors: Douglas Joanne T.
Published: October 2014

Cancer gene therapy is the transfer of genetic material to the cells of an individual with the goal of eradicating cancer cells, both in the primary tumor and metastases. Cancer gene therapy strategies exploit our expanding knowledge of the genetic basis of cancer, thereby allowing rationally targeted interventions at the molecular level. The successful implementation of cancer gene therapy in the clinic awaits the development of vectors capable of specific and efficient gene delivery to cancer cells. The first clinical applications of cancer gene therapy are likely to be in combination with conventional therapies, such as radiotherapy and immunotherapy.
Gentlemen (and Ladies), Choose your Weapons: Gamma Knife vs. Linear Accelerator Radiosurgery
Authors: Stieber Volker W. , Bourland J. Daniel , Tomé Wolfgang A. , Mehta Minesh P.
Published: October 2014

“In a sense, every tool is a machine—the hammer, the ax, and the chisel. And every machine is a tool. The real distinction is between one man using a tool with his hands and producing an object that shows at every stage the direction of his will and the impression of his personality; and a machine which is producing, without the intervention of a particular man, objects of a uniformity and precision that show no individual variation and have no personal charm. The problem is to decide whether the objects of machine production can possess the essential qualities of art.”

—Sir Herbert Read (1893–1968), British critic and poet. Art and Industry, pt. 1, Horizon (1953).

“But lo! men have become the tools of their tools.”

—Henry David Thoreau (1817–1862),

U.S. philosopher, author, naturalist. “Economy,” Waiden (1854).

This article compares and contrasts Gamma Knife® radiosurgery with linear accelerator-based radiosurgery; where appropriate, Cyberknife™ technology is discussed. Topics covered are: positioning of the head (invasive versus non-invasive positioning systems); collimator construction; beam properties; beam arrangements; treatment planning; and issues regarding manpower (including a discussion of patient repositioning during treatment), machine availability, and financial considerations.
The Evolving Role of Biological Imaging in Stereotactic Radiosurgery
Authors: Bourland J. Daniel , Shaw Edward G.
Published: October 2014

Stereotactic radiosurgery is used for highly focused radiation treatment of relatively small intracranial targets. Extracranial treatment systems are currently in development and used at a few centers. Approaches are image-based or image-guided, using CT and/or MR anatomical imaging. Biological imaging may provide non-invasive detection of the biological character and spatial extent of intracranial and extracranial targets. Potential uses of biological imaging in stereotactic radiosurgery include target delineation and normal tissue identification. These aspects are reviewed to explore the potential uses and impact these images may have on radiosurgery treatment.
Foreword: Immunotherapy
Authors: Gridley Daila S.
Published: October 2014

Cancer remains a devastating disease worldwide, with more than 10 million new cases and more than 6 million cancer-related deaths reported each year (1). In addition, cancer prevalence is expected to continue to increase into the foreseeable future. Although great strides have been made with a variety of treatment modalities such as radiation, surgery, and chemotherapy, there is not only ample room for improvement, but also an urgent need to develop new strategies that will be applicable to large numbers of patients. Furthermore, cancer prevention by immunization with tumor antigens, altered tumor cells, or other innovative alternative approaches needs to be more fully explored.
Solid Tumor Therapy: Manipulation of the Vasculature with TNF
Authors: Hagen Timo L. M. ten , Eggermont A. M. M.
Published: October 2014

Drug delivery to solid tumors is one of the most challenging aspects in cancer therapy. Whereas agents seem promising in the test tube, clinical trials often fail due to unfavorable pharmacokinetics, poor delivery, low local concentrations, and limited accumulation in the target cell. A major step forwards in the treatment of solid tumors is the recognition of the tumor-associated vasculature as an important target for therapy. Inhibition of tumor vascular development has a direct effect on the growth and progression of the tumor. Destruction of an existing vasculature also directly inflicts serious damage to the tumor cell. Moreover, the tumor vascular bed can be manipulated facilitating enhanced permissiveness of the tumor for administered chemotherapeutics. In this review, we focus on the use of tumor necrosis factor α (TNF) in local and systemic therapy in conjunction with chemotherapy. In these settings TNF demonstrates potent and selective activity on the tumor vascular bed, which strongly improves tumor response.
Assessment of the Accuracy of a Conventional Simulation for Radiotherapy of Head and Skull Base Tumors
Authors: Gross Markus W. , Spahn Ute , Engenhart-Cabillic Rita
Published: October 2014

In this prospective study we investigated the absolute accuracy of the conventional simulation in head and skull base tumors. 41 isocenters in 40 consecutive patients with tumors of the head and skull base were included. In all cases a rigid stereotactic mask system was used for non-invasive fixation. The stereotactic (“calculated”) coordinates of the isocenter were defined by the treatment planning computer. Each patient underwent a physical simulation using exclusively anatomical reference points to define the “preliminary” isocenter. The displacement between its coordinates and those of the stereotactic target point was recorded in X-, Y- and Z-direction with help of the targeting device, and the spatial error was calculated. Additionally, the patients were stratified by basal or calvarial tumor site to estimate the importance of the basal bone structures in the simulation accuracy. The influence of the learning effect on simulation accuracy was also determined.

The results showed an accuracy of set-up at the linac within 1 mm in all three directions as calculated from orthogonal portal films. Mean shift of the isocenter coordinates obtained from physical simulation compared to the calculated stereotactic coordinates was 2.15 mm, 2.54 mm, and 2.69 mm for X-, Y-, and Z-direction, respectively. Mean spatial displacement amounted 5.06 mm, and the median was 4.50 mm. No significant difference could be noted between basal and calvarial location of the isocenter. A significant “learning effect” was observed with a decrease in spatial shift with increasing patient numbers. This effect was stronger in basal lesions, whereas calvarial lesions showed only a minor, insignificant effect. In conclusion, a physical simulation requires a safety margin of 5 mm in PTV definition in addition to other factors, e.g. organ movement.