Admission plasma potassium and length of hospital stay: a meta-analysis.

OBJECTIVE: Hypokalaemia and hyperkalaemia ('dyskalaemia') are commonly seen in patients requiring emergency hospital admission. The adverse effect of dyskalaemia on mortality is well described but there are few data for the effect on hospital length of stay. We sought to determine the association of serum potassium concentration with in-hospital length of stay. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A structured search of MEDLINE, PubMed and SCOPUS databases to 19 March 2021. ELIGIBILITY CRITERIA: Observational cohort studies defining exposure of interest as serum potassium levels (at admission or within the first 72 hours) and with outcome of interest as length of hospital stay. Studies had to provide estimates of length of stay as a comparison between normokalaemia and defined ranges of hyperkalaemia or hypokalaemia. DATA EXTRACTION AND SYNTHESIS: We identified 39 articles published to March 2021 that met the inclusion and exclusion criteria. Study selection, data extraction and quality assessment were carried out by two reviewers working independently and in duplicate, to assessed eligibility and risk of bias, and extract data from eligible studies. Random effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan. RESULTS: Five studies were included in the meta-analysis. Compared with the reference group (3.5-5.0 mmol/L), the pooled raw differences of medians were 4.45 (95% CI 2.71 to 6.91), 1.99 (95% CI 0.03 to 3.94), 0.98 (95% CI 0.91 to 1.05), 1.51 (95% CI 1.03 to 2.0), 1 (95% CI 0.75 to 1.25) and 2.76 (95% CI 1.24 to 4.29) for patients with potassium levels of <2.5, 2.5 to <3.0, 3.0 to <3.5, <5 to 5.5, <5.5 to 6 and >6.0 mmol/L, respectively. CONCLUSION: Hospital length of stay follows a U-shaped distribution, with duration of admission being twofold greater at the extremes of the potassium range.

Effect of sodium-glucose co-transporter 2 inhibitors on plasma potassium: A meta-analysis.

AIMS: There has been uncertainty whether SGLT2 inhibition predisposes to hyperkalaemia or is protective from it. We therefore performed a meta-analysis to assess effects of SGLT2 inhibition on serum-potassium and hyperkalaemia-events in T2DM. METHODS: MEDLINE and PubMed databases were searched for 'hyperkalaemia' or 'potassium', with SGLT2 inhibitors in T2DM, to 31st December 2020. Randomised controlled trials, with potassium or hyperkalaemia as primary or secondary outcomes, were included. Cochran's Q test and I2 statistic assessed statistical heterogeneity. Meta-analyses were performed using Cochrane-RevMan with two outcomes: i) Odds ratio (OR) of hyperkalaemia-events between SGLT2 inhibitor and placebo (fixed-effects), ii) Mean difference (MD) in change from baseline potassium between SGLT2 inhibitor and placebo (random-effects). RESULTS: Of 1724 identified publications, nine were included in the meta-analysis (n = 3 hyperkalaemia event; n = 5 serum-potassium; n = 1 reported both outcomes). Pooled OR for hyperkalaemia-events for SGLT2 inhibitor vs placebo was 0.72 [95% confidence interval (CI) 0.61 to 0.85, P < 0.001], I2 of 9%. The pooled MD in serum-potassium concentration with SGLT2 inhibitor vs placebo was -0.04 mmol/L [95% CI -0.08 to 0.00 mmol/L; P = 0.04], I2 of 89%. CONCLUSIONS: Use of SGLT2 inhibitors in T2DM reduced odds of inducing hyperkalaemia but had a minimal effect of lowering serum potassium.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

OBJECTIVE: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). RESULTS AND CONCLUSIONS: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Abundant and persistent sulfur-oxidizing microbial populations are responsive to hypoxia in the Chesapeake Bay.

The number, size and severity of aquatic low-oxygen dead zones are increasing worldwide. Microbial processes in low-oxygen environments have important ecosystem-level consequences, such as denitrification, greenhouse gas production and acidification. To identify key microbial processes occurring in low-oxygen bottom waters of the Chesapeake Bay, we sequenced both 16S rRNA genes and shotgun metagenomic libraries to determine the identity, functional potential and spatiotemporal distribution of microbial populations in the water column. Unsupervised clustering algorithms grouped samples into three clusters using water chemistry or microbial communities, with extensive overlap of cluster composition between methods. Clusters were strongly differentiated by temperature, salinity and oxygen. Sulfur-oxidizing microorganisms were found to be enriched in the low-oxygen bottom water and predictive of hypoxic conditions. Metagenome-assembled genomes demonstrate that some of these sulfur-oxidizing populations are capable of partial denitrification and transcriptionally active in a prior study. These results suggest that microorganisms capable of oxidizing reduced sulfur compounds are a previously unidentified microbial indicator of low oxygen in the Chesapeake Bay and reveal ties between the sulfur, nitrogen and oxygen cycles that could be important to capture when predicting the ecosystem response to remediation efforts or climate change.

Laparoscopic Adjustable Gastric Banding-Should a Second Chance Be Given?

BACKGROUND: Obesity is a chronic relapsing-remitting disease and a global pandemic, being associated with multiple comorbidities. Laparoscopic adjustable gastric banding (LAGB) is one of the safest surgical procedures used for the treatment of obesity, and even though its popularity has been decreasing over time, it still remains an option for a certain group of patients, producing considerable weight loss and improvement in obesity-associated comorbidities. METHODS: The aim of this study was to evaluate the impact of weight loss following LAGB on obesity-associated comorbidities, and to identify factors that could predict better response to surgery, and patient sub-groups exhibiting greatest benefit. A total of 99 severely obese patients (81.2% women, mean age 44.19 ± 10.94 years, mean body mass index (BMI) 51.84 ± 8.77 kg/m2) underwent LAGB in a single institution. Results obtained 1, 2, and 5 years postoperatively were compared with the pre-operative values using SPPS software version 20. RESULTS: A significant drop in BMI was recorded throughout the follow-up period, as well as in A1c and triglycerides, with greatest improvement seen 2 years after surgery (51.8 ± 8.7 kg/m2 vs 42.3 ± 9.2 kg/m2, p < 0.05, 55.5 ± 19.1 mmol/mol vs 45.8 ± 13.7 mmol/mol, p < 0.05, and 2.2 ± 1.7 mmol/l vs 1.5 ± 0.6 mmol/l). Better outcomes were seen in younger patients, with lower duration of diabetes before surgery, and lower pre-operative systolic blood pressure. CONCLUSIONS: Younger age, lower degree of obesity, and lower severity of comorbidities at the time of surgery can be important predictors of successful weight loss, making this group of patients the ideal candidates for LAGB.

Complementing chronic frailty assessment at hospital admission with an electronic frailty index (FI-Laboratory) comprising routine blood test results.

BACKGROUND: Acutely ill and frail older adults have complex social and health care needs. It is important to understand how this complexity affects acute outcomes for admission to hospital. We validated a frailty index using routine admission laboratory tests with outcomes after patients were admitted to hospital. METHODS: In a prospective cohort of older adults admitted to a large tertiary hospital in the United Kingdom, we created a frailty index from routine admission laboratory investigations (FI-Laboratory) linked to data comprising hospital outcomes. We evaluated the association between the FI-Laboratory and total days spent in hospital, discharge to a higher level of care, readmission and mortality. RESULTS: Of 2552 admissions among 1750 older adults, we were able to generate FI-Laboratory values for 2254 admissions (88.3% of the cohort). More than half of admitted patients were women (55.3%) and the mean age was 84.6 (SD 14.0) years. We found that the FI-Laboratory correlated weakly with the Clinical Frailty Scale (CFS; r 2 = 0.09). An increase in the CFS and the equivalent of 3 additional abnormal laboratory test results in the FI-Laboratory, respectively, were associated with an increased proportion of inpatient days (rate ratios [RRs] 1.43, 95% confidence interval [CI] 1.35-1.52; and 1.47, 95% CI 1.41-1.54), discharge to a higher level of care (odd ratios [ORs] 1.39, 95% CI 1.27-1.52; and 1.30, 95% CI 1.16-1.47) and increased readmission rate (hazard ratios [HRs] 1.26, 95% CI 1.17-1.37; and 1.18, 95% CI 1.11-1.26). Increases in the CFS and FI-Laboratory were associated with increased mortality HRs of 1.39 (95% CI 1.28-1.51) and 1.45 (95% CI 1.37-1.54), respectively. INTERPRETATION: We determined that FI-Laboratory, distinct from baseline frailty, could be used to predict risk of many adverse outcomes. The score is therefore a useful way to quantify the degree of acute illness in frail older adults.

Reassessing the definition of basal metabolic rate: Circadian considerations in avian studies.

The importance of daily fluctuations in avian basal metabolic rate (BMR) was introduced in the classic paper by Aschoff and Pohl (1970) characterizing circadian differences. Since that time, there has been a shift in the BMR literature to accept only values measured in the ρ- (resting) phase of the day as true BMR. We argue that α- (active) and ρ-phases both represent BMR, analogous to the plasticity of BMR seen in seasonal variations, or associated with changes in body composition and restrictions in diet. Furthermore, we demonstrate that circadian differences in BMR are not even present in most polar birds and are sometimes absent in a variety of non-passerines. We argue for the ecological value of a 24 h BMR in order to compare with daily energy expenditure (field metabolic rate, FMR), which integrates entire days. We make recommendations for the reporting of BMR with sufficient information so readers will know time, season, etc. We also suggest that measures of BMR can be accepted during reproduction in birds, though with some caution.

Contaminants and energy expenditure in an Arctic seabird: Organochlorine pesticides and perfluoroalkyl substances are associated with metabolic rate in a contrasted manner.

Basal metabolic rate (BMR), the minimal energetic cost of living in endotherms, is known to be influenced by thyroid hormones (THs) which are known to stimulate in vitro oxygen consumption of tissues in birds and mammals. Several environmental contaminants may act on energy expenditure through their thyroid hormone-disrupting properties. However, the effect of contaminants on BMR is still poorly documented for wildlife. Here, we investigated the relationships between three groups of contaminants (organochlorines (OCs), perfluoroalkyl substances (PFASs), and mercury) with metabolic rate (MR), considered here as a proxy of BMR and also with circulating total THs (thyroxine (TT4) and triiodothyronine (TT3)) in Arctic breeding adult black-legged kittiwakes (Rissa tridactyla) from Svalbard, during the chick rearing period. Our results indicate a negative relationship between the sum of all detected chlordanes (∑CHLs) and MR in both sexes whereas perfluorotridecanoate (PFTrA) and MR were positively related in females only. MR was not associated with mercury. Additionally, levels of TT3 were negatively related to ∑CHLs but not to PFTrA. The findings from the present study indicate that some OCs (in both sexes) and some PFASs (only in females) could disrupt fine adjustment of BMR during reproduction in adult kittiwakes. Importantly, highly lipophilic OCs and highly proteinophilic PFASs appear, at least in females, to have the ability to disrupt the metabolic rate in an opposite way. Therefore, our study highlights the need for ecotoxicological studies to include a large variety of contaminants which can act in an antagonistic manner.

On the Identification of Associations between Five World Health Organization Water, Sanitation and Hygiene Phenotypes and Six Predictors in Low and Middle-Income Countries.

BACKGROUND: According to the most recent estimates, 842,000 deaths in low- to middle-income countries were attributable to inadequate water, sanitation and hygiene in 2012. Despite billions of dollars and decades of effort, we still lack a sound understanding of which kinds of WASH interventions are most effective in improving public health outcomes, and an important corollary-whether the right things are being measured. The World Health Organization (WHO) has made a concerted effort to compile comprehensive data on drinking water quality and sanitation in the developing world. A recent 2014 report provides information on three phenotypes (responses): Unsafe Water Deaths, Unsafe Sanitation Deaths, Unsafe Hygiene Deaths; two grouped phenotypes: Unsafe Water and Sanitation Deaths and Unsafe Water, Sanitation and Hygiene Deaths; and six explanatory variables (predictors): Improved Sanitation, Unimproved Water Source, Piped Water To Premises, Other Improved Water Source, Filtered and Bottled Water in the Household and Handwashing. METHODS AND FINDINGS: Regression analyses were performed to identify statistically significant associations between these mortality responses and predictors. Good fitted-model performance required: (1) the use of population-normalized death fractions as opposed to number of deaths; (2) transformed response (logit or power); and (3) square-root predictor transformation. Given the complexity and heterogeneity of the relationships and countries being studied, these models exhibited remarkable performance and explained, for example, about 85% of the observed variance in population-normalized Unsafe Sanitation Death fraction, with a high F-statistic and highly statistically significant predictor p-values. Similar performance was found for all other responses, which was an unexpected result (the expected associations between responses and predictors-i.e., water-related with water-related, etc. did not occur). The set of statistically significant predictors remains the same across all responses. That is, Unsafe Water Source (UWS), Improved Sanitation (IS) and Filtered and Bottled Water in the Household (FBH) were the only statistically significant predictors whether the response was Unsafe Sanitation Death Fraction, Unsafe Hygiene Death Fraction or Unsafe Water Death Fraction. Moreover, the fraction of variance explained for all fitted models remained relatively high (adjusted R2 ranges from 0.7605 to 0.8533). We find that two of the statistically significant predictors-Improved Sanitation and Unimproved Water Sources-are particularly influential. We also find that some predictors (Piped Water to Premises, Other Improved Water Sources) have very little explanatory power for predicting mortality and one (Other Improved Water Sources) has a counterintuitive effect on response (Unsafe Sanitary Death Fraction increases with increases in OIWS) and one predictor (Hand Washing) to have essentially no explanatory usefulness. CONCLUSIONS: Our results suggest that a higher priority may need to be given to improved sanitation than has been the case. Nevertheless, while our focus in this paper is mortality, morbidity is a staggering consequence of inadequate water, sanitation and hygiene, and lower impact on mortality may not mean a similarly low impact on morbidity. More specifically, those predictors that we found uninfluential for predicting mortality-related responses may indeed be important when morbidity is the response.

Biological and synthetic mesh use in breast reconstructive surgery: a literature review.

Mesh use in surgical breast reconstruction is becoming increasingly common; however, there is still no consensus on whether synthetic matrices or biological matrices produce the best outcomes. This review analyses these outcomes, namely the differences in aesthetic outcomes, cost, and the rates of the most commonly reported complications.The results indicate that breast reconstruction with a synthetic matrix produces comparable aesthetic outcomes to a biological matrix, with lower costs and complication rates. The individual results for complication rates show that biological matrixes are associated with lower infection rates and slightly lower capsular contracture, but higher haematoma rates, and slightly higher rates of skin necrosis and explantation--although many had post-op radiotherapy.The majority of the studies evaluated used biological matrices, and there are no randomised controlled trials directly comparing the two types of meshes; definite conclusions cannot be drawn from the available evidence. The authors suggest that a randomised controlled trial comparing these outcomes in synthetic and biological matrix use is needed.

Evaluating quality and its determinants in lipid control for secondary prevention of heart disease and stroke in primary care: a study in an inner London Borough.

OBJECTIVES: To assess quality of management and determinants in lipid control for secondary prevention of cardiovascular disease (CVD) using multilevel regression models. DESIGN: Cross-sectional study. SETTING: Inner London borough, with a primary care registered population of 378,000 (2013). PARTICIPANTS: 48/49 participating general practices with 7869 patients on heart disease/stroke registers were included. OUTCOME MEASURES: (1) Recording of current total cholesterol levels and lipid control according to national evidence-based standards. (2) Assessment of quality by age, sex, ethnicity, deprivation, presence of other risks or comorbidity in meeting both lipid measurement and control standards. RESULTS: Some process standards were not met. Patients with a current cholesterol measurement >5 mmol/L were less likely to have a current statin prescription (adjusted OR=3.10; 95% CI 2.70 to 3.56). They were more likely to have clustering of other CVD risk factors. Women were significantly more likely to have raised cholesterol after adjustment for other factors (adjusted OR=1.74; 95% CI 1.53 to 1.98). CONCLUSIONS: In this study, the key factor that explained poor lipid control in people with CVD was having no current prescription record of a statin. Women were more likely to have poorly controlled cholesterol (independent of comorbid risk factors and after adjusting for age, ethnicity, deprivation index and practice-level variation). Women with CVD should be offered statin prescription and may require higher statin dosage for improved control.

A methodology for exploring biomarker--phenotype associations: application to flow cytometry data and systemic sclerosis clinical manifestations.

BACKGROUND: This work seeks to develop a methodology for identifying reliable biomarkers of disease activity, progression and outcome through the identification of significant associations between high-throughput flow cytometry (FC) data and interstitial lung disease (ILD) - a systemic sclerosis (SSc, or scleroderma) clinical phenotype which is the leading cause of morbidity and mortality in SSc. A specific aim of the work involves developing a clinically useful screening tool that could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the likelihood to respond to therapeutic intervention. Ultimately this instrument could facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease and thus help in preventing bad outcomes from disease progression or unnecessary treatment side effects. The methods utilized in the work involve: (1) clinical and peripheral blood flow cytometry data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. (2) machine learning (Conditional Random Forests - CRF) coupled with Gene Set Enrichment Analysis (GSEA) to identify subsets of FC variables that are highly effective in classifying ILD patients; and (3) stochastic simulation to design, train and validate ILD risk screening tools. RESULTS: Our hybrid analysis approach (CRF-GSEA) proved successful in predicting SSc patient ILD status with a high degree of success (>82% correct classification in validation; 79 patients in the training data set, 40 patients in the validation data set). CONCLUSIONS: IRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our new approach combining Conditional Random Forests and Gene Set Enrichment Analysis was successful in identifying a subset of flow cytometry variables to create a screening tool that proved effective in correctly identifying ILD patients in the training and validation data sets. From a somewhat broader perspective, the identification of subsets of flow cytometry variables that exhibit coordinated movement (i.e., multi-variable up or down regulation) may lead to insights into possible effector pathways and thereby improve the state of knowledge of systemic sclerosis pathogenesis.

Exploring the forest instead of the trees: An innovative method for defining obesogenic and obesoprotective environments.

Past research has assessed the association of single community characteristics with obesity, ignoring the spatial co-occurrence of multiple community-level risk factors. We used conditional random forests (CRF), a non-parametric machine learning approach to identify the combination of community features that are most important for the prediction of obesogenic and obesoprotective environments for children. After examining 44 community characteristics, we identified 13 features of the social, food, and physical activity environment that in combination correctly classified 67% of communities as obesoprotective or obesogenic using mean BMI-z as a surrogate. Social environment characteristics emerged as most important classifiers and might provide leverage for intervention. CRF allows consideration of the neighborhood as a system of risk factors.

Endocrine and fitness correlates of long-chain perfluorinated carboxylates exposure in Arctic breeding black-legged kittiwakes.

Increasing levels of poly- and perfluorinated alkyl substances (PFASs) have recently been described in Arctic biota. These emerging substances are of concern given their resistance to degradation and metabolization. Some studies have reported endocrine disrupting effects for some PFASs. However, there is a gap of knowledge on the potential relationships between PFASs and hormones mediating the life-history trade-off between reproduction and survival, such as glucocorticoids. The aims of this study were to (1) describe the concentrations of plasma perfluoroalkyl sulfonates and perfluoroalkyl carboxylates in Svalbard black-legged kittiwakes (Rissa tridactyla) in relation to gender and body-condition, (2) explore the relationships between PFASs and corticosterone (the major glucocorticoid in birds), and (3) assess the consequences of PFAS exposure for reproductive success. Perfluorononanoate was positively related to body-condition in male kittiwakes; perfluorotridecanoate and perfluorotetradecanoate to decreased baseline corticosterone in both sexes; and perfluorododecanoate was related to lower hatching success. These results underline the importance of considering each compound separately when investigating the hazardous effects of PFASs on wildlife.

Flightless rails endemic to islands have lower energy expenditures and clutch sizes than flighted rails on islands and continents.

Data are presented on the standard energetics of six flighted and five flightless species of rails (Aves: Rallidae). The factors influencing these data and those from three additional species available from the literature, one of which was flightless, are examined. Basal rate of metabolism correlates with body mass, residency on islands or continents, volant condition, pectoral muscle mass, and food habits, but not with climate. The greatest capacity (96.2%) to account for the variation in basal rate of metabolism in 15 populations that belong to the 14 species occurs when body mass, volant condition, and food habits are combined. Then flighted species have basal rates that average 1.38 times those of flightless species and herbivorous rails have basal rates that are 1.37 times those of omnivorous species, which means that, independent of body mass, flighted gallinules have basal rates that are 1.9 times those of flightless, omnivorous rails. Distribution, pectoral muscle mass, and flight ability cannot be combined in the same analysis because they code for similar information. The evolution of a flightless condition in rails requires the absence of eutherian predators, but has occurred in the presence of marsupial predators. Each of the six studied flightless rails independently evolved a flightless condition and a low basal rate, whereas the evolution of herbivory and an associated high basal rate evolved at least twice in these species. Flightless rails on islands have clutch sizes that are only about one-half those of flighted rails living on continents, the reduction in clutch size correlating with a reduction in basal rate of metabolism. Thermal conductance in rails is correlated with body mass and food habits: herbivorous rails had conductances that were 1.43 times those of omnivores, i.e., conductances are highest in species with the highest basal rates.

Metrics matter: conflicting air quality rankings from different indices of air pollution.

Comparisons of air quality policies involve numerous considerations such as cost, health, effects on vegetation and materials, and aesthetics. Such assessments require difficult scientific and value judgments. These difficulties can also characterize comparisons that consider only physical and chemical air quality indices. We compare ambient tropospheric ozone concentrations from a baseline scenario and seven emissions scenarios for a case study. The resulting air qualities are evaluated based upon spatial and temporal distribution of impacts, exceedances of regulatory standards, concentrations weighted by population density, and a variety of averaging times. Results reveal that even when only a single pollutant is considered, comparisons of air quality can be ambiguous. Which scenario has better air quality depends on how (e.g., choice of averaging times, absolute vs. relative changes in concentrations), where (e.g., effects in specific areas vs. effects over the entire region), and when (e.g., the percent of time for which one alternative has higher concentrations than another) the comparison is made. This indicates that general descriptors of air quality such as the annual average ozone concentration do not fully describe the complexity of air quality. Use of such averages can result in different policy rankings than consideration of the full distribution of impacts.

Comparison of the 1-hr and 8-hr National Ambient Air Quality Standards for ozone using Models-3.

In 1997, the U.S. Environmental Protection Agency revised the National Ambient Air Quality Standard governing ozone (O3), adding an 8-hr standard of 0.08 ppm and phasing out the 1-hr requirement of 0.12 ppm. The 8-hr standard is intended to provide greater protection for human health. This research examines spatial and temporal patterns of exceedances of the standards using monitoring data and modeled estimates. The Penn State/National Center for Atmospheric Research Mesoscale Model and Models-3 framework were used to estimate hourly O3 concentrations for 4-km resolution in the Maryland/Virginia/Delaware/Washington, DC, and northern Georgia domains. Results reveal that the spatial and temporal nature of compliance is considerably different under the 8-hr standard. In the modeling simulations, the 8-hr standard was exceeded 2-5.2 times more often and in a 1.8-16.2 times larger area than the 1-hr standard. The 8-hr standard was exceeded in areas that generally comply with the 1-hr standard and are not well covered by the monitoring network. These results imply that a larger population resides in areas with unhealthy O3 levels than noncompliance with the original 1-hr standard suggests. For the MD/VA/DE/DC domains, 80 and 98% of the total population live in areas with 8-hr National Ambient Air Quality Standards (NAAQS) exceedances for the 1990 and 1995 episodes, respectively.