Radiofrequency and microwave ablation for treatment of recurrent gynecologic malignancies.

OBJECTIVE: Radiofrequency ablation and microwave ablation are used to vaporize tumors not amenable to surgical resection. We sought to evaluate the safety and efficacy of radiofrequency and microwave ablation for the treatment of isolated lesions in patients with recurrent gynecologic malignancy. METHODS: Patients with gynecologic malignancies treated with radiofrequency or microwave ablation at a university-affiliated cancer center from April 2007 to January 2020 were evaluated. Clinical records were reviewed for number of prior chemotherapy regimens, response to ablation, time to progression, and location of progression. RESULTS: Thirty-two patients received ablative therapy for treatment of isolated recurrences. Seventeen (53%) patients had ovarian cancer, seven (22%) had endometrial cancer, and eight (25%) had cervical cancer. Thirteen (41%) patients received radiofrequency ablation and 19 (59%) received microwave ablation. Patients had a median of 2 (range 1-12) prior lines of chemotherapy. Sixteen (50%) patients achieved a partial or complete response with two patients experiencing no progression at time of submission. Six (19%) patients had stable disease and 10 (31%) patients had progression at time of initial follow-up imaging. Median progression-free survival for the cohort was 7.3 months (range 1.4-64.7). No significant improvement in median progression-free survival was seen with the addition of adjuvant systemic therapy to radiofrequency or microwave ablation (6.9 vs 7.7 months; HR 0.7, 95% CI 0.3 to 1.7). Clinical benefit, defined as absence of definitive progression at the site of ablation or new target lesions at 4 months, was seen in 22 (68.8%) patients. No major complications occurred, with two patients reporting pain or weakness at the site of ablation. CONCLUSION: Radiofrequency and microwave ablation demonstrated that 68.8% (n=22) of patients experienced clinical benefit at 4 months. Ablative therapy may be considered for the treatment of isolated lesions in patients with recurrent gynecologic malignancies.

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting."

Burglar Target Selection: A Cross-national Comparison.

OBJECTIVES: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. METHODS: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. RESULTS: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. CONCLUSIONS: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments.

Spatial variability in socio-demographic factors affecting participation in the Australian national bowel cancer screening program.

Objectives: The objective of this paper is to analyse the socio-demographic and spatial patterns associated with bowel cancer screening in Australia. Despite the importance of screening in reducing mortality via early intervention, it remains the case that overall screening rates are uneven between different socio-demographic groups and geographic regions. Notwithstanding this, there is limited knowledge in Australia regarding the interplay between socio-demographics and geography in relation to bowel cancer screening. Thus, this paper explores the socio-demographic and spatial patterns of screening participation across Australian regions to better inform public health policy and programs. Study design: This is a nationwide ecological study based on aggregate spatial data. Methods: An ecological study is conducted using bowel cancer screening rates and selected socio-demographic data measured at the Statistical Area 3 level. Geographically weighted regression software is used to conduct global and spatial regression analysis. Results: The global regression results show that higher rates of screening participation were associated with employment/education disengagement and volunteering while in contrast, lower rates of participation were associated with higher rates of indigenous populations, people with chronic health conditions, and people with poor English skills. Considering the spatial analysis, the analysis shows that once the spatial non-stationarity in the data is considered the influence of the variables shown to be significant in the global model, has significant spatial variability. Conclusion: From a public health perspective, addressing shortfalls in bowel cancer screening participation is an important priority. In order to understand differences in participation rates it is important to consider both socio-demographic factors as well as the geographic or spatial distribution of these factors.

Exploring Disparities in Breast Cancer Screening: An Ecological Analysis of Australian Data.

OBJECTIVE: The objective of this study is to analyse the socio-spatial patterns of breast cancer screening across Australian regions. METHODS: The research is an ecological study. Data for breast screening participation and associated social and demographic factors are obtained from the Australian Institute of Health and Welfare and the Australian Bureau of Statistics. The unit of measurement for the analysis is spatially aggregated regions (Statistical Area 3). Geographically weighted regression is used to analyse the relationship between a dependent variable and one or more independent variables while considering the spatial or geographic relationships among the data points. RESULTS: Globally, there was a significant (p<0.05) association between screening participation and income, English ability, education level, Indigenous background, and transport availability. The geographically weighted regression model represented an improved fit with a higher R2 (R2=0.89) and the Akaike information criterion (AIC) has improved, (AIC= 391.92). The Monte-Carlo tests for spatial variability were significant for all independent variables (p<0.05). Visually, there was marked spatial variation in the association between breast cancer screening rates and the significant independent variables from the global model. CONCLUSION: The identification of significant spatial variability in the association between breast cancer screening participation and important social and demographic factors provides important input into the design of programs aimed at increasing participation in screening regimes.

Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice.

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently, there are no pharmacological therapeutic interventions for sarcopenia. Here, we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy-sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator-activated receptor gamma coactivator one alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

Age-Related Differences in the Gut Microbiome of Rhesus Macaques.

Aging is a multifactorial process characterized by progressive changes in gut physiology and the intestinal mucosal immune system. These changes, along with alterations in lifestyle, diet, nutrition, inflammation and immune function alter both composition and stability of the gut microbiota. Given the impact of environmental influences on the gut microbiota, animal models are particularly useful in this field. To understand the relationship between the gut microbiota and aging in nonhuman primates, we collected fecal samples from 20 male and 20 female rhesus macaques (Macaca mulatta), across the natural macaque age range, for 16S rRNA gene analyses. Operational taxonomic units were then grouped together to summarize taxon abundance at different hierarchical levels of classification and alpha- and beta-diversity were calculated. There were no age or sex differences in alpha diversity. At the phylum level, relative abundance of Proteobacteria and Firmicutes and Firmicutes to Bacteriodetes ratio were different between age groups though significance disappeared after correction for multiple comparisons. At the class level, relative abundance of Firmicutes_Bacilli decreased and Proteobacteria_Alphaproteobacteria and Proteobacteria_Betaproteobacteria increased with each successively older group. Only differences in Firmicutes_Bacilli remained significant after correction for multiple comparisons. No sex differences were identified in relative abundances after correction for multiple comparisons. Our results are not surprising given the known impact of environmental factors on the gut microbiota.

Correlates of Climate Variability and Dengue Fever in Two Metropolitan Cities in Bangladesh.

Dengue fever is a major public health concern in Bangladesh with increased incidence during monsoon. We aimed to assess the correlation of temperature, humidity, and rainfall on dengue fever in two dengue endemic cities in Bangladesh. It was a time series analysis of climate factors and dengue occurrence data in Dhaka and Chittagong cities from 1 January 2000 to 31 December 2009. Daily mean temperature, rainfall, and humidity data were obtained from the Bangladesh meteorological department and daily dengue cases data were obtained from the directorate general of health services (DGHS) of Bangladesh. The mean dengue incidence was 31.62 (SD 28.7) per 100,000 in Dhaka whereas it was 5.76 (SD 11.7) per 100,000 population in Chittagong. The incidence of dengue cases was found significantly associated with the monthly mean temperature, total rainfall, and mean humidity in Dhaka, though in Chittagong, the significantly associated factors​ ​​​​​​were monthly total rainfall and mean humidity. The autoregressive integrated moving average (ARIMA) model identified monthly mean humidity and total rainfall as the most significant contributing factors for dengue cases in Dhaka and Chittagong, respectively. Our study reinforces the relationship of climate parameters with dengue fever, which will support policy-makers in developing a climate-based early warning system for dengue in Bangladesh.

Metabolizable energy intake during long-term calorie restriction in rhesus monkeys.

Calorie restriction (CR) is a dietary intervention shown to increase maximum life-span. The aim of this study was to compare the metabolizable energy of the pelleted semi-purified diet with estimated energy intake from food weight. Energy density of diet, urine and feces were measured by bomb calorimetry in rhesus monkeys (23-29 years old) on CR (CR, n=11) and control (C, n=9). Food moisture was measured to be 2-fold higher (9+/-1%) than indicated on the label (approximately 5%). The measured gross energy of diet was 4.4 kcal/g dry weight of CR and 4.5 kcal/g dry weight of C diets. In a two-day trial, food intake (mean+/-SD) was 112+/-20 g and 136+/-26 g of dry mass/d in the CR and C monkeys, respectively (p=0.003). The fraction of the diet absorbed (CR=0.91; C=0.95) was different (p<0.001) between CR and C monkeys. Using these coefficients, the metabolizable energy intake averaged over 6 months was 450+/-53 and 534+/-97 kcal/d in CR and C monkeys, respectively (Diff=16%; p=0.03). These values were compared with energy expenditure (EE), as measured annually by indirect calorimetry (490+/-61 kcal/d in CR and 532+/-62 kcal/d in C monkeys). Adjusted for changes in body composition (2+/-10 kcal/d in CR and -7+/-12 kcal/d in C), energy balance was not different from zero in CR (-42+/-42 kcal/d) and C (9+/-61 kcal/d) monkeys. Use of diet weight is a reasonable estimate of the level of CR when food waste is assessed.

The residential context of health in Australia: No longer the lucky country?

This paper introduces the special issue focused on the relationship between residence and health in Australia. We present six papers conducted in different Australian states that demonstrate different elements of the complex impact of residential context on health. Through this series of papers, we demonstrate the impact of housing quality and safety on vulnerable populations, but also the way in which processes around housing (e.g., data collection, renewal, allocation) can have either negative or positive outcomes. The broader residential context (i.e., neighborhood, community, geographic location) also must be considered in housing decisions, along with variables that closely track housing (e.g., stigma, poverty). Australia is in the middle of a housing crisis that can still be resolved in positive ways if adequate attention is given to the nuances and complexities of housing decisions.

Self-assessed health status and neighborhood context.

In recent years, there has been growing interest in the relationship between the characteristics of neighborhoods and the health and well-being of residents. The focus on neighborhood as a health determinant is based on the hypothesis that residing in a disadvantaged neighborhood can negatively influence health outcomes beyond the effect of individual characteristics. In this article, we examine three possible ways of measuring neighborhood socio-economic status, and how they each impact on self-reported health status beyond the effect contributed by individual-level factors. Using individual-level data from the Household Income and Labor Dynamics Australia survey combined with neighborhood-level (suburb) data, we tested the proposition that how one measures neighborhood socio-economic characteristics may provide an important new insight into understanding the links between individual-level outcomes and neighborhood-level characteristics. The findings from the analysis illustrate that although individual-level factors may be important to understanding health outcomes, how one accounts for neighborhood-level socio-economic status may be equally important. The findings suggest that in developing place-based health programs, policy makers need to account for the complex interactions between individual drivers and the potential complexities of accounting for neighborhood socio-economic status.

High temperature and risk of hospitalizations, and effect modifying potential of socio-economic conditions: A multi-province study in the tropical Mekong Delta Region.

The Mekong Delta Region (MDR) in Vietnam is highly vulnerable to extreme weather related to climate change. However there have been hardly any studies on temperature-hospitalization relationships. The objectives of this study were to examine temperature-hospitalization relationship and to evaluate the effects of socio-economic factors on the risk of hospitalizations due to high temperature in the MDR. The Generalized Linear and Distributed Lag Models were used to examine hospitalizations for extreme temperature for each of the 13 provinces in the MDR. A random-effects meta-analysis was used to estimate the pooled risk for all causes, and for infectious, cardiovascular, and respiratory diseases sorted by sex and age groups. Random-effects meta-regression was used to evaluate the effect of socio-economic factors on the temperature-hospitalization association. For 1°C increase in average temperature, the risk of hospital admissions increased by 1.3% (95% CI, 0.9-1.8) for all causes, 2.2% (95% CI, 1.4-3.1) for infectious diseases, and 1.1% (95% CI, 0.5-1.7) for respiratory diseases. However the result was inconsistent for cardiovascular diseases. Meta-regression showed population density, poverty rate, and illiteracy rate increased the risk of hospitalization due to high temperature, while higher household income, houses using safe water, and houses using hygienic toilets reduced this risk. In the MDR, high temperatures have a significant impact on hospitalizations for infectious and respiratory diseases. Our findings have important implications for better understanding the future impacts of climate change on residents of the MDR. Adaptation programs that consider the risk and protective factors should be developed to protect residents from extreme temperature conditions.

Role of Genomic Instability in Immunotherapy with Checkpoint Inhibitors.

AIM: We evaluated whether tumor genome sequencing to detect the number and type of alterations could be used as a valuable biomarker for judging the potential utility of immune checkpoint inhibitors in patients with advanced cancers. MATERIALS AND METHODS: We identified patients with solid tumors who were treated with checkpoint inibitors and had received commercially available next generation sequencing (NGS). Tumors profiled by Caris Life Sciences, Foundation Medicine and Guardant360 between 2013 and 2015. Patients were divided into 5 quintiles based on mutational load (pathogenic mutations plus variants of undetermined significance). RESULTS: Fifty patients with solid tumors on immunotherapy that had NGS reports available were identified. Top quintile patients had more genomic alterations (median=16.5) than the others (median=2) and had more pathogenic mutations in cell-cycle regulatory genes (100% versus 48%). The overall survival (OS) was significantly superior for patients in the top quintile (722 days) versus the others (432 days). We found no significant difference in progression-free survival (PFS) between the two groups. The objective response rate was numerically higher for the top quintile (50%) vs. others (20%). Programmed cell death protein 1 (PD1) and programmed death-ligand 1 (PDL1) status by immunohistochemistry was not associated with outcomes. CONCLUSION: The use of immune checkpoint blockade in tumors with higher mutational load was associated with improved OS. Our results suggest that the evaluation of tumor genomes may be predictive of immunotherapy benefit.

Reference body composition in adult rhesus monkeys: glucoregulatory and anthropometric indices.

Rhesus monkeys have been used as models to study obesity and disease. The aim of this study was to define body mass indices for underweight and obesity in rhesus monkeys. Longitudinal data collected over 8-14 years from 40 male and 26 female rhesus monkeys were analyzed. Body weight, insulin sensitivity index, and disposition index were regressed against percent body fat (%BF). A minimal %BF beyond which further loss of body weight resulted in loss of lean mass was determined to be 11.5% in older males, 8% in adult females, and 9% in younger adult males. Insulin sensitivity index and disposition index reached minimum values at 23% fat in older males, 18% in adult females, and 21% in younger adult males, indicating obesity. The estimated reference range for %BF was 9%-23% in male and 8%-18% in female monkeys, corresponding to body mass indices of 32-44 kg/m(2) for male and 27-35 kg/m(2) for female monkeys.

Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys.

Polycystic ovary syndrome (PCOS) is a familial disease. Affected males harbor some of the metabolic deficits seen in affected females. The prenatally androgenized (PA) female rhesus monkey, an animal model for PCOS, manifests glucoregulatory and reproductive abnormalities similar to those seen in PCOS women. The purpose of this study was to determine whether exposure of fetal male rhesus monkeys to testosterone excess would induce glucoregulatory and reproductive deficits. Seven adult PA males and seven matched controls underwent somatometric measurements, sex steroid analysis, and a frequently sampled i.v. glucose tolerance test. Body measurements were similar in the two groups, although arm circumference was greater in control compared with PA males (P < 0.01). There were no differences in neonatal weight or serum levels of sex steroids between the two male groups. Measures of insulin sensitivity and pancreatic beta-cell compensation (disposition index) were clearly diminished in PA compared with control males [insulin sensitivity: PA, mean 0.8 (95% confidence interval, 0.11, 5.82); controls, 3.06 (1.51, 6.19) x 10(-4)/min/microU/ml; P < 0.05; disposition index: PA, 226.38 (69.54, 383.22); controls, 509.21/min (306.52, 711.89); P < 0.02]. PA males do not exhibit elevated androgens during adulthood, suggesting that insulin resistance and impaired pancreatic beta-cell function may result from fetal reprogramming of key metabolic tissues.

Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction.

Dietary restriction (DR) is currently the only paradigm that has consistently extended maximal life span and reduced the onset of age-related chronic diseases in all of the nonprimate species tested. Although it is controversial, some investigators have suggested that the underlying mechanisms may be mediated by adaptations in energy expenditure. We evaluated the extent to which DR alters energy metabolism in a unique cohort of rhesus monkeys submitted to DR for 11 yr. Total energy expenditure (doubly labeled water), resting energy expenditure (REE; indirect calorimetry), and nonbasal energy expenditure (calculated by difference) were measured in DR (n = 12) and control (n = 11) animals. Body composition was determined by dual energy x-ray absorptiometry. Both fat mass and fat-free mass were lower in the restricted animals (56 and 12%, respectively). DR induced a 17% lower total energy expenditure that was attributable to a 20% decrease in REE without changes in the nonbasal energy expenditure. Adjusted for fat-free mass, REE was 13% lower with DR (-250 kJ/d). Taken together with a reanalysis of previous DR experiments published in humans, rodents, and monkeys, these results suggest that DR may lower REE independent of the DR-induced changes in body composition. Whether this reduction in REE contributes to the life-extending properties of DR warrants further analysis, but it suggests that the long-standing debate regarding DR effects on metabolic rates may derive from the lack of consensus on how to adjust for body size and composition.

The spatial distribution of health vulnerability to heat waves in Guangdong Province, China.

BACKGROUND: International literature has illustrated that the health impacts of heat waves vary according to differences in the spatial variability of high temperatures and the social and economic characteristics of populations and communities. However, to date there have been few studies that quantitatively assess the health vulnerability to heat waves in China. OBJECTIVES: To assess the spatial distribution of health vulnerability to heat waves in Guangdong Province, China. METHODS: A vulnerability framework including dimensions of exposure, sensitivity, and adaptive capacity was employed. The last two dimensions were called social vulnerability. An indicator pool was proposed with reference to relevant literatures, local context provided by relevant local stakeholder experts, and data availability. An analytic hierarchy process (AHP) and a principal component analysis were used to determine the weight of indicators. A multiplicative vulnerability index (VI) was constructed for each district/county of Guangdong province, China. RESULTS: A total of 13 items (two for exposure, six for sensitivity, and five for adaptive capacity) were proposed to assess vulnerability. The results of an AHP revealed that the average VI in Guangdong Province was 0.26 with the highest in the Lianzhou and Liannan counties of Qingyuan (VI=0.50) and the lowest in the Yantian district of Shenzhen (VI=0.08). Vulnerability was gradiently distributed with higher levels in northern inland regions and lower levels in southern coastal regions. In the principal component analysis, three components were isolated from the 11 social vulnerability indicators. The estimated vulnerability had a similar distribution pattern with that estimated by AHP (Intraclass correlation coefficient (ICC)=0.98, p<0.01). CONCLUSIONS: Health vulnerability to heat waves in Guangdong Province had a distinct spatial distribution, with higher levels in northern inland regions than that in the southern coastal regions.

Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys.

BACKGROUND: Short-term (<1 year) calorie restriction (CR) has been reported to decrease physical activity and metabolic rate in humans and non-human primate models; however, studies examining the very long-term (>10 year) effect of CR on these parameters are lacking. OBJECTIVE: The objective of this study was to examine metabolic and behavioral adaptations to long-term CR longitudinally in rhesus macaques. DESIGN: Eighteen (10 male, 8 female) control (C) and 24 (14 male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old were examined after 13 and 18 years of moderate adult-onset CR. Energy expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory chamber (24 h EE). Physical activity was assessed both by metabolic equivalent (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of movements during 24 h was also calculated. Age and fat-free mass were included as covariates. RESULTS: Adjusted total and 24 h EE were not different between C and CR. Sleeping metabolic rate was significantly lower, and physical activity level was higher in CR than in C independent from the CR-induced changes in body composition. The duration of physical activity above 1.6 METs was significantly higher in CR than in C, and CR had significantly higher accelerometer activity counts than C. Metabolic cost of movements during 24 h was significantly lower in CR than in C. The accelerometer activity counts were significantly decreased after seven years in C animals, but not in CR animals. CONCLUSIONS: The results suggest that long-term CR decreases basal metabolic rate, but maintains higher physical activity with lower metabolic cost of movements compared with C.