bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased effect of the ApoE gene on survival at advanced age in healthy and long‐lived Danes: two nationwide cohort studies
Authors: Jacobsen Rune , Martinussen Torben , Christiansen Lene , Jeune Bernard , Andersen‐Ranberg Karen , Vaupel James W. , Christensen Kaare
Published: September 2010

Studies of Nordic twins suggest an increased genetic influence on mortality with age. Contrary to this, the heterogeneity hypothesis predicts that the mortality of individuals carrying a ‘frail’ or ‘risky’ genotype in a population will approach that of noncarriers with age because of selection pressure. The ApoE ε4 allele is associated with an increased mortality risk, and its effect has been suggested to decrease with age. Here, we investigated the effect of ApoE ε4 allele on survival in a sample of the healthiest and long‐lived Danes. The study population comprised Danes born in 1905 and a replicate sample of the 1895 cohort. For the 1905 cohort, a total of 350 carriers and 1256 noncarriers of the ApoE ε4 allele were followed from 1998 until death or end of follow‐up. Cox regression models were used for the analysis. Of the 1606 persons with known ApoE ε4 status in 1998, 1546 had died at the end of the 10‐year follow‐up. Carriers of the ApoE ε4 allele had an increased mortality compared to noncarriers, and the influence of ApoE status on mortality increased in the age interval 92–103. For the covariates sex and independency status, the difference in relative risk of death between groups decreased with advancing age. Our findings of increasing influence of ApoE ε4 allele on mortality with age do not support previous findings of decreased influence ApoE ε4 allele on mortality with age, and alternative models such as the multifactorial threshold models should be considered for understanding the genetic effects on mortality at advanced age.
Employee Choice of a High‐Deductible Health Plan across Multiple Employers
Authors: Lave Judith R. , Men Aiju , Day Brian T. , Wang Wei , Zhang Yuting
Published: September 2010

Objective. To determine factors associated with selecting a high‐deductible health plan (HDHP) rather than a preferred provider plan (PPO) and to examine switching and market segmentation after initial selection.

Data Sources/Study Setting. Claims and benefit information for 2005–2007 from nine employers in western Pennsylvania first offering HDHP in 2006.

Study Design. We examined plan growth over time, used logistic regression to determine factors associated with choosing an HDHP, and examined the distribution of healthy and sick members across plan types.

Data Extraction. We linked employees with their dependents to determine family‐level variables. We extracted risk scores, covered charges, employee age, and employee gender from claims data. We determined census‐level race, education, and income information.

Principal Findings. Health status, gender, race, and education influenced the type of individual and family policies chosen. In the second year the HDHP was offered, few employees changed plans. Risk segmentation between HDHPs and PPOs existed, but it did not increase.

Conclusions. When given a choice, those who are healthier are more likely to select an HDHP leading to risk segmentation. Risk segmentation did not increase in the second year that HDHPs were offered.
Provider‐Hospital “Fit” and Patient Outcomes: Evidence from Massachusetts Cardiac Surgeons, 2002–2004
Authors: Huesch Marco D.
Published: September 2010

Objective. To examine whether the “fit” of a surgeon with hospital resources impacts cardiac surgery outcomes, separately from hospital or surgeon effects.

Data Sources. Retrospective secondary data from the Massachusetts Department of Public Health's Data Analysis Center, on all 12,983 adult isolated coronary artery bypass surgical admissions in state‐regulated hospitals from 2002 through 2004. Clinically audited chart data was collected using Society of Thoracic Surgeons National Cardiac Surgery Database tools and cross‐referenced with administrative discharge data in the Division of Health Care Finance and Policy. Mortality was followed up through 2007 via the state vital statistics registry.

Study Design. Analysis was at the patient level for those receiving isolated coronary artery bypass surgery (CABG). Sixteen outcomes included 30‐day mortality, major morbidity, indicators of perioperative, and predischarge processes of care. Hierarchical crossed mixed models were used to estimate fixed covariate and random effects at hospital, surgeon, and hospital × surgeon level.

Principal Findings. Hospital volume was associated with significantly reduced intraoperative durations and significantly increased probability of aspirin, β‐blocker, and lipid‐lowering discharge medication use. The proportion of outcome variability due to unobserved hospital × surgeon interaction effects was small but meaningful for intraoperative practices, discharge destination, and medication use. For readmissions and mortality within 30 days or 1 year, unobserved patient and hospital factors drove almost all variability in outcomes.

Conclusions. Among Massachusetts patients receiving isolated CABG, consistent evidence was found that the hospital × surgeon combination independently impacted patient outcomes, beyond hospital or surgeon effects. Such distinct local interactions between a surgeon and hospital resources may play an important part in moderating quality improvement efforts, although residual patient‐level factors generally contributed the most to outcome variability.
Twenty Years of Coverage: An Enhanced Current Population Survey—1989–2008
Authors: Ziegenfuss Jeanette Y. , Davern Michael E.
Published: September 2010

Objective. To create a consistent time series to understand coverage trends by harmonizing 20 years of insurance coverage estimates from the Current Population Survey (CPS) that are an available public resource.

Data Source. 1990–2009 CPS Annual Social and Economic Supplement data.

Study Design. CPS data are enhanced to account for methodological and conceptual changes in health insurance measurement and population control totals.

Principal Findings. The enhancements to the CPS result in an approximately 1 percent reduction in uninsurance rates. Reductions vary over time and by age group. Changes over the last two decades differ slightly using the two data sources. For example, the enhanced data show a greater erosion of private coverage.

Conclusion. The enhanced data provide the most consistent measure of health insurance coverage over the past two decades.
Immunohistochemical detection of HER‐2/neu expression in spontaneous feline mammary tumours
Authors: Winston J. , Craft D. M. , Scase T. J. , Bergman P. J.
Published: September 2010

Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER‐2/neu protooncogene encodes a 185‐kDa transmembrane tyrosine receptor kinase protein. Approximately 25–30% of human MGT demonstrate HER‐2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis. No reports have been published, to date, investigating the expression of Her‐2/neu in cats or cats with spontaneous mammary tumours. Based on the increased percentage of malignant mammary cancers in cats, compared to that in dogs, and the correlation of an increased malignancy and a decreased prognosis with Her‐2 overexpression in human mammary cancer, we hypothesized that cats with spontaneous malignant mammary adenocarcinoma overexpress Her‐2/neu in the neoplastic mammary epithelial cells. Thirty cats with MGT were assayed for Her‐2/neu immunohistochemical expression. The median percentage of cells from feline MGT expressing Her‐2/neu by utilizing the Dako polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her‐2/neu expression intensity grades 2 and 3 consistent with the overexpression by utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90 and 76.7% of cats with MGT, respectively. The level of overexpression concordance across the two antibodies was 70%. The results from this study suggest that Her‐2/neu overexpression is common in cats with spontaneous MGT, and therefore appears to represent an excellent model for Her‐2/neu‐overexpressing human breast cancer.
Canine PHA‐stimulated adherent cell enhance interferon‐gamma production and proliferation of autologous peripheral blood mononuclear cells
Authors: Ide Kaori , Momoi Yasuyuki , Iwasaki Toshiroh
Published: September 2010

Dendritic cells are specialized antigen‐presenting cells with immuno‐modulating functions that are attractive for clinical applications for cancer immunotherapy. This study examined immunostimulatory functions of phytohemagglutinin (PHA)‐stimulated adherent cells (PHA‐Ad cells) from peripheral blood mononuclear cells (PBMCs) in dogs. PHA‐Ad cells enhanced interferon‐γ from autologous PBMC in vitro. PHA‐Ad cells also stimulated antigen‐independent proliferation of peripheral blood lymphocytes. These results suggest that PHA‐Ad cells from PBMC possess a stimulatory function to evoke anti‐tumour immunity and that they demonstrate potential for therapeutic applications in dogs.
Total Skin Electron Beam Irradiation for Generalized Cutaneous Lymphoma
Authors: Prescott D. M. , Gordon J.
Published: September 2010

Introduction:  Generalized cutaneous T‐cell lymphoma (CTCL) in canines has many similarities to CTCL in humans. In humans, early stage mycosis fungoides (MF) patients that do not have lymph node or any systemic involvement can do very well with total skin electron beam irradiation (TSE). In fact, if these early stage patients were treated with 30–35 Gy, the median overall survival was not reached at 15 years. Only one dog with CTCL has been treated with total skin irradiation using orthovoltage irradiation. The patient died the night of the 2nd fraction of RT. Now that more veterinary RT facilities have linear accelerators with electron beam capabilities, it is possible canines with CTCL can be treated with TSE. This paper describes an adaptation of the Modern TSE technique used in human MF patients and its application in canine patients with MF/CTCL.

Methods:  The modified Modern TSE technique and its application for canine MF/CTCL patients involves 20 treatments given M‐F over 4 weeks. The entire skin surface is treated from multiple directions.

Results:  Four canine patients with CTCL have been treated with this TSE technique. All patients responded to the treatment initially with the first patient having tumor control for >20 months. One patient has failed the therapy at this date.

Conclusions:  The TSE technique adapted for use in canines with CTCL was well tolerated with no significant toxicity noted. Development of a collaborative study with other veterinary RT centers having electron beam capabilities is being evaluated through VRTOG.
Feline Sinonasal Neoplasia: CT Staging and Prognosis with Mega Voltage Radiation Therapy
Authors: De Lorimier L. P. , Fan T. M. , Haney S. , Grimm J. B. , Charney S. C. , Clifford C. A.
Published: September 2010

Introduction:  Megavoltage radiation is considered standard therapy for feline sinonasal neoplasia, but a paucity of published reports and the lack of a staging system based on advanced sectional imaging render accurate prognostication difficult. The aims of this retrospective study on feline sinonasal neoplasia were to adapt or develop a staging system based on advanced imaging, and to further define the prognosis with megavoltage radiation therapy.

Methods:  Medical records were reviewed, and CT images were evaluated by a single radiologist (JBG) and staged using a modified system previously reported for dogs. Further follow‐up information was obtained by telephone interviews with the referring veterinarians or owners.

Results:  Thirty‐six cats received megavoltage radiation for sinonasal neoplasia. Carcinomas (n = 17) and lymphomas (n = 16) were most common, followed by sarcomas (n = 3). A majority of immunophenotyped lymphomas were B‐cell (89%). Diagnostic CT images were available for review on 33 cats. The stage distribution was as follows: T1 (n = 3), T2 (n = 11), T3 (n = 5), T4 (n = 14). Lymphomas were more commonly T2 (n = 8) while a majority of carcinomas were T4 (n = 8). The median survival times have not yet been reached for any stage or disease subtype. The most common cause for euthanasia was local recurrence (15/19, 79%). Four cats that died of other causes lived between 1,124 and 2,322 days.

Conclusions:  Feline sinonasal neoplasia is uncommon, with carcinomas and lymphomas being most frequently encountered. Megavoltage radiation therapy appears to offer improved quality and duration of life for most patients, despite advanced staged at diagnosis in a majority.
Association of p53 Gene Mutation with the Prognosis of Canine Lymphoid Tumors
Authors: Koshino A. , Setoguchi A. , Ohno K. , Tsujimoto H.
Published: September 2010

Introduction:  Many dogs with lymphoid tumors develop resistance to chemotherapy. As a mechanism of drug resistance in canine lymphoma, ATP‐dependent drug efflux by P‐glycoprotein was reported, however, inhibition of apoptosis mediated by P53 inactivation has not been investigated. In this study, we investigated the relationship between p53 gene mutation and clinical drug resistance in canine lymphoid tumors.

Methods:  Tumor specimens were obtained from 44 dogs with lymphoid tumors. Mutations of p53 gene at exon 4–8 of these tumor tissues were examined by PCR‐SSCP (single strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. The cases were treated with UW‐Madison protocol, and its response was evaluated by the tumor size or the number of peripheral leukemic cells.

Results:  Of the 44 dogs, 15 dogs (34%) had p53 mutation, whereas 29 dogs (66%) were devoid of p53 mutation, before or during the chemotherapeutic protocol. Rate of good response (CR and PR) to chemotherapy was significantly lower in the dogs with p53 mutation (20%) than those without p53 mutation (55%)(p = 0.022). Median overall survival duration after examination of p53 mutation was significantly shorter in dogs with p53 mutation (101days) than those without p53 mutation (223days)(p = 0.008).

Conclusions:  Lymphoid tumors with p53 mutations were shown to have worse prognosis than those without p53 mutation.
COX‐2 Expression in Feline Oral Squamous Cell Carcinoma (FOSCC)– An Immunohistochemical Study and Analysis of Survival
Authors: Hayes A. , Scase T. , Miller J. , Murphy S , Sparkes A. , Adams V.
Published: September 2010

Introduction:  Cyclooxygenase‐2 (COX‐2) catalyses the rate‐limiting step in the conversion of arachidonic acid to eicosanoids and has been found to be overexpressed in many human and some animal cancers. Overexpression of COX‐2 in head and neck SCC in humans is associated with shorter survival times. Non‐resectable, FOSCC is a devastating disease with no effective therapy. Overexpression of COX‐2 in FOSCC may support the anecdotal use of NSAID therapy. Identification of a prognostic marker in cats may permit more effective, targeted therapy.

Methods:  Immunohistochemistry was performed on formalin‐fixed, paraffin‐embedded tissue from 59 FOSCC cases using an indirect staining technique and feline foetal kidney as positive control. Polyclonal antiserum specific to COX‐1 and COX‐2 were used after antigen retrieval with pH6 citrate buffer. Retrospective, observational data were collected by practitioner questionnaires. A Kaplan‐Meier survival plot was derived.

Results:  55/59 questionnaires were returned (93% response rate). Median age at presentation was 10.9 years (range 7–15.5). Median survival time was 44 days (95% CL: 31, 79). Preliminary results show that COX‐1 staining was positive in all tumour tissues and in 86.7%(13/15 cases) of normal tissues. COX‐2 staining was positive in 67.3%(37/55) of tumour tissues and absent in normal tissue. Results of proportional hazards regression for survival and multiple logistic regression for COX expression including age, sex, breed, prior NSAID administration, other medication and COX expression as potential explanatory variables will be presented.

Conclusions:  These results indicated that COX‐1 and COX‐2 expression is seen in FOSCC but may not be predictive for survival.
Xenogeneic Human Tyrosinase DNA Vaccination Induces Specific Immune Response in Dogs with Advanced Malignant Melanoma
Authors: Liao J. , Gregor P. , Orlandi F. , Craft D. M. , Leung C. , Houghton A. N. , Wolchok J. D. , Bergman P. J.
Published: September 2010

Introduction:  Xenogeneic melanosomal differentiation antigens, delivered in the form of a plasmid DNA vaccine, can overcome host immune ignorance/tolerance in preclinical animals to melanoma by: 1) generating humoral and cytotoxic T cell responses and 2) inducing protection from tumor challenge. Initial trials of human tyrosinase (huTyr) DNA vaccination of dogs with advanced malignant melanoma (Bergman et al, 2003) demonstrated safety and prolongation of survival with this therapeutic modality. We investigated antigen‐specific immunity in dogs receiving huTyr DNA vaccination.

Methods:  Three cohorts of three dogs each with advanced (WHO stage II‐IV) canine malignant melanoma (CMM) received four biweekly IM injections (dose levels 100, 500, or 1,500 ug, respectively/vaccination) of huTyr plasmid DNA via the Biojector2000 jet delivery device. Sera samples were taken before and after vaccination to detect specific antibody formation to huTyr by Enzyme‐Linked ImmunoSorbent Assays (ELISAs) and flow‐cytometry.

Results:  Three dogs have measurable, 2 to 4 fold huTyr‐specific antibody titers. Preliminary studies by flow‐cytometry have confirmed antibody response to huTyr by positive binding to endogenous human tyrosinase in SK‐Mel188 cells using post‐vaccinate serum.

Conclusions:  Xenogeneic (huTyr) DNA vaccination generates antigen‐specific humoral responses, which may partially explain the previously reported clinical efficacy and anti‐tumor responses. Ongoing studies include: 1) a comprehensive analysis by flow‐cytometry to detect huTyr‐specific antibodies and 2) a quantitative measure of potential cytotoxic T‐cell responses in these dogs by the DNA vaccination.
A Candidate Second‐Generation Photosensitizer for Photodynamic Therapy in Veterinary Medicine
Authors: Borgatti‐Jeffreys A. , Hooser S. B. , Miller M. A. , Thomas R. M. , DeGortari A. , Lucroy M. D.
Published: September 2010

Introduction:  Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second‐generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available.

Methods:  Increasing intraperitoneal doses of ZnPcS4 were given to Swiss Webster mice to assess acute toxicity. Based on mouse toxicity data, a phase I clinical trial of ZnPcS4‐based PDT in tumor‐bearing dogs was designed, using an accelerated titration scheme starting at 0.5% of the minimum toxic dose in mice. 24‐hours after ZnPcS4 administration tumors were irradiated with 675 nm light and dogs were evaluated by routine hematology and serum biochemistry at regular intervals after PDT.

Results:  Doses >125 mg/kg were associated with acute toxicity and mortality in Swiss Webster mice, suggesting the minimum toxic dose is 120–125 mg/kg. One dog, a Golden retriever with a massive malignant fibrous histiocytoma, has been entered into the phase I clinical trial. No deleterious effects were noted after ZnPcS4 administration. Within 48 hours of PDT, the tumor was dark and necrotic, with no grossly visible changes to the surrounding normal tissues. Histological examination of the PDT‐treated tumor confirmed widespread necrosis and thrombosis consistent with PDT‐mediated damage. The owner reported no adverse effects after treatment.

Conclusions:  Although preliminary data are encouraging, additional evaluation of ZnPcS4‐based PDT is required to determine its role in veterinary medicine.
The Biologic Behavior of Mast Cell Tumors in Pug Dogs
Authors: Prink A. L. , McNiel E. A. , O'Brien T. D.
Published: September 2010

Introduction:  The purpose of this study was to quantitate the risk and to describe the behavior of mast cell tumors (MCT) in Pugs.

Methods and Materials:  Using the Veterinary Medicine Database, the frequency of MCT in Pugs was compared to the frequency in other dogs using a Chi‐square test. To describe the biologic behavior of MCT in pugs, cases with histologically confirmed diagnosis were identified through the University of Minnesota (UMN) Diagnostic Laboratory and Veterinary Medical Center. Histology was reviewed by a single pathologist. Survival analysis was performed to determine the impact of clinical and histologic data on survival.

Results:  The frequency of MCT diagnosis in Pugs was significantly increased compared to other dogs (OR = 2.28, 95% CI = 1.81–2.86). Twenty‐five purebred Pugs with a diagnosis of MCT were identified through UMN. Multiple cutaneous tumors were documented in 14 (56%) of the dogs. Most tumors were low to intermediate grade. Only three dogs have died of their disease. Sixteen are still living (median follow‐up = 660 days). The only factors predicting survival were grade, mitotic index and tumor size.

Discussion:  Our data confirms MCT predisposition in Pugs and suggests that mast cell tumors in Pugs are relatively benign, despite the presence of multiple cutaneous tumors in most cases. Multiple tumors in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.

This work was supported in part by NCI grants R03‐CA101030 and K08‐CA89530.
131‐I therapy for Advanced, Unresectable Thyroid Tumors in Dogs
Authors: Turrel J. , Burke B. , Ullman S. , McEntee M. , Page R.
Published: September 2010

Introduction:  Greater than 50% of dogs with thyroid tumors present with surgically unresectable disease for which external beam radiotherapy has been reported to prolong survival. The success of 131I for control of thyroid tumors in cats and in humans suggests such therapy may also play a role in the management of canine thyroid cancer.

Methods:  Thirty‐nine dogs with WHO stage II/III (invasive or ectopic; n = 32) or IV (metastatic; n = 7) thyroid tumors were treated with 131I alone. Changes in thyroid function, 99MTc‐pertechnetate (99MTc) scintigraphic changes, and tumor response were recorded. Dogs with ventral cervical tumors were evaluated for feasibility of surgical resection following 131I.

Results:  Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.

Conclusions:  These findings suggest 131I should be investigated more thoroughly in dogs with thyroid tumors not considered surgical candidates to more clearly characterize the indications for therapy and followup recommendations. 131I dosimetry in dogs with thyroid tumors remains problematic. Administration of 131I is currently based on empiric recommendations and, in general, the treatment is well tolerated although additional studies are indicated to optimize response and minimize toxicity.
Identification of a Splice Variant of gp100 Expressed in Canine Melanoma Tumours
Authors: Stell A. , Dobson J. , Catchpole B.
Published: September 2010

Introduction:  The melanoma‐associated antigen (MAA) gp100 is a glycoprotein expressed by melanocytes and is considered to be an important target for anti‐tumour immunity in human melanoma. The aim of the current study was to characterise the canine gp100 gene with a view to its inclusion in a DNA vaccine for treatment of canine oral malignant melanoma.

Methods:  RNA was extracted from eight canine oral melanomas and seven control samples (pigmented oral mucocutaneous tissue) and cDNA synthesised. PCR was performed using human gp100 primers designed to generate a 421base pair (bp) fragment. In addition to the expected pcr product, a smaller amplicon (∼260 bp) was present in all tumours and control tissues. Both PCR amplicons were cloned and sequenced. The gp100 genomic DNA sequence was identified from the dog genome resource (NCBI).

Results:  The 421 bp fragment of canine gp100 shared 90.8% identity with human gp100. This partial sequence was located on dog chromosome 10 (CFA10_contig 2982). Further analysis, using the human gp100 gene as a reference, allowed the complete canine gp100 coding sequence to be identified from the dog genome. Sequence analysis of the small PCR product showed it to be a splice variant of gp100 with exon 5 deleted.

Conclusion:  The canine gp100 sequence has been identified and this will allow DNA vaccine constructs containing this MAA to be developed. The splice variant of gp100 with exon 5 deleted was not tumour‐specific and was expressed in both melanomas and normal pigmented tissue.
RT‐PCR based Tyrosine Kinase Display Profiling of Canine Melanoma: IGF‐1 Receptor as a Potential Therapeutic Target
Authors: Huelsmeyer M. K. , Mitzey A. , Baker T. , Swaab M. , Thamm D. H.
Published: September 2010

Introduction:  There is a wealth of information available regarding tyrosine kinase (TK) expression in human cancer, however there is minimal information regarding the expression and function of TKs in canine melanoma, and no attempt has been made to systematically define the repertoire of TKs expressed. This study employed a molecular technique called RT‐PCR display to simultaneously evaluate the expression of up to 30 different TKs in a canine melanoma cell line.

Materials and Methods:  mRNA was extracted and reverse‐transcribed from the 17CM98 canine melanoma line, then subjected to PCR using degenerate primers coding for highly conserved regions which flank the kinase domains of many receptor and nonreceptor TKs. The resulting product was ligated into a plasmid vector and used to transform E. coli. Multiple colonies were isolated, and the cDNA inserts sequenced.

Results and Conclusions:  Sequencing 46 clones yielded canine homologs of IGF‐1R (50%), JAK1 (17%), PDGFR‐α(11%), FGFR1 (9%), Axl (7%), c‐Abl (4%), and PTK2 (2%). Interestingly, IGF‐1R, JAK1 and Axl were detected using a similar technique in human melanoma, supporting the cross‐species validity of this assay. Given the abundance of IGF‐1R clones, we sought to determine the biologic effect of rhIGF‐1 in 17CM98 cells. IGF‐1 stimulated IGF‐1R phosphorylation, cell proliferation and VEGF production in 17CM98, and protected the cells from serum starvation‐induced apoptosis. Expression of IGF‐1R mRNA was detected in 5 of 5 additional canine melanoma cell lines evaluated, suggesting that IGF‐1R expression may be common in canine melanoma cells and providing a novel target for future therapy.
Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer
Authors: Jonasdottir T. J. , Borrebæk J. , Bruland ØS , Salberg G. , Moe L. , Larsen R. H.
Published: September 2010

Introduction:  Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha‐particle emitter 223Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx®/Doxil®).

Methods:  Caelyx® was given before the injection of liposomal 223Ra to reduce the reticulo‐endothelial‐system uptake. A pilot study was conducted to determine the optimal time interval between the pre‐treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma.

Results:  Optimal blood‐to‐liver and blood‐to‐spleen ratios of liposomal radium was achieved in animals that received pre‐treatment with Caelyx® 4 days in advance. Blood clearance was relatively slow, in mice t1/2 was ∼28 h (BalbC mice) and in the dog t1/2 was ∼ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non‐calcified tumor metastases of different organs, than in normal tissue.

Conclusions:  Liposomal 223Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal‐tissue ratio in a dog with spontaneous osteosarcoma.
REVIEWS OF EXHIBITIONS
Authors: Hankins James
Published: September 2010

Virgilio e il Chiostro. Manoscritti di autori classici e civiltà monastica, Abbazia di Montecassino, 8 July 1996–8 December 1996; Virgilio e il Chiostro. Manoscritti di autori classici e civiltà monastica, edited by Mariano Dell'Omo, Rose, Rome, 1996

Vedere i Classici. L'illustrazione libraria dei testi antichi dall'età romana a1 tardo medioevo', Musei Vaticani, Salone Sistino, 9 October 1996–19 April 1997. Vedere i Classici. L'illustrarione libraria dei testi antichi dall'età romanu a1 tardo medioevo, edited by Marco Buonocore, Rose, Rome, 1996

Umanesimo e Padri della Chiesa. Manoscritti e incunaboli di testi patristici da Francesco Petrarca a1 primo Cinquecento, Biblioteca Medicea Laurenziana, 5 February 1997–9 August 1997. Umanesimo e Padri della Chiesa. Manoscritti e incunuboli di testi patristici da Francesco Petrarca a1 primo Cinquecento, edited by Sebastiano Gentile, Rose, Rome, 1997
Lucan the Christian Monarchist: the anti‐republicanism of the De tyranno and the De bello civili
Authors: Bond Christopher
Published: September 2010

In an early Quattrocento tract, the De tyranno, Coluccio Salutati, Chancellor of the Florentine Republic, defended Dante's damnation of the assassins of Caesar, and offered a thorough condemnation of the flaws of the Roman Republic and a spirited endorsement of the succeeding autocracy. Salutati's apparent conversion to Dante's Christian Monarchism has puzzled scholars and has led to his characterisation as a somewhat outmoded figure. But a more complex picture emerges from an analysis of an overlooked feature of the De tyranno: its extraordinary use of Lucan's historical epic, the De bello civili. While his contemporaries regarded the poem as an anti‐Caesarian polemic, Salutati identified and exploited the ironies of this deeply ambivalent work toward the republican ideal it was taken to espouse. Through a strategy of quotation, allusion, and paraphrase, he expressed his own monarchist arguments in the language of the favourite literary authority of Renaissance republicanism. This strategy was apparently original and probably influential, and is detectable, too, in Salutati's other works. These borrowings demonstrate the degree of dexterity with which a Florentine humanist might apply the classical learning of the Trecento to the political debates of the Quattrocento, and also the undiminished powers of the ageing Chancellor as reader and rhetorician.
An unpublished letter of Isabella of Aragon, Duchess of Milan1
Authors: Zutshi Patrick
Published: September 2010

The purpose of the article is to consider the form and contents of a letter from Isabella of Aragon, Duchess of Milan and of Bari, and the circumstances in which it was written, as well as to print its text. The letter, which survives in Cambridge University Library, is autograph, written in Italian and dates from 2 September 1501. It alludes to various misfortunes that had befallen Isabella. It asks its addressee, Ferdinand the Catholic, the conqueror of the kingdom of Naples, to confirm her in possession of the duchy of Bari and her lands in Calabria, a request that was successful. The letter is compared with other letters of Isabella and with letters of other female members of the Aragonese house of Naples.
The Italian Johannes Opicius on Henry VII of England's 1492 invasion of France: historical witness and antique convention
Authors: Carlson David R.
Published: September 2010

The paper explicates the literary and historical contexts of Latin verse writings of a young Italian, Johannes Opicius (fl. 1492–1515), on the 1492 invasion of France by the Tudor sovereign Henry VII (r. 1485–1509). Opicius had access to veracious information about the overseas campaign of the English king and army, as is confirmed by other surviving documentary and narrative sources. On the other hand, after the fashion of the Tudor laureate Bernard André (c. 1450–1522), Opicius’ poetry is also shaped by his close imitation of ancient poetry, including the Laus Pisonis (c. 62) and writings by and about M. Annaeus Lucanus (d. 65), as well as standard curricular authors. Classical emulation and historiographical veracity are not inimical to one another in Opicius’ work, however; it is argued finally that both contributed to the English king's glorification. Critical texts and annotations are appended. (pp. 520–546)
Carbon Sequestration and Conservation of Tropical Forests Under Uncertainty
Authors: Reddy S. Rama Chandra , Price Colin
Published: September 2010

Concern for global warming has focused attention on the role of tropical forests in the reduction of ambient CO2levels and mitigation of climate change. Deforestation is a major land use change in the tropics, with forest resources undergoing degradation through the influence of logging and conversion to other uses. Land use change is a product of varied local and regional resource use policies. Management of forest resources is one such major temporal factor, influencing resource stability and the carbon pool. Under a given management policy, both the long period of forest growth, and the slow turnover and decay of the carbon pool, enhance the relevance of stand level management policies as cost‐effective mechanisms mitigating climate change. Apart from regional level uncertainties like the nature of land use and the estimation of carbon storage in vegetation and soil, the carbon flux of tropical forests is greatly influenced by uncertainty in regenerative capacity of forests and in harvest and management policies. A case study from India is used to develop a transition matrix model of natural forest management, and to explore the economic implications of maintaining and expanding existing carbon sinks. The study further explores the significance of investments in additional carbon sinks in plantation forests, given continued uncertainty in natural forest management.
Consumer Behaviour in a Country in Transition with a Strongly Contracting Economy: The Case of Food Consumption in Bulgaria
Authors: Balcombe K. , Davidova S. , Morrison J. A.
Published: September 2010

This paper presents estimates of demand elasticities in Bulgaria using the Almost Ideal Demand system while using interval priors for the parameters. Expenditure elasticities are found to be considerably higher than unity for food items. These results are interpreted as being due to a substantial divergence between consumption and expenditure on food items. It is concluded that under conditions of falling incomes, policies which focus exclusively on food provision may not be appropriate. In the event of a return to income growth, an initial increase in demand for selected food items could outstrip the potential to increase domestic supply, and lead to an increase in imports, or decrease in exports, of a number of agricultural products.
Scale Effects and Mark‐ups in the US Food and Fibre Industries: Capital Investment and Import Penetration Impacts
Authors: Paul Catherine J. Morrison
Published: September 2010

Capital investment patterns and import penetration are often alleged to influence firms' costs and prices, and thus economic performance. We examine the impacts of these factors on measures of scale economies, input demand/composition, and market power in the US food and fibre industries. Flexible variable cost functions incorporating quasi‐fixity of three categories of private (internal) capital and two external technological and trade (import) factors represent the cost structures of the two industries. Pricing equations, based on inverse demand functions including import prices, represent output decisions. Cost and demand elasticities constructed from this model indicate reduced manufacturing costs from technical and trade, scale and capital effects. This increased cost efficiency arises largely from materials savings in the textiles industry and reduced labour use in the food industry. Mark‐up behaviour is exhibited for most of the sample period in the textiles industry, and neither industry appears heavily affected by import prices.
A Cost Function Approach to Dynamic Duality: An Application to the US Cigarette Manufacturing Industry
Authors: Rezitis Anthony N. , Foster William E. , Brown A. Blake
Published: September 2010

The dynamic duality econometric approach with the case of multiple outputs is applied to the US cigarette manufacturing industry to test for the presence of adjustment costs and quasifixed inputs with regard to stocks of capital and tobacco. Capital and tobacco stocks are found to be quasi‐fixed inputs and the empirical results indicate that there are significant adjustment costs associated with adjusting these inputs. Short‐ and long‐run own‐ and cross‐price elasticities of factor demands are estimated for domestic and imported tobaccoes, materials, tobacco stocks, and capital. Output demand elasticities are also estimated. The two outputs, cigarettes produced for export and for the US market, are examined for equality of marginal costs. No evidence of differences in marginal costs was found. There is evidence that government restrictions on advertising have negative effects on output demand.
Estimates of Food Demand Elasticities for Great Britain: 1972–1994
Authors: Tiffin Abigail , Tiffin Richard
Published: September 2010

This paper reports the results of the estimation of Almost Ideal Demand Systems (AIDS) for UK food demand using time series data from the National Food Survey. A Bayesian approach is used to impose curvature restrictions in the model. The aim is to obtain estimates of Hicksian, Marshallian and expenditure demand elasticities for UK food which are fully consistent with static optimisation by consumers. Overall, the results concur with expectations as aggregate food demand is both price and income inelastic and individual food categories are mostly price and income inelastic. The notable exception being meat, specifically pork, beef and chicken.
Efficient Contract Design for Agri‐Environment Policy
Authors: Moxey Andrew , White Ben , Ozanne Adam
Published: September 2010

This paper evaluates alternative designs for contracts between a regulator and an agricultural producer to increase the supply of environmental public goods. Contract design, based on the principal‐agent model, takes into account an asymmetry of information between the regulator and producer whereby the regulator is unable to observe precisely the producer's compliance costs. An example is included of contracts designed for nitrate abatement.
Forecasting Prices at the Dutch Flower Auctions
Authors: Steen Marie , Gjølberg Ole
Published: September 2010

Prices at the Dutch flower auctions are extremely volatile. Price changes of +/‐20 per cent one week to the next represents a normal event, and +/‐50 per cent is not uncommon. Since production planning in the flower business offers a complicated variation over the Newsboy Problem, good price forecasts would improve decision making on space allocation; what species to plant; the timing of harvesting, etc. This paper analyses weekly prices for three major species, i.e., roses, chrysanthemums and carnations, 1993–1996. We find that there are strong calendar regularities particularly for roses and chrysanthemums. Establishing a model in which we combine information on seasonal regularities and autoregressive price patterns, we manage to explain a substantial part of the short‐term price variability for all three species. The model is tested in an out‐of‐sample dynamic forecasting experiment during the first 35 weeks of 1997.
Household Food Demand Analysis in India
Authors: Abdulai Awudu , Jain Devendra K. , Sharma Ashok K.
Published: September 2010

Price and expenditure elasticities and estimates of the effect of household demographic variables on Indian food items are estimated using a recent household survey data in rural and urban areas. Using a linear approximate almost ideal demand system (LA/AIDS), the results indicate that for commodity groups (milk and milk products; cereals and pulses; edible oils; meat, fish, and eggs; vegetables and fruits; other foods) demand is elastic only for milk and milk products in both rural and urban areas of India. The impact of demographic variables such as region, household size, education level of household head, and seasonality, was generally significant.
An Assessment of the Impact of Implementing the European Commission's Agenda 2000 Cereal Proposals for Specialist Wheatgrowers in Denmark
Authors: Fraser Rob , Rygnestad Hild
Published: September 2010

This paper undertakes an assessment of the impact of implementing the European Commission's Agenda 2000 cereal proposals for specialist wheatgrowers in Denmark. The economic model of a representative farm developed in Rygnestad and Fraser (1996) is extended to include a model of nitrate leaching and then used to simulate the impact of implementing the proposals. The results of this simulation are compared and contrasted with those of the sectoral and regional impact studies reported in European Commission (1998b). In particular, the proposals are shown to have an environmentally‐beneficial effect in terms of reduced nitrate leaching, with the magnitude of this effect dependent both on the quality of land and on the ex ante set‐aside rate.
The Challenge of Sustainability at the Farm Level: Presidential Address
Authors: Webster Paul
Published: September 2010

The sustainability of farming systems is currently under debate. There is concern that technological and other changes have long‐run consequences, which may compromise future levels of desired outputs from agricultural and other resources. The paper traces developments in the theory of sustainability and discusses their application at the farm level. Findings include firstly, that sustainability should be regarded as an emergent property of an agricultural system. Its operational definition at the farm level thus may not apply at other levels in the hierarchy. Secondly, whilst individual farmers may attach value to “sustainability” goods, they are unlikely to adopt socially optimal levels without regulation or incentive. Finally, since sustainability issues at the farm level are usually long‐run, dynamic and have social dimensions, a central task for farm management researchers lies in investigations which allow tradeoffs between different sustainability criteria to be determined and then optimised according to society's norms.
Productivity and the Returns to Levy‐Funded R&D for Sugar Production in the Eastern Counties of England
Authors: Thirtle Colin
Published: September 2010

Estimates of the rate of return (ROR) to publicly funded‐agricultural research are getting lower as private expenditures and spill‐overs are more adequately handled. For UK sugar beet there is a pool of technology available and the spill‐ins are not measurable. An alternative approach is to assume that the difference between productivity growth in sugar and the rest of UK agriculture is attributable to the Sugar Beet Research and Education Committee's R&D and extension expenditures, funded by the only long‐standing producer levy in the UK. These expenditures are used to explain the difference between total factor productivity (TFP) growth in sugar (3.5 per cent per annum) and the rest of UK agriculture (2.0 per cent per annum). The producer's ROR calculated using this approach is 11 per cent and the lower bound on the total return, to producers and consumers is 21 per cent, whereas the conventional methodology gives returns of 87 per cent. Thus, the upward bias in ROR calculations may be removed by changing the approach to the problem.
A Statistical Analysis of Wheat Price Fluctuations in England: 1685–1850
Authors: Chambers Marcus J. , Bailey Roy E.
Published: September 2010

For some commodities and time periods, the analysis of price fluctuations must necessarily rely on the existence of price data alone. A theory applicable in such circumstances is outlined for commodities that are storable, traded in open markets and subject to net supply shocks which are heterogeneously distributed across the months of the year. Market prices are predicted to vary autoregressively except at times when wheat stocks become negligible and observed market prices exceed threshold prices (which may themselves differ across months). The model is applied to a monthly time series of wheat prices for southern England from 1685 to 1850. The autoregressive parameter and the threshold prices are estimated, substantial empirical support being found for the models tested. Historical events from the late seventeenth century through to the continental wars in the late eighteenth and early nineteenth centuries are used to illustrate the mechanisms underlying the theory.
Food Import Demand in the Czech Republic
Authors: Janda Karel , McCluskey Jill J. , Rausser Gordon C.
Published: September 2010

This paper provides an overview of Czech food import demand in the transition period of the 1990s. It provides econometric estimates of own‐ and cross‐price elasticities as well as group expenditure elasticities of Czech import demand for sixteen lower level and four upper level food groups. Based on the Hausman test for endogeneity, which supported the hypothesis that Czech import prices were exogenously determined outside of the Czech economy, we estimated five demand models as direct‐demand systems of the AIDS type. The econometric estimation of elasticities used bimonthly data from March 1993 to August 1997.
The Dynamics of Low Pay in Rural Households: Exploratory Analysis Using the British Household Panel Survey
Authors: Phimister Euan , Shucksmith Mark , Vera‐Toscano Esperanza
Published: September 2010

This paper considers a low pay dynamics of rural residents by comparing rural and non‐rural sub‐samples of individuals drawn from the British Household Panel Survey. Descriptive analysis suggests that the overall rate of rural exits from low pay was less and that rural low pay persistence was higher than those found in the non‐rural case. Results from regression analysis indicate that rural differences in overall mobility can be attributable to differences in the characteristics of the rural and non‐rural samples, e.g., education levels, structure of employment, etc. However, once sample selection problems are controlled there remains a residual rural effect consistent with the claim that ‐ all other things being equal ‐ rural low pay is a more persistent phenomenon than its non‐rural counterpart.