Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

Reliability and validity of the translated Chinese version of comprehensive assessment of acceptance and commitment therapy processes (CompACT-C) in breast cancer survivors.

Purpose: This study aimed to translate and validate a Chinese version of the Comprehensive assessment of Acceptance and Commitment Therapy processes (CompACT-C), a 23-item questionnaire for measuring an individual's level of psychological flexibility among Chinese breast cancer survivors for utilisation of Acceptance and commitment therapy (ACT)-based interventions in breast cancer patients. Methods: Six translators translated the original English version into Chinese according to Brislin's Translation Model. Psychometric properties tests were conducted on the CompACT-C, including internal consistency, test-retest reliability (two-week interval), face validity, content validity, convergent validity with experiential avoidance, and construct validity (confirmatory factor analysis). Results: 308 Chinese breast cancer survivors with mastectomies were conveniently recruited. The translated scale showed satisfactory test-retest reliability (two-week interval, r = 0.53-0.72, p < 0.001), face validity, and content validity (CVI-Scale/CVS-Item = 1.00). According to the confirmatory factor analysis results, the final Chinese version remained the 23 items and three dimensions, with the modification of item six from the dimension of openness to experience to behavioural awareness for better model fitness [structural equation model analysis, χ2 = 559.486, df = 226, NC (χ2/df) = 2.476, RMSEA = 0.069, CFI = 0.834, TLI = 0.815, SRMR = 0.079] and satisfactory internal consistency (Cronbach's α = 0.71), convergent validity with AAQ-2 (r = -0.57, p < 0.001) in these breast cancer patients. Conclusions: The Chinese version of the CompACT showed good reliability and validity among Chinese breast cancer patients. Future research is suggested to confirm its psychometric properties with diverse breast and other cancer groups.

Towards the carbon neutrality of sludge treatment and disposal in China: A nationwide analysis based on life cycle assessment and scenario discovery.

Motivated by the carbon neutrality target, strategic planning for a low-carbon transition of sludge treatment and disposal in China is challenging due to the unpredictability of technical, regional, socioeconomic, and political factors affecting greenhouse gas (GHG) emissions. This study combines the use of a Life Cycle Assessment and the Patient Rule Induction Method, accounting for possibilities that could achieve net-zero carbon emissions by exploring multiple plausible future profiles of sludge treatment and disposal. Results show that reducing sludge landfill and increasing anaerobic digestion are effective methods to facilitate GHG reduction. Achieving carbon neutrality is closely linked to developing a cleaner electricity mix. Based on a cascaded scenario analysis considering regional differences for 31 Chinese provinces, results demonstrated a maximum cumulative reduction potential of 371 Mt CO2 equivalents from 2020 to 2050, equal to 59.84% of the business-as-usual scenario. Together with GHG reductions, terrestrial acidification and ecotoxicity as well as freshwater ecotoxicity are synergistically reduced. However, the shifting environmental burden results in freshwater eutrophication, human toxicity, marine ecotoxicity, marine eutrophication, and photochemical oxidant formation. This study presents a novel method for systematically identifying possible future development paths toward carbon neutrality. The findings may support policy designs for achieving target carbon reduction effects for sludge disposal.

SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment.

AIMS: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS). METHODS: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases. RESULTS: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA. CONCLUSIONS: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

SCC-UEFAS, an urban-ecological-feature based assessment system for sponge city construction.

An effective sponge city construction evaluation system plays a crucial role in evaluating sponge city construction schemes. The construction of a sponge city evaluation system still faces challenges related to incomplete index selection and unscientific weight division. Limited studies have focused on the comprehensive assessment of sponge city construction in the early stages. This study constructed a scientific assessment indicator system and a quantitative indicator weight at all levels by literature review and statistical analysis methods from an objective perspective. To demonstrate how to utilize our evaluation methods, three construction schemes randomly generated by MATLAB were evaluated under evaluation states of constant weight and variable weight, respectively. Scheme 3 had the highest score of 0.638 under the constant weight assessment, but it cannot practically be the final construction scheme due to the imbalance between indicators. Compared to the constant weight assessment, a variable weight assessment can effectively balance the states of the evaluation index with changes in the decision variable. Among the three schemes, Scheme 2 is the best choice with a value of 0.0355 under variable weight evaluation due to punishment and incentives in the variable weight method. The concept of "punishing" a disadvantageous indicator and "motivating" an advantageous indicator increases the relative advantages of the indices, ultimately affecting the assessment results of schemes and leading to a more balanced state. This study provides reasonable analysis and decision-making mechanisms to support decision-making and guide the scientific selection of a construction scheme.

Perinatal depression screening: a systematic review of recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD).

Perinatal depression (PND) screening recommendations are made by national, state-based and professional organisations; however, there is disagreement regarding screening timing, provider responsible, screening setting, screening tool as well as the follow-up and referral pathways required post-screening. This systematic review aimed to identify, describe and compare PND screening recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD). Publications were identified through systematically searching PubMed, Google and the Guidelines International Network (GIN). Recommendations regarding PND screening endorsement, timing, frequency, responsible provider, tools/assessments and follow-up and referral were extracted. Twenty-one publications, including guidelines, from five countries were included. Most made recommendations in support of PND screening using the Edinburgh Postnatal Depression Scale. Details differed regarding terminology used, as well as frequency of screening, follow-up mechanisms and referral pathways. A broad range of health providers were considered to be responsible for screening. This is the first review to identify and compare PND screening recommendations from OECD member countries; however, only online publications published in English, from five countries were included. Heterogeneity of publication types and inconsistency in definitions rendered quality assessment inappropriate. While most publications generally endorsed PND screening, there are exceptions and the associated details pertaining to the actual conduct of screening vary between and within countries. Developing clear, standardised recommendations based on current evidence is necessary to ensure clarity amongst healthcare providers and a comprehensive approach for the early detection of PND.

Spatial and Temporal Evolutionary Characteristics and Its Influencing Factors of Economic Spatial Polarization in the Yangtze River Delta Region.

Economic spatial polarization is a manifestation of unbalanced urban development. To study the unbalanced development of Chinese cities, this paper selects 41 cities in the Yangtze River Delta (YRD) region, introduces the polarization index and exploratory spatio-temporal analysis to portray their spatio-temporal evolution process, and analyzes the differences in spatial polarization patterns of economic development in three dimensions of economic quantity, quality, and structure. Finally, we use the geographic detector model to explore the driving factors and then propose corresponding policy recommendations. The results show that: (1) the degree of difference in economic development in the YRD region narrowed from 2000 to 2019, and the spatial polarization level of urban economic development showed a fluctuating downward trend, among which the spatial polarization level of the economic structure dimension has been increasing. (2) In terms of spatial distribution, the "Yangtze River Delta urban agglomeration" has economic spatial polarization in the YRD region has become the peak contiguous zone, and the spatial polarization of economic quantity and quality dimensions has formed a "polycentric" pattern, while the spatial polarization of economic structure dimensions shows a stable "one core, multiple sub-center" distribution. (3) From the evolution of spatial polarization, most cities have strong spatial locking characteristics without a transition. Spatially positive polarized are concentrated in the YRD urban agglomeration, and the inter-city neighboring relations are mainly positive synergistic growth, while the negatively polarized cities are mostly distributed in the peripheral areas of the YRD and the neighboring relations are negative synergistic growth. At the same time, the spatially positive polarization effect of the economic quantity dimension and the spatially negative polarization effect of the economic structure dimension among cities are more significant. (4) The economic spatial polarization in the YRD region is mainly dominated by market prosperity and urbanization level, while the driving effect of scientific and technological innovation development on the urban economy has also been expanding in recent years. Promoting the reasonable allocation of marketization, urbanization, and technology among cities with positive and negative spatial polarization in the future will contribute to balanced urban and regional economic development in a coordinated and orderly manner.

Assessment of Non-contrast-enhanced Dixon Water-fat Separation Compressed Sensing Whole-heart Coronary MR Angiography at 3.0 T: A Single-center Experience.

RATIONALE AND OBJECTIVES: The clinical utility of Dixon water-fat separation coronary MR angiography (CMRA) with compressed sensing (CS) reconstruction has not been determined in a patient population. This study was designed to evaluate the performance of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA sequence in vitro and in vivo. MATERIALS AND METHODS: In vitro phantom MRI, we compared key parameters of the SENSE and CS images. And in this prospective in vivo study, from November 2019 to October 2020, 94 participants were recruited for 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography (CA) as the reference method. RESULTS: Compared with SENSE, CS with an appropriate acceleration factor offers both higher SNR/CNR (p < 0.05) and a shortened acquisition. Fifty-eight patients successfully completed the CMRA and CA. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA according to a patient-based analysis were 96.4%, 66.7%, 73.0%, 95.2% and 81.0%, respectively. The area under the receiver-operator characteristic (ROC) curve (AUC) of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA for detecting significant coronary artery stenosis is 0.908, 0.895, and 0.904 in patient-, vessel-, and segment-based analyses respectively. CONCLUSION: 3.0 T non-contrast-enhanced Dixon water-fat separation whole-heart CMRA using appropriate CS is a promising noninvasive and radiation-free technique to detect clinically significant coronary stenosis on patients with suspected CAD.

Comparative life cycle assessment of biochar-based lignocellulosic biohydrogen production: Sustainability analysis and strategy optimization.

Lignocellulose has been considered a potential feedstock for biohydrogen production. Recently, a novel closed-loop concept of biochar approach was developed for enhanced lignocellulosic biohydrogen production. This study therefore targets to analyze the environmental impacts of the three existing lignocellulosic biohydrogen production processes, and evaluate the environmental performance of applying biochar in each process at this early stage of technological development. The results suggest that biochar dosing shows better environmental performance for all impact categories, especially in the consolidate bioprocessing case. Electricity consumption was found to be the dominant cause of environmental impact over the life cycle, while by-products generation was also found to have an effect on the life-cycle impacts. Future research focuses on the biohydrogen production scale, the electricity generation scheme transition towards renewable and cleaner energetic systems, and recovery the by-products to the maximum extent, that will make lignocellulosic biohydrogen production more environmentally sustainable.

Resource recovery in life cycle assessment of sludge treatment: Contribution, sensitivity, and uncertainty.

This study focused on the resource recovery of sludge treatment by quantifying the environmental contributions, identifying the influential factors, and comparing different scenarios. Life cycle assessment (LCA) of sewage sludge treatment was carried out to estimate the environmental impacts of six scenarios: (1) co-digestion of sludge and food waste; (2) co-gasification of sludge and woody waste; (3) co-incineration of sludge and used oil; (4) landfilling; (5) incineration; and (6) anaerobic digestion combined with incineration. Results demonstrate that the resource recovery had a substantial contribution to the environmental performance of the sludge treatment, while the degree of contribution was largely affected by various treatment scenarios and diverse impact categories. To gain deep insight into the parameters related to resource recovery, sensitivity analysis was performed to investigate the influence of the parameters on the LCA results, including the organic content, conversion efficiency of organic matter to methane, and other energy conversion efficiencies. After integrating the inventory variation of those parameters into the decision process via the Monte Carlo simulation, results indicate that no obviously superior scenario could be identified. Conversely, when parameter uncertainty was not considered, co-gasification of sludge and woody waste exhibited the most preferable environmental performance. Overall, this study demonstrates that considering the parameter uncertainty of resource recovery will contribute to a more transparent evaluation process, but will inevitably increase the complexity of the decision-making process based on LCA results because it is difficult to determine a sludge treatment scenario that decisively outperforms the others.

Underdiagnosis of Hereditary Colorectal Cancers Among Medicare Patients: Genetic Testing Criteria for Lynch Syndrome Miss the Mark.

PURPOSE: Strict clinical criteria used by Medicare for germline testing for Lynch syndrome (LS) could lead to missed diagnoses of hereditary cancer syndromes given variable individual and family phenotypes. The aim of this study was to compare rates and spectrum of pathogenic or likely pathogenic (P/LP) variants in LS and other hereditary cancer genes on the basis of meeting Medicare LS testing criteria. METHODS: Retrospective review of Medicare beneficiaries who had multigene panel testing with an indication of personal or family history of colorectal cancer (CRC) was performed. Ordering providers determined if Medicare LS criteria were met. The results of genetic testing were compared on the basis of whether or not Medicare testing criteria were met. RESULTS: Among 639 Medicare beneficiaries, 495 (77.5%) met testing criteria. Overall rates of P/LP variant identification were similar between those meeting and not meeting testing criteria (18.4% v 11.8%; P = .06). LS was diagnosed more frequently among those meeting testing criteria (10.1% v 4.9%; P = .05). No statistical differences were found in rates of P/LP variant identification for non-LS CRC genes (5.3% v 5.6%; P = .89) or non-CRC genes (4.2% v 2.1%; P = .23). PMS2, MUTYH, and ATM P/LP variants were found at higher rates among those outside of criteria. CONCLUSION: Among Medicare beneficiaries undergoing genetic testing for suspected LS, rates of P/LP variants in actionable cancer genes were similar regardless of whether testing criteria were met. Current testing criteria fail to identify individuals with P/LP variants in PMS2 and other actionable cancer genes. Relaxing LS testing criteria could improve identification of individuals with hereditary cancer syndromes among Medicare beneficiaries.

Role of free-breathing motion-corrected late gadolinium enhancement technique for image quality assessment and LGE quantification.

OBJECTIVE: To compare the image quality and late gadolinium enhancement (LGE) quantification between free-breathing motion-corrected and conventional breath-hold LGE method in a variety of cardiovascular diseases. MATERIALS AND METHODS: 149 consecutive patients underwent contrast-enhanced cardiac magnetic resonance examination employing both free-breathing motion-corrected LGE and conventional breath-hold LGE method. Scan time, contrast-to-noise ratio, overall image quality score and LGE mass were measured and analyzed statistically. RESULTS: Free-breathing motion-corrected LGE method had a shorter scan time and higher overall image quality score in comparison with conventional breath-hold LGE method (p < 0.001). Univariate/multivariate logistic regression analysis showed that breath-holding difficulty, high heart rate and arrhythmia could be predictive factors possibly for an inferior image quality score (p < 0.05 for all). The contrast-to-noise ratios of free-breathing motion-corrected LGE images were higher than those of conventional breath-hold LGE images (p < 0.001). In the cases with subepicardial and/or transmural myocardial enhancement, the measured LGE masses were larger on free-breathing motion-corrected LGE images in comparison with those on conventional breath-hold LGE images (p < 0.05). CONCLUSION: Free-breathing motion-corrected LGE could be a better choice for patients who need contrast-enhanced cardiac MRI and have one or more of the risk factors for an inferior image quality score, including breath-holding difficulty, high heart rate and arrhythmia. However, an overestimation of LGE mass on free-breathing motion-corrected LGE image should be taken into consideration when LGE pattern involves subepicardial and/or transmural myocardium.

Asymmetric and Spatial Non-Stationary Effects of Particulate Air Pollution on Urban Housing Prices in Chinese Cities.

Fine particulate matter(PM2.5) pollution will affect people's well-being and cause economic losses. It is of great value to study the impact of PM2.5 on the real estate market. While previous studies have examined the effects of PM2.5 pollution on urban housing prices, there has been little in-depth research on these effects, which are spatially heterogeneous at different conditional quantiles. To address this issue, this study employs quantile regression (QR) and geographically weighted quantile regression (GWQR) models to obtain a full account of asymmetric and spatial non-stationary effects of PM2.5 pollution on urban housing prices through 286 Chinese prefecture-level cities for 2005-2013. Considerable differences in the data distributions and spatial characteristics of PM2.5 pollution and urban housing prices are found, indicating the presence of asymmetric and spatial non-stationary effects. The quantile regression results show that the negative influences of PM2.5 pollution on urban housing prices are stronger at higher quantiles and become more pronounced with time. Furthermore, the spatial relationship between PM2.5 pollution and urban housing prices is spatial non-stationary at most quantiles for the study period. A negative correlation gradually dominates in most of the study areas. At higher quantiles, PM2.5 pollution is always negatively correlated with urban housing prices in eastern coastal areas and is stable over time. Based on these findings, we call for more targeted approaches to regional real estate development and environmental protection policies.

Automobile exhaust particles retention capacity assessment of two common garden plants in different seasons in the Yangtze River Delta using open-top chambers.

Particulate matter (PM) pollution is a serious environmental problem in most of the cities in the Yangtze River Delta region. Plants can effectively filter ambient air by adsorbing PM. However, only a few studies have paid attention to the dynamic changes and seasonal differences in particle retention capacities of plants under long-term pollution. In this study, we investigated the dynamic changes in particle retention capabilities of the evergreen, broad-leaved, greening plants-Euonymus japonicus var. aurea-marginatus and Pittosporum tobira-in spring and summer. We employed an open-top chamber to simulate the severity of the tail gas pollution. The results showed that, both the plants reached a saturated state in 18-21 days, under continuous exposure to pollution (daily concentration of PM2.5: 214.64 ± 321.33 µg·cm-3). This was 6-8 days longer than that in the field experiments. In spring, the maximum retention of total particulate matter per unit leaf area of E. japonicus var. aurea-marginatus and P. tobira was 188.47 ± 3.72 µg cm-2 (18 days) and 67.63 ± 2.86 µg cm-2 (21 days), respectively. In summer, E. japonicus var. aurea-marginatus and P. tobira reached the maximum retention of the particle on the 21st day, with a net increase of 94.10 ± 3.77 µg cm-2 and 27.81 ± 3.57 µg cm-2, respectively. Irrespective of season, the particle retention capacity of E. japonicus var. aurea-marginatus was higher than that of P. tobira, and it showed a better effect on reducing the concentration of fine particles in the atmosphere. The particle retention of the two plants was higher in spring than that in summer. E. japonicus var. aurea-marginatus displayed a significant difference in particle retention between the seasons, while P. tobira did not show much difference. These results will provide a foundation for future studies on the dynamic changes and mechanism of particle retention in plants and management practices by employing plants for particle retention in severely polluted areas.

Asymmetrically Spatial Effects of Urban Scale and Agglomeration on Haze Pollution in China.

Rapid urbanization in China not only promotes the rapid expansion of urban population and economic agglomeration, but also causes the aggravation of haze pollution. In order to better clarify the asymmetric and nonlinear effects of urban scale and agglomeration on haze pollution, this paper quantitatively evaluates the spatial spillover effects of population size and economic agglomeration on haze pollution in 342 Chinese cities from 2001 to 2016 by using exploratory spatial data analysis (ESDA) and spatial econometric model. The results show the following: (1) During the research period, the distribution of urban scale, agglomeration, and haze pollution in China presented complex asymmetrical features, with the former two presenting a "core-periphery" distribution mode, while the latter having a tendency to spread around. In addition, under the influence of urban population size and economic agglomeration, haze pollution in Chinese cities presents significant spatial autocorrelation, with the agglomeration degrees showing a fluctuating upward trend during the study period. (2) Both urban scale and urban agglomeration have positive global spatiotemporal correlation with haze pollution. Local spatial correlation features are more obvious in China's emerging urban agglomerations like Beijing-Tianjin-Hebei and Yangtze River Delta. (3) The spatial effects of haze pollution are better evaluated by spatial Durbin model (SDM) with spatial fixed effects, obtaining a coefficient of 0.416, indicating haze in neighboring cities affected each other and had significant spillover. By decomposing the effect of urban scale and agglomeration on haze as direct and indirect effects, the direct effect of urban population size and the indirect effect of urban economic agglomeration are found to be more prominent, reflecting that significant asymmetrical characteristics exist in the spatial effects of urban size and agglomeration on urban haze. (4) Among the control variables that affect China's rapid urbanization, the level of urban economic development has a positive effect on haze pollution, while the high-level industrial structure and improved technical level can effectively reduce haze pollution. Continuous decline of haze concentration of Chinese cities in recent years has been indicating the spatial relationships between haze and urban size and agglomeration have a decoupling trend. The findings contribute to theory by emphasizing the spillover effect and spatial heterogeneities of geographical factors, and have implications for policy makers to deal with haze pollution reasonably and effectively.

Underdiagnosis of Hereditary Breast and Ovarian Cancer in Medicare Patients: Genetic Testing Criteria Miss the Mark.

BACKGROUND: An estimated 5-10% of breast and ovarian cancers are due to hereditary causes such as hereditary breast and ovarian cancer (HBOC) syndrome. Medicare, the third-party payer that covers 44 million patients in the United States, has implemented a set of clinical criteria to determine coverage for the testing of the BRCA1 and BRCA2 genes. These criteria, developed to identify carriers of BRCA1/2 variants, have not been evaluated in the panel testing era. This study investigated a series of Medicare patients undergoing genetic testing for HBOC to determine the efficacy of genetic testing criteria in identifying patients with hereditary risk. METHODS: This study retrospectively examined de-identified data from a consecutive series of Medicare patients undergoing genetic testing based on personal and family history of breast and gynecologic cancer. Ordering clinicians indicated whether patients did or did not meet established criteria for BRCA1/2 genetic testing. The genetic test results were compared between the group that met the criteria and the group that did not. Patients in families with known pathogenic (P) or likely pathogenic (LP) variants were excluded from the primary analysis. RESULTS: Among 4196 unique Medicare patients, the rate of P/LP variants for the patients who met the criteria for genetic testing was 10.5%, and for those who did not, the rate was 9% (p = 0.26). CONCLUSIONS: The results of this study indicate that a substantial number of Medicare patients with clinically actionable genetic variants are being missed by current testing criteria and suggest the need for significant expansion and simplification of the testing criteria for HBOC.

Effects of 13-Hour Hyperglucagonemia on Energy Expenditure and Hepatic Glucose Production in Humans.

Glucagon (GCG) acutely stimulates energy expenditure (EE) and hepatic glucose production (HGP) in humans, but whether these effects persist during hyperglucagonemia of longer duration is unclear. Using a prospective, randomized, single-blind, crossover study design, we therefore measured EE and rates of glucose appearance (glucose RA) during three separate infusion protocols in healthy lean males: A) 10-h overnight GCG infusion (6 ng/[kg × min]) followed by 3-h infusion of GCG, octreotide (OCT), and insulin (INS) for basal replacement; B) overnight saline (SAL) infusion followed by GCG/OCT/INS infusion; and C) overnight SAL infusion followed by SAL/OCT/INS infusion. Sleep EE, measured at 6 to 7 h of the overnight infusion, was increased 65-70 kcal/24 h in A compared with B and C. During the 3-h infusion, mean resting EE remained significantly increased in A versus C by ∼50 kcal/24 h; in B, resting EE increased with a statistical trend but was not significantly greater than in C. Glucose RA increased to comparable levels in A and B. We conclude that in healthy lean males, stimulation of EE and HGP is sustained during hyperglucagonemia of longer duration when insulin secretion is inhibited. The increase in EE at the present GCG dose was of marginal clinical significance.

Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.

IMPORTANCE: The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown. OBJECTIVE: To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort. DESIGN, SETTING, AND PARTICIPANTS: Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations. INTERVENTIONS: We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals. MAIN OUTCOMES AND MEASURES: We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history. RESULTS: Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients. CONCLUSIONS AND RELEVANCE: In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.

Economical evaluation of sludge reduction and characterization of effluent organic matter in an alternating aeration activated sludge system combining ozone/ultrasound pretreatment.

An ozone/ultrasound lysis-cryptic growth technology combining a continuous flow anaerobic-anoxic-microaerobic-aerobic (AAMA+O3/US) system was investigated. Techno-economic evaluation and sludge lyses return ratio (r) optimization of this AAMA+O3/US system were systematically and comprehensively discussed. Economic assessment demonstrated that this AAMA+O3/US system with r of 30% (AAMA+O3/US2# system) was more economically feasible that can give a 14.04% saving of costs. In addition to economic benefits, a 55.08% reduction in sludge production, and respective 21.17% and 5.45% increases in TN and TP removal efficiencies were observed in this AAMA+O3/US2# system. Considering the process performances and economic benefits, r of 30% in AAMA+O3/US2# system was recommended. Excitation-emission matrix and Fourier transform infrared spectra analyses also proved that less refractory soluble microbial products were generated from AAMA+O3/US2# system. Improvement in 2,3,5-triphenyltetrazolium chloride electron transport system (TTC-ETS) activity in AAMA+O3/US2# further indicated that a lower sludge lyses return ratio stimulated the microbial activity.

Changes in BMI before and during economic development and subsequent risk of cardiovascular disease and total mortality: a 35-year follow-up study in China.

OBJECTIVE: It is unclear whether changes in BMI during rapid economic development influence subsequent mortality. RESEARCH DESIGN AND METHODS: We analyzed whether BMI in 1976 and 1994 and changes in BMI during 1976-1994 predict cardiovascular disease (CVD) and all-cause mortality in a 35-year follow-up cohort of 1,696 Chinese (1,124 men and 572 women, aged 35-65 years) in Xi'an, China. Participants were categorized as underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), and overweight (≥25.0 kg/m(2)). RESULTS: During 51,611 person-years of follow-up, we identified 655 deaths from all causes and 234 from CVD. From 1976 to 1994, the prevalence of overweight rose from 9.2 to 27.8%. With each unit increment in 1976 BMI, multivariate hazard ratios (HRs) (95% CI) were 0.78 (0.72-0.84) for CVD and 0.91 (0.87-0.95) for all-cause mortality. In contrast, corresponding HRs were 1.14 (1.08-1.19) and 1.05 (1.01-1.08) in 1994 BMI. The HRs for each unit increment in BMI change from 1976 to 1994 were 1.35 (1.25-1.41) for CVD and 1.09 (1.05-1.13) for all-cause mortality. Compared with participants with stable normal weight in 1976 and 1994, HRs of all-cause mortality for those who had normal weight in 1976 but became overweight in 1994 and for those who were persistently overweight during 1976-1994 were 1.42 (1.12-1.80) and 1.80 (1.04-3.14), respectively. CONCLUSIONS: Gaining weight with increased BMI at middle age in Chinese during economic development was associated with elevated risks of all-cause and CVD mortality. Higher BMI measured before economic development was associated with lower mortality risk, whereas BMI measured afterward was associated with increased mortality.