With the rapid increase in utilization of imaging endpoints in multicenter clinical trials, the amount of data and workflow complexity have also increased. A Clinical Trial Imaging Management System (CTIMS) is required to comprehensively support imaging processes in clinical trials. The US Food and Drug Administration (FDA) issued a guidance protocol in 2018 for appropriate use of medical imaging in accordance with many regulations including the Good Clinical Practice (GCP) guidelines. Existing research on CTIMS, however, has mainly focused on functions and structures of systems rather than regulation and compliance.We aimed to develop a comprehensive CTIMS to meet the current regulatory guidelines and various required functions. We also aimed to perform computerized system validation focusing on the regulatory compliance of our CTIMS.Key regulatory requirements of CTIMS were extracted thorough review of many related regulations and guidelines including International Conference on Harmonization-GCP E6, FDA 21 Code of Federal Regulations parts 11 and 820, Good Automated Manufacturing Practice, and Clinical Data Interchange Standards Consortium. The system architecture was designed in accordance with these regulations by a multidisciplinary team including radiologists, engineers, clinical trial specialists, and regulatory medicine professionals. Computerized system validation of the developed CTIMS was performed internally and externally.Our CTIMS (AiCRO) was developed based on a two-layer design composed of the server system and the client system, which is efficient at meeting the regulatory and functional requirements. The server system manages system security, data archive, backup, and audit trail. The client system provides various functions including deidentification, image transfer, image viewer, image quality control, and electronic record. Computerized system validation was performed internally using a V-model and externally by a global quality assurance company to demonstrate that AiCRO meets all regulatory and functional requirements.We developed a Good Practice–compliant CTIMS—AiCRO system—to manage large amounts of image data and complexity of imaging management processes in clinical trials. Our CTIMS adopts and adheres to all regulatory and functional requirements and has been thoroughly validated. In the last decade, the number of clinical trials including multicenter trials has increased worldwide and consequently, the related clinical data have increased and grown more complex in many types of sources. Furthermore, medical imaging involvement in the recent clinical trials is another main reason for increasing the intricacies of clinical data -3. TheseSince image biomarkers have been used in a variety of clinical trials , the US According to the FDA imaging guidance, the standardization of clinical trials imaging endpoints describes processes to manage imaging acquisition, quality check, anonymization, transfer, archive, quantitative image analysis, and independent blinded image review by multiple readers . These pRecently, several different IT platforms have been developed specifically for clinical trials that enable integrated imaging data management and efficient imaging workflows ,9. Such The GxP is a collection of quality guidelines and regulations to ensure medical product safety; their intended use; and quality processes during clinical development, manufacturing, and distribution -14. AlthMany studies have focused on CTIMS ,11,19, bBased on the 2018 FDA imaging guidance, which is the most important regulation covering a wide range of imaging processes required in clinical trials, we extracted key functions of CTIMS to perform imaging processes and enhance efficient workflow in the clinical trials.To systematically extract key GxP requirements, which are not described in the 2018 FDA imaging guidance, we thoroughly reviewed the related regulations/guidelines from regulatory agencies and international societies  as folloRegulatory agency: ICH-GCP E6 (R2) , HIPAA, International society: Good Automated Manufacturing Practice (GAMP) 5 Guide for Compliant GxP Computerized Systems , EuropeaBased on extracted regulatory requirements, we designed the AiCRO system architecture and functional modules. Java and HTML5 programming languages were used to develop a platform-independent system, which can be executed on a standalone system or Web-based system regardless of the operating system. The image viewer in AiCRO system was developed using JDK [computer software] .A multidisciplinary software development team was organized, including radiologists, imaging technicians, clinical trial specialists, regulatory medicine professionals, and IT engineers, who worked toward the same goal. We also recruited potential AiCRO system users, including medical researchers, and pharmaceutical company staff.The AiCRO system was validated both internally and externally. We validated the AiCRO system internally using the V-model in accordance of the US FDA CFR 21 Part 820 and GAMP 5 guidelines, which are currently regarded as the global standards for computerized system validation for clinical trials  17]. Ac. Ac17]. Operational qualification and performance qualification verify that a system operates and performs all activities under normal and challenging conditions. Design qualification verifies individual system designs for different projects to ensure that they proceed efficiently through the work process. Internal validations are to be performed once a year using at least 10 personal computers in Korea, the United States, China, Australia, and France. For test purposes, we built a sample project that requires typical work processes used in clinical trials for cancer. The AiCRO system was externally validated for global clinical trial use by a global quality assurance and auditing company. Use of a third party enabled different perspectives on our system, including those related to adherence to regulatory requirements.The key regulatory requirements extracted through our systematic review of the FDA guidelines and regulations are summarized in The FDA has continuously emphasized and recommended compliance with regulations for computerized system use in the clinical trial, including the FDA 21 CFR part 11 and many other regulations, as illustrated in The predominant factor in the system design was compliance with a diverse set of regulations. We developed the AiCRO system for imaging processes in clinical trials in strict accordance with the relevant guidelines, with a focus on FDA 21 CFR Part 11 and the FDA imaging guidance. AiCRO system is developed based on Server and Client system architecture, as illustrated in The client system was designed with various modules to manage clinical information data. The system transfers the eCRF clinical data to an AP server via API and transfers images to the server through database API after the image data are deidentified. Reviewers can also check the uploaded DICOM image with the image viewer and analyze images to, for example, measure the tumor size or volume. These measurement values are delivered to the AP server by the client system. If the client system is installed on the user’s laptop, clinical data can be easily managed and images can be viewed and analyzed from any location. The screen snapshots of modules are presented in Every medical image acquired from the participating sites should be uploaded to the AiCRO system in DICOM format by each site’s staff. Uploaded image data are anonymized, transferred, and archived in the central server of CTIMS . DeidentPersonal identification information is recorded in the DICOM file metadata or presented in the medical images as graphical information. The metadata contains both patient identification information such as patient name; date of birth; hospital name; and hospital medical record number; and imaging modality/protocol information such as manufacturer and software of the modality, sequence, field of view, or slice thickness. According to the DICOM standard part 15 , the AiCBesides metadata in the DICOM file, patients’ identification information is presented on medical images as graphical texts or image pixel data, especially in the ultrasonography, 3D rendering computed tomography images, radiation dose reports, screen shot images, and endoscopy images. We implemented two functional modules to remove this type of information by incorporating the fully automatic text-removal function and semiautomatic imaging-processing blackout function.Specifically, graphical patient identification information was detected through the incorporation of optical character recognition, which is based on the convolutional recurrent neural network algorithm to detect text burned in the images . SubsequThe semiautomatic and manual blackout deidentification functions enable uploaders to select regions of interest that need to be removed  either in a single image or multiple series of images . If the Data storage and security are other significant points emphasized by FDA guideline 21 CFR part 11. Hence, all DICOM files are centralized and stored on the AiCRO server system . Web-PACMost hospitals and institutions use DICOM metadata tagging in accordance with DICOM standards, but specific information therein may vary across sites depending upon the institutional policy. If the metadata does not follow standard DICOM protocols, image upload and view may be disabled by the Web-PACS. We resolved this issue by developing a custom DICOM library for the standardization of DICOM metadata. The custom DICOM library enables creation of new metadata by modifying the pre-existing DICOM metadata. These changes are stored as per the custom DICOM library, which must be regularly updated to apply to different or emergent circumstances.Regarding a system security to prevent different types of system attack, we established an IT system security plan. For example, separation of the AP server and database server can localize any damage in the server. To protect the local computer, we adopted a zero footprint design and symmetric encryption algorithms based on advanced encryption standards. Images can be only loaded into our custom-built DICOM viewer due to the encryption key, and there are no plugins or data in the local personal computer.To protect against any unforeseen disaster , backup data are stored regularly with a dedicated program using NAS hardware physically located at different sites. When any issue arises, the server administrator receives an automatic email alert with the relevant information for troubleshooting. Backup data include the database, audit trails, DICOM, and configuration files. These overall securities allow us to guarantee data integrity.All uploaded medical images should pass through quality control (QC) before image analysis in accordance with the FDA imaging guidance . The imaOur image QC module is composed of an automatic quantitative QC module and a manual qualitative QC module. The automatic quantitative QC module extracts several DICOM elements containing imaging modality/protocol information such as machines, sequences, matrix size, spatial resolution, field of view, slice thickness, and interslice gap. The module automatically decides whether the extracted values meet the predefined image quality requirements. For instance, if a trial requires axial and coronal computed tomography images with a matrix size of 512 × 512 and slice thickness of ≤5 mm with 0 interslice gap, the automatic quantitative QC module checks whether the uploaded images meet those specific requirements.Image QC staff is involved in the manual qualitative QC module. The AiCRO system supports image QC staff to perform qualitative image quality checks for presence of image artifacts, appropriateness of scan coverage, image reconstruction, and contrast enhancement. The image QC staff can generate the quality assessment report after the QC check . The quaThe AiCRO image viewer was developed to provide a viewer platform, interfaces, and image processing tools . Our vieAs there are already established image processing tools in most image viewers  25], we, we25], All textual data including subject information and image analysis and review results in the AiCRO system adhere to CDISC standards for data formats for multicenter and multinational trials, a prerequisite for FDA submission. The FDA insists on the use of study data standards for data consistency, particularly in computer systems -28.A diverse and customized eCRF, also known as an imaging CRF including Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, Immune RECIST, or Lugano classification, was developed to retain records of all data related to study images. Customized eCRFs were created for different study designs by anatomical location of tumor, tumor measurement, or type of drug or analysis, leading to inherent variations in data formats. We streamlined data formats according to the CDISC terminology for each therapeutic area, such as cardiology, neurology, or oncology, so that all data are collected using standardized CDISC terminology from the start to enable data management across the sites. These data collection process adhere to the Clinical Data Acquisition Standards Harmonization of CDISC standards .Collected data in the system need to be organized to standard structures for submission to regulatory agencies, as discussed in the CDISC standards, in the study data tabulation model . ImplemeAiCRO complies suitable CDISC terminology for all these processes , which aAs the AiCRO system maintains electronic data, data validation is an important consideration for clinical trials. Data validation in an electronic system is mandated by regulations specific to electronic signatures. We thereby incorporated an electronic signature function into the system, as per FDA 21 CFR part 11, wherein electronic signatures must be “the equivalent of handwritten signatures, initials, and other general signings required by predicate rules” .FDA 21 CFR part 11  stipulatThe query and alarm functions are designed to adhere to GAMP guidelines for corrective and preventive action (CAPA). CAPA outlines a process for the investigation, discussion, and correction of any problems as well as recognition and prevention of potential problems . When deAppropriate data entry is key in clinical trials and usually managed via “edit check,” a process for the detection and correction of data when they are first entered . The “QuAccounts for accessing the AiCRO system are organized into different types depending on the individual’s role, such as site CRC, image QC, central reviewer, and many others. According to GAMP guidelines, definitions of the roles and responsibilities attached to each account are recommended for validation purposes, including the testing of computerized systems . The AiCFor internal system validation, we organized the overall validation plan according to the V-model , which iFor installation qualification, the AiCRO’s client system was successfully installed in all test personal computers, regardless of the operating system such as Windows and Mac as well as Web-browsers including Chrome, Internet Explorer versions 10 and 11, and Firefox. The AiCRO’s server system was installed appropriately on our institutional server and Amazon Web Services Clouds in Seoul and China (Beijing).For operational qualification, the system developer created test scripts to prove the proper functioning of all functional specifications and system operation. Subsequently, an independent tester executed test scripts in a predefined testing environment and recorded the test log and all results including test date, observations made, completeness of each function, problems/deviations encountered, and other information relevant to the operational qualification. These assessments found that all AiCRO functions could be operated without difficulty.For performance qualification, we prepared a sample project with real data and different user accounts. An independent tester then evaluated module function using the sample project with different amounts of imaging data, work load sizes, and computing and network environments. All functions of the AiCRO worked appropriately under normal operating conditions of minimum required personal computer specifications, and the upload and download of several computed tomography/magnetic resonance imaging scans was performed at usual internet speeds of over 10 megabytes per second. However, during testing under challenging conditions, limiting factors that might cause an interruption or significant delay in activity were identified, which were machines with less than 4 GB RAM, uploading and downloading large image data for at least 3000 DICOM files at one time, internet speeds below 10 MB per second, and viewing large image data for at least 3000 DICOM files at once.For design qualification, AiCRO validation is essential because each clinical trial project will have a different study design. We checked whether AiCRO was able to create a customizable data entry form and working algorithm per user specifications. Using a test project that simulated a sophisticated clinical trial for stroke, our imaging clinical research associate wrote the user specification, and our system developer created the customizable project in the AiCRO system. Thereafter, a test team, including a project manager, image analyst, and radiologist, performed user acceptance tests. The customized test project was successfully created, and its functional modules garnered acceptance from different kinds of users.Finally, the AiCRO system was validated by Zigzag , an external global quality assurance company. A professional quality manager from Singapore visited the core lab in Seoul for 3 days and reviewed all validation documents. This manager also required a demonstration of the process, including creation of a new customized project and associated functions. The quality manager verified that installation qualification, operational qualification, performance qualification, and design qualification were performed appropriately in accordance with the relevant regulations and guidelines.During the 2000s, the FDA  was concCTIMS thus needed to comply with FDA guidelines, which comprehensively cover the functional and regulatory aspects of imaging, thereby underscoring the importance of developing a CTIMS that was GxP-compliant. The appropriate use of medical imaging in clinical trials necessitates specific considerations including standardization of imaging acquisition, archiving, and QC; centralized independent blinded image review; and systems that can handle complex workflows while maintaining regulatory compliance.Asan Image Metrics , an academic imaging core lab, developed a CTIMS—the AiCRO system—which adheres to all regulatory requirements for medical imaging in clinical trials and enables stakeholders to access easily medical images obtained from different sites. It contains modules including deidentification, data transfer, data archive, eCRF, image viewing/analysis, data management according to CDISC, audit trail, query/alarm, complex workflow algorithm, and security. The platform thus ensures quality of results and minimizes data risks during and after clinical trial periods. In the last 2 years, we have implemented the AiCRO system on more than 20 domestic and international pharmaceutical multicenter clinical trials, and several audits and inspections have been conducted as well.The main advantage of AiCRO is that it is an all-in-one system that meets virtually all regulatory and functional requirements for clinical trial imaging while maintaining considerable user flexibility. For example, if a user needs a new function for the specific trial, our development team can easily build or customize the necessary function according to user specifications, after which our quality assurance and data management teams offer continuous user and regulatory support for the new function. For example, in the cases of trials on rare diseases requiring sophisticated magnetic resonance imaging analyses, a dedicated imaging postprocessing module and disease-specific terminology can be added in the CDISC data format.Although our system has several advantages, one of the limitations is that each site or hospital has its own security system containing firewalls to protect their patients’ information. Nowadays, many institutions strictly regulate the external transfer of medical data, and hospital network system firewalls are becoming stronger. Ideally, a CTIMS should strike a balance between security and function within the boundaries of regulations and institutional policies. Another limitation is that AiCRO is an independent system separated from other EDC system. Thus, in clinical trials, we need to link our system to other EDC systems. Otherwise, users have to use two different IT systems in a clinical trial.We introduced a CTIMS, called AiCRO system, to conduct clinical trials more efficiently in accordance with regulatory requirements. In this paper, we discussed the development of the AiCRO system to meet a diverse array of regulatory requirements and the design of multiple modules for users to customize the system to the needs of their clinical trials. We also discussed the internal and external validation of AiCRO according to the GxP guidelines and FDA 21 CFR. The AiCRO system is an all-in-one platform enabling high-quality clinical trial imaging data, but further study is required to describe the results of implementation obtained for different types of trials and any necessary systemic improvements.


Interpersonal interventions use Patient Navigators to support navigation to EB tobacco cessation resources and lung cancer screening. Community level support within the SEM is developed by ongoing partnerships with local and national partners such as the American Lung Association (ALA) and the American Cancer Society (ACS). Lastly, at the policy level, the UI Cancer Center acknowledges the role of policy implications in lung cancer screening and advocates for policies and screening recommendations that examine the current guidelines from the United States Preventive Services Task Force (USPTF).Lung cancer is the leading cause of cancer morbidity and mortality in the U.S. and racial/ethnic minorities carry the greatest burden of lung cancer disparities with African Americans (AAs) impacted disproportionately. Inequities in lung cancer health disparities are often associated with multiple bio-behavioral and socio-cultural factors among racial/ethnic minorities. Epigenetic research has advanced the understanding of the intersectionality between biological and socio-cultural factors in lung cancer disparities among AAs. However, gaps exist in the engagement of diverse populations in epigenetic lung cancer research, which poses a challenge in ensuring the generalizability and implementation of epigenetic research in populations that carry an unequal cancer burden. Grounding epigenetic lung cancer research within a socio-ecological framework may prove promising in implementing a multi-level approach to community engagement, screening, navigation, and research participation among AAs. The University of Illinois Cancer Center (UI Cancer Center) is employing an evidence–based (EB) model of community/patient engagement utilizing the socio-ecological model (SEM) to develop a culturally sensitive epigenetic lung cancer research program that addresses multiple factors that impact lung cancer outcomes in AAs. By implementing epigenetic research within a group of Federally Qualified Health Centers (FQHCs) guided by the SEM, the UI Cancer Center is proposing a new pathway in mitigating lung cancer disparities in underserved communities. At the  Lung cancer remains the leading cause of cancer mortality in the United States (U.S.) with a projected estimate of 234,030 new cases and 154,050 deaths from lung cancer in 2018 , 7. As oFQHCs also provide care to a large number of smokers who meet criteria for lung cancer screening , 8. HoweThe study of epigenetics and social epigenomics enables researchers to understand the complex intersectionality of biology and socio-cultural factors such as diet, stress, built environment and cancer development and progression . HoweverThe National Lung Screening Trial (NLST) funded by the National Cancer Institute (NCI NCT00047385) demonstrated that lung cancer screening with the use of low-dose computed topography (LDCT) resulted in a reduction of lung cancer mortality . AlthougThe Mile Square Health Center (MSHC) is a network of 11 (FQHCs) providing comprehensive, high quality health services through the continuum of care . MSHC is the third oldest FQHC in the U.S.; it opened in 1967 to address the needs of Chicago's public housing residents . Today, MSHC's strong and positive presence in the communities it serves is evidenced by its cancer prevention initiatives, which reached more than 2,000 new patients in 2016. The “Mile Square Smoking Cessation Program” (MI-QUIT), funded by the March of Dimes Foundation, was launched in 2014. Originally, the objective of MI-QUIT was to focus on smoking cessation solely among women of reproductive age. However, the burden of chronic conditions experienced by tobacco users within the MSHC patient population extended beyond the original focus of the program. To respond to identified health disparities related to higher rates of tobacco use in the MSHC patient population, the funder approved an expansion of MI-QUIT to navigate all persons 18 and older to cessation services, with a dual emphasis on women of reproductive age and older adults at elevated risk of cancer, cardiovascular disease, diabetes, and other chronic conditions. Since the program's inception from 2014 to 2016, MI-QUIT navigated ~576 high risk patients to cessation services. In 2017, the MI-QUIT project was then funded by the Chicago Department of Public Health (CDPH) to address tobacco cessation in some of Chicago's most underserved communities. From 2017 to 2018, the MI-QUIT program navigated 327 tobacco users within the MSHC network to EB tobacco cessation services supported by training by the American Lung Association (ALA). Cessation services include lay and clinical patient navigation to care coordination, tobacco cessation motivational interviewing, facilitated EB tobacco cessation support group, and nicotine replacement therapies (NRTs).individual, interpersonal, organizational, community, and policy levels 16), resulting in increased access, detection, and tobacco cessation as evidenced by the MI-QUIT program.Disparities in lung cancer screening and tobacco cessation in racial and ethnic minorities, particularly in AA communities, is a multi-layered health inequity. Therefore, a multi-level solution is needed to examine the barriers and facilitators to lung cancer screening in high risk AA populations . The UI At the individual level, patient navigators play an integral role in accessing patients' knowledge and beliefs about lung cancer risk factors and screening . Patientfacilitate and minimize individual level barriers that patients may face through promotion of patient support services  to develop client and provider reminders, implement provider level training, or utilize the Uniform Data Systems (UDS) metrics to develop and evaluate goals for mitigating risk factors for lung cancer such as tobacco cessation occur at this level , 22. Addulations . The MI-Nobody Quits Like Chicagoland and other lung cancer prevention and smoking cessation events. As part of our community level partnership, MI-QUIT coordinates dissemination of educational information to various community based organizations (CBOs), such as local tribal health clinics and LGBTQ organizations. Patient navigators also facilitate community cancer screening and prevention engagement through health fairs sponsored by local CBOs and elected officials. Partnerships with the CDPH provide resources to support EB navigation to the Illinois Tobacco Quitline and other local and statewide resources for tobacco cessation  and the American Cancer Society (ACS) Lakeshore Division in its cancer prevention and control efforts . The ALAessation .Policy Level demonstrates a similar dual role that FQHCs play at both the interpersonal and community level, community stakeholders, CBOs and public health partners also play vital roles at both the community and policy levels. One of the aims of the Office of Community Engaged Research and Implementation Science (OCERIS) which sits within the Cancer, Prevention and Control (CPC) program of the UI Cancer Center is to identify and develop health policy and research priorities that are relevant to the catchment population, MSHC, community agencies, and other health delivery stakeholders. The SEM places a much needed focus on the ability to translate national lung cancer screening recommendations and evidence based guidelines for tobacco cessation into local cancer center policies supported by multiple stakeholders. Additionally, a critical examination of existing policies also informs an important research framework that assesses the applicability and generalizability of existing guidelines and recommendations for high risk populations. For example, the existing USPSTF lung cancer screening guidelines were based on the results of the NLST, which were biased by the underrepresentation of racial and ethnic minorities. Additionally, the policy level of the SEM also addresses environmental factors. Underserved communities and predominantly racial/ethnic minority communities, including AA communities, are known to have greater environmental exposure to air pollution and other environmental carcinogens  has been shown to cause altered methylation of stress pathways . In breaApproximately a third of the U.S. population is comprised of racial/ethnic minorities, but recent reports suggest that minorities make up <18% of the patient population in clinical trials supported by the National Cancer Institute (NCI) and 17% of all Food and Drug Administration (FDA) clinical trial participants . Minoritresearchers range from broad to specific challenges. Historical use and misuse of minority populations in research  have contributed to generational medical and research mistrust  to develop a policy brief to highlight the importance of lung cancer screening using LDCT in high risk populations  team to develop: (1) a diagnostic screening investigation that monitors non-cancer patients following their initial laboratory results and determines the strength of the correlation between positive epigenetic screening results and clinical diagnoses of cancer; and (2) a diagnostic validation investigation, which will compare laboratory results from cancer and non-cancer patients to determine if the strength of the positive predictive values and negative predictive values observed in a prior study with a non-diverse population hold true in a new more diverse patient population. Using a panel of DNA methylation based biomarkers, whose efficacy was previously established in a another study, the CELLI Team will collect blood and urine specimens from patients at three FQHCs in high risk communities, the Englewood, Back of the Yards, and Near West (Main) MSHC sites . Cell frTo deploy theory into practice, the UI Cancer Center is implementing a multi-level approach to address lung cancer screening within high risk AA and FQHC populations. Guided by the CDC's SEM, the UI Cancer Center utilizes Implementation and Dissemination Science to continue to implement both standard-of-care lung cancer screening and navigation along with innovative epigenetic and health disparities research . Early sAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Overfishing is a major threat to the survival of shark species, primarily driven by international trade in high-value fins, as well as meat, liver oil, skin and cartilage. The Convention on the International Trade in Endangered Species of Wild Fauna and Flora (CITES) aims to ensure that commercial trade does not threaten wild species, and several shark species have recently been listed on CITES as part of international efforts to ensure that trade does not threaten their survival. However, as international trade regulations alone will be insufficient to reduce overexploitation of sharks, they must be accompanied by practical fisheries management measures to reduce fishing mortality. To examine which management measures might be practical in the context of a targeted shark fishery, we collected data from 52 vessels across 595 fishing trips from January 2014 to December 2015 at Tanjung Luar fishing port in East Lombok, Indonesia. We recorded 11,920 landed individuals across 42 species, a high proportion of which were threatened and regulated species. Catch per unit effort depended primarily on the number of hooks and type of fishing gear used, and to a lesser degree on month, boat engine power, number of sets and fishing ground. The most significant factors influencing the likelihood of catching threatened and regulated species were month, fishing ground, engine power and hook number. We observed significant negative relationships between standardised catch per unit effort and several indicators of fishing effort, suggesting diminishing returns above relatively low levels of fishing effort. Our results suggest that management measures focusing on fishing effort controls, gear restrictions and modifications and spatiotemporal closures could have significant benefits for the conservation of shark species, and may help to improve the overall sustainability of the Tanjung Luar shark fishery. These management measures may also be applicable to shark fisheries in other parts of Indonesia and beyond, as sharks increasingly become the focus of global conservation efforts. Overfishing is the greatest global threat to marine fish stocks –5. SeverIt is also increasingly acknowledged that sharks play a critical role in maintaining functional and productive ocean ecosystems , as wellAlopias spp.) and silky shark  recently coming into force, this is likely to have huge implications for Indonesia’s economically important shark industry, and the coastal communities depending on it. In order to balance conservation and socioeconomic objectives, robust management systems must be put in place that ensure and allow sustainable fishing and trade. This necessitates the identification of practical management measures that can reduce mortality of threatened and regulated species at the point of catch, and provide realistic options for fishers to effectively and measurably improve the sustainability of their fishing practices.Indonesia is the world’s largest shark fishing nation , 14, andThis study analyses two years of qualitative and quantitative data from one of Indonesia’s targeted shark fisheries in Tanjung Luar, West Nusa Tenggara Province. We outline the key characteristics of the fishery, including fishing behaviour and overall catch volumes and composition. We analyse the impacts of different fishing techniques, and present factors influencing overall catch per unit effort (CPUE) of individual shark fishing trips, as well as factors influencing the likelihood of catching threatened and regulated species. Finally, we discuss the implications of our findings, and provide practical recommendations for fisheries management measures, which can support CITES implementation for sharks and reduce the catch of threatened and regulated species, in Indonesia and beyond.This work was conducted under a Memorandum of Understanding (MoU) and Technical Cooperation Agreement (TCA) between the Wildlife Conservation Society (WCS) and the Ministry of Environment and Forestry (MoEF), Ministry Marine Affairs and Fisheries (MMAF) and the Marine and Fisheries Agency (MFA) of West Nusa Tenggara Province. These documents were approved and signed by Sonny Partono , Sjarief Widjaja , and Djoko Suprianto (Acting Head of MFA of West Nusa Tenggara Province). Due to this MoU and TCA no specific research permit was required. We collected data by measuring sharks that were already caught, dead, and landed by fishers in Tanjung Luar, with no incentives, compensation or specific requests for killing sharks for this study. WCS participates in the Conservation Initiative on Human Rights and the rules and guidelines of our Internal Review Board ensures that any research protects the rights of human subjects. We did not apply for an IRB permit for this study because our study design focused on collecting fish and fisheries data as opposed to personal socio-economic data. The FDGs and interviews were conducted to obtain early scoping information about fishing practices, and to establish protocols for more detailed fisheries data collection (as used in this study), and socio-economic data collection , which Tanjung Luar, located in East Lombok, West Nusa Tenggara Province, Indonesia , is a laa priori sampling decisions were not possible [In January 2014 we conducted preliminary scoping research to better understand the operational and socioeconomic characteristics of Tanjung Luar’s shark fishery. During a three-week scoping visit a team of four trained Indonesian enumerators conducted semi-structured interviews and focus group discussions (FDGs) with fishers, boat owners and traders, alongside naturalistic observation in the field. Respondents were selected through purposive sampling, since the research was exploratory in nature and possible . We condpossible .Shark landings data were collected by three experienced enumerators, who were trained in species identification and data collection methods during a two-day workshop and three weeks of field mentoring to ensure the accuracy of the data collected. Landings were recorded every morning at the Tanjung Luar shark auction facility where shark fishers usually landed dead sharks, from 5am to 10am from January 2014 to December 2015. The enumerators recorded data on catch composition and fishing behaviour  from 52 From fishing behaviour and catch data we calculated the overall species composition of catch. We calculated catch per unit effort (CPUE) by number of individuals using both catch per set (hereafter CPUE per set) and catch per 100 hooks per set (hereafter standardised CPUE) ,26. ThisTo understand factors influencing overall CPUE we log transformed CPUE per trip to fit a normal distribution, and fitted linear models (LMs) of CPUE per trip to fishing behaviour variables . We consTo inform the development of practical fisheries management measures (e.g. gear restrictions), we also specifically analysed differences in CPUE for surface and bottom longline gears employed in the fishery, using two-way ANOVAs.To identify variables influencing the catch of threatened and regulated species we conducted a two-step process. In the first step, we identified factors influencing the likelihood of catching any threatened/regulated species during a given fishing trip, by creating binary response variables for whether a threatened species had been caught during a trip , and separately for whether a regulated species had been caught during a trip . We then fitted generalised linear models (GLMs) with binomial errors to the binary response variables, separately for catch of threatened species and catch of regulated species. In the second step we identified variables that significantly influenced the CPUE of threatened species and the CPUE of regulated species, given that any were caught. We removed all records in which no threatened or regulated species were caught, log transformed standardised CPUE of threatened and regulated species, and fitted linear models (LMs) of standardised CPUE of threatened species and standardised CPUE to regulated species to fishing behaviour variables. Again, we considered all meaningful models and used minimum AIC values with stepwise analysis of variance to identify the best fit  and mostA total of 52 shark fishing vessels operate from Tanjung Luar, all of which are classified as small-scale according to the Indonesian Ministry of Marine Affairs and Fisheries (MMAF) vessel categorisation system, with <7GT capacity. These vessels are operated by approximately 150 highly-specialised shark fishers, from Tanjung Luar village and Gili Maringkik, who make up roughly 5% of the local fisher population. The shark industry is more profitable than non-shark fisheries, and shark fishers report high household dependency on shark resources, low occupational diversity, and limited capacity and aspirations to move into other fisheries or industries.Euthynnus spp., Rastrellinger spp.) used as bait. Surface and bottom longlines systematically vary in length, depth deployed, number of sets, number of hooks used, and soak times  with higher horsepower (HP) engines spend more time at sea than smaller vessels (≤12m) (p<0.001), and reach fishing grounds outside of West Nusa Tenggara. These vessels primarily fish in southern Sumbawa and Sumba Islands, however, they also reach as far as eastern Flores, Timor Island, and the Java Sea . Larger,Carcharhinus falciformis), black tip shark (Carcharhinus limbatus) and scalloped hammerhead (Sphyrna lewini).During the study period we recorded shark catch from a total of 595 fishing trips. We recorded 11,678 individual sharks, with an average total catch of 963 individuals per month (SD ± 434) and 19.7 individuals per trip (SD ± 15.6). Standardised CPUE (per 100 hooks per set) ranged from 0.05 to 22.13 individuals, with an average of 0.96 and a mode of 0.20. Catch consisted of 42 different species from 18 families . 22% of Measures of CPUE for the Tanjung Luar shark fishery vary spatially and temporally, and with several aspects of fishing effort including gear type, hook number, engine power and number of sets. An initial comparison of average catch per trip and catch per set of the two major gear types, surface longline and bottom longline, indicates that CPUE of surface longlines was significantly higher than that of bottom longlines . CPUE  was also positively associated with number of hooks, engine power, and number of sets . HoweverWhen controlling for hook number using standardised CPUE  the relationships were reversed, with standardised CPUE of bottom longlines significantly higher than that of surface longlines . Month, engine power, number of sets and fishing ground were also identified as significant variables , althougBest fit GLMs indicated that the most significant factors influencing the likelihood of catching threatened species were month  and fishing ground (Other (i.e. fishing grounds outside of WNTP and ENTP) was significantly higher: p<0.01). Significant factors associated with standardised CPUE of threatened species were number of hooks (p<0.001), fishing ground , engine power (p<0.001) and trip length (p<0.001) .The most significant factors influencing the likelihood of catching regulated species were month (January was significantly lower: p<0.001), number of hooks (p<0.001) and engine power (<0.01). Significant factors associated with standardised CPUE of regulated species were number of hooks (p<0.001), fishing gear (<0.001), number of sets (p<0.001), engine power (p<0.01) and month (November and January: p<0.05) .Although Tanjung Luar’s targeted shark fishery is small in scale, considerable numbers of shark are landed, including a large proportion of threatened and regulated species. A key finding is that measures of CPUE, for all sharks and for threatened and regulated species, vary spatially and temporally, and with several aspects of fishing effort including gear type, hook number, engine power and number of sets. Moreover, the relationships between CPUE and fishing behaviour variables are different for different measures of CPUE . This highlights the importance of using appropriate standardisation for meaningful comparisons of CPUE across different gears and vessel types, and has important implications for fisheries management.Unstandardised CPUE  was significantly lower in January. This is during the west monsoon season, which is characterised by high rainfall and adverse conditions at sea for fishing. Unstandardised CPUE was also significantly lower in West Nusa Tenggara Province (WNTP) than East Nusa Tenggara Province (ENTP) and other provinces, suggesting a lower abundance of sharks in this area. Engine power had a significant positive influence on unstandardised CPUE, and was also associated with longer trips and more sets, which was likely due to the ability of vessels with larger engines to travel longer distances, over longer time periods, and with higher numbers of sets, to favoured fishing grounds. Unstandardised CPUE was also significantly higher for surface longlines than bottom longlines. However, when standardising CPUE for the number of hooks  this relationship was reversed. Bottom longlines exhibit a higher standardised CPUE, with negative relationships between catch per 100 hooks per set and number of hooks and frequency of sets. Vessels with moderate engine horsepower (50-59hp) also had the highest standardised CPUE. Since surface longlines systematically employ significantly more hooks than bottom longlines (400–600 vs 25–200 hooks), and tend to be associated with larger boats, longer trips and more sets, these findings suggest that although increasing fishing effort increased total catch for these gears and trips, there were diminishing returns of this increased effort above low to moderate levels.Carcharhinus falciformis), which are circum-tropical and coastal-pelagic, and exhibit limited site-fidelity or aggregation behaviour, while threatened species catch is dominated by scalloped hammerheads (Sphyrna lewini), which are known to aggregate in schools. These schools of scalloped hammerheads may be more restricted to specific aggregation sites outside of WNTP and ENTP waters, while silky sharks are found in uniform abundance throughout fishing grounds.A large proportion of Tanjung Luar’s shark catch consisted of threatened (22%) and regulated species (46%). Month is a significant factor in explaining standardised CPUE of both threatened and regulated species, which could indicate seasonal variation in the abundance of these species in the Tanjung Luar fishing grounds, or seasonal impacts on CPUE due to poor weather conditions. Fishing ground was a significant factor in explaining the catch of threatened species but not the catch in regulated species. This may be due to differences in range, distribution and relative abundance of species within these groups. Threatened species make up a relatively small proportion of Tanjung Luar’s catch in comparison to regulated species, which make up almost half of the catch (46%). As such, regulated species may generally be more abundant and spatially diffuse than threatened species, and therefore caught more uniformly across fishing grounds. For example, regulated species catch is dominated by silky sharks  of threatened and regulated species and number of hooks, but a significant negative relationship between standardised CPUE (catch per 100 hooks per set). This was likely due to diminishing returns of adding additional hooks, and indicates that the effort for threatened and regulated species was exceeding maximum sustainable yield effort, such that increases in effort (e.g. hook number) were leading to decreases in catch –30.Due to the profitability of the shark industry in Tanjung Luar, and limited adaptive capacity and willingness of shark fishers to move into other industries, it is necessary to identify practical and ethical management interventions that can improve the sustainability of the fishery whilst also mitigating the negative socio-economic consequences for coastal communities. Our findings indicate that spatiotemporal closures and restrictions on fishing effort could improve the overall catch per unit effort and sustainability of the Tanjung Luar shark fishery, and lead to positive conservation outcomes for priority species.Sphyrna lewini) aggregation sites. Well-targeted spatial closures for this species could significantly reduce catch of threatened species in this fishery.Since the location of shark fishing grounds plays a significant role in determining the likelihood of catching threatened species and their associated CPUE, improved marine spatial planning, with the identification of marine protected areas (MPAs) that protect critical shark habitat and shark populations, could reduce catch of species of conservation concern –33 and iThe relationships between gear type, several aspects of fishing effort , standardised CPUE of all shark species and standardised CPUE of threatened and regulated species suggest that there is an optimal effort that could increase overall CPUE of the fishery and significantly reduce fishing mortality of species of conservation concern. For example, our data suggest that CPUE peaks with low to intermediate trip lengths and gear sets, intermediate engine power and hook numbers of less than 75 per set longline. Although standardised CPUE of threatened and regulated species is also higher when fewer hooks are deployed, the catch per set and overall mortality is significantly lower. Regulations that control the number of hooks in combination with incentives for shark fishers to tightly manage the number of hooks they deploy could significantly reduce mortality of threatened and endangered species, maximise the overall CPUE of the fishery, and reduce operational costs for fishers, making shark fishing in Tanjung Luar more sustainable and more cost effective –41.Acknowledging that almost half of Tanjung Luar’s shark catch consists of CITES-listed species, developing measures that ensure both the sustainability of the fishery, and full traceability and control of onward trade, will be crucial for implementing CITES . The IndAs baseline data on shark population health are limited, and there is no standardised, fisheries-independent system for monitoring long-term changes in shark populations, indirect bio-indicators  coulThese lessons may also apply to shark fisheries in other parts of the world. As sharks increasingly become the focus of global conservation efforts it should be acknowledged that species protection alone will not be enough to reduce mortality of priority species. More needs to be done to identify practical fisheries management measures that can reduce pressure on the most vulnerable species and populations, but also support sustainable use of species that are less susceptible to overfishing. Shark fishing forms an integral part of the livelihood strategies of many coastal communities , 23, andS1 Dataset(XLSX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.


GBD 2017 SDG Collaborators. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392: 2091–138—2018; In this Global Health Metrics paper, affiliation details have been amended for Mina Anjomshoa, Joseph Adel Mattar Banoub, Behzad Khafaei, and Yasin Jemal Yasin; and the declaration of interests statement has been amended for Boris Bikbov. Additionally, the reference numbering has been updated. These corrections have been made to the online version as of June 20, 2019.


With the aging of the worldwide population, films inevitably include an increasing number of stories about aging and its vicissitudes. Gerontologists acknowledge that aging  includes elements of decline, loss, and fear– along with opportunities for new learning and creativity, contributions, love, and satisfactions. However given mainstream society’s predominant demand for the status quo, we should not be surprised that films made for popular, commercial audiences tend to reflect self-reinforcing, negative stereotypes and defenses against them . This symposium seeks to: 1) Name and illustrate this filmic process of reinforcing negative stereotypes and misconceptions; 2) Describe and illustrate two existing theories that. explain positive processes associated with healthy aging; 3) Identify and illustrate films that constitute positive alternatives to the status quo and, in so doing, open the door to films presenting realistic stories of the positive balancing of later-life Integrity with Despair. The first presenter will articulate and illustrate this filmic process of reinforcing negative stereotypes and misconceptions. Presenters #2 and 3 will describe and illustrate two existing theories that explain positive processes associated with healthy aging . Presenter #1 will return to identify and illustrate films that constitute positive alternatives to the status quo and, in so doing, open the door to discussing films that present realistic stories of older adulthood’s complexities.


Preterm and low birth weight infants are at greater risk for mortality and a variety of health and developmental problems. Data from the Finger Lakes Perinatal Data System database on 316,956 deliveries occurring between 2004–2014 and pregnancy outcomes were analyzed to assess the association of periodontal (gum) disease with depression, other maternal factors and adverse birth outcomes. Adjusted effects of periodontal disease and depression on adverse birth outcomes were estimated using multiple logistic regression models and path analysis. Having preterm delivery was associated significantly with depression , having adequate health care , smoking during pregnancy , and being less educated . Having low birth weight was significantly associated with depression , smoking during pregnancy , and being less educated . Periodontal disease was significantly associated with alcohol use during pregnancy  and white race . Depression was significantly associated with periodontal disease  and alcohol use during pregnancy . We concluded that a positive association existed between depression during pregnancy and adverse birth outcomes, and that depression served as a mediator in the association of periodontal disease with adverse birth outcomes. Maintaining good oral health during pregnancy is an important aspect of maintaining overall good health during pregnancy and throughout a woman’s lifespan. According to the Advisory Committee for Oral Health Care During Pregnancy, in years 2007–2009, 35% of U.S. women did not attend a dental visit within the past year and 56% of women did not visit a dentist during pregnancy . NumerouAccording to the literature, maternal depression during pregnancy is also associated with adverse perinatal and infant outcomes. A systematic review and meta-analysis of thirty studies suggested that premature delivery was significantly associated with maternal depression . A largePoor oral health, especially gingivitis and periodontitis, is recognized as a source of systemic inflammation. Currently, there is emerging evidence that depression is also an inflammatory disorder, indicated by increased levels of CRP and other pro-inflammatory factors; persons diagnosed with depression have been found to have higher levels of proinflammatory cytokines, acute phase proteins, chemokines and cellular adhesion molecules. Additionally, proinflammatory cytokines have been found to interact with many of the pathophysiological domains that characterize depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior . There aConsidering similar mechanisms related to systemic inflammation that are associated with depression and periodontal disease, we hypothesize that there is a positive association between periodontal disease and adverse birth outcomes and there is a positive association between depression and adverse birth outcomes. Further, we examine the positive association of periodontal disease with adverse birth outcomes mainly through the mediating effect of depression. A mediator is a variable that is in a causal sequence between two variables . MediatiIn this study, we therefore sought to examine the association between periodontal disease and depression and between adverse birth outcomes among women who gave birth between 2004–2014 in thirty counties surrounding Rochester and Syracuse, New York.The Perinatal Data System (PDS) initiative began in New York State (NYS) in the early 1990s as a perinatal quality improvement initiative funded by the New York State Department of Health. The Upstate New York Regional Perinatal Centers in Albany, Syracuse, Rochester, and Buffalo were among the first demonstration centers for the regionalization of perinatal services in the United States; all evolved into NYS-supported Regional Perinatal Centers with both quality of care and regional perinatal service responsibilities. The PDS effort was envisioned to support a data infrastructure to serve the quality improvement and evaluative needs of the Perinatal Centers, resulting in the PDS demonstration projects starting in 1993. The PDS database includes information on demographics of both infants and parents, access to care, pre-pregnancy risks, antepartum risky behaviors, antepartum infections, antepartum risks, maternal and birth outcomes. The PDS data used for the current analysis was collected between 2004 and 2014. The PDS database contains data on more than 345,000 deliveries that occurred between 2004 and 2014 in thirty counties surrounding Rochester and Syracuse and includes data on pregnancy outcomes; data on 316,956 deliveries formed the basis for the analyses. The University of Rochester Research Subject Review Board (RSRB) approved the study prior to its initiation. The data used in the study were fully anonymized before retrieval.The database includes a dichotomous survey question asked of all postpartum mothers that states: “Did you have any problems with your gums at any time during pregnancy, for example, swollen or bleeding gums?” The depression information was collected using the following question in the PDS survey questionnaire: “During your pregnancy, would you say that you were (select one): Not depressed at all, A little depressed, Moderately depressed, Very depressed, Very depressed and had to get help”. The depression question was adopted from the CDC’s PRAMS (Pregnancy Risk Assessment and Monitoring System) –19. The Characteristics of subjects with and without periodontal disease in the perinatal database were compared using Chi-Square tests for categorical variables and Student’s t-tests or Wilcoxon rank sum tests for continuous variables. Unadjusted effects of periodontal disease and depression on adverse outcomes such as small for gestational age (yes/no), large for gestational age (yes/no), preterm delivery (yes/no), and low birth weight (yes/no) were examined using both chi-square tests and logistic regression. Adjusted effects of periodontal disease and depression were estimated from multiple logistic regression models using SAS version 9.4  and path analysis using Mplus, version 7.3 . The covariates adjusted in multiple logistic regression models and path analysis included mother’s age at delivery, parity, adequacy of health care during pregnancy , insurance type , mother’s race, tobacco use during pregnancy (yes/no), alcohol use during pregnancy (yes/no), and mother’s education level . A P-value <0.05 was considered statistically significant. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated from both simple and multiple logistic regression models to assess the unadjusted and adjusted effects of periodontal disease and depression on adverse birth outcomes. The pathway analysis coefficients are the estimated coefficients from the logistic regression models in the pathway analysis that are equivalent to the log of estimated odds ratios.The distribution of maternal characteristics in the study population is presented in The distribution of birth outcomes characterized by maternal periodontal disease is presented in As presented in The results from path analysis are presented in In Our findings obtained from a large perinatal database in the Finger Lakes region of NY State suggest that depression during pregnancy is associated with all adverse birth outcomes under study, including being small for gestational age, being large for gestational age, being preterm and having low birth weight. Depression often remains untreated during pregnancy despite the fact that the prevalence of psychosocial stress is substantial . ContrarPositive associations between periodontal disease and adverse birth outcomes are well documented in the literature, however treatment of periodontal disease during pregnancy does not prevent preterm birth, fetal growth restriction, or preeclampsia –5, 23. IOur results also suggest that adverse birth outcomes were associated with smoking and alcohol use during pregnancy. Smoking and alcohol use during pregnancy are detrimental for the developing fetus and pregnancy outcomes; our analyses suggest that they were both harmful for pregnancy outcomes; women who reported smoking during pregnancy and use of alcohol were more likely to have preterm delivery and deliver babies with low birth weight. Reporting socially undesirable lifestyles occurring during pregnancy may have resulted in under-reported, yet significant findings. The key strength of our study was the analysis of data from a large, well-characterized sample from the general population of women who delivered babies in the Finger Lakes region of New York State, thereby enhancing the robustness and generalizability of the findings. A further strength was the availability of birth outcome data, including detailed information on infant weight, gestational age and preterm or term delivery of the baby. Limitations, in addition to the cross-sectional nature of the study, included the self-reported information about periodontal status and depression during pregnancy, and lack of data on use of anti-depressive medications. Thus, data must be interpreted cautiously with respect to the potential for recall bias and over- or under-estimation of the findings. Although the PDS database is broadly representative, our data may not be generalizable beyond the Finger Lakes region of New York State.We conclude that a positive association exists between depression during pregnancy and adverse birth outcomes, and that depression serves as a mediator in the association of periodontal disease with adverse birth outcomes. Considering the theorized link between infection, inflammation and adverse pregnancy outcomes, it is biologically plausible to consider depression as a mediator in the association of periodontal disease with adverse pregnancy outcomes. Potential pathways identified may include behavioral, infectious, endocrine and inflammatory mechanisms , especiaPreterm and low birth weight infants are at greater risk for mortality and a variety of health and developmental problems. As a result, the birth of a preterm or low birth weight infant may have significant emotional and economic effects on the infant’s family. The infant mortality rate for low birth weight infants is about 25 times that of the infant mortality rate for normal weight babies . Rates oConsidering the results of our study, depression may serve as a mediator in the association of periodontal disease with adverse birth outcomes. As such, obstetricians and dental providers caring for pregnant women should be made aware that women who have periodontal issues are more likely to be depressed during pregnancy and more likely to experience adverse birth outcomes. Future studies should include prospective studies that focus on oral health assessment of expectant mothers, administration of diagnostic interviews to assess depression during pregnancy, consideration for the use of anti-depressive medications during pregnancy, and counseling related to detrimental health behaviors such as smoking and alcohol use during pregnancy.


Federal policies related to forestry and forest health  have the potential to affect management practices, terms of international and interstate trade, and long-term sustainability and conservation. Our objectives were to review existing federal policies, the role of federal agencies in managing forest health, and guidance for future policy efforts. Since the 1940s, various federal policies relevant to forest health have been established, and several US Department of Agriculture (USDA) agencies have been empowered to assist with prevention, quarantine, detection, management, and control of insects and diseases. Overall, our review showed that relatively few national policies directly address forest health as a stand-alone objective, as most of them are embedded within forestry bills. Federal funding for forest health issues and the number of personnel dedicated to such issues have declined dramatically for some agencies. Concomitantly, native species continue to gain pestiferous status while non-native species continue to establish and cause impacts in the US. To enhance our ability and capacity to deal with current and future threats, concerted efforts are needed to advocate for both resources and stand-alone policy tools that take seriously the complexity of emerging sustainability challenges in both private and public forestlands. Natural and planted forests encompass ~300 million hectares and ~32% of total land area in the US. . Of thesPinus palustris Mill.) and ponderosa (Pinus ponderosa Dougl. ex Laws.) pines have unique biotic components associated with them, and the Appalachian Mountains have high rates of endemism for salamander and bird species [America’s extensive and diverse forests, including those in urban areas, provide a basis for multiple uses, including but not limited to timber and fiber extraction; non-timber products; recreation; wildlife habitat; clean water, soil, and air; and carbon sequestration, and are of high economic values to local communities, worth billions of dollars each year ,4,5,6. F species ,8,9. LonHistorically, US forests have been subjected to both natural and anthropogenic disturbances ,10. ExamUlmus americana L.) due to Dutch elm disease (Ophiostoma novo-ulmi Brasier vectored by Scolytus multistriatus Marsh.), whitebark pine  due to blister rust (Cronartium ribicola. J.C. Fisch.), ash (Fraxinus spp.) due to emerald ash borer (Agrilus planipennis Fairmaire), hemlocks (Tsuga spp.) in eastern US due to hemlock woolly adelgid (Adelges tsugae Annand), and red bays (Persea borbonia (L.) Spreng.) due to laurel wilt disease (Raffaelea spp. vectored by Xyleborus glabratus Eichhoff)   [20,21,2Public policies are enacted to address an issue or a problem with implications for public values and interests ,27. PublDendroctonus ponderosae Hopkins) in the Rocky Mountains, the American Southwest, and the Sierra Nevada, and southern pine beetle  in the northeastern states point to the importance of both climate change and forest conditions in driving insect activity outside of historic patterns of variability [Forest managers may treat native and non-native insects and diseases alike, viewing both as equally unwelcome invaders whose presence should be minimized or eliminated. Contemporary understanding of forest dynamics, however, suggests that native insects and diseases can play important roles in stand dynamics, nutrient cycling, and the creation of stand- and landscape-level heterogeneity and that some control measures may have reduced overall forest resilience ,32. At tiability ,25,32,33iability .Castanea dentata (Marsh.) Borkh) since the mid-20th century.The continued establishment and spread of non-native forest insects create additional impacts and damage to those created by native insects. For example,  estimateAs our collective understanding of forest insect dynamics advances, policy tools and mandates informed by high-quality scientific information are essential for sustainable forest management . Public The mission of the USDA Forest Service is “to sustain the health, diversity, and productivity of the Nation’s forests and grasslands to meet the needs of present and future generations” . Linked The Forest and Rangeland Renewable Resources Research Act of 1978—which builds on a similar act in 1974 . This acThe Healthy Forests Restoration Act (HFRA) of 2003 (House of Representatives (H.R.) 1904), —aimed primarily at addressing increases in the scale and impact of wildfires and insect outbreaks in forests nationwide . SpecifiThis act was amended in the 2014 Farm Bill; Title VI, Section 602 (Designation of Treatment Areas) established priorities for projects in areas that would reduce and ameliorate insect and disease outbreaks . SimilarThe “Wyden Amendment” (Public Law (P.L.) 105–277, Section 323) authorizes the USDA Forest Service to enter into cooperative agreements with “federal, tribal, state and local governments, private and nonprofit entities and landowners” to benefit federal lands and related investments at the watershed scale . These aFederal forest insect policy reflects a longstanding model of public–private cooperation in which the federal government provides technical and financial resources for treating both native and non-native forest insects and diseases across ownership boundaries. Federal agencies and federally funded scientific research have been central components of managing forest insects and diseases in the US. For the early US Department of Agriculture (under which the USDA Forest Service is located), eliminating bark beetles, defoliators, and other agents of tree mortality was a logical component of a larger vision of a regulated forest efficiently producing timber for human needs . The fedFederal policy content specifically focused on forest insects has become more common in recent proposed and enacted congressional legislation ,49, largIn addition to formal federal policymaking responses to forest insect outbreaks, the creation of regional place-based networks as a means of providing direction and resources for outbreak response has been observed in some geographies ,52,53. TIps and southern pine beetle outbreaks, while private properties surrounding the District had low levels of bark beetle infestations . Similar trends have been observed for southern pine beetle outbreaks in some National Forests in Mississippi [Overall, the task and mandate of the USDA Forest Service to protect and maintain forests  from forest health issues as defined by federal policy has increased, while the funding and resources to accomplish it have significantly decreased. This trend has been in place for at least two decades, and greatly hampers the recovery and restoration of forest stands. In the case of native insects achieving pest status, some of the forest health issues appear to be emerging primarily from the National Forests in the southeastern region . An examsissippi .Through its Forest Health Management (FHM) program under the State and Private Forestry program of Forest Health Protection (FHP), the USDA Forest Service assists non-federal government agencies—state and municipal—in evaluating and providing early warning on threats from both native and non-native forest pests . The FHMThe USDA Forest Service FHP also provides funding for various forest health projects related to evaluating the risk of insects and diseases, pesticide impact assessment, biocontrol of invasive plants, and new technology on the prediction and management of insects and diseases . Many ofThe USDA Forest Service Research and Development program funds in-house and extramural research on issues affecting the detection and management of insect pests. Funding for invasive species represents a small proportion of the total research and development budget and there is no specific line item for this function. Funding for research—both overall funding and funding targeting invasive species—has declined precipitously. Funding for invasive tree pests declined from $8 million in 2010 to $3 million in 2018. The Southern Research Station’s research division had 70 entomologists and 50 pathologists in the mid-1980s . By 2007The US Department of Agriculture’s Animal and Plant Health Inspection Service (USDA APHIS) has the principal responsibility for managing non-native insects and pathogens that attack native trees . This inUSDA APHIS’ programs are carried out primarily under the authority of the Plant Protection Act (PPA) of 2000 ) . This stThe statute provides the legal foundation for USDA APHIS to regulate the importation, exportation, and interstate movement of plant pests and articles (including plants) that could transport these pests . RegulatUSDA APHIS inspects imports of living plants at one of its 16 Plant Inspection Stations . All othLycorma delicatula (White)), and polyphagous and Kuroshio shot hole borers . USDA APHIS does provide some funding to address these pests, especially through grants funded through the Plant Pest and Disease Management and Disaster Program (§7721 of the Plant Protection Act).Similar to other federal agencies, USDA APHIS’ actual efforts to manage plant pests—especially those that threaten tree species—have been severely hampered by funding shortfalls. Funding for the management of “tree and wood pests” has declined from $85 million in 2009 to $54 million in 2018. At the same time, the number of pests has risen and the extent of known infestations and difficulty of addressing them have also increased. Among high-risk insect pests that USDA APHIS has not officially designated as “quarantine pests” are redbay ambrosia beetle, spotted lanternfly  established the Plant Pest and Disease Management and Disaster Program, which provided permanent funding drawn from the Commodity Credit Corporation to support enhanced pest analysis, improved pest surveillance, improved pest identification and technology enhancement, targeted domestic surveillance, enhanced mitigation capabilities, safeguard nursery production, and outreach . The AgrDuring the last few decades, there have been some major policies embedded as part of the larger farm and forestry bills that have indirectly and directly affected forest health issues in the US. While it is hard to quantify how these polices have directly shaped forest health and its management, such investments have been critical to allowing detection, control, and management to proceed as needed at multiple levels  in addiInsect and disease policy on federal lands has increasingly reflected prevailing social and political contestations regarding the proper role of human intervention in relatively natural forest systems. The emergence of regional governance networks with access to various tools for planning, responding to, and recovering from insect outbreaks—as well as to scientific information—suggests possible constructive pathways forward through conflict to achieving adaptive responses. However, long-term declines in funding for federal forest management   complicaIntroduction, establishment, and spread of non-native insects and diseases are managed by a separate USDA agency, the APHIS. Under the Plant Protection Act, USDA APHIS operates under mandates to both facilitate international trade and “reduce, to the extent practicable” the associated risk of pest introductions (PPA Sec. 7701 (3))—this creates a balancing situation. Clearly, greater and more comprehensive phytosanitary measures are needed as many sources demonstrate that forest pest and pathogen arrivals and introductions continue to occur in the US ,76,77,78Reference  reviewedMany scientists have opportunities to be involved in policy advocacy, depending upon the guidelines of their respective agencies and institutions ,80. AdvoOverall, we recommend a push for stand-alone major policy and funding efforts focused solely on enhancing the health of our forests. Such efforts will rebuild our capacity to respond effectively to insect and disease outbreaks, as they happen in real time. Policies that strengthen the research, outreach, and managerial capacity of federal agencies while also providing support to regional multi-stakeholder networks of practice would go a long way toward improving the acceptability and effectiveness of insect and disease management strategies and their impacts on US forests.


Macroautophagy  is a lysosome-dependent quality control process to degrade and turnover damaged or senescent organelles and proteins for cellular renewal. This essential process occurs in many eukaryotes to determine the cellular fitness and tissue homeostasis of organisms. Basal autophagy plays important roles during development and differentiation. Remarkably, autophagy is also a defense mechanism employed against environmental stress such as nutrient deprivation, aging, pathogen invasion, and various disease states . As suchIn this Special Issue, we focus on the roles of autophagy in systemic, specific tissue (organs and cells) injury or organ failure associated with sepsis, inflammation, metabolic disorder, toxic chemicals, ischemic–reperfusion, hypoxic oxidative stress, tissue fibrosis, trauma, nutrient starvation, cancer biology, and aging. This Special Issue contains 5 research papers and 10 review articles addressing the impact of autophagy on various organ injuries and homeostasis. Each of the reviews is authored by experts in their fields and our intention is to provide comprehensive updates in specific areas relating autophagy to tissue injury and homeostasis in which there has been considerable recent progress. The knowledge gained from the identification and characterization of new molecular mechanisms will shed light on biomedical applications for tissue protection through the modulation of autophagy.db/db mice. Eid et al.’s [Three articles focus on the role of mitochondrial ubiquitin kinase PINK1 and Parkin E3 ubiquitin ligase (PINK1/Parkin)-dependent mitophagy in organ homeostasis. Work by Zhou et al.  demonstret al.’s . Diet reet al.’s .Metformin, a biguanide drug, is the most commonly prescribed drug for the treatment of type 2 diabetes as a glucose-lowering and insulin-sensitizing agent. Previous work has shown that metformin disrupts mitochondria energetics and represses the mechanistic target of rapamycin complex 1 (mTORC1) signaling in cancer cells . SaladinIn the review articles, we included topics summarizing the current progress on the cardioprotective effects of autophagy in sepsis . The speTwo articles summarized the contribution of autophagy in the homeostasis and pathogenesis of the intestine, focusing on inflammatory bowel disease (IBD) from the aspects of intestinal innate immune cells response  and the Weiskirchen and Tacke  excellenLee et al.  offer a Finally, Wu et al.  discusseCells editorial office for their work on this Special Issue.The 15 publications in this Special Issue summarize the significant amount of progress that has contributed to our understanding of autophagy in normal tissue homeostasis and in disease states during dysfunction. Importantly, these publications provide future research directions for the design of therapeutic strategies targeting autophagy to combat disease and tissue injuries. I wish to thank all the authors for their contributions, the scientific communities for peer reviewing, and the staff at the


Universal health coverage (UHC) assures all types of health service and protects all citizens financially in any conditions due to illness. Globally, the UN sustainable development goal (SDG) provides high priority for UHC as a health related goal. The National health system of Nepal has prioritized in similar way. The aim of this study is to explore the challenges and opportunities on the road to UHC in Nepal.We used varieties of search terminologies with popular search engines like PubMed, Google, Google Scholar, etc. to identify studies regarding Nepal’s progress towards UHC. Reports of original studies, policies, guidelines and government manuals were taken from the web pages of Ministry of Health and its department/division. Searches were designed to identify the status of service coverage on UHC, financial protection on health particularly, health insurance coverage with its legal status. Other associated factors related to UHC were also explored and presented in Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.We found 14 studies that were related to legal assurance, risk pulling and financing of health service, 11 studies associated to UHC service coverage status and, 7 articles linked to government stewardship, health system and governance on health care. Constitutional provision, global support, progress on the health insurance act, decentralization of health service to the grass root level, positive trends of increasing service coverage are seen as opportunities. However, existing volunteer types of health insurance, misleading role of trade unions and high proportion of population outside the country are main challenges. The political commitment under the changing political context, a sense of national priority and international support were identified as the facilitating factors towards UHC.To achieve UHC, service and population coverage of health services has to be expanded along with financial protection for marginalized communities. Government stewardship, support of stakeholders and fair contribution and distribution of resources by appropriate health financing modality can speed up the path of UHC in Nepal. Universal health coverage (UHC) is a broad concept that has been implemented in several ways. The common denominator for all such programs is some form of government action aimed at extending access to health care as widely as possible and setting minimum standards. Universal health care should be implemented through legislation, regulation and taxation. In UHC, all people can use the health promotion, prevention, assistance, rehabilitation and palliative care services that they need, in sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship . UHC invOperationally, UHC is defined as legislation provision for universal health insurance and > 90% coverage for skill birth attendance and prepayment health insurance that assures the service coverage with legal guarantees . In thisThere is gross inequality in health status between developing and developed countries, poor and rich, male and female and other groups. Beyond health inequalities, approximately 44 million households, or say more than 150 million individuals worldwide, face catastrophic health-care expenditures; of these, about 25 million households containing more than 100 million people are pushed into poverty by these costs . Beyond Since 1950, Nepal has been profoundly able to increase the health status and in South East Asia all aspects of health care have been improved but still there are some challenges. From 1950 to 1990, there was a great challenge to extend primary health care, from 1990 to 2006, there were challenges regarding health service integration and after 2006, there have been cumulative challenges of service extension, integration, quality health service, equity, access and financial protection during illness . At thisSearch strategies to identify studies regarding UHC in Nepal included searching Google, Google Scholar, PubMed, WHO research portal; the Health Inter-Network Access to Research Initiative (HINARI) and web page of Ministry of Health and Population (MoHP). We applied all of the following key words: ‘universal health coverage’, ‘insurance’, ‘social insurance’, health service, health service coverage, financing, financial protection, legal assurance in health care, ‘Nepal’ in conjugation with boolean operators  in PubMed  AND universal[All Fields] AND  AND  AND .We additionally included equivalent terms from medical subject headings such as ‘Social Security’, ‘Insurance’, ‘Insurance coverage’. As policy documents in general, neither covered in PubMed/Medline nor published electronically elsewhere, we further expanded our search to the web pages of the Ministry of Health and respective departments. For the Scholar Google we used the above terminology and fixed the search by date  and relevance (proximity to the terms).Global research related to health for specific country was found in Health Inter-Network Access to Research Initiative (HINARI) and we used this portal too and fixed the search with WHO regional sites (South East Asia), content type (publication and guideline) and all available formats. The selected articles reference list were the potential sources for this study as bibliographical search. The remaining source was taken from Google search as grey materials. The search approaches were targeted on UHC indicators, index and financial protection indicators like out of pocket expenditure, catastrophic health cost, government health spending, total health expending, etc.In the first stage, we found 2118 records from Scholar Google, PubMed/Medline, HINARI, web pages of Ministry of Health and Population and its branches and Google search which met the inclusion criteria. In first stage screening we removed 2063 sources due to record duplication and title twisted. We assessed 55 full text articles and excluded 23 sources . Finally we identified 32 perfectly matched sources for this study , usually published since 2010. In wide concept of UHC all types of health services; preventive, promotional, curative, rehabilitative and palliative and in operational term 16 UHC health service indicators and area related to financial protection. The final selection of articles at this stage was based on the following criteria, i) content relevance to the theme of the sources , and ii) detail scope for Nepal. Items irrelevant to Nepal, specific health slogans and campaigns, sources from unpublished data were excluded from study.We found 32 resources related to the challenges and opportunities for UHC in Nepal where there could be 3 dimensions on challenges and opportunities viz. “legal assurance, risk pulling and financing of health service”; “UHC service coverage status” and “government stewardship, health system and governance on health care in Nepal”. We found 14 research articles related to legal assurance, risk pulling and financing of health service in Nepal. Likewise 11 articles are associated to service coverage status to the scope of UHC and remaining 7 sources are categorized under stewardship, health system and governance on health care in Nepal  on ANC and institutional service etc. are the potentialities but the poor achievement of the UHC index, an insufficient awareness level on utilization of health services, inadequate space to provide health services, double burden (infectious and non-communicable) of diseases in health care facilities and community and average quality of water sanitation and hygiene are the main challenges for health service coverage in Nepal Table .It is necessary to have strong government leadership to achieve UHC. External development partners (EDPs) are just supporting in own their interest but the government role would be influential in a wider area. Restructuring of health service for center, province and local level, upgrading of the health information system through online availability, involvement of private health facilities for quality health service are significant positive factors. Political ignorance about health service due to previous service delivery structure, improper coordination among departments and divisions under MoHP, poor dynamism in health system and donor dependent health financing approach, etc. are the main factors hindering achievement UHC Table .In this study, the opportunities and factors hindering achievement of UHC in Nepal were explored. Those challenges are multidimensional. Nepal started an insurance scheme recently after a serious lobby of visionary health care professionals, international organizations and interest groups. However, small community based health insurance (CBHI) have been on the scene since 1990s providing small subsidy to people. The coverage of health insurance was small, new enrollment was limited; renewal of health insurance membership dwindled rapidly after some years of implementation. The service coverage of health care was not satisfactory. The quality of health service and financial protection were inadequate. Grass root level health workers were confused about the changing policy of government like user fee, community drug program, free health service, special health care services to minority groups, etc. and none of them ensures comprehensive package of health service with universal access.UHC is multidimensional because it’s legal, political, health system and socioeconomic agenda arose at the same time and same way all over the world . In mostFinancial protection of health care and economic sustainability are interlinked with each other but there has not been enough discussion on it. The health insurance coverage potentially contributes the sustainable economic growth and economic empowerment contributes for SDG and prosperity . There iThis is a crucial time to take action for UHC in Nepal because the political system has shifted and the UN SDG is highly focused on UHC in health related goals. Of course, there are some challenges to achieving UHC but those challenges can be addressed with high level political commitment and a businesslike accountable workforce. Population coverage for quality care and financial protection would be major breakthroughs to achieve UHC. Government stewardship, support of stakeholders, policy contribution of experts can only speed up the path towards UHC in Nepal.


Intersecting stigmatized social identities  and structural forms of privilege and oppression  can contribute to poor psychological wellbeing and clinical outcomes among older men with HIV (OMH). Using data from 6 focus groups and 15 interviews with 45 gay, bisexual and heterosexual OMH in Brooklyn, NY and inductive thematic analysis methods, we explored the impact of heteronormative gender roles and ideologies associated with masculinity on healthy aging with HIV. We found that changing physical and sexual function, appearance and growing financial expectations created threats to masculinity, fueling fears of perceived weakness, internalized feelings of shame, depression, anticipated loss of social status (partner loss), and loss of independence and autonomy. These findings suggest that normative gender beliefs, a key social determinant of men’s health, aging and intersectional stigma combined undermine psychosocial support and wellbeing and self-care needed to achieve healthy aging.