Systemic considerations with pigmented fundus lesions and retinal pigment epithelium hamartomas in Turcot syndrome.

PURPOSE OF REVIEW: To illustrate retinal pigment epithelium hamartomas (RPEHs) in a patient with known Turcot syndrome and to demonstrate the significance of these lesions in other colonic polyposis syndromes. RECENT FINDINGS: The presence of multiple, bilateral RPEHs is a specific marker for familial adenomatous polyposis (FAP). Recent studies have noted RPEHs in associated syndromes including Gardner and Turcot syndromes. Herein, we illustrate an 18-year-old male patient with known brain medulloblastoma who was documented 7 years later to have asymptomatic RPEHs in both eyes, demonstrating hypo-autofluorescence. SUMMARY: This patient with previous medulloblastoma and known Turcot syndrome was later found to have typical RPEHs, a feature that is important in family screening. Confirmation of RPEHs related to Turcot syndrome was made, and genetic evaluation confirmed germline mutation in the adenomatous polyposis coli (APC) gene. Observation was advised. Due to the fairly rapid progression to colorectal cancer if untreated, ophthalmologists should be aware that RPEHs can be the first extracolonic manifestation of FAP, Gardner syndrome, and Turcot syndrome.

Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments.

Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. Despite their widespread use, a comprehensive view of their tumor-immune compositions and their relevance to human tumors has only begun to emerge. We propose each model possesses a unique tumor-immune infiltrate profile that can be probed with immunotherapies to inform on anti-tumor mechanisms and treatment strategies in human tumors with similar profiles. In support of this endeavor, we characterized the tumor microenvironment of four commonly used models and demonstrate they encompass a range of immunogenicities, from highly immune infiltrated RENCA tumors to poorly infiltrated B16F10 tumors. Tumor cell lines for each model exhibit different intrinsic factors in vitro that likely influence immune infiltration upon subcutaneous implantation. Similarly, solid tumors in vivo for each model are unique, each enriched in distinct features ranging from pathogen response elements to antigen presentation machinery. As RENCA tumors progress in size, all major T cell populations diminish while myeloid-derived suppressor cells become more enriched, possibly driving immune suppression and tumor progression. In CT26 tumors, CD8 T cells paradoxically increase in density yet are restrained as tumor volume increases. Finally, immunotherapy treatment across these different tumor-immune landscapes segregate into responders and non-responders based on features partially dependent on pre-existing immune infiltrates. Overall, these studies provide an important resource to enhance our translation of syngeneic models to human tumors. Future mechanistic studies paired with this resource will help identify responsive patient populations and improve strategies where immunotherapies are predicted to be ineffective.

Representing causal knowledge in environmental policy interventions: Advantages and opportunities for qualitative influence diagram applications.

This article develops and explores a methodology for using qualitative influence diagrams in environmental policy and management to support decision-making efforts that minimize risk and increase resiliency. Influence diagrams are representations of the conditional aspects of a problem domain. Their graphical properties are useful for structuring causal knowledge relevant to policy interventions and can be used to enhance inference and inclusivity of multiple viewpoints. Qualitative components of influence diagrams are beneficial tools for identifying and examining the interactions among the critical variables in complex policy development and implementation. Policy interventions on social-environmental systems can be intuitively diagrammed for representing knowledge of critical relationships among economic, environmental, and social attributes. Examples relevant to coastal resiliency issues in the US Gulf Coast region are developed to illustrate model structures for developing qualitative influence diagrams useful for clarifying important policy intervention issues and enhancing transparency in decision making. Integr Environ Assess Manag 2018;14:381-394. Published 2018. This article is a US Government work and is in the public domain in the USA.

Representing causal knowledge in environmental policy interventions: Advantages and opportunities for qualitative influence diagram applications.

This article develops and explores a methodology for using qualitative influence diagrams in environmental policy and management to support decision making efforts that minimize risk and increase resiliency. Influence diagrams are representations of the conditional aspects of a problem domain. Their graphical properties are useful for structuring causal knowledge relevant to policy interventions and can be used to enhance inference and inclusivity of multiple viewpoints. Qualitative components of influence diagrams are beneficial tools for identifying and examining the interactions among the critical variables in complex policy development and implementation. Policy interventions on social-environmental systems can be intuitively diagrammed for representing knowledge of critical relationships among economic, environmental, and social attributes. Examples relevant to coastal resiliency issues in the U.S. Gulf Coast region are developed to illustrate model structures for developing qualitative influence diagrams useful for clarifying important policy intervention issues and enhancing transparency in decision making. This article is protected by copyright. All rights reserved.

One health-Transdisciplinary opportunities for SETAC leadership in integrating and improving the health of people, animals, and the environment.

One Health is a collaborative, transdisciplinary effort working locally, nationally, and globally to improve health for people, animals, plants, and the environment. The term is relatively new (from ∼2003), and it is increasingly common to see One Health included by name in interinstitutional research partnerships, conferences, communications, and organizational frameworks, particularly those championed by the human health and veterinary medical communities. Environmental quality is arguably the least developed component within the One Health framework, but can be guided by expertise within the Society of Environmental Toxicology and Chemistry (SETAC). Despite SETAC's long history of tripartite (academic, government, business) interdisciplinary environmental science activities, the term "One Health" is seldom used in SETAC communications (i.e., many of SETAC's activities are guided by One Health, but it is called by other names in SETAC's journals, newsletters, and presentations). Accordingly, the objective of this Focus article is to introduce the One Health concept to the SETAC membership. The article discusses the origins, evolution, and utility of the One Health approach as an organizational framework and provides key examples of ways in which SETAC expertise can benefit the One Health community. The authors assert that One Health needs SETAC and, to be most effective, SETAC needs One Health. Given that One Health to date has focused too little on the environment, on ecosystems, and on contaminants, SETAC's constructive involvement in One Health presents an opportunity to accelerate actions that will ultimately better protect human and ecosystem health. Environ Toxicol Chem 2016;35:2383-2391. © 2016 SETAC.

Mental health disorders among an invisible minority: depression and dementia among american Indian and alaska native elders.

According to the 2010 Census, 5.2 million people identified themselves as American Indian or Alaska Native (AIAN) in the United States. This was an increase of 39% from the prior Census, making AIANs one of the nation's fastest growing populations. The health and social programs reaching them, however, have experienced documented devastating shortfalls. Decades of inadequate resources have resulted in significant health and socioeconomic disparities. AIANs are often considered an "invisible minority." In 2012, there were 266,000 AIAN elders 65 or older who claimed one race alone. That number is projected to almost triple by 2030-when the nation's baby boomers move into the ranks of the older population. This article provides an overview of two primary mental health issues-depression and dementia-that will confront this emerging AIAN elder population. Although other health and social issues exist, this article addresses depression and dementia because they are hidden from the community and from health care agencies. This paper focuses both on the unique characteristics of the AIAN population and why it is important to address depression and dementia. The conclusion explores pragmatic policy recommendations for improving the health and long-term mental health care status of AIAN elders.

Infrared imaging enhances retinal crystals in Bietti's crystalline dystrophy.

Infrared imaging dramatically increased the number of crystalline deposits visualized compared with clinical examination, standard color fundus photography, and red free imaging in patients with Bietti's crystalline dystrophy. We believe that this imaging modality significantly improves the sensitivity with which these lesions are detected, facilitating earlier diagnosis and may potentially serve as a prognostic indicator when examined over time.

Sustainable watersheds: integrating ecosystem services and public health.

Sustainable management of aquatic ecosystems is a worldwide priority; the integrity of these systems depends, in turn, on the integrity of the watersheds (catchments) in which they are embedded. In this article, we present the concepts, background, and scientific foundations for assessing, both nationally and at finer scales, the relationships between ecosystem services, human health, and socioeconomic values in the context of water quality, water quantity, landscapes, the condition of watersheds, and the connectivity of waters, from headwaters to estuaries and the coastal ocean. These assessments will be a foundation for what we have termed "watershed epidemiology," through which the connections between ecosystems and human health can be explored over broad spatial and temporal scales. Understanding and communicating these relationships should lead to greater awareness of the roles watersheds play in human well-being, and hence to better management and stewardship of water resources. The U.S. Environmental Protection Agency is developing the research, models, and planning tools to support operational national assessments of watershed sustainability, building upon ongoing assessments of aquatic resources in streams, rivers, lakes, wetlands and estuaries.

Polling places, pharmacies, and public health: Vote & Vax 2012.

US national elections, which draw sizable numbers of older voters, take place during flu-shot season and represent an untapped opportunity for large-scale delivery of vaccinations. In 2012, Vote & Vax deployed a total of 1585 clinics in 48 states; Washington, DC; Guam; Puerto Rico; and the US Virgin Islands. Approximately 934 clinics were located in pharmacies, and 651 were near polling places. Polling place clinics delivered significantly more vaccines than did pharmacies (5710 vs 3669). The delivery of vaccines was estimated at 9379, and approximately 45% of the recipients identified their race/ethnicity as African American or Hispanic. More than half of the White Vote & Vax recipients and more than two thirds of the non-White recipients were not regular flu shot recipients.

Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.

G protein-coupled receptor 119 (GPR119) is a G protein-coupled receptor expressed predominantly in pancreatic ß-cells and gastrointestinal enteroendocrine cells. Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans. In this study, we investigated the effects of GSK2041706 [2-([(1S)-1-(1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl)ethyl]oxy)-5-[4-(methylsulfonyl)phenyl]pyrazine], a GPR119 agonist, and metformin as monotherapy or in combination on body weight in a diet-induced obese (DIO) mouse model. Relative to vehicle controls, 14-day treatment with GSK2041706 (30 mg/kg b.i.d.) or metformin at 30 and 100 mg/kg b.i.d. alone caused a 7.4%, 3.5%, and 4.4% (all P < 0.05) weight loss, respectively. The combination of GSK2041706 with metformin at 30 or 100 mg/kg resulted in a 9.5% and 16.7% weight loss, respectively. The combination of GSK2041706 and metformin at 100 mg/kg caused a significantly greater weight loss than the projected additive weight loss of 11.8%. This body weight effect was predominantly due to a loss of fat. Cumulative food intake was reduced by 17.1% with GSK2041706 alone and 6.6% and 8.7% with metformin at 30 and 100 mg/kg, respectively. The combination of GSK2041706 with metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels compared with their monotherapy groups. In addition, we characterized the effect of GSK2041706 and metformin as monotherapy or in combination on neuronal activation in the appetite regulating centers in fasted DIO mice. In conclusion, our data demonstrate the beneficial effects of combining a GPR119 agonist with metformin in the regulation of body weight in DIO mice.

Identifying evaluation considerations for the recovery and restoration from the 2010 Gulf of Mexico oil spill: An initial appraisal of stakeholder concerns and values.

Understanding what can be achieved and what should be avoided by environmental management decisions requires an understanding of values, or what is cared about in a decision. Decision analysis provides tools and processes for constructing objectives that transparently reflect the values being considered in environmental management decisions. The present study demonstrates parts of the initial decision analysis steps for identifying a decision context and constructing objectives for the recovery and long-term restoration of the Gulf of Mexico following the 2010 Deepwater Horizon oil spill. From a review of multiple reports, including those developed by policy makers and nongovernmental organizations, a preliminary structuring of concerns and considerations into objectives was derived to highlight features of importance in the recovery from the spill and long-term restoration. The fundamental objectives constructed for the long-term restoration context reflect broader concerns regarding well-being and quality of life. When developed through stakeholder engagement processes, clarifying objectives can potentially 1) lend insight into the values that can be affected, 2) meaningfully include stakeholders in the decision-making process, 3) enhance transparency and communication, and 4) develop high-impact management strategies reflecting broad public interests. This article is a US government work and is in the public domain in the United States of America.

Clinical and community delivery systems for preventive care: an integration framework.

Although clinical preventive services (CPS)-screening tests, immunizations, health behavior counseling, and preventive medications-can save lives, Americans receive only half of recommended services. This "prevention gap," if closed, could substantially reduce morbidity and mortality. Opportunities to improve delivery of CPS exist in both clinical and community settings, but these activities are rarely coordinated across these settings, resulting in inefficiencies and attenuated benefits. Through a literature review, semi-structured interviews with 50 national experts, field observations of 53 successful programs, and a national stakeholder meeting, a framework to fully integrate CPS delivery across clinical and community care delivery systems was developed. The framework identifies the necessary participants, their role in care delivery, and the infrastructure, support, and policies necessary to ensure success. Essential stakeholders in integration include clinicians; community members and organizations; spanning personnel and infrastructure; national, state, and local leadership; and funders and purchasers. Spanning personnel and infrastructure are essential to bring clinicians and communities together and to help patients navigate across care settings. The specifics of clinical-community integrations vary depending on the services addressed and the local context. Although broad establishment of effective clinical-community integrations will require substantial changes, existing clinical and community models provide an important starting point. The key policies and elements of the framework are often already in place or easily identified. The larger challenge is for stakeholders to recognize how integration serves their mutual interests and how it can be financed and sustained over time.

Broader perspective on ecosystem sustainability: consequences for decision making.

Although the concept of ecosystem sustainability has a long-term focus, it is often viewed from a static system perspective. Because most ecosystems are dynamic, we explore sustainability assessments from three additional perspectives: resilient systems; systems where tipping points occur; and systems subject to episodic resetting. Whereas foundations of ecosystem resilience originated in ecology, recent discussions have focused on geophysical attributes, and it is recognized that dynamic system components may not return to their former state following perturbations. Tipping points emerge when chronic changes (typically anthropogenic, but sometimes natural) push ecosystems to thresholds that cause collapse of process and function and may become permanent. Ecosystem resetting occurs when episodic natural disasters breach thresholds with little or no warning, resulting in long-term changes to environmental attributes or ecosystem function. An example of sustainability assessment of ecosystem goods and services along the Gulf Coast (USA) demonstrates the need to include both the resilient and dynamic nature of biogeomorphic components. Mountain road development in northwest Yunnan, China, makes rivers and related habitat vulnerable to tipping points. Ecosystems reset by natural disasters are also presented, emphasizing the need to understand the magnitude frequency and interrelationships among major disturbances, as shown by (i) the 2011 Great East Japan Earthquake and resulting tsunami, including how unsustainable urban development exacerbates geodisaster propagation, and (ii) repeated major earthquakes and associated geomorphic and vegetation disturbances in Papua New Guinea. Although all of these ecosystem perturbations and shifts are individually recognized, they are not embraced in contemporary sustainable decision making.

Strategic priorities to increase use of clinical preventive services among older US adults.

The objective of this project was to obtain professionals' perceptions of system-level strategies with potential to increase use of clinical preventive services (CPS) among adults aged 50 years or older through community settings. Public health, aging services, and medical professionals participated in guided discussions and a modified Delphi process. Priority strategies, determined on the basis of a 70% or higher a priori agreement level, included enhancing community capacity; promoting the design of health information technologies to exchange data between clinical and community settings; promoting care coordination; broadening scope of practice; providing incentives to employers; and eliminating cost-sharing. Findings provide insights about preferences for system-level strategies that align with national and state initiatives to increase CPS use.

Vaccinations and preventive screening services for older adults: opportunities and challenges in the USA.

Vaccinations and disease-screening services occupy an important position within the constellation of interventions designed to prevent, forestall or mitigate illness: they straddle the worlds of clinical medicine and public health. This paper focuses on a set of clinical preventive services that are recommended in the USA for adults aged 65 and older, based on their age and gender. These services include immunisations against influenza and pneumococcal disease, and screening for colorectal and breast cancers. We explore opportunities and challenges to enhance the delivery of these interventions, and describe some recently developed models for integrating prevention efforts based in clinician offices and in communities. We also report on a state-level surveillance measure that assesses whether older adults are 'up to date' on this subset of preventive services. To better protect the health of older Americans and change the projected trajectory of medical costs, expanded delivery of recommended vaccinations and disease screenings is likely to remain a focus for both US medicine and public health.

Sediment quality in near coastal waters of the Gulf of Mexico: influence of Hurricane Katrina.

The results of the present study represent a synoptic analysis of sediment quality in coastal waters of Lake Pontchartrain and Mississippi Sound two months after the landfall of Hurricane Katrina. Posthurricane conditions were compared to prehurricane (2000-2004) conditions, for sediment quality data. There were no exceedances of effects range median (ERM) sediment quality guideline values for chemical contaminants in any of the sediment samples collected from the Lake Pontchartrain or the Mississippi Sound study areas following the hurricane. Lower threshold effects range low (ERL) values were exceeded for As, Cd, and Ni at several stations in both survey areas, similar to levels of contamination observed prior to the hurricane. The comparison of sediment quality indicators before and after the hurricane suggests considerable stability of these systems with respect to short-term ecological impacts. Although other studies have shown storm-related changes could be detected (e.g., effects on benthic communities associated with shifts in salinity), there were no indications of widespread sediment contamination.

Accounting for natural resources and environmental sustainability: linking ecosystem services to human well-being.

One of society's greatest challenges is to sustain natural resources while promoting economic growth and quality of life. In the face of this challenge, society must measure the effectiveness of programs established to safeguard the environment. The impetus for demonstrating positive results from government-sponsored research and regulation in the United States comes from Congress (General Accountability Office; GAO) and the Executive Branch (Office of Management and Budget; OMB). The message is: regulatory and research programs must demonstrate outcomes that justify their costs. Although the concept is simple, it is a complex problem to demonstrate that environmental research, policies, and regulations cause measurable changes in environmental quality. Even where changes in environmental quality can be tracked reliably, the connections between government actions and environmental outcomes seldom are direct or straightforward. In this article, we describe emerging efforts (with emphasis on the role of the U.S. Environmental Protection Agency; EPA) to frame and measure environmental outcomes in terms of ecosystem services and values-societally and ecologically meaningful metrics for gauging how well we manage environmental resources. As examples of accounting for outcomes and values, we present a novel, low-cost method for determining relative values of multiple ecosystem services, and describe emerging research on indicators of human well-being.

Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring: hurdles, achievements, and future outlook.

BACKGROUND: In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics-Moving into Regulation and Monitoring, held 21-23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada). OBJECTIVES: The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets. DISCUSSION: Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data. CONCLUSIONS: The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach.