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Pressure transient propagation within building services utility systems is an inevitable consequence of any change in the system operating condition. In common with a wide range of pressure surge applications, these conditions may be analysed and modelled by solving the applicable St Venant equations numerically via the method of characteristics. This paper presents the underlying basis for such models and presents applications within building services utility systems that feature trapped or entrained air as a major modifier of either the transient propagation or the system boundary conditions. In particular, surge pressures exacerbated by the effect of trapped or entrained air are considered, including dry riser and sprinkler applications. The role of entrained air in the occurrence of physical injury following the violent fracturing of a w.c. bowl is discussed and explained in terms of a transient analysis. [ABSTRACT FROM AUTHOR]

Abstract We recently demonstrated the utility of quantifying spontaneous pain in mice via the blinded coding of facial expressions. As the majority of preclinical pain research is in fact performed in the laboratory rat, we attempted to modify the scale for use in this species. We present herein the Rat Grimace Scale, and show its reliability, accuracy, and ability to quantify the time course of spontaneous pain in the intraplantar complete Freund's adjuvant, intraarticular kaolin-carrageenan, and laparotomy (post-operative pain) assays. The scale's ability to demonstrate the dose-dependent analgesic efficacy of morphine is also shown. In addition, we have developed software, Rodent Face Finder®, which successfully automates the most labor-intensive step in the process. Given the known mechanistic dissociations between spontaneous and evoked pain, and the primacy of the former as a clinical problem, we believe that widespread adoption of spontaneous pain measures such as the Rat Grimace Scale might lead to more successful translation of basic science findings into clinical application.

Abstract Introduction Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC) transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. Methods HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT). The immortalized cells were passaged in vitro and studied by a combination of G- banding and Spectral Karyotyping (SKY). H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. Results Immortal HMEC alone were not tumorigenic in γ-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. Conclusion Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene.

Purpose: The Genetic Risk Assessment for Cancer Education and Empowerment Project demonstrated that tailored counseling and navigation (TCN) substantially increased the rate of genetic evaluation (GE) in women with high-risk breast or ovarian cancer (odds ratio, 8.9 [95% CI, 3.4 to 23.5] for TCN v usual care [UC]). This study sought to estimate the cost and cost-effectiveness of TCN in a clinic setting from a societal perspective., Methods: We identified the components of the intervention and downstream outcomes which would result in resource use. We assessed time spent by staff, cost of mailings, cost of patient time, and cost of testing and counseling in 6 months. Incremental cost-effectiveness ratios were calculated for outcomes of interest. We assessed the sensitivity of our results to assumptions via one-way sensitivity analyses. In addition, we assessed how results would change if a higher volume of patients was given TCN, with a health coach working full-time., Results: TCN costs $68,924 in US dollars (USD) to deliver per 212 patients, or $325 USD per patient. The intervention cost was $2,154 USD per record-verified GE. Much of this was attributed to training costs for health coaches ($50,223 USD). When including testing and counseling, the incremental cost effectiveness ratio (ICER) of TCN versus UC was $3,250 USD per additional GE. This was most sensitive to TCN effectiveness (ie, GE rate in TCN patients) and cost of testing. Cost-effectiveness would be more favorable with higher coaching volume (ICER of $1,730 USD/GE)., Conclusion: Implementing TCN in a clinic setting would come with notable costs, and current reimbursement policies for telemedicine may not be sufficient. Cost-effectiveness of TCN can be improved if subsequent interventions are more efficacious or are delivered to greater patient volumes.

Screening for food insecurity and other social determinants of health is being integrated into oncology practice. We performed a pilot randomized trial to investigate whether an unconditional cash transfer (UCT) could be used to address food insecurity among female breast and gynecological cancer survivors. Food-insecure cancer survivors completed a baseline survey and were randomly assigned to receive $100/month for 3 months (UCT) or usual care (UC). Participants (n = 14) completed a follow-up survey after 3 months, and we compared changes in health-related quality of life, indicators of food insecurity, diet quality, and whether a participant had to forgo, delay, or make changes to medical care because of cost. The UCT was associated with higher physical health scores, fewer indicators of food insecurity, better diet quality, and a lower likelihood of forgoing medical care than those who received UC. Our results suggest that UCTs can improve outcomes for food-insecure cancer survivors., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Social risks are common among cancer survivors who have the fewest financial resources; however, little is known about how prevalence differs by age at diagnosis, despite younger survivors' relatively low incomes and wealth., Methods: The authors used data from 3703 participants in the Detroit Research on Cancer Survivors (ROCS) cohort of Black cancer survivors. Participants self-reported several forms of social risks, including food insecurity, housing instability, utility shut-offs, not getting care because of cost or lack of transportation, and feeling unsafe in their home neighborhood. Modified Poisson models were used to estimate prevalence ratios and 95% confidence intervals (CIs) of social risks by age at diagnosis, controlling for demographic, socioeconomic, and cancer-related factors., Results: Overall, 35% of participants reported at least one social risk, and 17% reported two or more risks. Social risk prevalence was highest among young adults aged 20-39 years (47%) followed by those aged 40-54 years (43%), 55-64 years (38%), and 65 years and older (24%; p for trend < .001). Compared with survivors who were aged 65 years and older at diagnosis, adjusted prevalence ratios for any social risk were 1.75 (95% CI, 1.42-2.16) for survivors aged 20-39 years, 1.76 (95% CI, 1.52-2.03) for survivors aged 40-54 years, and 1.41 (95% CI, 1.23-1.60) for survivors aged 55-64 years at diagnosis. Similar associations were observed for individual social risks and experiencing two or more risks., Conclusions: In this population of Black cancer survivors, social risks were inversely associated with age at diagnosis. Diagnosis in young adulthood and middle age should be considered a risk factor for social risks and should be prioritized in work to reduce the financial effects of cancer on financially vulnerable cancer survivors., (© 2024 American Cancer Society.)

Addressing social risks in cancer prevention and control presents a new opportunity for accelerating cancer health equity. As members of the American Society of Preventive Oncology (ASPO) Cancer Health Disparities Special Interest Group, we describe the current state of science on social risks in oncology research and practice. To reduce and eliminate the unjust burden of cancer, we also provide recommendations for multilevel research examining social risks as contributors to inequities and the development of social risks-focused interventions. Suggestions for research and practice are provided within levels of the socio-ecological model, including the interpersonal, organizational, community, and policy levels., (©2024 American Association for Cancer Research.)

In 2022, the catchment area of the Fred Hutchinson/University of Washington/Seattle Children's Cancer Consortium (the Consortium) grew from 13-counties in Western Washington State to include all 39 counties in Washington. Widening the catchment area provided new opportunities for the Consortium to monitor the cancer burden, identify cancer-related health disparities, use a bidirectional approach to develop cancer focused programming, and facilitate research in clinical and community settings. In this commentary, we describe the exploratory process of catchment area change led by the Consortium's Office of Community Outreach and Engagement and new initiatives that followed that growth. We hope that by sharing the ongoing, data-driven community engagement approach in the Consortium's current, statewide catchment area, our experience will be of value to other cancer centers looking to engage with communities and develop bidirectional partnerships in new areas., Competing Interests: Disclosure of interest: The authors report there are no competing interests to declare.

Purpose: Cancer genetic risk assessment (CGRA) is recommended for women with ovarian cancer or high-risk breast cancer, yet fewer than 30% receive recommended genetic services, with the lowest rates among underserved populations. We hypothesized that compared with usual care (UC) and mailed targeted print (TP) education, CGRA uptake would be highest among women receiving a phone-based tailored risk counseling and navigation intervention (TCN)., Methods: In this three-arm randomized trial, women with ovarian or high-risk breast cancer were recruited from statewide cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TP received a mailed educational brochure. Participants assigned to TCN received the mailed educational brochure, an initial phone-based psychoeducational session with a health coach, a follow-up letter, and a follow-up navigation phone call., Results: Participants' average age was 61 years, 25.4% identified as Hispanic, 5.9% identified as non-Hispanic Black, and 17.5% lived in rural areas. At 6 months, more women in TCN received CGRA (18.7%) than those in TP (3%; odds ratio, 7.4; 95% CI, 3.0 to 18.3; P < .0001) or UC (2.5%; odds ratio, 8.9; 95% CI, 3.4 to 23.5; P < .0001). There were no significant differences in CGRA uptake between TP and UC. Commonly cited barriers to genetic counseling were lack of provider referral (33.7%) and cost (26.5%), whereas anticipated difficulty coping with test results (14.0%) and cost (41.2%) were barriers for genetic testing., Conclusion: TCN increased CGRA uptake in a group of geographically and ethnically diverse high-risk breast and ovarian cancer survivors. Remote personalized interventions that incorporate evidence-based health communication and behavior change strategies may increase CGRA among women recruited from statewide cancer registries.

Defined as an inability to acquire enough food because of insufficient money or other resources, the prevalence of food insecurity is markedly higher among cancer survivors than the general population. The objective of this qualitative study was to understand and characterize the experience of food insecurity from the perspective of cancer survivors' and their informal caregivers using qualitative interviews. Barriers to healthy eating, behaviors and strategies in times of food shortage, and unmet educational needs shaped the experience of food insecurity. These experiences and insights for addressing food insecurity in oncology practice have broad implications for future interventions.

Purpose: Cancer treatment often leads to work disruptions including loss of income, resulting in long-term financial instability for cancer survivors and their informal caregivers., Methods: In this sequential explanatory study, we conducted a cross-sectional survey of employment experiences among ethnically diverse, working-age individuals diagnosed with breast, colorectal, or prostate cancer. Following the survey, we conducted semi-structured interviews with cancer survivors and informal caregivers to explore changes in employment status and coping techniques to manage these changes., Results: Among employed survivors (n = 333), cancer caused numerous work disruptions including issues with physical tasks (53.8%), mental tasks (46.5%) and productivity (76.0%) in the workplace. Prostate cancer survivors reported fewer work disruptions than female breast and male and female colorectal cancer survivors. Paid time off and flexible work schedules were work accommodations reported by 52.6% and 36.3% of survivors, respectively. In an adjusted regression analysis, household income was positively associated with having received a work accommodation. From the qualitative component of the study (survivors n = 17; caregivers n = 11), three key themes emerged: work disruptions, work accommodations, and coping mechanisms to address the disruptions. Survivors and caregivers shared concerns about lack of support at work and resources to navigate issues caused by changes in employment., Conclusions: This study characterized employment changes among a diverse group of cancer survivors. Work accommodations were identified as a specific unmet need, particularly among low-income cancer survivors. Addressing changes in employment among specific groups of cancer survivors and caregivers is critical to mitigate potential long-term consequences of cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Immunotherapy or chemoimmunotherapy is now standard treatment for most patients with metastatic non-small-cell lung cancer (mNSCLC), yet patient supportive care needs (SCNs) on immunotherapy are not well defined. This study characterized the SCNs and financial hardship of patients with mNSCLC treated with immunotherapy or chemoimmunotherapy and examined the relationship between patient and caregiver cancer-related employment reductions and patient financial hardship., Methods: Patients with mNSCLC on immunotherapy or chemoimmunotherapy from a single academic medical center completed the SCNs Survey-34, items indexing material, psychological, and behavioral financial hardship, and the Comprehensive Score for Financial Toxicity. Univariate and bivariate analyses examined care needs, financial hardship, and impact of cancer-related employment reductions on patient financial hardship., Results: Sixty patients (40% male; 75% White, mean age = 62.5 years, 57% on immunotherapy alone) participated. Fifty-five percent reported unmet needs in physical or daily living and psychological domains. Financial hardship was common (33% material, 63% psychological, and 57% behavioral). Fifty-two percent reported hardship in at least two domains. Forty percent reported a caregiver cancer-related employment reduction. Caregiver employment reduction was related to patient financial hardship (68% of those reporting caregiver employment reduction reported at least two domains of hardship v 40% of those without reduction, P = .03) and patient financial distress (mean Comprehensive Score for Financial Toxicity = 19.6 among those with caregiver employment reduction v 26.8 without, P = .01)., Conclusion: Patients with mNSCLC treated with immunotherapy or chemoimmunotherapy report multiple unmet care needs and financial hardship. Psychological, functional, financial, and caregiver concerns merit assessment and intervention in this population., Competing Interests: Thomas W. LycanTravel, Accommodations, Expenses: Incyte Jimmy RuizConsulting or Advisory Role: AstraZenecaSpeakers' Bureau: AstraZeneca, GenentechResearch Funding: AstraZeneca, Roche, BeyondSpring Pharmaceuticals, ER SquibTravel, Accommodations, Expenses: AstraZeneca, Genentech/Roche Stefan C. GrantEmployment: TheraBionicLeadership: TheraBionicStock and Other Ownership Interests: TheraBionicResearch Funding: Genentech Mypath, Loxo, Bristol-Myers Squibb, Rafael Pharmaceuticals, Guardant HealthTravel, Accommodations, Expenses: Florence Healthcare W. Jeffrey PettyConsulting or Advisory Role: Jazz PharmaceuticalsResearch Funding: Merck Sharp & Dohme, AbbvieTravel, Accommodations, Expenses: Dava OncologyNo other potential conflicts of interest were reported.

Background: Social needs may affect cancer survivors' health-related quality of life (HRQOL) above and beyond sociodemographic and cancer-related factors. The purpose of this study was to estimate associations between social needs and HRQOL., Methods: Results included data from 1754 participants in the Detroit Research on Cancer Survivors cohort, a population-based study of African American survivors of breast, colorectal, lung, and prostate cancer. Social needs included items related to food insecurity, utility shutoffs, housing instability, not getting health care because of cost or a lack of transportation, and perceptions of neighborhood safety. HRQOL was measured with the validated Functional Assessment of Cancer Therapy-General (FACT-G). Linear regression models controlled for demographic, socioeconomic, and cancer-related factors., Results: More than one-third of the survivors (36.3%) reported social needs including 17.1% of survivors reported 2 or more. The prevalence of social needs ranged from 14.8% for food insecurity to 8.9% for utility shutoffs. FACT-G score differences associated with social needs were -12.2 (95% confidence interval [CI] to -15.2 to -9.3) for not getting care because of a lack of transportation, -11.3 (95% CI, -14.2 to -8.4) for housing instability, -10.1 (95% CI, -12.7 to -7.4) for food insecurity, -9.8 (95% CI, -12.7 to -6.9) for feeling unsafe in the neighborhood, -8.6 (95% CI, -11.7 to -5.4) for utility shutoffs, and -6.7 (95% CI, -9.2 to -4.1) for not getting care because of cost., Conclusions: Social needs were common in this cohort of African American cancer survivors and were associated with clinically significant differences in HRQOL. Clinical oncology care and survivorship care planning may present opportunities to screen for and address social needs to mitigate their impact on survivors' HRQOL., (© 2020 American Cancer Society.)

Background: Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities., Methods: We identified females diagnosed with a first primary, stage I-III breast cancer between the ages of 20-69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI)., Results: Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09-3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13-3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36-0.88)., Conclusions: Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed <70 years of age was low, instrumental social support, patient support services, and communication with doctors and their staff emerged as potential multilevel intervention targets for improving breast cancer care delivery., Impact: This study supports extending the reach of interventions designed to improve guideline concordance., (©2020 American Association for Cancer Research.)

Purpose: Financial hardship is increasingly understood as a negative consequence of cancer and its treatment. As patients with cancer face financial challenges, they may be forced to make a trade-off between food and medical care. We characterized food insecurity and its relationship to treatment adherence in a population-based sample of cancer survivors., Methods: Individuals 21 to 64 years old, diagnosed between 2008 and 2016 with stage I-III breast, colorectal, or prostate cancer were identified from the New Mexico Tumor Registry and invited to complete a survey, recalling their financial experience in the year before and the year after cancer diagnosis. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95%CIs., Results: Among 394 cancer survivors, 229 (58%) were food secure in both the year before and the year after cancer diagnosis (persistently food secure), 38 (10%) were food secure in the year before and food insecure in the year after diagnosis (newly food insecure), and 101 (26%) were food insecure at both times (persistently food insecure). Newly food-insecure (OR, 2.82; 95% CI, 1.02 to 7.79) and persistently food-insecure (OR, 3.04; 95% CI,1.36 to 6.77) cancer survivors were considerably more likely to forgo, delay, or make changes to prescription medication than persistently food-secure survivors. In addition, compared with persistently food-secure cancer survivors, newly food-insecure (OR, 9.23; 95% CI, 2.90 to 29.3), and persistently food-insecure (OR, 9.93; 95% CI, 3.53 to 27.9) cancer survivors were substantially more likely to forgo, delay, or make changes to treatment other than prescription medication., Conclusion: New and persistent food insecurity are negatively associated with treatment adherence. Efforts to screen for and address food insecurity among individuals undergoing cancer treatment should be investigated as a strategy to reduce socioeconomic disparities in cancer outcomes.

Objective: This study aimed to describe obstetric outcomes in a large cohort of young women with breast cancer, considering the chronological relationship of pregnancies with breast cancer diagnosis., Study Design: From a population-based cohort study of young women with breast cancer from 2004 to 2010, we conducted secondary interviews to obtain detailed obstetric histories. Pregnancies were categorized based on timing of breast cancer diagnosis: prior, postpartum, and subsequent pregnancies after breast cancer diagnosis. A generalized estimated equation model was used to account for correlated data., Results: In this cohort ( n  = 366), median age at breast cancer diagnosis was 40.1 years, and 84.7% were Caucasian. Tumor type was notable for 25.1% triple negative, and 56.1% had Stage I disease. There were 922 prior pregnancies, 21 with postpartum diagnosis of breast cancer, and 24 pregnancies subsequent to breast cancer diagnosis. Non-live birth outcomes occurred significantly more often in the postpartum group ( p -value: 0.001) compared with the other groups, which had higher live birth rates, after adjustment for maternal age, parity, body mass index, and race., Conclusion: Overall, pregnancy outcomes before and after breast cancer diagnosis are reassuring., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective : To understand the different methodologies used to elicit willingness to pay for health and the value of a statistical life year through surveys. Methodology : A systematic review of the literature was undertaken to identify studies using surveys to estimate either willingness to pay for health or the value of a statistical life year. Each study was reviewed and the study setting, sample size, sample description, survey administration (online or face to face), survey methodology, and results were extracted. The results of the studies were then compared to any published national guidelines of cost-effectiveness thresholds to determine their accuracy. Results : Eighteen studies were included in the review with 15 classified as willingness to pay and 3 value of a statistical life. The included studies covered Asia (n = 6), Europe (n = 4), the Middle East (n = 1), and North America (n = 5), with one study taking a global perspective. There were substantial differences in both the methodologies and the estimates of both willingness to pay and value of a statistical life between the different studies. Conclusion : Different methods used to elicit willingness to pay and the value of a statistical life year resulted in a wide range of estimates., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: For individuals with hepatocellular carcinoma (HCC), type of insurance may be an important prognostic factor because of its impact on access to care. This study investigates the relationship between insurance type at diagnosis and stage-specific survival., Methods: This retrospective cohort analysis used data from 18 Surveillance, Epidemiology, and End Results Program cancer registries. Individuals ages 20 to 64 years, diagnosed with primary HCC between 2010 and 2015, with either private, Medicaid, or no insurance were eligible for cohort inclusion. Adjusted Cox proportional-hazards regression models were used to generate HRs and 95% confidence intervals (CI) for associations between insurance type at diagnosis and overall survival. All models were stratified by stage at diagnosis., Results: This analysis included 14,655 cases. Compared with privately insured individuals with the same stage of disease, those with Medicaid had a 43% (HR = 1.43; 95% CI, 1.13-1.32), 22% (HR = 1.22; 95% CI, 1.13-1.32), and 7% higher risk of death for localized, regional, and distant stage, respectively. Uninsured individuals had an 88% (HR = 1.88; 95% CI, 1.65-2.14), 59% (HR = 1.59; 95% CI, 1.41-1.80), and 35% (HR = 1.35; 95% CI, 1.18-1.55) higher risk of death for localized, regional, and distant stage, respectively, compared with privately insured individuals., Conclusions: Disparities in survival exist by the type of insurance that individuals with HCC have at the time of diagnosis., Impact: These findings support the need for additional research on access to and quality of cancer care for Medicaid and uninsured patients., (©2019 American Association for Cancer Research.)

Purpose: Lifestyle factors may have a synergistic effect on health. We evaluated the correlates of poor adherence to a healthy lifestyle among a diverse sample of colorectal cancer (CRC) survivors to inform future lifestyle promotion programs., Methods: Lifestyle questions from a cross-sectional survey were completed by 283 CRC survivors (41% Hispanic, 40% rural, 33% low income). Adherence to recommendations (yes/no) for physical activity, fruit and vegetable servings/day, avoiding tobacco, and healthy weight was summed to create an overall lifestyle quality score. Polytomous logistic regression was used to evaluate correlates of good (reference group), moderate, and poor overall lifestyle quality. Potential correlates included sociodemographic characteristics, cancer-related factors, and indicators of health and well-being., Results: CRC survivors with poor adherence were 2- to 3.4-fold significantly more likely to report multiple comorbidities, poor physical functioning, fatigue, anxiety/depressive symptoms, and poor social participation. In multivariable analyses, poor physical functioning was the only significant correlate of poor adherence to lifestyle recommendations, compared to good adherence [OR (95% CI) 3.4 (1.8-6.4)]. The majority of survivors, 71% and 78%, indicated interest in receiving information on exercise and eating a healthy diet, respectively., Conclusion: Future lifestyle promotion programs for CRC survivors should carefully consider indicators of physical and psychosocial health and well-being, especially poor physical functioning, in the design, recruitment, and implementation of these health programs.

Purpose: In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences., Methods and Materials: SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008-2011) were linked with Medicare claims (2007-2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis., Results: Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p<0.001). Mean expenditure in the year after diagnosis was $8,499 greater (p<0.001) among women receiving IMRT versus cRT., Conclusion: We found highly variable use of IMRT and higher expenditure in the year after diagnosis among women treated with IMRT (vs. cRT) with early-stage breast cancer and Medicare insurance. Our findings suggest a considerable opportunity to reduce treatment variation and cost of care while improving alignment between practice and clinical guidelines., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Improvements in colorectal cancer (CRC) prevention, early detection, and treatment have resulted in substantial gains in survival. However, the health-related quality of life (HRQoL) of CRC survivors often depends on access to supportive care, which differs by survivors' socioeconomic characteristics. The purpose of this study was to investigate the relationship between socioeconomic characteristics and HRQoL in a diverse group of CRC survivors., Methods: We conducted a population-based, cross-sectional study to examine the association between socioeconomic factors (household income, health literacy, and insurance status) and HRQoL domains of pain interference, fatigue, physical function, sleep disturbance, anxiety, and depression. PROMIS® Short Forms v.2.0 were used to assess domains of HRQoL. Linear regression modeling was used to estimate the coefficient representing the average HRQoL domain score and its 95% confidence interval (CI)., Results: Three hundred one CRC survivors participated in the survey. Low-income (≤ $30,000) CRC survivors had, on average, a 4.70-point (95% CI 1.10-8.28) higher pain interference score, a 7.02-point (95% CI 3.27-10.77) higher fatigue score, a 5.13-point (95% CI - 8.56 to - 1.71) lower physical function score, and a 4.44-point (95% 1.40-7.49) higher depression score than CRC survivors with an income ≥ $70,000. Survivors with Medicaid insurance reported significantly greater pain interference and worse physical function than privately insured survivors. Survivors with low health literacy reported significantly greater pain interference compared with survivors with high health literacy., Conclusions: Substantial socioeconomic disparities in HRQoL were observed in this diverse population of CRC survivors., Implications for Cancer Survivors: Designing supportive care interventions to improve HRQoL among low-income and Medicaid-insured CRC survivors is critical for eliminating disparities in CRC outcomes.

Background: Cancer survivors increasingly report financial hardship as a consequence of the high cost of cancer care, yet the financial experience of rural cancer survivors remains largely unstudied. The purpose of this study was to investigate potential rural disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy. Methods: Individuals diagnosed with localized or regional colorectal cancer between 2004 and 2012 were ascertained by the population-based New Mexico Tumor Registry. Participants completed a mailed questionnaire or telephone survey about their colorectal cancer survivorship experience, including treatment-related financial hardship and receipt of surveillance colonoscopy. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Compared with urban colorectal cancer survivors ( n = 168), rural colorectal cancer survivors ( n = 109) were slightly older; more likely to be married (65% vs. 59%) and have an annual income <$30,000 (37% vs. 27%); and less likely to be employed (35% vs. 41%), have a college degree (28% vs. 38%), or a high level of health literacy (39% vs. 51%). Rural survivors were twice as likely as urban survivors to report treatment-related financial hardship (OR, 1.86; 95% CI, 1.06-3.28) and nonadherence to surveillance colonoscopy guidelines (OR, 2.28; 95% CI, 1.07-4.85). In addition, financial hardship was independently associated with nonadherence to surveillance colonoscopy (OR, 2.17; 95% CI, 1.01-4.85). Conclusions: Substantial rural disparities in the likelihood of financial hardship and nonadherence to surveillance colonoscopy exist. Impact: Treatment-related financial hardship among rural colorectal cancer survivors may negatively affect adherence to guideline-recommended follow-up care. Cancer Epidemiol Biomarkers Prev; 27(11); 1275-82. ©2018 AACR., (©2018 American Association for Cancer Research.)

Background: Although national guidelines for cancer genetic risk assessment (CGRA) for hereditary breast and ovarian cancer (HBOC) have been available for over two decades, less than half of high-risk women have accessed these services, especially underserved minority and rural populations. Identification of high-risk individuals is crucial for cancer survivors and their families to benefit from biomedical advances in cancer prevention, early detection, and treatment., Methods: This paper describes community-engaged formative research and the protocol of the ongoing randomized 3-arm controlled Genetic Risk Assessment for Cancer Education and Empowerment (GRACE) trial. Ethnically and geographically diverse breast and ovarian cancer survivors at increased risk for hereditary cancer predisposition who have not had a CGRA are recruited through the three statewide cancer registries. The specific aims are to: 1) compare the effectiveness of a targeted intervention (TP) vs. a tailored counseling and navigation(TCN) intervention vs. usual care (UC) on CGRA utilization at 6 months post-diagnosis (primary outcome); compare the effectiveness of the interventions on genetic counseling uptake at 12 months after removal of cost barriers (secondary outcome); 2) examine potential underlying theoretical mediating and moderating mechanisms; and 3) conduct a cost evaluation to guide dissemination strategies., Discussion: The ongoing GRACE trial addresses an important translational gap by developing and implementing evidence-based strategies to promote guideline-based care and reduce disparities in CGRA utilization among ethnically and geographically diverse women. If effective, these interventions have the potential to reach a large number of high-risk families and reduce disparities through broad dissemination., Trial Registration Number: NCT03326713; clinicaltrials.gov., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p < 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p < 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p < 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers.

The national opioid epidemic is severely impacting Indian Country. In this article, we draw upon data from the Centers for Disease Control and Prevention to describe the contours of this crisis among Native Americans. While these data are subject to significant limitations, we show that Native American opioid overdose mortality rates have grown substantially over the last seventeen years. We further find that this increase appears to at least parallel increases seen among non-Hispanic whites, who are often thought to be uniquely affected by this crisis. We then profile tribal medical and legal responses to the opioid epidemic, ranging from tribally-operated medication-assisted therapy to drug diversion courts rooted in traditional tribal cultures.

Purpose: We aimed to determine whether the association between late-stage cancer and American Indian/Alaska Native (AI/AN) race differed by enrollment in the Indian Health Service Care System (IHSCS)., Methods: We used Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare files to compare the odds of late-stage breast, colorectal, lung, or prostate cancer between non-Hispanic Whites (NHWs) (n=285,993) and AI/ANs with (n=581) and without (n=543) IHSCS enrollment., Results: For AI/ANs without IHSCS enrollment, the odds of late-stage disease were higher in AI/ANs compared with NHWs for breast (OR=3.17, 95%CI: 1.82-5.53) and for prostate (OR=2.59, 95%CI:1.55-4.32) cancer, but not for colorectal or lung cancers. Among AI/ANs with IHSCS enrollment, there was not a significant association between late-stage disease and AI/AN race for any of the four cancers evaluated., Conclusion: Our results suggest that enrollment in the IHSCS reduced the disparity between AI/ANs and NHWs with respect to late-stage cancer diagnoses.

Objective: To identify and summarize the published and gray literature on the use of telemedicine for the diagnosis and management of inflammatory and/or autoimmune rheumatic disease., Methods: We performed a registered systematic search (CRD42015025382) for studies using MEDLINE (1946 to July 2015), Embase (1974 to July 2015), Web of Science (1900 to July 2015), and Scopus (1946 to July 2015) databases. We included studies that demonstrated the use of telemedicine for diagnosis and/or management of inflammatory/autoimmune rheumatic disease. Following data extraction, we performed a descriptive analysis., Results: Our literature search identified 1,468 potentially eligible studies. Of these studies, 20 were ultimately included in this review. Studies varied significantly in publication type, quality of evidence, and the reporting of methods. Most demonstrated a high risk of bias. Rheumatoid arthritis was the most commonly studied rheumatic disease (42% of patients). Studies demonstrated conflicting results regarding the effectiveness of telemedicine (18 found it effective, 1 found it effective but possibly harmful, and 1 found it ineffective). A limited number of studies included some component of a cost analysis (n = 6; 16% of patients); all of these found telemedicine to be cost-effective., Conclusion: Studies identified by this systematic review generally found telemedicine to be effective for the diagnosis and management of autoimmune/inflammatory rheumatic disease; however, there is limited evidence to support this conclusion. Further studies are needed to determine the best uses of telemedicine for the diagnosis and management of these conditions., (© 2016, American College of Rheumatology.)

Background: Approximately 40% of men diagnosed with metastatic prostate cancer experience one or more skeletal-related events (SREs), defined as a pathological fracture, spinal cord compression, or surgery or radiotherapy to the bone. Accurate assessment of their effect on survival, health care resource utilization (HCRU), and cost may elucidate the value of interventions to prevent SREs., Materials and Methods: Men older than age 65 years with prostate cancer and bone metastasis diagnosed between 2004 and 2009 were identified from linked Surveillance Epidemiology and End Results-Medicare records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk for death associated with SREs were calculated by using Cox regression. HCRU and costs (in 2013 U.S. dollars) were evaluated in a propensity score-matched cohort by using Poisson regression and Kaplan-Meier sample average estimators, respectively., Results: Among 3,297 men with prostate cancer metastatic to bone, 40% experienced ≥1 SRE (median follow-up, 19 months). Compared with men who remained SRE-free, men with ≥1 SRE had a twofold higher risk for death (HR, 2.29; 95% CI, 2.09-2.51). Pathological fracture was associated with the highest risk for death (HR, 2.77; 95% CI, 2.38-3.23). Among men with ≥1 SRE, emergency department visits were twice as frequent (95% CI, 1.77-2.28) and hospitalizations were nearly four times as frequent (95% CI, 3.20-4.40). The attributable cost of ≥1 SRE was $21,191 (≥1 SRE: $72,454 [95% CI, $67,362-$76,958]; SRE-free: $51,263 [95% CI, $45,439-$56,100])., Conclusion: Among men with prostate cancer metastatic to bone, experiencing ≥1 SRE is associated with poorer survival, increased HCRU, and increased costs. These negative effects emphasize the importance of SRE prevention in this population., (©AlphaMed Press.)

Background: Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use., Methods: We used data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. Nine hundred sixteen invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases in patients 55 to 74 years of age diagnosed between 2000 and 2008 were compared with 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid-lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression., Results: Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared with never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC (OR: 2.04, 95% CI: 1.17-3.57) and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared with never users., Conclusion: In this contemporary population-based case-control study, long-term use of statins was associated with increased risks of both IDC and ILC., Impact: Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding., (©2013 AACR.)

Recent studies have suggested seasonal variation in the diagnosis of acute myeloid leukaemia (AML), and the aetiological role seasonal factors may play in this group of haematological neoplasms remains unclear. We evaluated potential seasonality of AML diagnosis among adults. Cases included were ascertained from the Surveillance, Epidemiology, and End Results (SEER) 13 registries from 1992-2008. Chi-square analysis for heterogeneity and multiple Poisson regression using parametric harmonic modelling and bootstrap testing were used to detect possible monthly variation. Months of peak diagnoses were December and January, although some variation was present by sex and age. Heterogeneity across months was statistically significant (P < 0·001). In stratified analyses, monthly variation was detected only among males (P = 0·009) and in cases aged 65 years and older (P = 0·031). Poisson regression found no seasonal effect among all cases when fit to the sinusoidal model (P = 0·110). However, similar variation among males (P = 0·009) and cases aged 65 years and older (P = 0·018) was present. There is growing evidence of seasonality in AML diagnosis, particularly among older persons and men. Investigation of specific seasonal risk factors would be informative in explaining the aetiology behind the observed variation., (© 2012 Blackwell Publishing Ltd.)

Breast cancer survivors have a 60 % higher risk of developing a second primary asynchronous contralateral breast cancer (CBC) compared to women's risk of developing a first primary breast cancer (FBC). However, little is known about how expression of tumor markers in first breast cancers influences CBC risk. We conducted a population-based nested case-control study among women 20-74 years of age diagnosed with a first breast cancer between 1996 and 2008 in western Washington State to evaluate the association between their tumor's estrogen receptor (ER), progesterone receptor (PR) and HER2-neu (HER2) expression, and risk of CBC. The study included 482 cases diagnosed with both a FBC and a CBC and 1,506 control women diagnosed only once with breast cancer identified through our local Surveillance, Epidemiology and End Results (SEER) cancer registry. Compared to the women whose FBC was ER+/PR+, those with ER-/PR- first tumors had a 1.6-fold (95 % confidence interval (CI): 1.2-2.3) increased risk of developing a CBC. When evaluated by joint ER/PR/HER2 status, compared to women with ER+/HER2- first cancers, those with HER2-overexpressing (ER-/HER2+) and triple-negative disease (ER-/PR-/HER2-) had 2.0-fold (95 % CI: 1.1-3.8) and 1.4-fold (95 % CI: 0.9-2.3) elevated risks of developing CBC, respectively. Beyond the known higher risks of mortality among patients diagnosed with more aggressive BC subtypes, here, we observe that they may also have increased risks of developing CBC.

Radiation exposure is related to risk of numerous types of cancer, but relatively little is known about its effect on risk of multiple primary cancers. Using follow-up data through 2002 from 77,752 Japanese atomic bomb survivors, we identified 14,048 participants diagnosed with a first primary cancer, of whom 1,088 were diagnosed with a second primary cancer. Relationships between radiation exposure and risks of first and second primary cancers were quantified using Poisson regression. There was a similar linear dose-response relationship between radiation exposure and risks of both first and second primary solid tumors [excess relative risk (ERR)/Gy = 0.65; 95% confidence interval (CI), 0.57-0.74 and ERR/Gy = 0.56; 95% CI, 0.33-0.80, respectively] and risk of both first and second primary leukemias (ERR/Gy = 2.65; 95% CI, 1.78-3.78 and ERR/Gy = 3.65; 95% CI, 0.96-10.70, respectively). Background incidence rates were higher for second solid cancers, compared with first solid cancers, until about age 70 years for men and 80 years for women (P < 0.0001), but radiation-related ERRs did not differ between first and second primary solid cancers (P = 0.70). Radiation dose was most strongly related to risk of solid tumors that are radiation-sensitive including second primary lung, colon, female breast, thyroid, and bladder cancers. Radiation exposure confers equally high relative risks of second primary cancers as first primary cancers. Radiation is a potent carcinogen and those with substantial exposures who are diagnosed with a first primary cancer should be carefully screened for second primary cancers, particularly for cancers that are radiation-sensitive., (©2010 AACR.)

Background: The length of the interval between age at menarche and age at first birth is positively associated with breast cancer risk. We examined the risk of breast cancer in atomic bomb survivors to investigate whether women exposed to radiation between menarche and first birth had a higher risk of radiogenic breast cancer than women exposed at the same age but outside this interval., Methods: Women (n = 30,113) were classified into three reproductive status at the time of the bombings (ATB) categories (premenarche, between menarche and first birth, or after first birth). Poisson regression was used to test the primary hypothesis., Results: When the background rate of breast cancer was taken to depend on city, age ATB, and attained age only, the radiation-related excess relative risk (ERR) varied significantly among the three categories (P = 0.049). However, after controlling for significant heterogeneity in the baseline risk of breast cancer between reproductive status ATB groups (P < 0.001), no significant heterogeneity (P = 0.88) was observed in the ERR, with an ERR per Gy of 1.36 [95% confidence interval (CI), 0.54-2.75] for women exposed between menarche and first birth ATB, and 1.07 (95% CI, 0.22-3.62) and 1.53 (95% CI, 0.63-2.90) for those exposed premenarche or after first birth, respectively., Conclusions: The radiation-associated risk of breast cancer does not vary significantly by reproductive status ATB., Impact: It is possible that radiation exerts similar carcinogenic effects on the breast regardless of its stage of differentiation, or that the differences in radiosensitivity are too small to be detected in this cohort.

Differential utilization of cancer screening between populations could lead to changes in cancer disparities. Evaluating incidence rates trends is one means of monitoring these disparities. Using Surveillance, Epidemiology, and End Results data, we compared annual percent changes (APC) in age-adjusted incidence rates of distant-stage breast, colorectal, and prostate cancer between non-Hispanic whites (NHW) and African Americans (AA). From 1992 to 2004, distant-stage breast cancer incidence rates remained essentially constant among both AA and NHW women, though rates were 30-90% higher among AA women throughout. NHW men and women experienced declines in distant-stage colorectal cancer incidence rates [APC = -1.6, 95% confidence interval (CI) -2.3, -0.9], but AA men and women did not. Distant-stage prostate cancer incidence rates declined for both AA (APC = -5.8, 95% CI -7.9, -3.8) and NHW (APC = -5.1, 95% CI -6.7, -3.4). Despite now having nearly equal mammography screening rates, the persistent breast cancer disparity observed among AAs compared to NHWs may be due to the greater susceptibility of AAs to more aggressive tumors, particularly hormone-receptor-negative disease, which is more difficult to detect by mammography. For colorectal cancer, greater utilization of screening tests among NHWs vs. AAs is likely a primary contributor to the observed widening disparity. Wider recognition of AA race as a prostate cancer risk factor may contribute to the narrowing disparity in the incidence of disease.

Objective: Differences in cervical cancer incidence rates by race/ethnicity persist in the United States. We examined these differences by histologic type and by various patient and socioeconomic characteristics., Methods: Thirteen U.S. cancer registries were used to identify women 20-79 years of age diagnosed from 1992 to 2003 with invasive cervical cancer. Age-adjusted incidence rates and annual percent changes were calculated for four different races/ethnicities (Non-Hispanic whites, Hispanic whites, African-Americans, and Asians/Pacific Islanders) for cervical cancer overall, squamous cell carcinoma (SCC), and adenocarcinoma (AC)., Results: Hispanic whites had the highest incidence rate of cervical cancer overall (24.2/100,000), SCC (18.3/100,000), and AC (4.6/100,000). Non-Hispanic whites had the lowest rates of cervical cancer overall (10.8/100,000) and SCC (7.2/100,000), while African-Americans had the lowest rate of AC (2.3/100,000). Incidence rates of cervical cancer overall and SCC declined across all racial/ethnic groups. Numerous variations in incidence rates and annual percent changes were observed when analyses were stratified by county level socioeconomic characteristics., Conclusions: Variations in screening utilization and socioeconomic status may account for the majority of racial/ethnic disparities in cervical cancer incidence. Targeting groups with the greatest burdens of cervical cancer is of public health importance, particularly as we enter the human papillomavirus vaccine era.

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P

The TP53 tumor suppressor protein (formerly known as p53) responds to a wide variety of environmental insults. To evaluate the safety of cellular telephones, TP53 responses in human fibroblast cells were studied after exposure to 837 MHz microwaves. Cells were exposed in a temperature-controlled transverse electromagnetic (TEM) chamber to a specific absorption rate (SAR) of 0.9 or 9.0 W/kg at 837 MHz continuous-wave (CW) microwave irradiation for 2 h. The TP53 protein levels were measured by Western blot at 2, 8, 24 and 48 h after treatment. The TP53 protein levels in microwave-treated cells, sham-treated cells, and untreated cells remained unchanged relative to each other at all times tested (Fisher test and Student-Newman-Keuls test, P > 0.05). No morphological alterations were observed in microwave-treated cells compared to sham-treated cells. We conclude that TP53 protein expression levels in cultured human fibroblast cells do not change significantly during a 48-h period after exposure to 837 MHz continuous microwaves for 2 h at SAR levels of 0.9 or 9.0 W/kg.

The aim of this project was to develop an animal exposure system for the biological effect studies of radio frequency fields from handheld wireless telephones, with energy deposition in animal brains comparable to those in humans. The finite-difference time-domain (FDTD) method was initially used to compute specific absorption rate (SAR) in an ellipsoidal rat model exposed with various size loop antennas at different distances from the model. A 3 x 1 cm rectangular loop produced acceptable SAR patterns. A numerical rat model based on CT images was developed by curve-fitting Hounsfield Units of CT image pixels to tissue dielectric properties and densities. To design a loop for operating at high power levels, energy coupling and impedance matching were optimized using capacitively coupled feed lines embedded in a Teflon rod. Sprague Dawley rats were exposed with the 3 x 1 cm loop antennas, tuned to 837 or 1957 MHz for thermographically determined SAR distributions. Point SARs in brains of restrained rats were also determined thermometrically using fiberoptic probes. Calculated and measured SAR patterns and results from the various exposure configurations are in general agreement. The FDTD computed average brain SAR and ratio of head to whole body absorption were 23.8 W/kg/W and 62% at 837 MHz, and 22.6 W/kg/W and 89% at 1957 MHz. The average brain to whole body SAR ratio was 20 to 1 for both frequencies. At 837 MHz, the maximum measured SAR in the restrained rat brains was 51 W/kg/W in the cerebellum and 40 W/kg/W at the top of the cerebrum. An exposure system operating at 837 MHz is ready for in vivo biological effect studies of radio frequency fields from portable cellular telephones. Two-tenths of a watt input power to the loop antenna will produce 10 W/kg maximum SAR, and an estimated 4.8 W/kg average brain SAR in a 300 g medium size rat.

Twenty-five patients with primary squamous cell carcinoma of the oesophagus were treated with intracavitary hyperthermia combined with external beam radiation and intraluminal radiation at Nanjing Jinling Hospital, China. External beam radiation was given with a 6-MV X-ray; 1.8-2.0 Gy per fraction and five fractions per week; this brought the total dose to 60 Gy. Two weeks later, hyperthermia was applied with 915 MHz microwave intracavitary applicators, which were designed at the City of Hope. Temperature measurements were obtained while moving fibreoptic temperature sensors at 1.0 cm intervals in each of the six peripheral channels of the applicator. Hyperthermia was applied for 1 h before and after the intraluminal radiation. Intraluminal radiation was provided by low dose-rate iridium-192 ribbons in the same intracavitary applicator, giving 30 Gy at 0.75 cm from the applicator surface. The 3-month post-treatment responses showing complete response, partial response, no change and progressive disease were 60% (15/25), 24% (6/25), 8% (2/25) and 8% (2/25) respectively. The median follow-up time was 17 months (range 4-29 months). The 1- and 2-year overall survival rates were 72% (18/25) and 32% (8/25) respectively, and disease-free survival rates were 47 and 30% respectively. The median overall survival and disease-free survival periods were 17 and 10 months respectively. Fourteen patients had local recurrence (either at the primary site or in the lymph node) or had local progression, and five developed metastases. The median duration of the onset of local recurrence or of local progression was 9.5 months (range 0-20 months); the median of distant metastases was 8 months (range 2-16 months). Seventeen patients died. Of these, 15 died of cancer: six with local recurrence alone, four with local progression primary cancer alone, three with distant metastases alone, and two with both local and distant failure. Two patients with complete response of the primary disease died of other diseases. The toxicity was mild. According to the mucous reaction scoring criteria of the Radiation Therapy Oncology Group, the acute toxicity grades I, II, III and IV were 0% (0/25), 20% (5/25), 48% (12/25) and 32% (8/25) respectively. The major late complication was a mild oesophagus fibrosis and difficult swallowing. No serious side effects (grade IV), fistulas or perforations were seen. These results indicate that this method is safe and feasible for treating oesophageal carcinoma.

The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.

Radio frequency (RF) heating of an implanted spinal fusion stimulator (SpF) during magnetic resonance imaging (MRI) was studied on a full-size human phantom. Heating during MRI scans (GE Signa 4X, 1.5 T) was measured with RF-transparent fiberoptic sensors. With the implant correctly connected, the maximum temperature rises were less than 2 degrees C during the 26 min that the scans were at maximum RF power. At the tip of a broken stimulator lead (connecting the SpF generator and its electrodes), the maximum temperature rise was 11-14 degrees C. Regular 4-min scans of the spinal cord produced similar temperature rises at the broken tip. After the generator and the leads were removed, heating at the electrode connector tip was less than 1.5 degrees C. The control temperature rises at the same locations, without the stimulator, were less than 0.5 degree C. This study shows that spinal fusion stimulator heating is within the Food and Drug Administration safety guideline of 2 degrees C. However, if a lead wire is broken, it is unsafe during MRI scans. Radiological examinations will be necessary to ensure the integrity of the implant.

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten rats in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study, i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice. and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.

In the presence of iron, dihydroartemisinin forms free radicals and causes cell death. Since most cancer cells have high rates of iron intake, dihydroartemisinin would have selective cytotoxic effect on cancer cells. The present experiment was designed to study the effect of dihydroartemisinin and ferrous sulfate on the growth of implanted fibrosarcoma in the rat. We found that the growth rate of the tumor was significantly retarded by daily oral administration of ferrous sulfate followed by dihydroartemisinin. No significant tumor growth retardation effect was observed in rats treated with either dihydroartemisinin or ferrous sulfate alone. The drug treatment did not significantly affect body weight compared with untreated tumor-implanted animals and no apparent toxic effect was observed after drug treatment. An artemisinin analog-ferrous salt combination may provide a novel approach for cancer therapy.

A finite-difference time-domain (FDTD) algorithm was used to compute SAR distributions in planar fat-muscle phantom exposed to the Clini-Therm microwave applicators. The models consisted of a 30 X 30 X 7.5 cm phantom and a 15 X 15 cm, 10 X 10 cm or 7.5 X 7.5 cm aperture dielectric slab loaded applicator. The phantom was either filled with muscle material or with 1.0 cm fat on 6.5 cm muscle. A mineral oil bolus was placed on the fat-muscle model with its integrated water channels parallel to the electric or magnetic field. The FDTD resolution was 3 mm and the applicators were excited with a Gaussian pulse. The computations required 6000-8000 time steps to reach steady state, with 45-48 Mwords on a Cray Y-MP C-90 in 1000-1200 CPU seconds. The electric field components at 915 MHz were obtained by summing the Fourier coefficients at each grid point during each time step and SAR was determined. The results were qualitatively compared to existing and published thermographic heating patterns with good agreement. The computed electric field distributions had provided a three dimensional view into the problem space to investigate and understand wave propagation phenomena in complex inhomogeneous configurations that were not feasible with experimental models.

The possibility of tissue heating due to an auditory brainstem implant (ABI) or a modified cochlear implant (CI) during magnetic resonance imaging (MRI) of the head was tested on a full-sized human phantom using a realistic phantom head consisting of simulated skull, brain, and muscle. Dielectric properties of the brain, muscle, and bone materials were similar to those of human tissues at 64 MHz. The body consisted of homogeneous phantom muscle enclosed in a human-shaped fiberglass shell. Thermographic and fiber-optic temperature measurements were conducted to reveal any heating. Thermograms of sagittal, frontal, and horizontal planes of the head with the ABI and CI electrodes were taken immediately before and after a 26 min MRI scan. The MRI sequence was set at 94 excitations and 25 ms echo time to induce maximum radiofrequency heating, as suggested by the General Electric Company. The difference of these two thermograms gives the heating results. In two uncut phantom heads. Teflon tubes were placed along the implanted ABI and CI, and temperature data were recorded via fiber-optic probes before, during, and after the MRI. Results showed no observable heating associated with the ABI and the modified CI during worst-case MRI of the head.

In this paper a model based on transmission line theory is used to predict the behavior of an eccentrically coated asymmetric antenna applicator for use in intracavitary hyperthermia. Theoretical results for the heating rate (HR) of the applicators are compared to experimental results. The experimental results were obtained at City of Hope National Medical Center using four different 915-MHz applicators, each with a different antenna size and eccentricity of the coating. A parameter delta is defined where delta << 1.0 is a thin wire approximation; delta is primarily a function of the eccentricity of the coating, the antenna diameter, and the coating diameter. It is found that when delta approximately less than 0.5, the theoretical model works well. In particular, it predicts the directivity due to the eccentricity of the coating. However, as this eccentricity is increased or as the antenna diameter is increased (delta approximately greater than 0.6), the model no longer accurately predicts directivity. Thus, the model that can be used to predict the HR profiles for an eccentrically coated asymmetric antenna only when delta approximately less than 0.5.