Evaluating an equity-focused approach to assess climate resilience and disaster priorities through a community survey.

As the Duwamish Valley community in Seattle, Washington, U.S.A. and other environmental justice communities nationally contend with growing risks from climate change, there have been calls for a more community-centered approach to understanding impacts and priorities to inform resilience planning. To engage community members and identify climate justice and resilience priorities, a partnership of community leaders, government-based practitioners, and academics co-produced a survey instrument and collected data from the community using the Seattle Assessment for Public Health Emergency Response (SASPER), an approach adapted from the Centers for Disease Control and Prevention's Community Assessment for Public Health Emergency Response (CASPER). In addition, we conducted a process and outcome project evaluation using quantitative survey data collected from volunteers and qualitative semi-structured interviews with project team members. In October and November 2022, teams of volunteers from partner organizations collected 162 surveys from households in the Duwamish Valley. Poor air quality, extreme heat, and wildfires were among the highest reported hazards of concern. Most Duwamish Valley households agreed or strongly agreed that their neighborhood has a strong sense of community (64%) and that they have people nearby to call when they need help (69%). Forty-seven percent of households indicated willingness to get involved with resilience planning, and 62% of households said that they would use a Resilience Hub during an emergency. Survey volunteers evaluated their participation positively, with over 85% agreeing or strongly agreeing that they learned new skills, were prepared for the survey, and would participate in future assessments. The evaluation interviews underscored that while the SASPER may have demonstrated feasibility in a pre-disaster phase, CASPER may not meet all community/partner needs in the immediate disaster response phase because of its lack of focus on equity and logistical requirements. Future research should focus on identifying less resource intensive data collection approaches that maintain the rigor and reputation of CASPER while enabling a focus on equity.

Cumulative Impacts and COVID-19: Implications for Low-Income, Minoritized, and Health-Compromised Communities in King County, WA.

Few studies have assessed how the intersection of social determinants of health and environmental hazards contributes to racial disparities in COVID-19. The aim of our study was to compare COVID-19 disparities in testing and positivity to cumulative environmental health impacts, and to assess how unique social and environmental determinants of health relate to COVID-19 positivity in Seattle, King County, WA, at the census tract level. Publicly available data (n = 397 census tracts) were obtained from Public Health-Seattle & King County, 2018 ACS 5-year estimates, and the Washington Tracking Network. COVID-19 testing and positive case rates as of July 12, 2020, were mapped and compared to Washington State Environmental Health Disparities (EHD) Map cumulative impact rankings. We calculated odds ratios from a series of univariable and multivariable logistic regression analyses using cumulative impact rankings, and community-level socioeconomic, health, and environmental factors as predictors and having ≥ 10% or < 10% census tract positivity as the binary outcome variable. We found a remarkable overlap between Washington EHD cumulative impact rankings and COVID-19 positivity in King County. Census tracts with ≥ 10 % COVID-19 positivity had significantly lower COVID-19 testing rates and higher proportions of people of color and faced a combination of low socioeconomic status-related outcomes, poor community health outcomes, and significantly higher concentrations of fine particulate matter (PM2.5). King County communities experiencing high rates of COVID-19 face a disproportionate cumulative burden of environmental and social inequities. Cumulative environmental health impacts should therefore systematically be considered when assessing for risk of exposure to and health complications resulting from COVID-19.

Community-Level Factors Associated with COVID-19 Cases and Testing Equity in King County, Washington.

Individual-level Coronavirus Disease 2019 (COVID-19) case data suggest that certain populations may be more impacted by the pandemic. However, few studies have considered the communities from which positive cases are prevalent, and the variations in testing rates between communities. In this study, we assessed community factors that were associated with COVID-19 testing and test positivity at the census tract level for the Seattle, King County, Washington region at the summer peak of infection in July 2020. Multivariate Poisson regression was used to estimate confirmed case counts, adjusted for testing numbers, which were associated with socioeconomic status (SES) indicators such as poverty, educational attainment, transportation cost, as well as with communities with high proportions of people of color. Multivariate models were also used to examine factors associated with testing rates, and found disparities in testing for communities of color and communities with transportation cost barriers. These results demonstrate the ability to identify tract-level indicators of COVID-19 risk and specific communities that are most vulnerable to COVID-19 infection, as well as highlight the ongoing need to ensure access to disease control resources, including information and education, testing, and future vaccination programs in low-SES and highly diverse communities.

Health impact assessment of urban waterway decisions.

Health impact assessments (HIA) promote the consideration of health in a wide range of public decisions. Although each HIA is different, common pathways, evidence bases, and strategies for community engagement tend to emerge in certain sectors, such as urban redevelopment, natural resource extraction, or transportation planning. To date, a limited number of HIAs have been conducted on decisions affecting water resources and waterfronts. This review presents four recent HIAs of water-related decisions in the United States and Puerto Rico. Although the four cases are topically and geographically diverse, several common themes emerged from the consideration of health in water-related decisions. Water resource decisions are characterized by multiple competing uses, inter-institutional and inter-jurisdictional complexity, scientific uncertainty, long time scales for environmental change, diverse cultural and historical human values, and tradeoffs between private use and public access. These four case studies reveal challenges and opportunities of examining waterfront decisions through a "health lens". This review analyzes these cases, common themes, and lessons learned for the future practice of HIA in the waterfront zone and beyond.

Computer-aided 2D and 3D quantification of human stem cell fate from in vitro samples using Volocity high performance image analysis software.

Accurate automated cell fate analysis of immunostained human stem cells from 2- and 3-dimensional (2D-3D) images would improve efficiency in the field of stem cell research. Development of an accurate and precise tool that reduces variability and the time needed for human stem cell fate analysis will improve productivity and interpretability of the data across research groups. In this study, we have created protocols for high performance image analysis software Volocity® to classify and quantify cytoplasmic and nuclear cell fate markers from 2D-3D images of human neural stem cells after in vitro differentiation. To enhance 3D image capture efficiency, we optimized the image acquisition settings of an Olympus FV10i® confocal laser scanning microscope to match our quantification protocols and improve cell fate classification. The methods developed in this study will allow for a more time efficient and accurate software based, operator validated, stem cell fate classification and quantification from 2D and 3D images, and yield the highest ≥94.4% correspondence with human recognized objects.

Is there a limit to dose escalation for rectal cancer?

The radiation tolerance of the rectum is not fully understood. Published studies on the radiation treatment of cancers of the prostate, cervix and rectum have been reviewed to determine currently recommended dose-volume guidelines. The need for further studies directed specifically at the treatment of primary rectal cancer and perirectal node metastases is discussed. There seems to be room for escalation of the external beam doses currently given.

Anal canal cancer and chemoradiation treatment in two patients with systemic lupus erythematosus treated by chronic therapeutic immunosuppression.

Two case reports of anal cancer developing during chronic therapeutic immunosuppression for systemic lupus erythematosus (SLE) and their cancer management are presented. The complex issues of delivery of curative chemoradiation treatment for anal cancer in the context of co-existing autoimmune connective tissue disease (AICD) are discussed. These two cases show that combined chemotherapy and radiation regimens are possible in patients with SLE. However, frequent, careful assessment with judicious and prompt management of haematological and other complications during treatment is important.

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region.

BACKGROUND: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region. METHODS: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced. The authors identified or derived a measure for each criterion and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). Data were from a retrospective chart review on 642 cases of carcinoma of the tonsillar region treated with radiotherapy for cure at the Princess Margaret Hospital from 1970-1991. None of the patients had distant metastases. RESULTS: The scheme proposed by Synderman and Wagner, which was published in Otolaryngology Head and Neck Surgery in 1995 (vol.112, pages 691-4), scored best at 1.2. The UICC/AJCC scheme scored worst at 6.1. The hazard consistency ranged from a 3.1% average survival difference to 6.7% across the 8 schemes. The hazard discrimination measure varied by 28% from the best to worst scheme. Prediction varied by up to almost twofold across the schemes assessed. The distribution of patients varied from expected by between 0.13% and 0.57%. CONCLUSION: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically-derived schemes the authors evaluated. The results of the current study suggest that the usefulness of the TNM system can be enhanced by optimizing the design of stage groupings through empirical investigation.

Local excision and postoperative radiotherapy for distal rectal cancer.

PURPOSE: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. MATERIALS AND METHODS: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months). RESULTS: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). CONCLUSION: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

Management of persistent or locally recurrent epidermoid cancer of the anal canal with abdominoperineal resection.

We retrospectively evaluated the outcome of 22 patients with epidermoid cancer of the anal canal who underwent surgical salvage after failure of primary chemoradiotherapy. Patients who required surgery had significantly more advanced T-stage than those who did not fail chemoradiotherapy. Eighteen patients failed surgical salvage. Invasion through the muscle wall of the bowel was present in 16 of 18 patients compared with two of four patients who have no evidence of disease (follow-up 5-10 years). Failure occurred only in the pelvis in 13 of the patients who died of disease. The mean time to death after surgery was 19 months. We confirm the overall poor results of conventional abdominoperineal resection in those patients who have failed previous therapy. Most failures occur in the pelvis. Transanorectal ultrasound and magnetic resonance imaging (MRI) may allow better selection of patients for exenterative procedures and identify those not amenable to successful salvage.

Potential molecular prognostic markers in head and neck squamous cell carcinomas.

BACKGROUND: Current management strategies for squamous cell carcinoma of the head and neck (HNSCC) rely on an understanding of the natural history of the disease, along with the use of prognostic factors to guide selection of appropriate treatment. However, it is recognized that tumor heterogeneity limits the reliable use of currently available prognostic markers. With the evolving understanding of the genetic and molecular basis of human malignancies, there has been much interest in determining whether specific molecular changes in HNSCC might guide treatment decisions. METHODS: A literature review of potential molecular markers relevant to HNSCC was undertaken and evaluated. It is evident that the published information is promising but, oftentimes, limited by a scarcity of large, uniformly staged and treated patients, from which the value of novel molecular markers can be assessed. RESULTS: On the basis of the review of more than 100 articles, some of the emerging molecular markers that might provide independent prognostic information include epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), cyclin D1, and p53. This review will discuss the current status of these molecular factors and consequent implications for novel therapeutic approaches for patients with HNSCC. CONCLUSION: With the evolving understanding that human malignancies have developed and progressed on the basis of accumulated molecular abnormalities, there is an existing body of work trying to determine whether such abnormalities can predict clinical behavior of HNSCC. Such studies have to be conducted rigorously to derive useful information. Nevertheless, the role of such molecular markers, and the possibility to exploit them for therapeutic gain, is already at the horizon.

Carcinoma-in-situ of the glottic larynx: results of treatment with radiation therapy.

PURPOSE: Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to invasive disease if untreated. Treatment approaches include vocal cord stripping, radiation therapy (RT), and laser excision. The purpose of this analysis was to assess the efficacy and safety of a standard RT regimen in the treatment of this condition. METHODS AND MATERIALS: Between January 1980 and December 1994, 67 patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2 vocal cord stripping procedures, and 1 had been treated with laser. RESULTS: With a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer, giving a 5-year actuarial local control rate of 98%. This patient recurred 14 months after treatment and was salvaged with laryngectomy. He is currently free of disease 2 years after surgery. There were no serious acute or late treatment complications. Sixteen patients (24%) developed subsequent malignancies, 8 of these being in the upper aerodigestive tract, although none were in the radiation field. CONCLUSIONS: Moderate-dose radiation therapy is an effective treatment for glottic CIS. It is well tolerated, produces no serious acute or long-term side effects, with an excellent cure rate.

Proliferation parameters in epidermoid carcinomas of the anal canal.

PURPOSE: In a prospective study, we assessed the proliferation parameters in primary epidermoid carcinomas of the anal canal, and results were compared with those in cervical carcinomas. METHODS: Between January 1992 and December 1996, 32 patients with primary epidermoid carcinoma of the anal canal were studied prospectively. Patients were given i.v. bromodeoxyuridine and proliferation parameters were obtained using flow cytometry. The treatment protocol consisted of radiation therapy (XRT) (24 Gy/12-3.5 week split-28 Gy/14) and concurrent 5-fluorouracil and mitomycin C. Proliferation parameters were not obtained in six patients, leaving 26 patients in the analysis. There were 16 females and ten males, with two T1, 16 T2, five T3 and three T4 lesions. Median follow-up was 3.6 years. There were 22 squamous cell and four basaloid carcinomas. Six tumors were aneuploid. RESULTS: Median values for T(s) and S-phase fraction were 7.7 h and 8.2%, respectively. The median LI was 6.8% (0.9-35.7%), and the median T(pot) was 4.1 days (0.9-30 days). There was no correlation of LI or T(pot) with gender, age, tumor stage, size or histology. Local failure was observed in five patients (T(pot)>4.1 days, n=3; LI>6.8%, n=4). Isolated regional failure or distant disease in the absence of local failure was not observed. The small number of outcome events precluded a definitive analysis of the prognostic role of LI and T(pot). Values for the proliferation parameters were similar to those in our updated study of patients with carcinoma of the uterine cervix (n=107), median LI of 6.7% and median T(pot) of 5.5 days. CONCLUSIONS: We conclude that proliferation parameters in anal carcinomas are similar to those in cervical carcinomas. Rapid tumor proliferation does not have an apparent adverse impact on outcome in anal carcinomas managed by split-course XRT with concurrent 5-florouracil and mitomycin C.

An analysis of 78 breast sarcoma patients without distant metastases at presentation.

PURPOSE: A retrospective review of a single cancer center experience was undertaken to identify clinical or treatment prognostic factors for these unusual tumors, to allow for a recommendation regarding management. METHODS AND MATERIALS: The charts of 76 women and 2 men with breast sarcoma and without distant metastases at presentation registered from 1958 to 1990 were reviewed. Pathology was centrally reviewed in 54 cases. Histology, tumor size, grade, nodal status, age, menopausal status, history of benign breast disease, extent of surgery, resection margins, and radiation dose were each examined as potential prognostic factors by univariate analysis. To allow an analysis of radiation dose, total dose was normalized to a daily fraction size of 2 Gy. RESULTS: The median age at diagnosis was 50.5 years (13-82 years). The pathologic diagnosis was found to be malignant cystosarcoma phyllodes in 32 patients, with the remainder being stromal sarcoma (14), angiosarcoma (8), fibrosarcoma (7), carcinosarcoma (5), liposarcoma (4), other (8). Eighteen patients had grade I or II tumors, 43 had grade III or IV, and 18 were not evaluable. The 5- and 10-year actuarial rates for all 78 patients were 57% and 48% for cause-specific survival (CSS), and 47% and 42% for the relapse-free rates (RFR), respectively. The local relapse-free rate (LRFR) was 75% at both 5 and 10 years. The 5-year CSS for grade I or II tumors was 84% versus 55% for grade III or IV tumors (p = 0.01). Conservative surgery versus mastectomy did not lead to statistically significant different outcomes for CSS, RFR, or LRFR. The comparison of positive versus negative margins showed a 5-year LRFR of 33% versus 80% (p = 0.009). Pairwise comparisons of the 5-year CSS of 91% for > 48 Gy versus either 50% for < or = 48 Gy or 50% for no radiation showed p-values of 0.03 and 0.06, respectively. CONCLUSION: The authors propose that if negative surgical margins can be achieved, breast sarcoma should be managed by conservative surgery with postoperative irradiation to a microscopic tumoricidal dose (50 Gy) to the whole beast, and at least 60 Gy to the tumor bed. The decision to treat should be preceded by a preoperative multidisciplinary assessment. It is also recommended that an axillary lymph node dissection is not indicated, with the possible exception of patients with carcinosarcoma.

DNA damage and apoptosis in the aged canine brain: relationship to Abeta deposition in the absence of neuritic pathology.

1. In addition to beta-amyloid (Abeta) deposition and cytoskeletal neuropathology, both the Alzheimer's disease (AD) and Down's syndrome (DS) human brain exhibit marked evidence of DNA damage, however, it is difficult to separate events that occur in conjunction with neurofibrillary pathology versus Abeta pathology in these systems. 2. In contrast, the aged canine brain exhibits the accumulation of Abeta into diffuse deposits similar to those found in early AD and DS in the absence of neurofibrillary pathology. Furthermore, Abeta deposition in canine brain is correlated with cognitive deficits. 3. In order to test the hypothesis that TUNEL labeling for DNA damage in AD is not simply a consequence of agonal artifacts, postmortem artifacts, or neurofibrillary pathology, and may be directly related to Abeta deposition, we examined Abeta immunoreactivity, PHF-1 immunoreactivity, and TUNEL labeling in this animal model. 4. These experiments reveal a relationship between the amount of DNA damage detected by TUNEL labeling and levels of Abeta deposition. Further, in animals with no TUNEL labeling, we detected no Abeta immunoreactivity. 5. These data support the hypothesis that TUNEL labeling in AD ans DS is not a consequence of agonal artifact, postmortem artifact, or tau pathology, and may be directly related to Abeta deposition and perhaps AD pathogenesis.

Prognostic role of p53 protein expression in epidermoid carcinoma of the anal canal.

PURPOSE: To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC). METHODS AND MATERIALS: From January 1991 to December 1993, 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospectively designed protocol of XRT (24 Gy/12--3(1/2) wk split--28 Gy/14) and concurrent 5-FU (1000 mg/m2/day 1-4) and MMC (10 mg/m2 day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 patients, leaving 49 patients in the study. Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining. Actuarial survival and disease-free survival (DFS) rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. A Cox proportional hazard model was used for the multivariable analysis. RESULTS: There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor sizes ranged from 1-15 cm with a median of 4 cm. There were 6 patients with nodal metastases. Median follow-up was 4.5 years. Positive nuclear immunostaining for p53 was observed in 40 of 49 patients. The median percent positive staining was 5%, with 13, 9, and 18 patients showing staining in <5%, 5 to <10%, and 10-50% of tumor nuclei respectively. There was no correlation of percent p53 staining with gender, age, tumor stage, size, or histology. Local, regional, and distant failures were observed in 12, 2, and 2 patients respectively. The 5-yr survival and DFS were 84% and 64% respectively. In univariate analysis, the only prognostic variable for survival was gender. For DFS, advanced T category and large tumor size were predictive of poor DFS. In multivariate analysis, poor DFS was associated with high T category (p = 0.0008), basaloid histology (p = 0.001), male gender (p = 0.002), and increasing percent of p53 protein expression (p = 0.01). CONCLUSIONS: It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal. For patients managed with combined XRT, 5-FU, and MMC, percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category, gender, and histology.

The effects of antitumor irradiation on mandibular opening and mobility: a prospective study of 58 patients.

OBJECTIVE: The purpose of this study was to analyze the effects of head and neck radiation therapy on jaw opening and mobility. STUDY DESIGN: Maximum jaw opening and mandibular mobility were measured before and after radiation treatment in 58 patients presenting for angle down wedge, homolateral wedge pair, and parallel pair head and neck radiation treatment. RESULTS: As dose to the temporomandibular joint and pterygoid muscles increased, maximal jaw opening decreased linearly. Mandibular dysfunction appeared to increase as radiation dose to the pterygoid muscles increased. Similar effects were not observed with temporomandibular joint irradiation. Irradiation of the pterygoid muscles appeared critical in the development of trismus. Angle down wedge treatment irradiated the temporomandibular joint and pterygoid muscles with clinical effects similar to those seen in homolateral wedge pair and parallel pair patients. Doses as low as 1493 cGy resulted in functional impairment. CONCLUSIONS: Future investigations into radiotherapy delivery and appropriate postradiation trismus treatment may reduce head and neck radiation morbidity.

Benefits of accelerated hyperfractionation for head and neck cancer.

Accelerated hyperfractionation is a strategy intended to improve the likelihood of cancer control by delivery of a higher total dose of radiation without an offsetting increase in severe late normal tissue complications. The early results of a recently completed randomized trial of a 4-week hyperfractionated radiation schedule, and of two other regimens of accelerated hyperfractionation, confirm to some degree the biological hypotheses on which this strategy is based. The clinical benefits seen so far are limited, but are sufficient to support further refinement of the strategy and additional clinical trials.