bluuebunny/crossref_metadata_2025 huggingface dataset:
A Conceptual Review of Family Resilience Factors
Authors: Black Keri , Lobo Marie
Published: February 2008

Family resilience is the successful coping of family members under adversity that enables them to flourish with warmth, support, and cohesion. An increasingly important realm of family nursing practice is to identify, enhance, and promote family resiliency. Based on a review of family research and conceptual literature, prominent factors of resilient families include: positive outlook, spirituality, family member accord, flexibility, family communication, financial management, family time, shared recreation, routines and rituals, and support networks. A family resilience orientation, based on the conviction that all families have inherent strengths and the potential for growth, provides the family nurse with an opportunity to facilitate family protective and recovery factors and to secure extrafamilial resources to help foster resilience.
Families' Importance in Nursing Care
Authors: Benzein Eva , Johansson Pauline , Årestedt Kristofer Franzén , Berg Agneta , Saveman Britt-Inger
Published: February 2008

This article describes the development and testing of a research instrument, Families' Importance in Nursing Care—Nurses' Attitudes (FINC-NA), designed to measure nurses' attitudes about the importance of involving families in nursing care. The instrument was inductively developed from a literature review and tested with a sample of Swedish nurses. An item-total correlation and a first principal component analysis were used to validate the final instrument, including a second principal component analysis to analyze dimensionality, and Cronbach's alpha was used to estimate internal consistency. The instrument consists of 26 items and reveals four factors: families as a resource in nursing care, family as a conversational partner, family as a burden, and family as its own resource . Cronbach's alpha was 0.88 for the total instrument and 0.69 to 0.80 for the subscales. The instrument requires further testing with other nurse populations.
Living the As-Yet Unanswered
Authors: McLeod Deborah L. , Wright Lorraine M.
Published: February 2008

A serious illness often creates suffering and precipitates a search for spiritual meaning. The purpose of this hermeneutic inquiry was to explore the meaning of spirituality and spiritual care practices in family systems nursing. The videotapes of 12 therapeutic conversations with three families living with serious illness were the primary data for the inquiry. Findings suggest that suffering embodies an invitation to respond to the spiritual. Identified spiritual care practices included gathering stories of illness and faith, opening space to reinterpret experiences from a spiritual perspective, drawing on imagination and metaphor, and listening with an opening silence. The therapeutic work with one family is highlighted. This inquiry revealed that spiritual care requires literacy in reading the spiritual, a willingness to respond to the particular and the unpredictable, and a belief that good care demands a wise and thoughtful response to the suffering other.
Racial Context and Voting over Taxes
Authors: Roch Christine H. , Rushton Michael
Published: February 2008

The authors investigate the impact of racial diversity and segregation on white voter support for a comprehensive, progressive tax reform, focusing on a 2003 referendum held in Alabama, which if approved would have raised substantial additional revenues for public education and at the same time greatly increased the progressivity of the tax system. The authors use King's method of ecological inference to obtain estimates of white and black support for the referendum proposal and then attempt to explain the variance across counties in white voter support. Findings show that the degree of racial segregation, rather than the proportion of blacks in a given county, is most critical in predicting support for the referendum among whites at the county level.
Indigenous Knowledge Translation: Baseline Findings in a Qualitative Study of the Pathways of Health Knowledge in Three Indigenous Communities in Canada
Authors: Smylie Janet , Kaplan-Myrth Nili , McShane Kelly ,   Métis Nation of Ontario-Ottawa Council,   Pikwakanagan First Nation,,   Tungasuvvingat Inuit Family Resource Centre
Published: February 2008

To acquire an understanding of the pathways of health information dissemination and use by Indigenous community members, the researchers applied an Indigenous participatory action research approach in partnership with one urban Inuit, one urban Métis, and one semirural First Nations community in Ontario, Canada. A descriptive community case study was conducted in each community through the use of focus groups, key informant interviews, and document inquiry. Results were corroborated by the communities. Each of the three community consultations generated distinct and striking data about health information sources and dissemination strategies; decision-making processes; locally relevant concepts of health, local health services, and programs; community structures; and mechanisms of interface with noncommunity systems. In addition, several crosscutting themes were identified. The participatory research approach successfully engaged community partners. These findings support the hypothesis that understanding local Indigenous processes of knowledge creation, dissemination, and utilization is a necessary prerequisite to effective knowledge translation in Indigenous contexts.
Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury
Authors: Werneck Claudio C. , Vicente Cristina P. , Weinberg Justin S. , Shifren Adrian , Pierce Richard A. , Broekelmann Thomas J. , Tollefsen Douglas M. , Mecham Robert P.
Published: February 2008

Mice lacking the extracellular matrix protein microfibril-associated glycoprotein-1 (MAGP1) display delayed thrombotic occlusion of the carotid artery following injury as well as prolonged bleeding from a tail vein incision. Normal occlusion times were restored when recombinant MAGP1 was infused into deficient animals prior to vessel wounding. Blood coagulation was normal in these animals as assessed by activated partial thromboplastin time and prothrombin time. Platelet number was lower in MAGP1-deficient mice, but the platelets showed normal aggregation properties in response to various agonists. MAGP1 was not found in normal platelets or in the plasma of wild-type mice. In ligand blot assays, MAGP1 bound to fibronectin, fibrinogen, and von Willebrand factor, but von Willebrand factor was the only protein of the 3 that bound to MAGP1 in surface plasmon resonance studies. These findings show that MAGP1, a component of microfibrils and vascular elastic fibers, plays a role in hemostasis and thrombosis.
Vascular dermatan sulfate regulates the antithrombotic activity of heparin cofactor II
Authors: He Li , Giri Tusar K. , Vicente Cristina P. , Tollefsen Douglas M.
Published: February 2008

Heparin cofactor II (HCII)–deficient mice form occlusive thrombi more rapidly than do wild-type mice following injury to the carotid arterial endothelium. Dermatan sulfate (DS) and heparan sulfate (HS) increase the rate of inhibition of thrombin by HCII in vitro, but it is unknown whether vascular glycosaminoglycans play a role in the antithrombotic effect of HCII in vivo. In this study, we found that intravenous injection of either wild-type recombinant HCII or a variant with low affinity for HS (K173H) corrected the abnormally short thrombosis time of HCII-deficient mice, while a variant with low affinity for DS (R189H) had no effect. When HCII was incubated with frozen sections of the mouse carotid artery, it bound specifically to DS in the adventitia. HCII was undetectable in the wall of the uninjured carotid artery, but it became concentrated in the adventitia following endothelial injury. These results support the hypothesis that HCII interacts with DS in the vessel wall after disruption of the endothelium and that this interaction regulates thrombus formation in vivo.
Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes
Authors: Wolk Kerstin , Witte Katrin , Witte Ellen , Proesch Susanna , Schulze-Tanzil Gundula , Nasilowska Katarzyna , Thilo John , Asadullah Khusru , Sterry Wolfram , Volk Hans-Dieter , Sabat Robert
Published: February 2008

IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29 are new members of the IL-10 interferon family. Monocytes are well-known sources of IL-19, IL-20, and IL-24. We demonstrated here that monocytes also expressed IL-29, and monocyte differentiation into macrophages (Mφ) or dendritic cells (DCs) strongly changed their production capacity of these cytokines. Maturation of DCs with bacterial stimuli induced high expression of IL-28/IL-29 and IL-20. Simulated T cell interaction and inflammatory cytokines induced IL-29 and IL-20 in maturing DCs, respectively. Compared with monocytes, DCs expressed only minimal IL-19 levels and no IL-24. The differentiation of monocytes into Mφ reduced their IL-19 and terminated their IL-20, IL-24, and IL-29 production capacity. Like monocytes, neither Mφ nor DCs expressed IL-22 or IL-26. The importance of maturing DCs as a source of IL-28/IL-29 was supported by the much higher mRNA levels of these mediators in maturing DCs compared with those in CMV-infected fibroblasts, and the presence of IL-28 in lymph nodes but not in liver of lipopolysaccharide-injected mice. IL-19, IL-20, IL-22, IL-24, and IL-26 do not seem to affect Mφ or DCs as deduced from the lack of corresponding receptor chains. The significance of IL-20 and IL-28/IL-29 coexpression in maturing DCs may lie in the broadly amplified innate immunity in neighboring tissue cells like keratinocytes. In fact, IL-20 induced the expression of antimicrobial proteins, whereas IL-28/IL-29 enhanced the expression of toll-like receptors (TLRs) and the response to TLR ligands. However, the strongest response to TLR2 and TLR3 activation showed keratinocytes in the simultaneous presence of IL-20 and IL-29.
Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer
Authors: Miller Andrew H. , Ancoli-Israel Sonia , Bower Julienne E. , Capuron Lucile , Irwin Michael R.
Published: February 2008

Patients with cancer experience a host of behavioral alterations that include depression, fatigue, sleep disturbances, and cognitive dysfunction. These behavioral comorbidities are apparent throughout the process of diagnosis and treatment for cancer and can persist well into the survivorship period. There is a rich literature describing potential consequences of behavioral comorbidities in patients with cancer including impaired quality of life, reduced treatment adherence, and increased disease-related morbidity and mortality. Medical complications of cancer and its treatment such as anemia, thyroid dysfunction, and the neurotoxicity of cancer chemotherapeutic agents account in part for these behavioral changes. Nevertheless, recent advances in the neurosciences and immunology/oncology have revealed novel insights into additional pathophysiologic mechanisms that may significantly contribute to the development of cancer-related behavioral changes. Special attention has been focused on immunologic processes, specifically activation of innate immune inflammatory responses and their regulation by neuroendocrine pathways, which, in turn, influence CNS functions including neurotransmitter metabolism, neuropeptide function, sleep-wake cycles, regional brain activity, and, ultimately, behavior. Further understanding of these immunologic influences on the brain provides a novel conceptual framework for integrating the wide spectrum of behavioral alterations that occur in cancer patients and may reveal a more focused array of translational targets for therapeutic interventions and future research. Such developments warrant complementary advances in identification of cancer patients at risk as well as those currently suffering, including an increased emphasis on the status of behavior as a “sixth vital sign” to be assessed in all cancer patients throughout their disease encounter.
Post-Traumatic Stress Outcomes in Non-Hodgkin's Lymphoma Survivors
Authors: Smith Sophia K. , Zimmerman Sheryl , Williams Christianna S. , Preisser John S. , Clipp Elizabeth C.
Published: February 2008

Purpose

A large body of evidence suggests that being diagnosed with and treated for cancer adversely affects functioning and quality of life, yet less is known about longer term outcomes. Therefore, this study aims to estimate the prevalence of post-traumatic stress disorder (PTSD) symptoms in survivors of adult non-Hodgkin's lymphoma (NHL) who are at least 2 years postdiagnosis and identify the risk factors associated with PTSD symptoms, with a focus on those that are amenable for screening and modifiable.

Patients and Methods

A total of 886 NHL survivors identified from the cancer registries of two hospitals in North Carolina participated, ranging in age from 25 to 92 years old and ranging from 2 to 44 years postdiagnosis. Survivors were mailed a survey that assessed PTSD symptoms and quality of life.

Results

Participants averaged 10.2 years postdiagnosis, and most (61%) reported no PTSD symptoms. The adjusted prevalence for full PTSD was 7.9%, with an additional 9.1% meeting criteria for partial PTSD. Modifiable risk factors that were independently associated with PTSD in multiple linear regression included less social support, negative appraisals of life threat and treatment intensity, and more employment and insurance issues. Additionally, several demographic characteristics (nonwhite race, less education, and younger age) and clinical or health-related factors (active disease, more recent diagnosis, and more comorbidity) were independently associated with PTSD.

Conclusion

Although only 8% of survivors met PTSD diagnostic criteria, the impact of a cancer diagnosis and treatment persists for many survivors, as evidenced in 39% of this sample. Early identification of those at risk could enable treatment to minimize PTSD symptomatology.
Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors
Authors: Ligibel Jennifer A. , Campbell Nancy , Partridge Ann , Chen Wendy Y. , Salinardi Taylor , Chen Haiyan , Adloff Kristie , Keshaviah Aparna , Winer Eric P.
Published: February 2008

Purpose

Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors.

Methods

One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks.

Results

Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 μU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 μU/mL, P = .65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P = .07). There was a trend toward improvement in insulin resistance in the exercise group (P = .09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition.

Conclusion

Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition.
Biomarkers of Response to Epidermal Growth Factor Receptor Inhibitors in Non–Small-Cell Lung Cancer Working Group: Standardization for Use in the Clinical Trial Setting
Authors: Eberhard David A. , Giaccone Giuseppe , Johnson Bruce E.
Published: February 2008

The body of literature on the correlations between molecular assessments and patient outcomes after treatment with epidermal growth factor receptor (EGFR) inhibitors continues to grow. It will be important in the future to determine how to most effectively integrate molecular assays that assess the likelihood of therapeutic benefit into clinical practice. Although EGFR-targeted therapies such as erlotinib have been approved for use without molecular testing, immunohistochemistry, fluorescence in situ hybridization, and mutational analyses of the EGFR gene have all been proposed as candidates to help predict response or survival benefit from EGFR-targeted therapy in patients with non–small-cell lung cancer (NSCLC). Further prospective validation from ongoing randomized studies will be needed to fully determine which assays are best to help predict patient outcome. In addition, it will be critical for these assays to undergo standardization before widespread clinical use. The Molecular Assays in NSCLC Working Group, under the sponsorship of Genentech Inc, Roche Pharmaceuticals, and OSI Pharmaceuticals, Inc, was convened to evaluate the available molecular assays for use in the clinical trial setting and provide recommendations for application and interpretation of these tests for future clinical trials. Recommendations of the Molecular Assays in NSCLC Working Group for the use of EGFR molecular assays are presented and include guidelines for tissue storage, handling, and processing. Recommendations for the standardization of molecular assays are also discussed.
Perceptions of Cancer Risks and Predictors of Colon and Endometrial Cancer Screening in Women Undergoing Genetic Testing for Lynch Syndrome
Authors: Hadley Donald W. , Jenkins Jean F. , Steinberg Seth M. , Liewehr David , Moller Stephanie , Martin Jean C. , Calzone Kathleen A. , Soballe Peter W. , Kirsch Ilan R.
Published: February 2008

Purpose

Lynch syndrome poses multiple cancer risks, yet attention has focused on screening for colorectal cancer. Estimated risks for endometrial cancer equal risks for colorectal cancer. This study (1) evaluated women's perceived risks for cancers, (2) compared endometrial cancer screening and colonoscopy, and (3) identified predictors of screening before and after genetic testing.

Patients and Methods

Sixty-five adult women at 50% risk for carrying a cancer-predisposing mutation, without a history of endometrial cancer or hysterectomy, participated in genetic counseling and received unequivocal genetic test results for Lynch syndrome. Participants completed questionnaires before and after receipt of genetic results.

Results

Pretest, perceived risks for colon cancer were significantly higher than for extracolonic cancers (P < .0001). Use of colonoscopy was significantly higher (P = .006) than endometrial cancer screening. Post-test, carriers demonstrated a significant (P < .0001) increase in their perceived risk for extracolonic cancers and increased both colonoscopy (P = .79) and endometrial cancer screening (P = .11). Mutation status, age, perceived likelihood of carrying a mutation, and communication of test results to their physician independently predicted cancer screening at follow-up.

Conclusion

Women in families with Lynch syndrome are less aware of their risks for extracolonic cancers and undergo endometrial cancer screening significantly less often than colonoscopy before genetic counseling. Given the significantly increased risks for endometrial and ovarian cancers and the mortality associated with ovarian cancer, additional efforts to inform families of cancer risks and screening recommendations seem prudent. Physicians play a critical role in ensuring appropriate cancer screening in women with Lynch syndrome.
Non-Overlapping and Non–Cell-Type–Specific Gene Expression Signatures Predict Lung Cancer Survival
Authors: Sun Zhifu , Wigle Dennis A. , Yang Ping
Published: February 2008

Purpose

Gene expression profiling for outcome prediction of non–small-cell lung cancer (NSCLC) remains clouded by heterogeneous and unvalidated results. This study applied multivariate approaches to identify and evaluate value-added gene expression signatures in two types of NSCLC.

Materials and Methods

Two NSCLC oligonucleotide microarray data sets of adenocarcinoma and squamous cell carcinoma were used as training sets to select prognostic genes independent of conventional predictors. The top 50 genes from each set were used to predict the outcomes of two independent validation data sets of 84 and 91 NSCLC cases.

Results

Adenocarcinomas with the 50-gene signature from adenocarcinoma in both validation data sets had a 2.4-fold (95% CI, 1.3 to 4.4 and 1.0 to 5.8) increased mortality after adjustment for conventional predictors. Squamous cell carcinoma with this high-risk signature had an adjusted risk of 1.1 (95% CI, 0.4 to 3.2) in one data set and 2.5 (95% CI, 1.1 to 5.8) in another consisting of stage I tumors. Adenocarcinoma with the 50-gene signature from squamous cell carcinoma had an elevated risk of 3.5 (95% CI, 1.4 to 9.0) after adjustment for conventional predictors. Squamous cell carcinoma with this high risk signature had an adjusted risk of 1.8 (95% CI, 0.7 to 4.6). Despite the little overlap in individual genes, the two gene signatures had significant functional connectedness in molecular pathways.

Conclusion

Two non-overlapping but functionally related gene expression signatures provide consistently improved survival prediction for NSCLC regardless of histologic cell type. Multiple sets of genes may exist for NSCLC with predictive value, but ones with independent predictive value beyond clinical predictors will be required for clinical translation.
Randomized Phase II Trial of Erlotinib or Standard Chemotherapy in Patients With Advanced Non–Small-Cell Lung Cancer and a Performance Status of 2
Authors: Lilenbaum Rogerio , Axelrod Rita , Thomas Sachdev , Dowlati Afshin , Seigel Leonard , Albert Donald , Witt Karsten , Botkin David
Published: February 2008

Purpose

A multicenter randomized phase II trial to evaluate two treatment strategies in the first-line management of advanced non–small-cell lung cancer (NSCLC) patients with a performance status (PS) of 2.

Patients and Methods

Patients were assigned to erlotinib 150 mg orally daily until progression or to carboplatin (area under the curve [AUC] 6) and paclitaxel (200 mg/m2 day 1 every 3 weeks) for up to four cycles. Patients who experienced progression or did not tolerate or refused further chemotherapy were allowed to cross over to erlotinib. The primary end point was progression-free survival (PFS). Secondary end points were response, survival, quality of life (QOL), and a retrospective molecular correlation.

Results

Fifty-two patients were randomly assigned to erlotinib and 51 to chemotherapy. Partial responses were 2% and 12%, respectively. Median PFS was 1.9 months in the erlotinib arm and 3.5 months in the chemotherapy arm (hazard ratio [HR] = 1.45; 95% CI, 0.98 to 2.15; P = .06). Median survival times were 6.5 and 9.7 months, respectively (HR = 1.73; 95% CI, 1.09 to 2.73; P = .018). Patients who crossed over to erlotinib had a median survival of 14.9 months. Sex, histology, skin rash, and smoking history predicted outcome with erlotinib. Rash and diarrhea were more common with erlotinib; emesis, alopecia, peripheral neuropathy, and fatigue were more common with chemotherapy. QOL was similar between the two arms. Molecular correlation was limited by available samples.

Conclusion

Unselected patients with advanced NSCLC and PS 2 are best treated with combination chemotherapy as first-line therapy. Erlotinib may be considered in patients selected by clinical or molecular markers.
VEGF Polymorphisms and Survival in Early-Stage Non–Small-Cell Lung Cancer
Authors: Heist Rebecca Suk , Zhai Rihong , Liu Geoffrey , Zhou Wei , Lin Xihong , Su Li , Asomaning Kofi , Lynch Thomas J. , Wain John C. , Christiani David C.
Published: February 2008

Purpose

Polymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non—small-cell lung cancer (NSCLC) patients.

Patients and Methods

We evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C>T (rs3025039), −460T>C ( rs833061 ), and +405G>C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test.

Results

There were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G>C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P = .006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P = .008). Five-year OS for patients carrying the variant C allele of the VEGF +405G>C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C>T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P = .07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P = .07). Moreover, patients with higher number of variant alleles of the +405G>C and +936C>T polymorphisms had better survival. There was no association found with the −460T>C polymorphism.

Conclusion

Polymorphisms in VEGF may affect survival in early-stage lung cancer.
Eicosanoid Modulation in Advanced Lung Cancer: Cyclooxygenase-2 Expression Is a Positive Predictive Factor for Celecoxib + Chemotherapy—Cancer and Leukemia Group B Trial 30203
Authors: Edelman Martin J. , Watson Dee , Wang Xiaofei , Morrison Carl , Kratzke Robert A. , Jewell Scott , Hodgson Lydia , Mauer Ann M. , Gajra Ajeet , Masters Gregory A. , Bedor Michelle , Vokes Everett E. , Green Mark J.
Published: February 2008

Purpose

Increased expression of eicosanoids in cancer has been associated with adverse prognosis. We performed a randomized phase II trial to test the hypothesis that inhibitors of two eicosanoid pathways (cyclooxygenase-2 [COX-2], celecoxib and 5-lipoxygenase [5-LOX], zileuton) added to chemotherapy would improve outcome in advanced non–small-cell lung cancer (NSCLC).

Patients and Methods

Patients with advanced NSCLC, a performance status of 0 to 2, and no prior therapy were eligible. All patients received carboplatin area under the curve (AUC) 5.5 mg/mL · min day 1 + gemcitabine (1,000 mg/m2) days 1 and 8. Patients were randomly assigned to: (a) zileuton 600 mg PO qid, (b) celecoxib 400 mg PO bid, or (c) celecoxib and zileuton at the same doses. Immunohistochemical staining for COX-2 and 5-LOX was performed without knowledge of outcomes.

Results

One hundred forty patients were entered and 134 were eligible and treated. There was no survival difference between the arms. COX-2 expression was a negative prognostic marker for overall survival (OS; hazard ratio [HR] = 2.51, P = .019 for index ≥ 4; HR = 4.16, P = .005 for index = 9) for patients not receiving celecoxib. Patients with increased COX-2 expression (index ≥ 4), receiving celecoxib had better survival than did COX-2–expressing patients not receiving drug (HR = .342, P = .005 for OS; HR = .294, P = .002 for failure-free survival). Multivariate analysis confirmed the interaction of COX-2 and celecoxib on survival. 5-LOX expression was neither prognostic nor predictive.

Conclusion

This study failed to demonstrate the value of dual eicosanoid inhibition or benefit from either agent alone in addition to chemotherapy. However, a prospectively defined subset analysis suggests an advantage for celecoxib and chemotherapy for patients with moderate to high COX-2 expression.
Phase I Clinical Trial of Cilengitide in Children With Refractory Brain Tumors: Pediatric Brain Tumor Consortium Study PBTC-012
Authors: MacDonald Tobey J. , Stewart Clinton F. , Kocak Mehmet , Goldman Stewart , Ellenbogen Richard G. , Phillips Peter , Lafond Deborah , Poussaint Tina Young , Kieran Mark W. , Boyett James M. , Kun Larry E.
Published: February 2008

Purpose

A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors.

Patients and Methods

Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m2. Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients.

Results

No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m2 experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m2, the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m2. Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months.

Conclusion

The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m2. A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.
Randomized Phase II Study of Carboplatin and Etoposide With or Without thebcl-2Antisense Oligonucleotide Oblimersen for Extensive-Stage Small-Cell Lung Cancer: CALGB 30103
Authors: Rudin Charles M. , Salgia Ravi , Wang Xiaofei , Hodgson Lydia D. , Masters Gregory A. , Green Mark , Vokes Everett E.
Published: February 2008

Purpose

To assess the efficacy and toxicity of carboplatin, etoposide, and the bcl-2 antisense oligonucleotide oblimersen as initial therapy for extensive-stage small-cell lung cancer (ES-SCLC). bcl-2 has been implicated as a key factor in SCLC oncogenesis and chemotherapeutic resistance.

Patients and Methods

A 3:1 randomized phase II study was performed to evaluate carboplatin and etoposide with (arm A) or without oblimersen (arm B) in 56 assessable patients with chemotherapy-naïve ES-SCLC. Outcome measures including toxicity, objective response rate, complete response rate, failure-free survival, overall survival, and 1-year survival rate.

Results

Oblimersen was associated with slightly more grade 3 to 4 hematologic toxicity (88% v 60%; P = .05). Response rates were 61% (95% CI, 45% to 76%) for arm A and 60% (95% CI, 32% to 84%) for arm B. The percentage of patients alive at 1 year was 24% (95% CI, 12% to 40%) with oblimersen, and 47% (95% CI, 21% to 73%) without oblimersen. Hazard ratios for failure-free survival (1.79; P = .07) and overall survival (2.13; P = .02) suggested worse outcome for patients receiving oblimersen. These results hold when adjusted for other prognostic factors, such as weight loss, in multivariate regression analysis.

Conclusion

Despite extensive data supporting a critical role for Bcl-2 in chemoresistance in SCLC, addition of oblimersen to a standard regimen for this disease did not improve any clinical outcome measure. Emerging data from several groups suggest that this lack of efficacy may be due to insufficient suppression of Bcl-2 in vivo. Additional evaluation of this agent in SCLC is not warranted.
Pharmacists' perspectives on the Pharmacy First Minor Ailments Scheme
Authors: Pumtong Somying , Boardman Helen F , Anderson Claire W
Published: February 2008

Objective

To investigate pharmacists' perspectives about the acceptability of the Pharmacy First Minor Ailments Scheme and barriers to the use of the scheme as well as to determine potential improvements to the scheme.

Method

Semi-structured interviews were conducted with 26 pharmacists between November 2004 and March 2005.

Setting

Community pharmacies within Nottingham City Primary Care Trust (PCT).

Key findings

The study has demonstrated that the Pharmacy First Minor Ailments Scheme was well received by the majority of pharmacists and they were positive about the benefits of the scheme to both patients and healthcare professionals, despite raising some problems. Our findings highlighted a number of important issues that might be barriers to running the minor ailments scheme, including the quantity of paperwork involved, the lack of privacy in a pharmacy, and the restrictive nature of the formulary and protocols of the scheme.

Conclusion

The Pharmacy First Minor Ailments Scheme has been developed and implemented as part of Nottingham City PCT's strategy to improve access to primary care. Findings show that the majority of the pharmacists were positive about the scheme. It can be seen as a way of improving patient access to medicines and advice as well as choice in primary care. In other countries, health policy makers may consider such a scheme if it would fit their healthcare system.
Exploring the patient perspective regarding community pharmacists' educational roles in diabetes medication and blood glucose management
Authors: Hermansen-Kobulnicky Carol J , Worley Marcia M
Published: February 2008

Objective

Applying role theory, we studied patients' beliefs about community pharmacists' roles and corresponding unaddressed educational needs in the area of diabetes medication and blood glucose management.

Setting

United States, nationwide sample.

Method

Persons with diabetes were surveyed by mail. Inclusion criteria required individuals to be non-institutionalised adults (≥18 years old) with type 1 or type 2 diabetes and taking at least one prescription diabetes medication.

Key findings

The most-frequent role beliefs for pharmacists included teaching patients about how to reduce the cost of their medications and about side-effects and symptom management. The most common unaddressed need reported by patients was reducing their drug costs, and those who reported at least one unaddressed need were more likely to be younger, female and black. Ten per cent of patients believed that only a pharmacist is able to educate them about medication and blood glucose management. Compared with the remainder of the study sample, these patients were on average more-highly educated, more-recently diagnosed, and visited their pharmacy more often in the last 30 days seeking advice from a pharmacist and non-prescription medications. Notably, they also reported fewer unaddressed needs overall.

Conclusion

Knowing the beliefs of a person with diabetes regarding who is capable of educating them about medication and blood glucose management, and knowing their related unaddressed educational needs is useful to community pharmacists who serve these patients as well as to pharmacy management as the profession continues to move forward to provide advanced care to patients with diabetes.
The Women's Health Initiative Study: individualisation of hormone replacement therapy in a defined South African population
Authors: Hanly Teia , Bellingan Michelle , Truter Ilse , Venter Danie
Published: February 2008

Objective

The aim of this study was to investigate the impact of the Women's Health Initiative (WHI) study on the prescribing of hormone replacement therapy (HRT) in a defined South African population and to establish whether patient therapy was appropriately individualised as a result of the WHI study.

Setting

Claims data from a South African managed healthcare organisation.

Method

A retrospective drug utilisation review (DUR) was conducted to identify HRT-related prescribing patterns in the defined study groups. This analysis included determining discontinuation and initiation rates for HRT during selected 6-month periods. An investigation into patient demographics and prescribing patterns followed, whereby trends observed among patients either initiating or discontinuing HRT in the 6-month period post-WHI publication were contrasted with patients using HRT prior to publication of the WHI study. The prevalence of concomitant disease states among these subgroups was also assessed.

Key findings

The discontinuation rate for HRT following publication of the WHI study increased from 3.47% to 7.54%, while the initiation rate decreased from 15.34% to 9.10%. Patients initiating HRT post-WHI publication were generally found to be in the younger menopausal age categories (40 to 49 years). These patients were more likely to have been initiated on HRT types other than those investigated in the WHI study and were at a higher risk for disease states for which HRT use is beneficial, such as osteoporosis. Patients discontinuing HRT post-WHI publication were generally found to be in the older menopausal age categories (60 to 69 years), were more likely to have been combined HRT users (although not necessarily the type investigated in the WHI study), and were at a higher risk for disease states for which HRT use is considered harmful, such as diseases affecting the cardiovascular system.

Conclusion

It can be concluded that HRT was appropriately individualised according to recommendations based on the results of the WHI study in the defined populations of this study.
Design Tools for Foldable Structures with Application of Fuzzy Logic
Authors: Wierzbicki Madalina N. , de Silva Clarence W.
Published: February 2008

Rigidly foldable shells offer tremendous potential for developing kinetic architectural structures. However, the added element of motion poses new design challenges. Initially, sketchy shell geometry is constructed to reflect the intended form. Further steps involve assuring an error free folding within a range that satisfies desired functional requirements. The kinematics of a parallel topology of the shell's geometry is difficult to express algorithmically what prevents from developing of automated adjustment tools based on computational methods. The geometry can be adjusted manually based on intuitive observations; however the process is tedious, time consuming and unpredictable. This paper develops automated adjustment tools based on the intuitive approach of a human designer. The study applies the fuzzy logic formalism as a computational interface between human approach and structured adjustments to the geometry. The advantages of fuzzy logic stem from its natural ability to represent human knowledge and effectiveness in reconciling ambiguities, uncertainties and redundancies that the intuitive human approach brings along. The development steps of fuzzy logic based algorithm are presented. Performed evaluation tests and the results are discussed.
Teaching Digital Design Exploration: Form Follows…
Authors: Iordanova Ivanka
Published: February 2008

This paper presents some challenges of teaching computational geometry to architectural students, and proposes a multi-level pedagogical scheme introducing associative geometry and parametric modeling/design into architectural design education. It reports on two pedagogical experiences: one held in the context of a spatial geometry course in the first year of education; and another one, in a digital design studio with third-year architectural students. More specifically, it discusses the impact on design exploration of a library of interactive referents models introduced into the architectural studio. Situated in the ‘performance’ paradigm of digital design methods, they allow for design object explorations based on modification of architecturally meaningful features (structural, environmental, functional, etc.). The form of a design object can thus ‘follow’ function, structure, or even sustainability. The digital methods and the design knowledge transferred by the interactive models, together with their visual nature, are found to amplify the processes of ‘seeing-as’ and the ‘reflective conversation with the situation’ considered essential for creative design.
Fuzzy Modelling for Early Architectural Design
Authors: Koutamanis Alexander
Published: February 2008

Fuzzy modelling is simultaneously an extension of existing modelling approaches and a negation of one of their main aspects, the crispness of their definition. As a digital equivalent of analogue sketching it allows designers to register and manipulate imprecise and uncertain information. In the framework of design representations fuzzy modelling supports the development of conceptual design models characterized by flexible definition and interaction. The main advantages of such models are fluency, abstraction and continuity, at a level similar to that of analogue techniques. In addition to that they offer the possibility of local autonomy, i.e. segmentation of a representation into self-regulating and cooperating components. Three alternative forms of fuzzy modelling are proposed: (1) Canonical objects with tolerances, (2) objects described by minimal and maximal values, and (3) point sets comprising discrete, autonomous particles that describe the object by their spatial or structural relationships.
Serum α2-HS Glycoprotein Predicts Survival in Patients with Glioblastoma
Authors: Petrik Vladimir , Saadoun Samira , Loosemore Alison , Hobbs Josie , Opstad Kirstie S , Sheldon Joanna , Tarelli Edward , Howe Franklyn A , Bell B Anthony , Papadopoulos Marios C
Published: February 2008

Background: Glioblastoma, the most common primary brain tumor, has variable prognosis. We aimed to identify serum biomarkers that predict survival of patients with glioblastoma.

Methods: In phase 1 (biomarker discovery), SELDI-TOF mass spectra were studied in 200 serum samples from 58 control subjects and 36 patients with grade II astrocytoma, 15 with anaplastic astrocytoma, and 91 with glioblastoma. To identify potential biomarkers, we searched for peptide peaks that changed progressively in size with increasing malignancy. One peak, identified as the B-chain of α2-Heremans-Schmid glycoprotein (AHSG), was less prominent with increasing tumor grade. We therefore investigated AHSG as a survival predictor in glioblastoma. We measured serum AHSG by turbidimetry and determined indices of malignancy, including tumor proliferation (Ki67 immunolabel) and necrosis (tumor lipids on magnetic resonance spectroscopy). In phase 2 (biomarker validation), the prognostic power of AHSG was validated in an independent group of 72 glioblastoma patients.

Results: Median survival was longer (51 vs 29 weeks) in glioblastoma patients with normal vs low serum AHSG concentrations (hazard ratio 2.7, 95% CI 1.5–5.0, P <0.001), independent of age and Karnofsky score. Serum AHSG inversely correlated with Ki-67 immunolabeling and tumor lipids. A prognostic index combining serum AHSG with patient age and Karnofsky score separated glioblastoma patients with short (<3 months) and long (>2 years) median survival. The prognostic value of serum AHSG was validated in a different cohort of glioblastoma patients.

Conclusions: We conclude that serum AHSG concentration, measured before starting treatment, predicts survival in patients with glioblastoma.
Identification of Loss of Heterozygosity on Circulating Free DNA in Peripheral Blood of Prostate Cancer Patients: Potential and Technical Improvements
Authors: Müller Imke , Beeger Cord , Alix-Panabières Catherine , Rebillard Xavier , Pantel Klaus , Schwarzenbach Heidi
Published: February 2008

Background: Accurate identification of loss of heterozygosity (LOH) on circulating free DNA is often restricted by technical limitations such as poor quality and quantity of tumor-specific DNA and contamination by normal DNA. However, plasma DNA may harbor tumor-specific genetic alterations and could therefore be an interesting target for noninvasive examinations of tumor DNA.

Methods: By PCR-based fluorescence microsatellite analysis using 12 polymorphic markers, we investigated LOH on cell-free DNA in blood plasma from 59 patients with localized prostate cancer (PCa) and 12 with metastatic disease (MPCa). In addition, plasma DNA from 21 PCa patients was fractionated into high- and low-molecular-weight DNA by 2 different column systems. To avoid appearance of artificial allelic loss and stabilize the amplification, TMAC (tetramethylammonium chloride) was added to each PCR.

Results: Overall incidences of LOH at all markers analyzed were 10% in PCa and 12% in MPCa samples. Highest frequencies were found at markers D11S898 (28%) in PCa and D6S1631 (27%) in MPCa. Statistical evaluation showed significant associations between LOH and increasing Gleason scores for the marker combinations D6S1631*D8S286*D9S171 (P = 0.03) and D8S286*D9S171 (P = 0.05). Fractionation of plasma DNA resulted in a higher overall LOH frequency in the low-molecular-weight DNA fraction (23%) compared with the high-molecular-weight DNA (7%).

Conclusions: LOH analysis of circulating DNA can provide tumor-specific genetic information on PCa patients. Fractionation of plasma DNA and addition of TMAC improved LOH detection and general assay performance.
Is Zoroastrianism an Ecological Religion?
Authors: Foltz Richard , Saadi-nejad Manya
Published: February 2008

In recent years a number of Zoroastrian scholars have sought to characterize Zoroastrianism as the ‘world’s first environmental religion’, pointing to a number of rituals and injunctions aimed at safeguarding nature from activities seen as polluting. However, while the tradition does indeed enjoin Zoroastrians to respect and protect many aspects of nature, pollution is seen in ritual terms, not ecological ones. Moreover, in the dualistic Zoroastrian worldview, which posits an ongoing struggle between the forces of good and evil, many animal and plant species are seen as being on the side of evil and are thus to be destroyed whenever possible. This worldview can at times set Zoroastrianism in opposition to that of contemporary science that, generally speaking, does not distinguish between good and bad species, but sees all species as integral to the healthy functioning of ecosystems.
Vegetarian or Franciscan? Flexible Dietary Choices Past and Present
Authors: Grumett David
Published: February 2008

Francis of Assisi is often understood, both by modern commentators and his contemporaries, to have been vegetarian. Textual evidence contradicts this supposition and shows that he sometimes ate meat. As a guest, Francis would not refuse meat if offered it, and when he himself received guests, normal dietary practices were sometimes disrupted. Sickness was a second reason for exemptions from normal dining practices. Moreover, as the Franciscan Rule developed, Francis opposed agitation for more rigorist discipline. This was because rigid abstention might have created boundaries that hindered the spread of the Gospel, and would have identified the nascent Franciscan order with heretical sects. Francis’s dietary practices should be seen in light of his hierarchical view of creation, according to which every living being praises God but is also available for human use and consumption as food, at least in the present age. This retrieval of a more accurate picture of Francis than the one dominant in modern popular imagination aids understanding of modern vegetarianisms by both scholars and the wider public.