POST-PROJECT ASSESSMENT OF PIT LATRINES IN RURAL PANAMA

In Panama, one of the Environmental Health (EH) Sector’s primary goals is to improve the health of rural Panamanians by helping them to adopt behaviors and practices that improve access to and use of sanitation systems. In complying with this goal, the EH sector has used participatory development models to improve hygiene and increase access to latrines through volunteer managed latrine construction projects. Unfortunately, there is little understanding of the long term sustainability of these interventions after the volunteers have completed their service. With the Peace Corps adapting their Monitoring, Reporting, and Evaluation procedures, it is appropriate to evaluate the sustainability of sanitation interventions offering recommendations for the adaptions of the EH training program, project management, and evaluation procedures. Recognizing the need for evaluation of past latrine projects, the author performed a post project assessment of 19 pit latrine projects using participatory analysis methodologies. First, the author reviewed volunteers’ perspectives of pit latrine projects in a survey. Then, for comparison, the author performed a survey of latrine projects using a benchmarking scoring system to rate solid waste management, drainage, latrine siting, latrine condition, and hygiene. It was observed that the Sanitation WASH matrix created by the author was an effective tool for evaluating the efficacy of sanitation interventions. Overall more than 75%, of latrines constructed were in use. However, there were some areas where improvements could be made for both latrine construction and health and hygiene. The latrines scored poorly on the indicators related to the privacy structure and seat covers. Interestingly those are the two items least likely to be included in project subsidies. Furthermore, scores for hygiene-related indicators were low; particularly those related to hand washing and cleanliness of the kitchen, indicating potential for improvement in hygiene education. Based on these outcomes, the EH sector should consider including subsidies and standardized designs for privacy structures and seat covers for latrines. In addition, the universal adoption of contracts and/or deposits for project beneficiaries is expected to improve the completion of latrines. In order to address the low scores in the health and hygiene indicators, the EH sector should adapt volunteer training, in addition to standardizing health and hygiene intervention procedures. In doing so, the sector should mimic the Community Health Club model that has shown success in improving health and hygiene indicators, as well as use a training session plan format similar to those in the Water Committee Seminar manual. Finally, the sector should have an experienced volunteer dedicated to program oversight and post-project monitoring and evaluation

The experience of accommodating privacy restrictions during implementation of a large-scale surveillance study of an osteoporosis medication.

PurposeTo explore whether privacy restrictions developed to protect patients have complicated research within a 15-year surveillance study conducted with US cancer registries.MethodsData from enrolling 27 cancer registries over a 10-year period were examined to describe the amount of time needed to obtain study approval. We also analyzed the proportion of patients that completed a research interview out of the total reported by the registries and examined factors thought to influence this measure.ResultsThe average length of the research review process from submission to approval of the research was 7 months (range, <1 to 24 months), and it took 6 months or more to obtain approval of the research at 41% of the cancer registries. Most registries (78%) required additional permission steps to gain access to patients for research. After adjustment for covariates, the interview response proportion was 110% greater (ratio of response proportion = 2.1; 95% confidence interval: 1.3, 3.3) when the least restrictive versus the most restrictive permission steps were required. An interview was more often completed for patients (or proxies) if patients were alive, within a year of being diagnosed, or identified earlier in the study.ConclusionsLengthy research review processes increased the time between diagnosis and provision of patient information to the researcher. Requiring physician permission for access to patients was associated with lower subject participation. A single national point of entry for use of cancer registry data in health research is worthy of consideration to make the research approval process efficient. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd

A dosimetric model for the heterogeneous delivery of radioactive nanoparticles In vivo: a feasibility study

Abstract ᅟ Accurate and quantitative dosimetry for internal radiation therapy can be especially challenging, given the heterogeneity of patient anatomy, tumor anatomy, and source deposition. Internal radiotherapy sources such as nanoparticles and monoclonal antibodies require high resolution imaging to accurately model the heterogeneous distribution of these sources in the tumor. The resolution of nuclear imaging modalities is not high enough to measure the heterogeneity of intratumoral nanoparticle deposition or intratumoral regions, and mathematical models do not represent the actual heterogeneous dose or dose response. To help answer questions at the interface of tumor dosimetry and tumor biology, we have modeled the actual 3-dimensional dose distribution of heterogeneously delivered radioactive nanoparticles in a tumor after systemic injection. Methods 24 h after systemic injection of dually fluorescent and radioactive nanoparticles into a tumor-bearing mouse, the tumor was cut into 342 adjacent sections and imaged to quantify the source distribution in each section. The images were stacked to generate a 3D model of source distribution, and a novel MATLAB code was employed to calculate the dose to cells on a middle section in the tumor using a low step size dose kernel. Results The average dose calculated by this novel 3D model compared closely with standard ways of calculating average dose, and showed a positive correlation with experimentally determined cytotoxicity in vivo. The high resolution images allowed us to determine that the dose required to initiate radiation-induced H2AX phosphorylation was approximately one Gray. The nanoparticle distribution was further used to model the dose distribution of two other radionuclides. Conclusions The ability of this model to quantify the absorbed dose and dose response in different intratumoral regions allows one to investigate how source deposition in different tumor areas can affect dose and cytotoxicity, as well as how characteristics of the tumor microenvironment, such as hypoxia or high stromal areas, may affect the potency of a given dose

Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality

Purpose: Long-acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma-related deaths, but the effect on asthma-related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources. Methods: Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.4 for the asthma mortality rate ratio and ≤0.40 per 10 000 person-years for the mortality rate difference, assuming no effect of new use of combined LABA + ICS (versus non-LABA maintenance therapy) on asthma mortality. Ten research institutions executed centrally distributed analytic code based on a standard protocol using an extracted (2000–2010) persistent asthma cohort (asthma diagnosis and ≥4 asthma medications in 12 months). Pooled results were analyzed by the coordinating center. Asthma deaths were ascertained by linkage with the National Death Index. Results: In a cohort of 994 627 persistent asthma patients (2.4 million person-years; 278 asthma deaths), probabilities of the upper 95% confidence limit for effect estimates being less than targeted values, assuming a null relation, were about 0.05. Modifications in cohort and exposure definitions increased exposed person-time and outcome events, but study size remained insufficient to attain study goals. Conclusions: Even with 10 data sources and a 10-year study period, the rarity of asthma deaths among patients using certain medications made it infeasible to study the association between combined LABA + ICS and asthma mortality with our targeted level of study precision

Relationship of Mammographic Density and Gene Expression: Analysis of Normal Breast Tissue Surrounding Breast Cancer

Previous studies of breast tissue gene expression have demonstrated that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density (MD) and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 breast cancer patients from the population-based Polish Women's Breast Cancer Study

Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models

Tumor cells are surrounded by a complex microenvironment. The purpose of our study was to evaluate the role of heterogeneity of the tumor microenvironment in the variability of nanoparticle (NP) delivery and efficacy

Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases

Purpose: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. Methods: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0–3+). Overall survival (OS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. Results: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2− 38% HR−/Her2− (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). Conclusion: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste