Few studies have examined the effects of race and region on dietary intakes and the evidence on racial and regional disparities among women is limited. We aimed to examine whether race and region were associated with nutrient intakes among black and white women living in the Stroke Belt, Stroke Buckle, and Other regions in the United States. We hypothesized that significant differences would be observed among population sub-groups and that the effects of race on dietary intakes would vary across regions.This study included dietary data from 12,105 women from the Reasons for Geographic and Racial Differences in Stroke study (United States). Dietary data were collected using the Block 98 food frequency questionnaire.P <0.05 for all); intakes were significantly lower among blacks living in the Belt and Buckle compared to those in the Other regions. Significant interactions between race and region were detected for trans fat, calcium, and cholesterol , where black women in the Other regions consumed the lowest dietary cholesterol and calcium while black women in the Belt consumed the lowest trans fat.Blacks consumed 1.05% lower energy from saturated fat , and intakes were also lower in the Buckle  and Belt  compared to the Other regions. Within each region, sodium, potassium, and magnesium intakes were all lower among black women compared to white women (Race and region were significantly associated with nutrient intakes in a large study of black and non-Hispanic white women in the United States. Intakes of trans fat, calcium, and cholesterol among black and white women differed across regions. Race and region thus interact to impact dietary intakes, and their effects may be mediated by such factors as the broader food environment and food availability as well as food customs and culture. Race, region, and their correlates should therefore be considered together when examining diet and disease associations and planning dietary advice for population sub-groups. In the United States, a higher prevalence of chronic diseases such as hypertension, stroke, and diabetes has been observed in Southern populations, particularly among blacks ,2. In adSeveral studies have examined dietary intakes across either racial/ethnic or regional groups in the United States. In an early investigation, black women aged 25-75 y consumed less saturated and total fat than whites in the National Health and Nutrition Examination Survey (NHANES) II 1976-1980) [-1980 [6]Our objective was to describe dietary intakes of women currently enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and determine whether there were race and regional differences in macro- and micronutrient intakes among black and white women living in the Stroke Belt  and Stroke Buckle  compared to those living in the Other regions of the United States. An additional goal was to examine whether race and region were independently related to selected nutrient intakes associated with health promotion and disease prevention and whether the two would interact synergistically. We hypothesized that significant differences would be observed among population sub-groups and that the effects of race on dietary intakes would vary across regions.Participants came from REGARDS, a national longitudinal cohort study which enrolled approximately 30,000 black (≈41%) and white (≈59%) individuals aged 45 years and older between 2003 and 2007; this paper examines dietary intakes at baseline. The study oversampled individuals in the Stroke Belt (20%) and Stroke Buckle (30%), and 50% came from the other 48 contiguous United States. Within each region, individuals were recruited via mail and telephone using commercially available lists of residents. After an initial telephone interview to obtain baseline demographic, socioeconomic, and health information, an in-home examination was conducted by trained personnel. At that appointment, the Block 98 food frequency questionnaire (FFQ) was left with participants to be self-administered and returned to the coordinating center. Informed consent was obtained from all participants, and all methods for the parent study were reviewed and approved by the Institutional Review Board for Human Use at the University of Alabama at Birmingham. The IRB at Boston Medical Center/Boston University School of Medicine also approved the protocol for this ancillary study.This study included only women who returned a completed FFQ , which was approximately 81% of the total sample of women in the main study. Of these, we excluded individuals who left more than 15% of food items blank (n = 965) and those with implausible values for energy intake . After all exclusions, data from 12,105 women were available for the analysis.Demographic information and medical history were obtained via computer-assisted telephone interview (CATI). Average annual dietary intakes were collected via self-administered questionnaire, the Block 98 FFQ. Details on how to complete dietary questionnaires were provided to participants, and questionnaires were mailed back to the study center at the University of Alabama at Birmingham.Race and region were our primary exposure variables. Race was determined via self-report on the CATI, where participants self-identified themselves as either black or white; a category for mixed race was not provided. Individuals who self-identified themselves as Hispanic during follow-up interviews were excluded from the study. Regions were defined as the Stroke Buckle , the Stroke Belt , and Other ("Other" = remaining states from the contiguous United States).Sociodemographic covariates were assessed from both the CATI and mail-in FFQ and categorized in this study as follows: age (y), sex , income , education , marital status , smoking status , multivitamin supplement use (% yes), hormone therapy use (% yes), television watching , and physical activity . Physical activity was assessed through questionnaire as the self-reported number of times per week an individual participated in intense activity.2). Presence of medical conditions was determined following standard assays, as described elsewhere [Anthropometric and physical measurements, including height, weight, waist circumference, and blood pressure, were performed by trained technicians at an in-home examination. Height was measured using an 8' metal tape measure and square and weight was measured using a calibrated, digital scale . Waist circumference was assessed using a cloth tape measure at the midpoint between the lowest rib on the right side and the top of the iliac crest by trained technicians. Blood pressure measures were performed in duplicate using an aneroid sphygmomanometer. BMI was calculated from measured weight and height  for processing. Nutrients were calculated using the Block nutrient database, which was developed from the USDA Nutrient Database for Standard Reference  and othea priori, as our study objective was to examine differences across these population sub-groups. We calculated sample means and standard deviations and frequencies for sociodemographic, anthropometric, and nutrient variables. Chi square analyses were used for categorical variables and analysis of variance (ANOVA) for continuous variables to test for differences in racial sub-groups within regions. Nutrient intakes were adjusted for total energy using the nutrient residual approach [t-test. Significant differences across the three regions were tested using the Kruskal-Wallis test.For all descriptive analyses, we stratified our sample by region and by race within region approach ; macronup values <0.05.Descriptive analyses of dietary intakes included energy, macronutrient, and micronutrient intakes. We then performed linear regression analyses to examine whether race and region were associated with selected nutrients that have been associated with health promotion and disease prevention, as follows: fiber (g), saturated fat (percent energy), trans fat (percent energy), sodium (mg), potassium (mg), magnesium (mg), calcium (mg), and dietary cholesterol (mg). Although nutrient intakes were not normally distributed, intakes were not transformed as this violation of normality did not appear to compromise model fit and facilitates comparison with our companion paper in men . For eacp < 0.05 for all analyses and all hypothesis tests were two tailed. Statistical analyses were performed using the Statistical Analysis System (SAS) for Windows, Version 9.2  [Alpha was set at ary, NC) .vs. 64.5 ± 9.2 y; p < 0.001 for both); there was no significant difference in age across racial groups in the Other regions (p = 0.06) . A significantly smaller proportion of black women within each region had an annual income ≥ $75,000/year and a college degree or higher . Within each region, a higher percentage of blacks viewed television >3 h/d compared to white women . With the exception of physical activity (p = 0.22), significant differences between regions were observed across all demographic and lifestyle characteristics.In the Buckle and Belt, black women were younger than white women .Compared to white women, black women within each region weighed significantly more and had a larger waist circumference; differences were not statistically significant between regions for either variable Table . A signip ≤ 0.005 for all) (Table p >0.05). Black women consumed more vitamin C than white women in all regions (p ≤ 0.0002) while white women in the Buckle and Belt consumed less vitamin C compared to those in the Other regions  . Compared with white women, black women consumed more cholesterol in the Belt region  and less cholesterol in the Other regions . Black women in the Buckle region also had higher cholesterol intakes compared to white women .Compared to white women, black women within each region consumed higher amounts of carbohydrate and lower amounts of total fat, fiber, and alcohol (l) Table . Regionas) Table . Black wp < 0.05 for all) thus these analyses were stratified to obtain independent effects of race within region (Table data not shown).In linear regression analyses, significant interactions between race and region were detected for trans fat, calcium, and cholesterol p < 0.0 for all Black Americans and those who reside in the Stroke Belt and Buckle have a greater risk of stroke ,19, and A major goal of this study was to disentangle the effects of race and region among black and white women living in the Stroke Belt, Stroke Buckle, and Other regions in the United States. Our results showed lower intakes of many key nutrients among blacks compared to non-Hispanic whites, as well as lower intakes in the Belt and Buckle. For intakes of trans fat, calcium, and cholesterol, the effect of region on nutrient intake was modified by race, showing significant differences comparing black to white women only in certain regions. Therefore, race and region have both independent and synergistic effects on diet and their effects may be mediated by diverse cultural influences as well as environmental factors influencing food availability, accessibility, and eating behaviors. For example, intakes of cholesterol were lower only among black women in the Other regions, but not in the Buckle and Belt. This implies that perhaps intakes of cholesterol in Southern diets are similar for women due to regional effects on diet, regardless of race, whereas significant racial differences in cholesterol intake between black and white women are seen only in Other regions, where a Southern dietary pattern is likely not as prominent. The United States is diverse and has many cultures with unique eating preferences, thus attention to both region and race and their correlates is needed when trying to understand what people are eating and why. This information is critical in creating effective dietary guidance for population sub-groups.While lower intakes of most nutrients were observed in the Belt and Buckle, blacks consistently consumed lower amounts of nutrients compared to whites, independent of region, as seen in our companion paper among men . Black wWe observed significant differences in fat intakes across race and region, but the body of literature in this area is limited and conflicting. Intake of saturated fat in our study was 1.05% lower among blacks and was also lower in the Buckle and Belt compared to those in the Other regions. Diaz et al.  similarlIt was interesting that the majority of our analyses where interactions were not present  showed stronger effects for race compared to region. While significant regional effects also were observed, estimates between the Buckle and Belt are similar for most analyses but are often half the magnitude of the effect of race. In another study in the REGARDS cohort, Cushman et al.  also shoWe elected to begin our examination of the dietary data in this population with nutrient intakes before expanding to the food, food group, and dietary patterns levels. However, individuals may choose from a variety of different foods and reach the same nutrient intake. For example, Mississippi Delta blacks had very similar intakes of total fat compared to white women, but blacks consumed more fat from fried chicken and sausage and whites consumed more fat from salad dressings and cheese . SimilarStrengths of our study include its sample size, large number of blacks, and regional data that includes the Belt and Buckle. We also adjusted our analyses for many important covariates, which were important in isolating unbiased effects of race and region on dietary intakes although residual confounding by other factors is always a possibility in epidemiologic studies. We performed an additional analysis among women with incomes < $25,000 and results were similar to those in the full sample, thus it is unlikely that the observed differences are a result of residual confounding by socioeconomic status. Whereas several studies have looked at race, region, or sex in separate analyses, we know of no other studies that specifically examined together the effects of race and region on dietary intakes in a large population of women using rigorous, multivariable analyses. Our study also has several limitations. This study is a cross-sectional analysis, although the potential for reverse causality is unlikely for our main exposures and outcomes . It is possible that disease status may have impacted our results, although we adjusted for several baseline diseases to reduce this potential bias. Selection bias may have resulted from using commercially available lists for recruitment, as not all individuals have listed telephone numbers and/or a mailing address. We are limited by the use of the Block 98 FFQ, which is now relatively old; however, this was among the main tools used to collect dietary data on racially diverse populations at the time this study was conceived (c. 2000) and it specifically included foods contributing to diets among blacks living in the United States . While this FFQ has been validated in a different population of women , it has Our study showed that race and region were significantly associated with nutrient intakes in a large study of black and non-Hispanic white women in the United States and that, in some cases, the effect of region was modified by race. Race and region thus interact to impact dietary intakes, and their effects may be mediated by such factors as the broader food environment and food availability as well as food customs and culture. Race, region, and their correlates should therefore be considered together when examining diet and disease associations and planning dietary advice for population sub-groups.CATI: Computer-assisted telephone interview; FFQ: food frequency questionnaire; NHANES: National Health and Nutrition Examination Survey; REGARDS: Reasons for Geographic and Racial Differences in Stroke.The authors declare that they have no competing interests.PKN was responsible for conception and design of this study; PKN, SJ, SEN, and RG all contributed to statistical programming; SJ, SEN, and PKN analyzed data; RG, SEN, and PKN wrote the paper; JMS, SJ, and JA provided feedback on all analyses and made critical comments on the manuscript. All authors participated in the preparation of the final manuscript and critically reviewed and approved the manuscript for publication.


Salmonella surveillance and outbreak tracking. Major drawbacks of commercially available PFGE analysis programs have been their difficulty in dealing with large datasets and the limited availability of analysis tools. There exists a need to develop new analytical tools for PFGE data mining in order to make full use of valuable data in large surveillance databases.Pulsed field gel electrophoresis (PFGE) is currently the most widely and routinely used method by the Centers for Disease Control and Prevention (CDC) and state health labs in the United States for Salmonella serotype prediction, hierarchical cluster analysis, distance matrix analysis and two-way hierarchical cluster analysis. PFGE band standardization makes it possible for cross-group large dataset analysis. The Salmonella serotype prediction approach allows users to predict serotypes of Salmonella isolates based on their PFGE patterns. The hierarchical cluster analysis approach could be used to clarify subtypes and phylogenetic relationships among groups of PFGE patterns. The distance matrix and two-way hierarchical cluster analysis tools allow users to directly visualize the similarities/dissimilarities of any two individual patterns and the inter- and intra-serotype relationships of two or more serotypes, and provide a summary of the overall relationships between user-selected serotypes as well as the distinguishable band markers of these serotypes. The functionalities of these tools were illustrated on PFGE fingerprinting data from PulseNet of CDC.In this study, a software package was developed consisting of five types of bioinformatics approaches exploring and implementing for the analysis and visualization of PFGE fingerprinting. The approaches include PFGE band standardization, Salmonella serotype information before conventional serological methods are pursued. The development of bioinformatics tools to distinguish the PFGE markers and serotype specific patterns will enhance PFGE data retrieval, interpretation and serotype identification and will likely accelerate source tracking to identify the Salmonella isolates implicated in foodborne diseases.The bioinformatics approaches included in the software package developed in this study were integrated with the PFGE database to enhance the data mining of PFGE fingerprints. Fast and accurate prediction makes it possible to elucidate  Salmonella enterica is one of the leading causes of illnesses among the top 31 known foodborne pathogens [Salmonella infections has changed over time, including changes in the frequency of antimicrobial-resistant Salmonella subtypes implicated and the frequency of different serotypes among isolates associated with human infections [Food safety remains an important concern due in part to the globalization of food supply and foodborne illnesses create an important public health burden in the United States. CDC data indicates that nearly 48 million people become ill, 128,000 are hospitalized, and 3,000 die due to foodborne illnesses each year, and non-typhoidal Salmonella subtyping methods have been developed to efficiently detect the cases of human salmonellosis [Salmonella outbreak strain identification and source tracking; however they each have their own strengths and weaknesses in terms of sensitivity, cost, speed, and robustness.Multiple phenotypic and genotypic nellosis . These mnellosis ; genotypnellosis ,5; DNA snellosis ,7, multinellosis ,9 and nenellosis -14. EachLarge amounts of molecular subtyping data have been generated by academia, private companies and government agencies. Along with the development of new technologies, it is anticipated that new analytical methods will be applied more often in combination with the conventional assays to characterize and subtype foodborne isolates, therefore, enhancing the current food safety and regulatory science paradigm . Facing Salmonella surveillance and outbreak investigation [Salmonella from human patients, foods, and food animal sources because of its discriminatory power, low cost and high reproducibility [http://www.cdc.gov/pulsenet), the CDC's molecular surveillance network used for foodborne infections, has the largest and most rich Salmonella subtyping database in the world, storing more than 350,000 PFGE patterns of more than 500 serotypes since 1996 [Salmonella serotypes.PFGE is currently the most widely and routinely used molecular subtyping method by CDC and state health labs in the US for tigation . Althougcibility ,5. Pulsence 1996 . Data miSeveral commercial software applications have been used to analyze PFGE data, such as BioNumerics , GelCompar II  and Fingerprinting II version 3 . BioNumerics is the default software in PulseNet standard protocol ,19 and hSalmonella isolates, BACPAK knowledgebase was created and systematic approaches assembled to build up a functional software package for PFGE data mining. The approaches include PFGE band standardization, Salmonella serotype prediction, hierarchical cluster analysis, distance matrix analysis and two-way hierarchical cluster analysis. The development of this software package and the application of its approaches provide a better understanding of Salmonella genetic diversity and epidemiology, and contribute to PFGE-based characterization and surveillance of Salmonella isolates in outbreak investigations.In this study, in order to systematically investigate and characterize PFGE patterns of bacterial pathogen knowledgebase (BACPAK) is being constructed and housed at the NCTR. As an information system which aims to support the research on foodborne bacterial pathogen detection, characterization and outbreak investigation, BACPAK integrates investigational data from NCTR and other government agencies as well as expert-curated published data on foodborne bacterial pathogens   and Supperprints ,24. The ning set .The distances of any two of the standardized PFGE patterns were measured and hierarchical cluster analysis was pursued by the complete linkage method using "hcluster package" in R . The scrSalmonella patterns within specific serotypes and among the targeted serotypes.In the approach of distance matrix analysis, scripts were written in R to calculate the Jaccard Distance  of PFGE In the two-way hierarchical cluster analysis, scripts were coded using R to calculate the average proportions of the bands present at every designated band location with values ranging from 0 to 1 to build the characteristic parameters of each target serotype. The hierarchical cluster analysis using the complete linkage was applied based on the dissimilarity measures of any two serotypes calculated by the Euclidean distance  of the cSalmonella Annual Report 2006 [Salmonella Annual Summary Tables 2009 from CDC [Salmonella reported over the past 14 years in the US [To begin to address the need to develop improved analytical tools for PFGE analysis, a software package consisting of the integrated data mining techniques and the PFGE database was established and stored within NCTR's BACPAK. BACPAK is capturing and storing data including antimicrobial susceptibility data, plasmid sequence data, PCR data on antimicrobial resistance genes and PFGE data Table . The PFGfrom CDC , isolaten the US .Salmonella serotype prediction in comparison to the conventional BioNumerics fixed band method [Band normalization is the key point to allow the comparison from different dataset. Since BioNumerics was unstable to handle more than 20,000 PFGE patterns, the implemented NCTR fixed band method was especially useful for large dataset analysis. It showed higher accuracies when used to normalize PFGE bands for d method , and madd method .Salmonella serotypes based on their PFGE patterns [The prediction algorithm was developed as described previously to identify patterns ,24. In tpatterns . TherefoFigure Salmonella isolates  and c9 (T3). At this cutting threshold, the predominant pure group of each of the five serotypes was identified  were clustered together with the predominant groups of their corresponding serotypes, respectively. T3 was mis-classified with 27 isolates of same serotype Hadar in Thompson predominant group C6, indicating that this subgroup of Hadar isolates had close relationship with serotype Thompson. The tool of hierarchical cluster analysis allows users to distinguish the underlying phylogenetic structures or to discover new subtypes between various PFGE patterns. With the emergence of NGS and other sequencing technologies, the subtypes distinguished by hierarchical cluster analysis tool will be clarified in detail.Unlike the supervised classification algorithm, hierarchical cluster analysis is unsupervised, where the samples are grouped into subsets based only on the pairwise similarities among their PFGE profiles without using serotype information . As a caes Table  which wees Table . The exces Table . Some sues Table . Serotypfor I 4, ,12:i:- aSalmonella serotypes. Five serotypes were selected to demonstrate the functionality of these tools. A total of 10,193 PFGE patterns belonging to the five serotypes  of band occurrences for each of the selected serotypes Figure . As a caSalmonella and other foodbornbe pathogens. The analysis tools included in the package allow the systematic analysis of PFGE data from various aspects and make it available to meta-analyze PFGE profiles from large data sets. The software package is currently available in the NCTR internal BACPAK knowledgebase. BACPAK, as a general-purposed bioinformatics pipeline for foodborne pathogen analysis, will be a new addition to the FDA bioinformatics tools at http://www.fda.gov/ScienceResearch/BioinformaticsTools/default.htm.The five functional tools were assembled and integrated into a software package to study PFGE profiles for better understanding the genetic diversity of Salmonella strains isolated from outbreaks[Salmonella serotype prediction tool based on PFGE patterns allows rapid and accurate prediction of Salmonella serotypes from outbreaks before the conventional serological methods are pursued. It also shows advantages in distinguishing an isolate that is serotyped as "unknown" by conventional methods, or for a laboratory where standard serotyping is not available. Hierarchical cluster analysis could be used to clarify the subsets of a group of PFGE patterns for source tracking and identification of outbreak isolates. Since Salmonella serotypes can be closely related in terms of their virulence, and antimicrobial resistance profiles [Salmonella isolates and to distinguish band markers and PFGE pattern diversity for serotype identification, especially for large dataset analysis. Theoretically, these approaches could be applied to other gel-based analysis and other pathogens in the future. Combined with the Salmonella genome sequencing data, the distinct serotype specific patterns and bands may provide useful information to aid in the distribution of serotypes in the population and potentially reduce the need for laborious analyses, such as traditional serotyping. In addition, the PFGE analysis tools in the software package are expected to help the in silico pattern construction to match PFGE data with NGS data in future studies.Although NGS and other sequencing technologies are advancing rapidly in foodborne pathogen subtyping, PFGE is still the most widely used method to characterize outbreaks. In the profiles ,30-33, oThe authors declare that they have no competing interests.WL, HC, WZ (Zhao) and WZ performed all calculations and data analysis, and WZ wrote the first draft of manuscript. WZ and JC developed the methods and had the original idea and guided the data analysis and presentation of results. WZ, SF and RN collected and generated data, and HT, JM and HF constructed the database and computerized the scripts into practical tools. All authors contributed in data verification, and approach evaluation and assisted with writing the manuscript. All authors read and approved the final manuscript.


Background: Nearly 3 billion people worldwide rely on solid fuel combustion to meet basic household energy needs. The resulting exposure to air pollution causes an estimated 4.5% of the global burden of disease. Large variability and a lack of resources for research and development have resulted in highly uncertain exposure estimates.Objective: We sought to identify research priorities for exposure assessment that will more accurately and precisely define exposure–response relationships of household air pollution necessary to inform future cleaner-burning cookstove dissemination programs.Data Sources: As part of an international workshop in May 2011, an expert group characterized the state of the science and developed recommendations for exposure assessment of household air pollution.Synthesis: The following priority research areas were identified to explain variability and reduce uncertainty of household air pollution exposure measurements: improved characterization of spatial and temporal variability for studies examining both short- and long-term health effects; development and validation of measurement technology and approaches to conduct complex exposure assessments in resource-limited settings with a large range of pollutant concentrations; and development and validation of biomarkers for estimating dose. Addressing these priority research areas, which will inherently require an increased allocation of resources for cookstove research, will lead to better characterization of exposure–response relationships.Conclusions: Although the type and extent of exposure assessment will necessarily depend on the goal and design of the cookstove study, without improved understanding of exposure–response relationships, the level of air pollution reduction necessary to meet the health targets of cookstove interventions will remain uncertain.http://dx.doi.org/10.1289/ehp.1206429Citation: Clark ML, Peel JL, Balakrishnan K, Breysse PN, Chillrud SN, Naeher LP, Rodes CE, Vette AF, Balbus JM. 2013. Health and household air pollution from solid fuel use: the need for improved exposure assessment. Environ Health Perspect 121:1120–1128;  In thes dioxins . Combust dioxins .Several large-scale initiatives are under way for the dissemination of cleaner-burning stoves ; howeverThe extreme variability within and between personal exposures to cookstove-related air pollution, as well as multiple sources of exposure measurement error, are major sources of uncertainty around the exposure–response curve. For example, In May 2011, an international workshop, “Health Burden of Indoor Air Pollution on Women and Children in Developing Countries,” led by the National Institutes of Health, convened > 150 participants to review the state of the science regarding the health impacts of exposures to air pollution from the household use of solid fuels including indoor, near household, and outdoor environments [household air pollution (HAP)]. Acknowledging the considerable progress achieved to date by previous research, the workshop’s Exposure Assessment and Biomarkers Working Group identified several research priorities as potentially having the biggest impact on the cookstove field, focusing specifically on information needed to better inform stove dissemination programs. The working group discussed questions regarding critical site-specific design choices, such as the duration of the measurement , the number of repeated measures necessary to characterize temporal variability, and the monitor type  and placement necessary to characterize spatial variability; the relevant pollutants of interest; as well as the appropriate methods to estimate pollutant dose. Here, we summarize the existing state of the knowledge, identify gaps, and provide recommendations for exposure assessment research needed to answer the question “How clean is clean enough?”http://www.who.int/indoorair/health_impacts/databases_iap/en/)]. Increasing evidence from household air pollution studies conducted in developing countries points to the complexity and heterogeneity in exposure patterns . In addition to exposure uncertainty, uncertainty in assessing the health outcome of interest may be similar in magnitude and therefore also weakens the ability to model exposure–response relationships. Depending on the source of the error, the magnitude of uncertainty may vary based on the location along the curve . For example, the amount of instrument measurement uncertainty likely increases with increasing exposure concentrations as hypothesized in The rapidly increasing investment in cookstove replacement programs around the world holds promise for addressing a long-standing public health crisis, but it also adds urgency to the need to better characterize the range of health effects related to household air pollution and the risks associated with specific exposure levels. Within this context, it cannot be overstated that more sophisticated approaches to exposure assessment are necessary to address and reduce the complex uncertainty and variability associated with household air pollution exposures, and that increased sophistication will require an increased allocation of study funds for exposure assessment. Reducing the public health impacts from exposure to cookstove emissions hinges on a better understanding of the exposure–response relationship to answer the fundamental question “How clean is clean enough?” Challenges exist in characterizing health outcomes in developing countries, but the historical tendency toward inadequate exposure assessment will not be sufficient to guide the design of improved cookstoves and to understand health benefits and emission reductions of such stove interventions in real-world settings. Of course, extensive exposure assessment for all participants of every health study may not be necessary or even feasible depending on resources and the goal of the study. Instead, at a minimum, coordinated approaches of in-depth exposure characterization nested within larger cookstove studies will leverage research resources. Describing and quantifying the various components of overall exposure error, as well as understanding how patterns of exposure drive the onset and severity of different health outcomes, are key issues for future studies. The answers to the research needs specified above are likely not widely generalizable; the information regarding spatial and temporal variability in exposure will vary by factors such as study location, climate, stove type, fuel characteristics, and home characteristics related to ventilation. Without an improved understanding of this exposure–response relationship, there will continue to be unacceptable uncertainty regarding the level of emissions reduction necessary to meet the health targets of major cookstove replacement interventions. As a result, these interventions may do little to improve health and could represent a squandering of limited resources available for public health programs in developing country settings.


Stormwater and wetlands infractions were documented at all the larger excavation sites and resulted in enforcement actions and fines in many cases; the broader environmental consequences of the loss/alteration of these forested uplands are harder to establish. The excavations are significant in terms of materials cycling: the movement of earth materials, when considered regionally, greatly exceeds natural denudation processes and is also greater than during other periods of high anthropogenic denudation. Our findings suggest that the region’s glacial landscapes are at risk given current development patterns. The accelerating rate of land-surface change is undoubtedly also generalizable to other fast-developing regions of the United States. The landform alterations documented are part of a changing pattern of land use and vegetation cover since the Colonial era and are linked to shortages of land for development, current development and building practices, and lack of explicit rationales for preservation of the region’s geoheritage.Drumlins are glacially derived landforms that are prominent in the landscape over much of southern New England. We carried out a comprehensive ground-based survey in a three-town study area in eastern Massachusetts with the goals of establishing the extent to drumlins have been altered and assessing the associated environmental consequences and probable driving factors. Results show that many drumlins have been significantly altered through levelling and truncation (creation of steep cut and fill slopes), with projects involving movement of 1−1.5×10 The drumlins of southern New England originated during the Wisconsinan  and Illinoian  glacial stages when they formed beneath massive ice sheets during the process of ablation Examples of drumlins being significantly altered in eastern Massachusetts motivated us to investigate this phenomenon and attempt to establish a context in which the significance of landform alterations could be assessed. One analysis we undertook showed that the excavations are extensive enough to be detected using remotely sensed data Drumlin alterations are part of the extensive changes to the land cover and land surface of the earth brought about by human activities. The impacts of these changes on natural processes at a variety of scales are of some concern. Here we pay special attention to drumlin alteration as an example of human-mediated movement of earth materials, which has been estimated at three to four times rates earlier in geologic time The study area, encompassing two towns (Hudson and Stow) and one municipality with a city-type government (Marlborough), lies along a major interstate highway (I-495) that is part of the outer beltway system of the Boston metropolitan area. Our survey of the drumlins in this area relied on information compiled as part of the USGS Glacial Aquifer Systems Stratigraphy Project; USGS maps provide precise delimitations of sands/gravels versus till deposits and show drumlins as ellipsoid areas of thick till. We defined significant alterations as excavations involving cut slopes or fill slopes greater than 3 m in height or loss of >3 m in elevation. We carried out a field-based survey to establish the presence of significant modifications. Alterations  were either measured by means of a hypsometer or determined through consultation of site plans in town records. We also determined the dates and types of building and development projects by accessing information in publically available on-line databases and town records.Although wetlands protection and stormwater controls are mandated by state and federal law, there is no centralized database at the federal or state level with information about infractions or enforcement actions. To obtain this information, we consulted newspaper reports and records in offices of city or town Conservation Commissions, the Massachusetts Department of Environmental Protection, and US Environmental Protection Agency and interviewed town conservation officers and staff at state and federal regulatory agencies. Instances of enforcement actions and fines levied serve as indicators of the seriousness of violations of laws regulating stormwater and protecting wetlands. We also documented occurrence of slope failures where we could get this information; slope failures were sometimes but not always linked to stormwater/wetlands infractions.2 area along Interstate 495  and detailed information allowing estimates of cut slope characteristics could also be obtained from site plans filed with local municipalities. The field survey did not present a threat to endangered or protected species.6 m3. Excavated cut slopes reach vertical heights of 23 m and slopes as high as 36°  of the landforms surveyed meet the criteria of experiencing significant modifications . The modh as 36° , a consiThe main environmental regulations relevant to the excavations are federal and state laws prohibiting stormwater from leaving building sites or being discharged to waterways, waterbodies, or wetlands. Information about environmental problems associated with alterations was not readily available owing to complexities in regulatory oversight, variations in record-keeping from town to town, and lack of reporting requirements and centralized records at the state level. It was possible, however, to document a high frequency of environmental problems in areas of drumlin excavation. Significant alterations were associated with problems and/or regulatory actions that included flooding of adjacent properties, stormwater infractions and violations of the Clean Water Act and Massachusetts Wetlands Protection Act, enforcement actions requiring extensive involvement of Conservation Commissions and officers, and fines at the local, state, and federal levels . In someThe landform alterations documented in the study area are part of the most recent chapter of changing land use in New England and can be put into the historical framework established by studies such as 1650. Prior to European settlement, extensive forests covered a glacially derived landscape with abundant wetlands and surface waters.1850. Clearing of forests for timber, agriculture, and sheep farming starting in the colonial era ∼1880–1920. Massachusetts’ forests have been regrowing since agricultural abandonment in the mid-1800s 1950–1980. Starting around 1950, housing developments were established on some drumlins where slopes permitted . Exacavations for the Massachusetts Turnpike in the 1950s also involved shearing off the top of at least one drumlin (The Mountain in Framingham 1980-present. The first examples of corporate offices and office parks being established on the tops of drumlins date to the High-Tech boom that started in the 1980s - notably Lucent Technologies and Boston Scientific on Addition Hill and 3-Com on Crane Hill (Marlborough) and Bose Corporation on The Mountain (Framingham). The significant alterations documented in this study - high cut and fill slopes and levelling to create flat plots – have been occurring since around 1990.Drumlins are mainly composed of compact tills that have low permeability, stay seasonally wet, and have high runoff rates when vegetation cover is lost. The climate of New England, with its wet springs and high levels of precipitation through the year, adds to the difficulties in controlling runoff, especially at large construction sites. Weather and substrate are factors that combine with slope characteristics  to influence slope stability. The instances of slope problems documented here occurred on slopes ranging from 20° to 36° . The rishttp://preservelandinghill.blogspot. com/2008/09/water-woes-on-drumlins.html and personal communication). Planning oversight should, in this view, take into account the need for lower housing densities in areas of compact till and give preference to preservation as forested open space. The regulatory and permitting environment in Massachusetts, important in understanding both the types of building practices permitted and the spatial pattern of drumlin alterations, is summarized in Supporting Information S1.Development projects in areas of “compact till” such as drumlins have been cited for difficulties in controlling erosion during site development, the tendency for wet-season flooding and dry season drought, pollution problems associated with low percolation rates, and increases in already high runoff rates and surface soil saturation when forest cover is lost , broader ecological consequences of drumlin alteration and loss  may include effects on continuity of forest cover and biological diversity and connectivity, especially where drumlins have persisted as isolated forested islands within developed areas. The gradational pattern produced is one in which materials are moved either highly locally  or over longer, but still rather localized, distances . The environmental consequences of this type of material movement  are largely unknown. Since drumlins have high runoff rates, conversion to hard surfaces is unlikely to have significant effects on groundwater recharge, although runoff patterns within watersheds could be changed. These projects do, however, contribute to the proliferation of storm water discharge structures  that are an increasingly visible part of the landscape.3 kg km−2 yr−1 over much of the Holocene, and similarly low values typify forested areas with little disturbance 3 kg km−2 yr−16 m3 of material), the total amount of material moved over a 5 year period would be ∼7×1010 kg. Averaged over the entire 25-town area, this figure corresponds to a rate of movement of materials of 10×106 kg km−2 yr−1, a value that dwarfs naturally occurring processes . High rates of development-driven movement of materials are undoubtedly also occurring elsewhere in the United States, especially along major roadways, with environmental correlates and consequences that vary by region but in eastern Massachusetts are clearly having an effect on the region’s glacial landscapes.Studies of anthropogenic sediment and movement of materials generally deal with soil loss from cropland or cleared areas and subsequent deposition of materials in lower-lying areas and river systems. The type of earth-movement studied here does not involve a widespread significant sedimentary signature of this sort but is likewise a type of denudational process in which material is removed from uplands and deposited at lower elevation. Brown The following factors may be important in facilitating or driving the increase in landform/land-surface alterations indicated: 1. Increased physical capacity to modify the land surface  2. Shortages of land for development. High population densities and limited developable land given the state’s extensive wetlands may be driving land-modification just as they did in 1800s Boston It also appears possible that drumlins have gone from being areas exempted from development, for reasons including water availability/difficulty of pumping water to higher elevations and physical limitations on building, to being targeted for development as non-wetland areas in an environment where developable land is limited and large commercial developments are highly profitable. The prediction can thus be advanced that significant landform modifications of the type documented here will continue, especially near interstates and interstate exits and along major arterials and in areas where preservation of these features is not given priority.An important issue, and one that cannot be addressed here in any complete fashion, is the valuation of drumlins as landscape elements and whether they should be considered part of the region’s historical, aesthetic, and geological heritage. Our findings that drumlins are being altered in significant numbers raises the very real possibility that the glacial landscapes of New England are at risk. Additionally, these landform alterations are part of a broad pattern of significantly accelerated materials cycling with both short- and long-term environmental consequences that are incompletely known or appreciated. For these reasons, the phenomenon of landform/land-surface alteration requires additional review.Supporting Information S1Regulatory considerations.(DOCX)Click here for additional data file.The first author appreciates assistance from Paul Bierman, Nathaniel Brown, Patrick Colgan, Raymond Coveney, Richard Cadwgan, Leslie Demichelle, Allison Field-Juma, Sigrun Gadwa, Dale Hattis, Gary Hollands, Ali Hosseini, Jeffrey Kopf, Steve Lambert, Syed Hasan, Peter LeTourneau, Larry Lewis, Stephen McCauley, Don Parsley, Priscilla Ryder, James Skehan, and town and city staff in Stow, Marlborough, and Hudson.


Increasing drug resistance among many infections of public health importance has created an urgent need for new and effective antimicrobial agents. However, existing economic incentives for research and development appear to be insufficient to meet the anticipated need for new antimicrobial drugs. U.S. Food and Drug Administration approval of new antibacterial agents has decreased by 56% in the past 20 years (1998–2002 vs. 1983–1987), and only 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotechnology companies are new antibacterial agents -plus pilot projects in low- and middle-income countries, projects that modify typical DOTS strategy in light of issues (such as the use of second-line drugs) specific to areas with a high prevalence of multidrug-resistant tuberculosis.The Medicines for Malaria Venture manages a portfolio of projects that are conducted by academic and pharmaceutical partners. Criteria for products to treat uncomplicated malaria include efficacy against drug-resistant strains, cure within 3 days, low propensity to generate rapid resistance, safety in children <6 years old and pregnant women, appropriate formulations and packaging, and low cost.The Accelerating Access Initiative, a joint project of UNAIDS, other international organizations, and several HIV-drug–producing pharmaceutical companies, has developed what it calls a common approach to accelerating access to HIV/AIDS care and treatment in developing countries. The approach calls for political will and commitment of governments; strengthened national healthcare capacity; safe, secure, and efficient distribution systems; involvement of all sectors of society; substantial additional funding from national and international sources; and continued investment in research and development by the pharmaceutical industry.


Service accreditation is a structured process of recognising and promoting performance and adherence to standards. Typically, accreditation agencies either receive standards from an authorized body or develop new and upgrade existing standards through research and expert views. They then apply standards, criteria and performance indicators, testing their effects, and monitoring compliance with them. The accreditation process has been widely adopted. The international investments in accreditation are considerable. However, reliable evidence of its efficiency or effectiveness in achieving organizational improvements is sparse and the value of accreditation in cost-benefit terms has yet to be demonstrated. Although some evidence suggests that accreditation promotes the improvement and standardization of care, there have been calls to strengthen its research base.Accreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork) project has been established to evaluate the effectiveness of Australian accreditation in achieving its goals. ACCREDIT is a partnership of key researchers, policymakers and agencies.In response, the ACCREDIT  evaluate current accreditation processes; (ii) analyse the costs and benefits of accreditation; (iii) improve future accreditation via evidence; and (iv) develop and apply new standards of consumer involvement in accreditation. These will be addressed through 12 interrelated studies designed to examine specific issues identified as a high priority. Novel techniques, a mix of qualitative and quantitative methods, and randomized designs relevant for health-care research have been developed. These methods allow us to circumvent the fragmented and incommensurate findings that can be generated in small-scale, project-based studies. The overall approach for our research is a multi-level, multi-study design.The ACCREDIT project will examine the utility, reliability, relevance and cost effectiveness of differing forms of accreditation, focused on general practice, aged care and acute care settings in Australia. Empirically, there are potential research gains to be made by understanding accreditation and extending existing knowledge; theoretically, this design will facilitate a systems view of accreditation of benefit to the partnership, international research communities, and future accreditation designers."Accreditation of health-care organisations is a multimillion dollar industry which shapes care in many countries. Recent reviews of research show little evidence that accreditation increases safety or improves quality. It's time we knew about the cost and value of accreditation and about its future direction."  Service accreditation is a system of organizational improvement centred on a certifying agency (or accrediting body) assessing performance against pre-determined standards, usually by multiple means. Internationally, accreditation is designed to improve organizations by developing new standards or upgrading existing standards through research or expert advice, and by defining criteria and performance indicators and applying these standards, criteria and indicators to organizational processes and outcomes. Although models differ in detail,  most accThe reach of accreditation is extensive and the investments in it in many sectors are considerable. Industries such as school education,  universiThe health sector, as an early adopter of accreditation, has promoted its use since 1951 (the Joint Commission in the United States of America), and in Australia since 1973. Stakeholders recognize its potential to improve organizational performance, quality of care, safety standards and consumer satisfaction. However, despite support for accreditation among informed groups, accreditation has had its share of criticism, including the lack of supporting evidence and concerns about the costs of uncertain benefits and whether it offers value for money -16. TherAccreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork) project is a partnership led by researchers in the Centre for Clinical Governance Research and Centre for Health Systems and Safety Research in the Australian Institute of Health Innovation (AIHI) at University of New South Wales with the three major Australian health-sector accreditation agencies , the leading quality improvement policy bodies , key Australian investigators, and international collaborators. These partners are dedicated to studying the impact of accreditation and to executing an extended research program, to provide evidence and empirical models for ways in which accreditation can be improved.The ACCREDIT (P = 0.005) and leadership (P = 0.005), but there was weaker statistical evidence on the relation to clinical indicator performance (P = 0.080)  ... insufficient studies by which to draw conclusions."[ p.181] AWe are funded to execute a multi-method, triangulated research agenda with 12 studies designed by the ACCREDIT stakeholders. The ACCREDIT partners met in August 2007 to draft the conceptual framework and research plan. They subsequently refined the plan and conducted various studies, ,26,31-33The specific aims of the research address four main areas. These link 12 interrelated studies of issues identified as requiring research evidence as a high priority   and to improve future accreditation approaches   and tracking patients on their journeys through the system, whereby services are assessed based on the quality of care delivered longitudinally. These initiatives require novel assessment methods, e.g., studies 9 and 10 , and public and private funders of health-care have raised for many years about the utility, reliability, and cost-effectiveness of accreditation. Our findings are designed to build on what we already know, fill a number of research gaps, and facilitate the improvement of accreditation and the transparency and credibility of the accreditation, surveying and standards-setting processes.Accreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork; ACHS: The Australian Council on Healthcare Standards; ACSAA: Aged Care and Standards Accreditation Agency; ACSQHC: Australian Commission on Safety and Quality in Health Care; AGPAL: Australian General Practice Accreditation Limited; AIHI: Australian Institute of Health Innovation; CEC: Clinical Excellence Commission; ISO: International Organization for Standardization; MARQuIS: Methods of Assessing Response to Quality Improvement StrategiesACCREDIT: The authors declare that they have no competing interests.JB and JW are the Chief Investigators of the ACCREDIT project. JB, JW, BJ, SC, MBr, MBa, CH, DG and MP contributed to developing the overarching research strategy. AC, AG and JC are responsible for specified studies. MW provided statistical advice and expertise. DD supported the development of the research proposal and provided advice on securing ethics approval. DG is senior research fellow working across the projects and MP provides expert advice. RH and MM are respectively responsible for qualitative and quantitative research across the projects. JØ, CP, RS and CS are members of the International Advisory Group, and offered strategic counsel on the program of studies. Team members are responsible, respectively, for leading studies 5, 6 and 7 [JB]; study 12 [JW]; study 1 [BJ]; study 3 [SC]; study 2 [MBr]; study 7 [MBa]; study 9 [CH]; studies 4 and 11 [DG and MP]; study 8 [AC]; and study 10 [AG and JC]. All authors read and approved the final manuscript.