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BACKGROUND Whole school, whole community, whole child (WSCC) approaches to education address contexts beyond school that influence young people's academic and life outcomes. These recommended approaches demand mobilization of an array of actors, but such mobilization is challenging. Little research has explored strategies for convening national experts to support local communities. METHODS This paper presents a case narrative of Every School Healthy (ESH), a grant‐funded effort to support organizations/school districts in 6 communities building WSCC initiatives by engaging national youth development organizations as expert advisors to ESH and communities. A thematic analysis of the narrative yielded 3 key learnings. RESULTS Three themes emerged as key learnings regarding implementation of national‐local initiatives: (1) baseline assessment of local communities should be conducted to identify opportunities for maximizing strengths; (2) national organizations must be flexible with the expertise they bring to the initiative; (3) national organizations should prioritize community‐cultivated solutions and meet communities where they are. CONCLUSIONS The 3 themes presented in this case narrative offer insights for effectively mobilizing national organizations to support healthy, equitable school environments at the local level.

BACKGROUND Urban black adolescents' wellbeing in the early high school years can be negatively impacted by exposure to racial discrimination. These impacts may be buffered by supportive relationships with adults at school. We considered both the protective and promotive effects of culturally responsive teachers and caring school police on school engagement for students exposed to racial discrimination across settings. METHOD This study leveraged baseline student report from a sample of urban, predominantly black high school students with elevated teacher‐rated levels of aggressive behavior (N = 397 9th graders; 91.2% black; 50.4% male; J = 10 schools). Using a path model with full‐information maximum likelihood estimation, we examined the associations of racial discrimination, teacher cultural responsiveness, and school police caring in relation to school engagement and school disconnection, adjusting for covariates, including family racial socialization. RESULTS Frequency of racial discrimination was significantly associated with lower school engagement and greater school disconnection. Teacher cultural responsiveness was significantly, favorably associated with all outcomes. Police caring had no significant direct associations; however, there were moderation effects. When police caring was below average, increased racial discrimination was associated with significantly poorer attitudes toward school. CONCLUSIONS Findings suggested that students' perceptions of school police caring may buffer links between racial discrimination experiences and school disconnection. Moreover, students who perceive that their teachers are culturally responsive may feel more engaged at school. Interventions to promote teachers' and school police officers' cultural responsiveness and caring may improve engagement among at‐risk urban youth who experience racial discrimination.

BACKGROUND Frameworks such as the WSCC model provide evidence‐based guidance for addressing school health at the school, district, and regional level. However, frameworks do not implement themselves; they require the mobilization and collaboration of stakeholders within communities and an understanding of the unique resources and barriers within each context. Furthermore, addressing school health presents a complex systems problem. METHODS Community‐based system dynamics (CBSD) is a participatory approach for engaging communities in understanding and changing complex systems. We used a descriptive multiple case study design to evaluate how and why CBSD was used as a tool for stakeholders to engage with the complexity of school health. RESULTS We analyzed 3 cases to understand how these methods were used to enhance collaboration, analysis, and community action at multiple levels, including in 2 school districts, with a city‐wide stakeholder committee, and with a group of high school students. CONCLUSIONS Community‐based system dynamics presents a promising approach for building shared language and ownership among stakeholders, tailoring to local community contexts, and mobilizing stakeholders for action based on new system insights. We close with a discussion of unique opportunities and challenges of expanding the use of CBSD in the field of school health.

BACKGROUND As attention to the potential negative outcomes of childhood trauma has grown, so have calls for schools to take an active role in supporting students experiencing trauma. These calls extend beyond efforts initiated by individual schools to include those mandated by state law, which largely focus on teacher training and on screening for adversity. METHODS This article explores the evidence base and limitations for current approaches in state law and explores how policies to address other student health, safety, and wellness issues can help either ameliorate or exacerbate students' experiences with trauma. RESULTS Few trainings for nonclinical staff have rigorous evidence of effectiveness, and based on evidence of teacher trainings on other topics, cannot work in environments that do not actively reinforce and encourage the application of that knowledge. Trainings also largely do not acknowledge the structures and systems, including systemic racism within schools, that may contribute to disparate rates of adversity for black and American Indian and Alaskan Native children. Screening carries several risks, including confounding adversity with experiencing trauma, missing broader contextual adversity, and potentially retraumatizing children. CONCLUSIONS State policymakers need to take a more holistic approach in creating policies to support students experiencing trauma.

BACKGROUND Individuals learn and develop across their lifespan in response to the people with whom they interact in settings, communities, cultures, and experiences. Collaborative research and policy efforts underscore the critical and reparative role of identity‐safe, culturally driven, and relationship‐rich environments—in classrooms, schools, and communities—for the healthy social, emotional, cognitive, and physical development of all learners. These themes align closely with the Whole School, Whole Community, Whole Child (WSCC) model. METHODS Collaborative research and policy efforts, combined with the WSCC model make a strong case to elevate the unusual suspects, the settings and people outside of instructional classrooms who are key actors in creating the conditions and relationships that promote student health and well‐being. RESULTS We describe promising cases of efforts aimed at bolstering adult capacity to foster student health and well‐being. We also discuss how these types of systemic efforts can move beyond system and program level actors to acknowledge the power of individual‐level implementation. CONCLUSIONS It is time to recognize the systemic efforts, programmatic opportunities, and individual roles adults have in implementing an ideal WSCC model that is aligned with the collaborative research and policy efforts.

BACKGROUND The Whole School, Whole Community, Whole Child (WSCC) framework supports the “whole child” across 10 domains. This study assessed state law and district policy WSCC coverage. METHODS Primary legal research was used to compile relevant district policies and state laws for a stratified random sample of 368 public school districts across 20 states for school year 2017‐18. Policies/laws were evaluated on 79 items across the WSCC domains (range: 3‐14 items/domain). Multivariable regressions examined the relationship between state laws and district policies, controlling for district characteristics, and weighted to account for the sample design and non‐response. RESULTS On average, district policies and state laws addressed 53% and 60% of the 79 items, respectively. State law predicted district policy WSCC attention across items (coeff. = 0.26, 95% CI = 0.14, 0.38) and 4 domains: physical activity (coeff. = 0.57, 95% CI = 0.29, 0.86); health services (coeff. = 0.50, 95% CI = 0.39, 0.62); social and emotional climate (coeff. = 0.34, 95% CI = 0.23, 0.45); and family engagement (coeff. = 0.41, 95% CI = 0.28, 0.54). State law was associated with lower district‐level coverage in 3 domains (health education; counseling, psychological, and social services; and community involvement). CONCLUSIONS Although WSCC implementation is locally‐driven, states have an active role to play in setting a policy “floor” for guiding district WSCC attention.

BACKGROUND The Whole School, Whole Community, Whole Child (WSCC) model is an evidence‐based comprehensive framework to address health in schools. WSCC model use improves health and educational outcomes, but implementation remains a challenge. METHODS Working with 6 schools in 2 districts in the Midwest, we used a mixed‐methods approach to determine the people, systems, and messages needed to activate WSCC implementation. We report on social network analysis and message testing findings and research translation to develop the Healthy Schools Toolkit. RESULTS Social networks for both districts included more than 150 individuals. Both demonstrated network densities less than half of the desirable threshold, with evidence of clustering by role and minimal cross‐school relationships, posing challenges for WSCC implementation. Across stakeholder groups, messages that emphasize empathy, teamwork, and action were well‐received, especially when shared by trusted individuals through communication channels that align with stakeholder needs. CONCLUSIONS The Healthy Schools Toolkit provides an example of a translational product that helps to bridge research with practice. With features that highlight 6 design principles, the toolkit provides complementary activities that schools and districts can use as they plan for integration of the WSCC model.

BACKGROUND Involving communities in school health has been purported as a practice integral to supporting a Whole School, Whole Community, Whole Child (WSCC) approach. Although community collaboration is often included in school‐based health initiatives, there is little research considering methods for increasing community engagement. The purpose of this study was to identify effective school‐based health interventions documenting changes in community engagement. METHODS Academic experts and school stakeholders guided procedures for a systematic review of studies published from 1987–2017 and gray literature (ie, best practice documents; policy documents, etc.) on comprehensive school health interventions including community engagement as a targeted outcome. RESULTS The search identified 9 studies addressing community as an outcome of school‐based health interventions; types of partnership mechanisms and partners' roles were classified. CONCLUSIONS Although involving communities is a WSCC component and commonly recommended as a strategy fundamental to school health, there is little empirical research examining effective strategies for engaging communities and engagement is often not measured as part of intervention studies. Further measurement and research in engaging communities in school health is warranted.

BACKGROUND In this case study, multiple participants in a large urban school district used the Whole School, Whole Community, Whole Child (WSCC) model to guide development of a district wellness policy. The model's health education component is highlighted, focusing on concerns for special needs students and ones speaking English as a New Language (ENL). METHODS Organizational structure was developed around the WSCC model and district wellness policy implementation through coordination, collaboration, and communication (3Cs) of programs, policies, and processes/practices (3Ps). RESULTS The WSCC approach guided the creation of a district wellness policy that influenced programming for students with special needs and required Youth Risk Behavior Survey (YRBS) data collection. Using YRBS and School Health Index (SHI) data in planning sexual health education illustrated improvements over time. Formation of the School Health and Wellness Collaborative under WSCC improved family engagement in sexual health education programs and practices. Relationships were established with community partners to impact student's sexual risk behaviors. Finally, the district co‐created and implemented an evidenced‐based sexual health curriculum, modifying it for special education and ENL students. CONCLUSIONS The WSCC approach is system changing. It takes time to develop the relationships vital to improve the 3Cs and 3Ps. Success is enhanced with a district wellness coordinator, the right people at the table, valid health data, and administrative and board support.

BACKGROUND Sexual and gender minority youth (SGMY) are at high risk for adverse health outcomes. Safer schools decrease this risk. The US Centers for Disease Control and Prevention has identified 6 practices that can make schools safer for SGMY, yet few US schools implement them all. We apply a structural competency framework to elucidate factors contributing to this implementation gap. METHODS We conducted 75 interviews and 32 focus groups with school professionals in 18 New Mexico high schools to assess factors impacting implementation of the practices over 2 years. We analyzed data using iterative coding, thematic identification techniques, and the sensitizing concept of structural competency. RESULTS Themes included: rendering an invisible population visible; critical thinking about LGBTQ inequalities; building school personnel capacity; intersecting cultural, religious, and political conflicts; and tackling community‐based sources of stigma and discrimination. Conclusions Underlying cultural and structural forces render SGMY invisible and constrain what schools can accomplish. Professional development encouraging critical thinking about structural inequities is foundational, but efforts to close the implementation gap must attend to structural forces producing disparities for SGMY. Structural competency can strengthen the ability of the Whole School, Whole Community, and Whole Child model's cross‐sector coordination of policy and process to meet the needs of every student.

BACKGROUND Student‐teacher relationships are associated with the social and emotional climate of a school, a key domain of the Whole School, Whole Community, Whole Child Model. Few interventions target student‐teacher relationships during the critical transition to high school, or incorporate strategies for enhancing equitable relationships. We conducted a mixed‐methods feasibility study of a student‐teacher relationship intervention, called Equity‐Explicit Establish‐Maintain‐Restore (E‐EMR). METHODS We tested whether students (N = 133) whose teachers received E‐EMR training demonstrated improved relationship quality, school belonging, motivation, behavior, and academic outcomes from pre‐ to post‐test, and whether these differences were moderated by race. We also examined how teachers (N = 16) integrated a focus on equity into their implementation of the intervention. RESULTS Relative to white students, students of the color showed greater improvement on belongingness, behavior, motivation, and GPA. Teachers described how they incorporated a focus on race/ethnicity, culture, and bias into E‐EMR practices, and situated their relationships with students within the contexts of their own identity, the classroom/school context, and broader systems of power and privilege. CONCLUSIONS We provide preliminary evidence for E‐EMR to change teacher practice and reduce educational disparities for students of color. We discuss implications for other school‐based interventions to integrate an equity‐explicit focus into program content and evaluation.

BACKGROUND School health services improve health and academic outcomes; however, sustainable funding for these services is an ongoing struggle. In December 2014, the Centers for Medicare & Medicaid Services clarified how Medicaid will reimburse school health services. School districts, once restricted to reimbursement for services delivered under specific conditions, can now receive Medicaid reimbursement for eligible services delivered to all Medicaid‐enrolled students. METHODS This article examines the literature exploring school health services' impact on health and academic outcomes and Medicaid's role in funding school health services. The article analyzes state, school‐based Medicaid policies and programs and the impact of the federal policy change. RESULTS As of August 2020, 13 states have used the federal policy change to expand their school‐based Medicaid programs to include all eligible services delivered to all Medicaid‐enrolled students. CONCLUSIONS This policy change creates an opportunity for states and school districts to leverage health care funding to implement multiple components of the Whole School, Whole Community, Whole Child model, including health services, counseling, psychological and social services, employee wellness, and school climate. The federal policy change can also improve health equity by increasing reimbursement for school districts serving higher percentages of Medicaid‐enrolled students.

BACKGROUND The benefits of youth engagement are well documented. In this paper, we examine youth engagement in America's Promise Alliance's Every School Healthy initiative, a part of the Robert Wood Johnson Foundation's Together for Healthy and Successful Schools Initiative (THSS). METHODS Six community acceleration sites were selected through a competitive grant‐making process. Sites were required to describe youth engagement strategies. A case study design was employed to examine how sites conceptualize youth engagement as well as youth engagement strategies employed across 6 sites. Data sources included observations, team member debriefs, and document review. RESULTS There was variation in how youth engagement and youth voice are conceptualized in educational settings, and readiness for youth engagement. Sites actively solicited and implemented youth engagement resources and strategies. CONCLUSIONS By failing to engage young people, well‐intentioned adults miss important opportunities. Youth engagement presents an exciting opportunity for school leaders, policymakers, and program planners to gain a deeper understanding of the factors that influence individual and community health and wellbeing and, in turn, helps them to develop responsive policies and programs.

Disruption of tissue barriers formed by cells is an integral part of the pathophysiology of many diseases. Therefore, a thorough understanding of tissue barrier function is essential when studying the causes and mechanisms of disease as well as when developing novel treatments. In vitro methods play an integral role in understanding tissue barrier function, and several techniques have been developed in order to evaluate barrier integrity of cultured cell layers, from microscopy imaging of cell-cell adhesion proteins to measuring ionic currents, to flux of water or transport of molecules across cellular barriers. Unfortunately, many of the current in vitro methods suffer from not fully recapitulating the microenvironment of tissues and organs. Recently, organ-on-chip devices have emerged to overcome this challenge. Organs-on-chips are microfluidic cell culture devices with continuously perfused microchannels inhabited by living cells. Freedom of changing the design of device architecture offers the opportunity of recapitulating the in vivo physiological environment while measuring barrier function. Assessment of barriers in organs-on-chips can be challenging as they may require dedicated setups and have smaller volumes that are more sensitive to environmental conditions. But they do provide the option of continuous, non-invasive sensing of barrier quality, which enables better investigation of important aspects of pathophysiology, biological processes, and development of therapies that target barrier tissues. Here, we discuss several techniques to assess barrier function of tissues in organs-on-chips, highlighting advantages and technical challenges.

There is growing recognition that cell deformability can play an important role in cancer metastasis and diagnostics. Advancement of methods to characterize cell deformability in a high throughput manner and the capacity to process numerous samples can impact cancer-related applications ranging from analysis of patient samples to discovery of anti-cancer compounds to screening of oncogenes. In this study, we report a microfluidic technique called multi-sample deformability cytometry (MS-DC) that allows simultaneous measurement of flow-induced deformation of cells in multiple samples at single-cell resolution using a combination of on-chip reservoirs, distributed pressure control, and data analysis system. Cells are introduced at rates of O(100) cells per second with a data processing speed of 10 min per sample. To validate MS-DC, we tested more than 50 cell-samples that include cancer cell lines with different metastatic potential and cells treated with several cytoskeletal-intervention drugs. Results from MS-DC show that (i) the cell deformability correlates with metastatic potential for both breast and prostate cancer cells but not with their molecular histotype, (ii) the strongly metastatic breast cancer cells have higher deformability than the weakly metastatic ones; however, the strongly metastatic prostate cancer cells have lower deformability than the weakly metastatic counterparts, and (iii) drug-induced disruption of the actin network, microtubule network, and actomyosin contractility increased cancer cell deformability, but stabilization of the cytoskeletal proteins does not alter deformability significantly. Our study demonstrates the capacity of MS-DC to mechanically phenotype tumor cells simultaneously in many samples for cancer research.

In the last decade, the advent of microfabrication and microfluidics and an increased interest in cellular mechanobiology have triggered the development of novel microfluidic-based platforms. They aim to incorporate the mechanical strain environment that acts upon tissues and in-vivo barriers of the human body. This article reviews those platforms, highlighting the different strains applied, and the actuation mechanisms and provides representative applications. A focus is placed on the skin and the lung barriers as examples, with a section that discusses the signaling pathways involved in the epithelium and the connective tissues.

PATH rapidly computes a path and a transition state between crystal structures by minimizing the Onsager-Machlup action. It requires input parameters whose range of values can generate different transition-state structures that cannot be uniquely compared with those generated by other methods. We outline modifications to estimate these input parameters to circumvent these difficulties and validate the PATH transition states by showing consistency between transition-states derived by different algorithms for unrelated protein systems. Although functional protein conformational change trajectories are to a degree stochastic, they nonetheless pass through a well-defined transition state whose detailed structural properties can rapidly be identified using PATH.

Metastatic cancer cells migrate through constricted spaces and experience significant compressive stress, but mechanisms enabling migration in confined geometries remain unclear. Cancer cell migration within confined 3-dimensional (3D) microfluidic channels has been shown to be distinct from 2D cell migration. However, whether 3D confined migration can be manipulated by mechanosensory components has not been examined in detail. In this work, we exogenously introduced a mechanosensitive channel of large conductance (MscL) into metastatic breast cancer cells MDA-MB-231. We discovered that inducing expression of a gain-of-function G22S mutant of MscL in MDA-MB-231 cells significantly reduced spontaneous lung metastasis without affecting the growth of orthotopic tumor implants. To further investigate the effects of G22S MscL on cell migration, we designed a microfluidic device with channels of various cross-sections ranging from a 2D planar environment to narrow 3D constrictions. Both MscL G22S and control breast cancer cells migrated progressively slower in more constricted environments. Migration of cells expressing MscL G22S did not differ from control cells, even though MscL was activated in cells in constricted channels of 3 μm width. Interestingly, we found MscL expressing cells to be more frequently “stuck” at the entrance of the 3 μm channels and failed to migrate into the microchannel. Our work demonstrates the possibility of engineering mechanotransduction for controlling confined cell migration.

The entire luminal surface of the lungs is populated with a complex yet confluent, uninterrupted airway epithelium in conjunction with an extracellular liquid lining layer that creates the air-liquid interface (ALI), a critical feature of healthy lungs. Motivated by lung disease modelling, cytotoxicity studies, and drug delivery assessments amongst other, in vitro setups have been traditionally conducted using macroscopic cultures of isolated airway cells under submerged conditions or instead using transwell inserts with permeable membranes to model the ALI architecture. Yet, such strategies continue to fall short of delivering a sufficiently realistic physiological in vitro airway environment that cohesively integrates at true-scale three essential pillars: morphological constraints (i.e., airway anatomy), physiological conditions (e.g., respiratory airflows), and biological functionality (e.g., cellular makeup). With the advent of microfluidic lung-on-chips, there have been tremendous efforts towards designing biomimetic airway models of the epithelial barrier, including the ALI, and leveraging such in vitro scaffolds as a gateway for pulmonary disease modelling and drug screening assays. Here, we review in vitro platforms mimicking the pulmonary environment and identify ongoing challenges in reconstituting accurate biological airway barriers that still widely prevent microfluidic systems from delivering mainstream assays for the end-user, as compared to macroscale in vitro cell cultures. We further discuss existing hurdles in scaling up current lung-on-chip designs, from single airway models to more physiologically realistic airway environments that are anticipated to deliver increasingly meaningful whole-organ functions, with an outlook on translational and precision medicine.

This paper describes a micro fluorescence in situ hybridization ({\mu}FISH)-based rapid detection of cytogenetic biomarkers on formalin-fixed paraffin embedded (FFPE) tissue sections. We demonstrated this method in the context of detecting human epidermal growth factor 2 (HER2) in breast tissue sections. This method uses a non-contact microfluidic scanning probe (MFP), which localizes FISH probes at the micrometer length-scale to selected cells of the tissue section. The scanning ability of the MFP allows for a versatile implementation of FISH on tissue sections. We demonstrated the use of oligonucleotide FISH probes in ethylene carbonate-based buffer enabling rapid hybridization within < 1 min for chromosome enumeration and 10-15 min for assessment of the HER2 status in FFPE sections. We further demonstrated recycling of FISH probes for multiple sequential tests using a defined volume of probes by forming hierarchical hydrodynamic flow confinements. This microscale method is compatible with the standard FISH protocols and with the Instant Quality (IQ) FISH assay, reduces the FISH probe consumption ~100-fold and the hybridization time 4-fold, resulting in an assay turnaround time of < 3 h. We believe rapid {\mu}FISH has the potential of being used in pathology workflows as a standalone method or in combination with other molecular methods for diagnostic and prognostic analysis of FFPE sections., Comment: Biomicrofluidics, 2018

We report on reversible electroporation of cells in a flow-through microfluidic device, whereby the required electric field is delivered through a set of integrated microcapillaries between a centre stream of cells and side streams of liquid electrolytes. The electrolytes are applied with a sine wave voltage and cells flow by the microcapillary openings encounter a burst of ac field with a duration and strength determined by their average speed and spatial proximity to the microcapillary openings, respectively. Effectiveness of the approach is presented through numerical simulations and empirical results on electroporation efficiency and cell viability against various flow rates (exposure time to the field) as well as frequencies and root-mean-square (rms) intensities of the field. High frequencies (80–400 kHz) and high intensities (e.g., 1.6 kV/cm, rms) are identified with increased electroporation efficiency 61% and viability 86% on average. These results suggest that the device demonstrated here with a simple design and robust operation offers a viable platform for flow-through electroporation.

This report investigated the distribution of serum zinc and the factors determining serum zinc concentration in a large random population sample. The 1977 participants (959 men and 1018 women), 20-80 years old, constituted a stratified random sample of the population of four Belgian districts, representing two areas with low and two with high environmental exposure to cadmium. For each exposure level, a rural and an urban area were selected. The serum concentration of zinc, frequently used as an index for zinc status in human subjects, was higher in men (13.1 mumole/L, range 6.5-23.0 mumole/L) than in women (12.6 mumole/L, range 6.3-23.2 mumole/L). In men, 20% of the variance of serum zinc was explained by age (linear and squared term, R = 0.29), diurnal variation (r = 0.29), and total cholesterol (r = 0.16). After adjustment for these covariates, a negative relationship was observed between serum zinc and both blood (r = -0.10) and urinary cadmium (r = -0.14). In women, 11% of the variance could be explained by age (linear and squared term, R = 0.15), diurnal variation in serum zinc (r = 0.27), creatinine clearance (r = -0.11), log gamma-glutamyltranspeptidase (r = 0.08), cholesterol (r = 0.07), contraceptive pill intake (r = -0.07), and log serum ferritin (r = 0.06). Before and after adjustment for significant covariates, serum zinc was, on average, lowest in the two districts where the body burden of cadmium, as assessed by urinary cadmium excretion, was highest. These results were not altered when subjects exposed to heavy metals at work were excluded from analysis.

Cage allocation designs for rodent carcinogenicity experiments are discussed and presented with the goal of avoiding dosage group biases related to cage location. Considerations in selecting a cage design are first discussed in general terms. Specific designs are presented for use in experiments involving three, four, and five dose groups and with one, four, and five rodents per cage. Priorities for balancing treatment groups include horizontal position on shelf and shelf of rack, nearest neighbor balance, and male-female balance. It is proposed that these balance criteria be considered together with practical issues, such as the ability to accurately conform to a design and to determine a sensible and efficient design for each experiment.

The phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used to control the growth of weeds and broadleaf plants. We convened a panel of 13 scientists to weigh the evidence on the human carcinogenicity of 2,4-D. The panel based its findings on a review of the toxicological and epidemiological literature on 2,4-D and related phenoxy herbicides. The toxicological data do not provide a strong basis for predicting that 2,4-D is a human carcinogen. Although a cause-effect relationship is far from being established, the epidemiological evidence for an association between exposure to 2,4-D and non-Hodgkin's lymphoma is suggestive and requires further investigation. There is little evidence of an association between use of 2,4-D and soft-tissue sarcoma or Hodgkin's disease, and no evidence of an association between 2,4-D use and any other form of cancer. Scientists on the panel were asked to categorize 2,4-D as a "known," "probable," "possible," or "unlikely" carcinogen or as a noncarcinogen in humans. The predominant opinion among the panel members was that the weight of the evidence indicates that it is possible that exposure to 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.

Cadmium is a cumulative environmental pollutant. For the general population mainly exposed by the oral route and through tobacco smoke inhalation, the kidney is the critical organ. Belgium is the principal producer of cadmium in Europe, and certain areas of the country are polluted by cadmium mainly because of past emissions from nonferrous industries. Preliminary studies carried out in one polluted area have suggested that environmental pollution might lead to an increased uptake of cadmium by the human body and possibly to health effects. Thus, a large-scale morbidity study has been initiated to assess the validity of this hypothesis. The present paper describes the protocol of this study. Its main objectives are to determine to what extent environmental exposure to cadmium resulting from industrial emissions may lead to accumulation of the metal in the human organism; to establish whether or not environmental exposure may induce renal changes and/or influence blood pressure; and to assess the acceptable internal dose of cadmium for the general population. The study design takes advantage of the fact that biological indicators of exposure, body burden, and early nephrotoxic effects of cadmium are available, which increase the likelihood of detecting a cause-effect relationship.

Semen was collected from 50 men occupationally exposed to carbaryl (1-naphthyl methyl carbamate) in a produciton plant for durations of 1 to 18 years and compared to semen from a control group of 34 unexposed, newly-hired workers. Employment, fertility, health, personal data, and blood samples were collected for each individual. Semen samples were analyzed for changes in sperm count, morphology, and frequency of sperm carrying double flourescent bodies (YFF). As a group, the exposed workers showed a significantly higher proportion of sperm with abnormal head shapes than did the control group (p < 0.005). Age, smoking habits, and medical problems did not appear to affect this result. This finding appears to be limited to men working in the carbaryl production area at the time of sampling. Sperm count and YFF did not show similar differences, which may be because they are known to be statistically less sensitive to small changes. Formerly exposed workers (away from carbaryl for an average of 6.3 years) showed a marginally significant elevation in sperm abnormalities compared to controls (p < .05, one-tailed statistical analyses) suggesting that the increase in abnormal morphology may not be reversible. However, the question of reversibility is sensitive to confounding factors and small sample sizes and, therefore, requires further study. With these data a definitive link between carbaryl exposure and human seminal defects cannot be established. Although a distinct effect on sperm morphology was seen in the exposed group, the increases in sperm shape abnormalities were not related to exposure dose (estimated by number of years on the job or job classification during the year prior to semen collection). Inexplicably, the increases in sperm abnormalities were seen primarily in currently exposed men who had worked with carbaryl for less than approximately 6 years. These findings suggest the need for further study since other workplace-related factor(s) may be responsible for the elevated sperm abnormalities seen in this study. ImagesFIGURE 1.

Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the “2,3,7,8-TCDD equivalent” concentration of a mixture in order to “predict” its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.

Factors contributing to urban differences in cancer mortality rates are difficult to specify because of migration and the delay between exposure to carcinogens and manifestations of the disease. Proxy measures for prior migration, motor vehicle emissions, industrial pollution, factors in the water supplies, and climate, explain more than half the intercity variation in age-adjusted cancer mortality rates among 98 cities in the U.S. in 1970. The potential importance of these environmental factors as the "urban factor" in cancer is discussed.

The disinfection of drinking water by chlorination has in recent years come under closer scrutiny because of the potential hazards associated with the production of stable chlorinated organic chemicals. Organic chemical contaminants are common to all water supplies and it is now well-established that chlorinated by-products are obtained under conditions of disinfection, or during tertiary treatment of sewage whose products can ultimately find their way into drinking water supplies. Naturally occurring humic substances which are invariably present in drinking waters are probably the source of chloroform and other halogenated methanes, and chloroform has shown up in every water supply investigated thus far. The Environmental Protection Agency is charged with the responsibility of assessing the public health effects resulting from the consumption of contaminated drinking water. It has specifically undertaken the task of determining whether organic contaminants or their chlorinated derivatives have a special impact, and if so, what alternatives there are to protect the consumer against bacterial and viral diseases that are transmitted through infected drinking waters. The impetus to look at these chemicals is not entirely without some prima facie evidence of potential trouble. Epidemiological studies suggested a higher incidence of cancer along the lower Mississippi River where the contamination from organic chemicals is particularly high. The conclusions from these studies have, to be sure, not gone unchallenged. The task of assessing the effects of chemicals in the drinking water is a difficult one. It includes many variables, including differences in water supplies and the temporal relationship between contamination and consumption of the finished product. It must also take into account the relative importance of the effects from these chemicals in comparison to those from occupational exposure, ingestion of contaminated foods, inhalation of polluted air, and many others. The susceptibility of different age, genetic, and ethnic groups within the population must also be carefully considered. The present review discusses: the reasons for disinfection; the general occurrence of chlorinated organics in drinking water; the chemistry in the synthesis of chlorinated organics under aqueous conditions; and alternatives to chlorine for disinfection.

The National Energy Plan announced by President Carter on April 29, 1977 proposed a significant increase in the utilization of the vast domestic deposits of coal to replace the dwindling supplies of oil and natural gas, and increasingly expensive oil from foreign sources, to meet national energy needs. At the same time, in recognition of possible adverse health and ecological consequences of increased coal production and use, the President announced that a special committee would be formed to study this aspect of the National Energy Plan. The Committee held a series of public meetings during November and December 1977 to review a number of special papers on particular problems associated with increased coal utilization. These papers, which were prepared by scientists of the US Environmental Protection Agency; the Department of Energy; the HEW National Institute for Occupational Safety and Health, and the National Institute of Environmental Health Sciences; New York University; and Vanderbilt University; provided essential background information for the deliberations of the Committee and were published in EHP Vol. 33, pp. 127–314, 1979. One paper by A. P. Altschuler et al. is published in this volume of EHP. The Committee's basic finding was that it is safe to proceed with plans to increase the utilization of coal if the following environmental and safety policies are adhered to: • Compliance with Federal and State air, water, and solid waste regulations • Universal adoption and successful operation of best available control technology on new facilities • Compliance with reclamation standards • Compliance with mine health and safety standards • Judicious siting of coal-fired facilities The Committee concluded that, even with the best mitigation policies, there will be some adverse health and environmental effects from the dramatic increase in coal use. However, these will not impact all regions and individuals uniformly. The Committee identified six major areas of uncertainty and concern requiring further investigation if the nation is to minimize undesirable consequences of increased coal utilization now, and in the future. Two critical health issues of concern are air pollution health effects and coal mine worker health and safety. Two critical environmental issues are global effects of carbon dioxide in the atmosphere and acid fallout. Two additional important issues of concern are trace elements in the environment and reclamation of arid land. Finally, because of the inadequate data and methodology used in the study of these matters, the Committee strongly recommended the establishment of an improved national environmental data collection, modeling and monitoring system.

Since the passage of the environmental legislation in the early 1970's, critics have attacked these laws as being unnecessary and for contributing significantly to the problem of inflation in the United States. This paper is an attempt to put the inflationary costs of air pollution into perspective by considering them in light of the cost, especially to public health, of not proceeding with pollution control. There is now a great deal of evidence that the concentration of certain pollutants in the air can contribute significantly to the incidence of respiratory and cardiovascular diseases and to certain forms of cancer. On the basis of the results of a recent study of the impacts of pollution control on inflation, the annual reduction in purchasing power of the average family is calculated to be $31 per family. To determine the average costs of air pollution on human health, research by Lave and Seskin is utilized. First, the implications of air pollution for mortality and morbidity rates are determined. Then, the reduction in direct health costs and indirect costs (lost productivity of workers) as a result of pollution abatement is estimated. These annual health costs from pollution total approximately $250 per family. The results suggest that the inflationary costs of air pollution control are more than offset by the damages to public health from unabated air pollution.

Anthracene, fluorene, carbazole, dibenzofuran, and dibenzothiophene are five typical by-products of coal conversion which are likely to be environmental pollutants. These were radiolabeled to high specific activity and purity by simple tritium exchange and evaluated for environmental fate in laboratory model ecosystems. Anthracene and fluorene were biologically converted to hydroxy and keto analogs. Carbazole was N-methylated and N-acetylated. Dibenzothiophene was microsomally oxidized to the sulfoxide and sulfone. Dibenzofuran was relatively inert to biodegradation. The octanol/water partition coefficient for the parent compounds was well correlated with ecological magnification indicating the possibility of predicting environmental behavior from physicochemical parameters.