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Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, and from tumor tissues to tumor microenvironment and liquid biopsy. When coupled with well-validated epidemiologic methodology and well-characterized epidemiologic resources, the rich tumor pathological and molecular tumor information provide new research opportunities at an unprecedented breadth and depth. This is the research space where Molecular Pathological Epidemiology (MPE) emerged over a decade ago and has been thriving since then. As a truly multidisciplinary field, MPE embraces collaborations from diverse fields including epidemiology, pathology, immunology, genetics, biostatistics, bioinformatics, and data science. Since first convened in 2013, the International MPE Meeting series has grown into a dynamic and dedicated platform for experts from these disciplines to communicate novel findings, discuss new research opportunities and challenges, build professional networks, and educate the next-generation scientists. Herein, we share the proceedings of the Fifth International MPE meeting, held virtually online, on May 24 and 25, 2021. The meeting consisted of 21 presentations organized into the three main themes, which were recent integrative MPE studies, novel cancer profiling technologies, and new statistical and data science approaches. Looking forward to the near future, the meeting attendees anticipated continuous expansion and fruition of MPE research in many research fronts, particularly immune-epidemiology, mutational signatures, liquid biopsy, and health disparities.

Individuals with intellectual disabilities face discrimination on a daily basis. The coronavirus disease (COVID-19) pandemic has highlighted the systemic ableism that is embedded within American culture, particularly through health care bias and discrimination. In turn, this creates further marginalization during diagnosis, triage, and treatment of the novel coronavirus. Multiple states have filed complaints against state triage protocols that suggest an abled life is more worthy than a life with a disability. Although many of these protocols have been updated and replaced, generalized triage statements fail to address health care bias that is embedded within the American system. In addition to the existing solutions, proposed solutions to addressing health care bias include integrating social workers into the emergency management process and the overall disaster management field. To combat bias and ableism across the health care system, a social justice perspective that highlights discrimination, inequalities, and inequities in overall individual care must be adopted.

In today’s society, the use of social media has increased the public’s desire to receive information quickly and to be able to interact with communicators. During a disaster, the trend to turn to social media for information has risen in popularity. Society’s reliance on social media and quick access to information has led the field of emergency management and the role of a Public Information Officer to adapt to include social media as a crisis communication channel for information dispersal. Existing frameworks for the use of social media as a channel for crisis communications provide guidance for emergency management agencies across all levels of government but fail to account for the varying access to communication resources at the local level. Due to the differing access to communication resources and unique relationships with stakeholders at the local level, there is a need for guidance on how local emergency management agencies can use social media to disperse essential information. The proposed Communication Hub Framework utilizes local emergency management professionals’ relationships with key community stakeholders to aid in the distribution of essential information to community members via social media during a disaster.

Purpose: Emergency medical services (EMS) responders are a group of medically skilled professionals who perform a wide range of essential medical services within a community including emergency response, patient transport, and mobile integrated healthcare. The proper functioning of the EMS system is paramount to the well-being of the medical system and public health. The intent of this paper is to review current EMS standards and practice to determine the danger a high consequence infectious disease (HCID) may pose to these healthcare workers and the community.Areas Addressed: Through the review of EMS practice several areas were identified as vulnerabilities to the EMS network. These vulnerabilities consisted of the lack of standardized licensing practice, inconsistent medical direction, and the inability to properly implement the use of personal protective equipment (PPE). The compounding of these vulnerabilities allows for HCIDs to pose a serious threat to EMS personnel with the possibility of devastating and crippling the EMS infrastructure within the US.Discussion: The vulnerabilities identified must be addressed both to protect EMS providers and to enhance the resilience of the US healthcare system. Ways to address the identified vulnerabilities should focus on improving the EMS curriculum and increasing minimum levels of education for first responders. Targeting minimum education and training standards could be the most effect method of reducing the dangers of HCIDs to EMS systems.

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system with significant innovation in interdisciplinary disaster management applicable generally to urban nuclear detonation medical response. Model estimates of nuclear war casualties employed ESRI’s ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency’s WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency’s (DTRA’s) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory’s LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kt detonations and a single 1 mt (1000 kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims. Of particular importance is the interdisciplinary cooperation necessary for such a large-scale emergency response event, which would be exemplified by efforts such as the application of a Nuclear Global Health Workforce.

ObjectiveMosquito-borne diseases pose a threat to individual health and population health on both a local and a global level. The threat is even more exaggerated during disasters, whether manmade or environmental. With the recent Zika virus outbreak, it is important to highlight other infections that can mimic the Zika virus and to better understand what can be done as public health officials and health care providers.MethodsThis article reviews the recent literature on the Zika virus as well as chikungunya virus and dengue virus.ResultsThe present findings give a better understanding of the similarities and differences between the 3 infections in terms of their characteristics, clinical presentation, diagnosis methodology, and treatment and what can be done for prevention. Additionally, the article highlights a special population that has received much focus in the latest outbreak, the pregnant individual.ConclusionEducation and training are instrumental in controlling the outbreak, and early detection can be lifesaving. (Disaster Med Public Health Preparedness. 2017;11:290–299).

Coastal hospitals are often faced with the challenging decision to either evacuate or shelter-in-place in anticipation of a hurricane predicted to make landfall. The costs associated with hospital evacuation not only include transportation of patients to inland areas, but also the loss of revenue due to interruption of regular operations and the cost of potential damage to the hospital's infrastructure. Financial data provided by Memorial Health University Medical Center (MUMC, Savannah, Georgia) such as average inpatient and outpatient revenues, personnel wages, and transportation costs, were used to estimate the potential economic impact of hurricane evacuations on a coastal hospital. The results indicate that even prior to the arrival of tropical storm force winds, the hospital will incur an estimated total expenditure of approximately $9.5 million which includes evacuation expenses and loss of revenue due to disruption of regular services. In case the hurricane makes landfall, revenue losses will continue to accumulate until the hospital is able to resume regular operations. The cost of relocating patients back to MUMC after the hurricane event and the cost of any hurricane-related damage to the hospital infrastructure must also be taken into consideration. In conclusion, even though hospital evacuation for hurricanes may be unavoidable in certain circumstances, the financial burden placed upon the hospital may be mitigated to a certain extent by forward planning, infrastructure upgrades, and the rapid resumption of regular hospital function.

2017 was a record year for disasters and disaster response in the U.S. Redefining and differentiating key response roles like "immediate responders" and "first responders" is critical. Traditional first responders are not and cannot remain the only cadre of expected lifesavers following a mass casualty event. The authors argue that the U.S. needs to expand its understanding of response roles to include that of the immediate responders, or those individuals who find themselves at the incident scene and are able to assist others. Through universal training and education of the citizenry, the U.S. has the opportunity increase overall disaster resiliency and community outcomes following large-scale disasters. Such education could easily be incorporated into high school curriculums or other required educational experiences in order to provide all persons with the knowledge, skills, and basic abilities needed to save lives immediately following a disaster.

Review of: "Ball Hawks: The Arrival and Departure of the NBA in Iowa," by Tim Harwood. Iowa

Background Amongst medical providers, even though radiological and nuclear events are recognized as credible threats, there is a lack of knowledge and fear about the medical consequences among medical personnel that could significantly affect the treatment of patients injured and/or contaminated in such scenarios. The results of the only two nuclear detonations in war so far and more recent nuclear reactor accidents have demonstrated the remarkably inefficient response of the medical community. This study was conducted to evaluate the relative knowledge, willingness to respond, and familiarity with nuclear/radiological contamination risks among U.S. and Asian emergency medical personnel. Methods An IRB approved anonymous paper survey was distributed at various medical and disaster conferences and medicine courses in Japan and the U.S. The Surveys were written in Japanese and English and collected 4 categories of information: generalized demographics, willingness to manage, knowledge of disaster systems, and contamination risks. Results A total of 416 surveys were completed and collected. Demographics showed that physicians and prehospital responders were the prevalent survey responders. The majority of responders, despite self professed disaster training, were still very uncomfortable with and unaware how to respond to a radiological/nuclear event. Conclusion Despite familiarity with disasters both through courses and actual events, there is a paucity of comfort and knowledge regarding nuclear and radiological events amongst the medical community. Further education including course development in multiple languages promoted in multiple venues needs to occur to better educate and prepare the medical community for inevitable upcoming radiological/nuclear events.

Introduction:The US, as well as many countries, are being beseeched by more natural and man-made events; both small (e.g., shootings) and geographically vast (e.g., floods). Due to a myriad of issues, traditional first responders i.e., EMS, fire department, and police cannot be expected to be the only trained lifesavers on the scene. In the US (as in many countries), it is imperative to begin the discussion to better understand the role of the “injured” and “immediate” responders and how they interact with the “first” responders.Aim:To open a discussion amongst disaster experts about the merits of training and subsequent promotion of a curriculum for “immediate” responders.Methods:Literature review.Discussion:After recent evaluations of events, it is postulated that there are three categories of responders: the injured, the immediate, and the first (EMS, fire department, police). The premise upon which disaster risk reduction and building community resilience are achieved begin with strengthening, empowering, and equipping local populations with the appropriate tools. This would involve education, skills, and training. With the average general public trained, and if they are one of the first two categories, then the community would not only be better able to assist themselves, but also be able to integrate into the recovery process much more quickly and fully. By doing this, they will be empowered to take care of themselves, neighbors, and community, which in turn increases local resilience.

Lung cancer is the leading cause of cancer-related death in men in 87 countries and in women in 26 countries. The commensal microbiota lives on the epithelial barriers of the host and is vital for the health of the organism. Specific microbial species have been described to affect neoplastic pathology both at the gastrointestinal tract level and systematically in organs that are not normally associated with the gut microbiota. Studies have revealed the importance of the gut microbiota in the efficacy of anti-cancer therapies (chemo and immunotherapy) However, the role of lung microbiome in lung cancer remains largely unknown. We aimed to study the role of the lung microbiota during lung carcinogenesis progression in the context of p53/K-ras mutation and its impact on the tumor microenvironment. To further analyze the impact of the lung microbiota on lung cancer initiation, P53-Kras mutant germ-free mice will be colonized by intranasal instillation with bacteria identified in human lungs samples from lung cancer patients such as Variovorax paradoxus (V.paradoxus) and Acidovorax temperans (A.temperans) and the tumor burden will be calculated. Our data indicates Germ-free mice instilled with V. paradoxus trended towards an increase tumor burden compared to respective controls while A. temperans -associated germ-free mice seems to delay tumor growth. Germ-free mice, at 18 and 24 weeks post-Ad-Cre virus instillation, tends to have an increased tumor burden than their SPF counterparts. Also, changes in immune infiltrate were observed after flow cytometric analysis with preliminary data showing a decrease in CD45 positives cells the cells in mice instilled with V. paradoxus as well as an increase in Monocytes and Macrophages populations.

The watershed events of September 11, 2001; the anthrax attacks; Hurricane Katrina; and H1N1 necessitated that the United States define alternative mechanisms for disaster response. Specifically, there was a need to shift from a capacity building approach to a capabilities based approach that would place more emphasis on the health care community rather than just first responders. Georgia responded to this initiative by creating a Regional Coordinating Hospital (RCH) infrastructure that was responsible for coordinating regional responses within their individual geographic footprint. However, it was quickly realized that hospitals could not accomplish community-wide preparedness as a single entity and that siloed planning must come to an end. To reconcile this issue, Georgia responded to the 2012 US Department of Health and Human Services concept of coalitions. Georgia utilized the existing RCH boundaries to define its coalition regions and began inviting all medical and nonmedical response partners to the planning table (nursing homes, community health centers, volunteer groups, law enforcement, etc). This new collaboration effectively enhanced emergency response practices in Georgia, but also identified additional preparedness-related gaps that will require attention as our coalitions continue to grow and mature.(Disaster Med Public Health Preparedness. 2016;10:174–179)

Radioactive iodide (131I−) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish 131I− urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered 131I− and 3 hours later dosed with either saline, 30 mg/kg of NH4ClO4 or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH4ClO4 treated animals excreted significantly more 131I− compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T4) was administered daily over a 3 day period. During the first 6–12 hour after 131I− dosing, rats administered NH4ClO4 excreted significantly more 131I− than the other treatment groups. T4 treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after 131I− administration. We speculate that the T4 treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to 131I− compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.

Nuclear reactor accidents and the threat of nuclear terrorism have heightened the concern for adverse health risks associated with radiation poisoning. Potassium iodide (KI) is the only pharmaceutical intervention that is currently approved by the Food and Drug Administration for treating (131)I(-) exposure, a common radioactive fission product. Though effective, KI administration needs to occur prior to or as soon as possible (within a few hours) after radioactive exposure to maximize the radioprotective benefits of KI. During the Chernobyl nuclear reactor accident, KI was not administered soon enough after radiation poisoning occurred to thousands of people. The delay in administration of KI resulted in an increased incidence of childhood thyroid cancer. Perchlorate (ClO(4)(-)) was suggested as another pharmaceutical radioprotectant for 131I- poisoning because of its ability to block thyroidal uptake of iodide and discharge free iodide from the thyroid gland. The objective of this study was to compare the ability of KI and ammonium perchlorate to reduce thyroid gland exposure to radioactive iodide (131I-). Rats were dosed with 131I- tracer and 0.5 and 3 h later dosed orally with 30 mg/kg of either ammonium perchlorate or KI. Compared to controls, both anion treatments reduced thyroid gland exposure to 131I- equally, with a reduction ranging from 65 to 77%. Ammonium perchlorate was more effective than stable iodide for whole-body radioprotectant effectiveness. KI-treated animals excreted only 30% of the (131)I(-) in urine after 15 h, compared to 47% in ammonium perchlorate-treated rats. Taken together, data suggest that KI and ammonium perchlorate are both able to reduce thyroid gland exposure to 131I- up to 3 h after exposure to 131I-. Ammonium perchlorate may offer an advantage over KI because of its ability to clear 131I- from the body.

ObjectiveWe designed and conducted a regional full-scale exercise in 2007 to test the ability of Atlanta-area hospitals and community partners to respond to a terrorist attack involving the coordinated release of 2 dangerous chemicals (toluene diisocyanate and parathion) that were being transported through the area by tanker truck.MethodsThe exercise was designed to facilitate the activation of hospital emergency response plans and to test applicable triage, decontamination, and communications protocols. Plume modeling was conducted by using the Defense Threat Reduction Agency’s (DTRA) Hazard Prediction and Assessment Capability (HPAC) V4 program. The scenario went through multiple iterations as exercise planners sought to reduce total injuries to a manageable, but stressful, level for Atlanta’s health care infrastructure.ResultsAtlanta-area hospitals rapidly performed multiple casualty triage and were able to take in a surge of victims from the simulated attack. However, health care facilities were reticent to push the perceived manageable numbers of victims, and scenarios were modified significantly to lower the magnitude of the simulated attack. Additional coordination with community response partners and incident command training is recommended. Security at health care facilities and decontamination of arriving victims are two areas that will require continued review.ConclusionAtlanta-area hospitals participated in an innovative regional exercise that pushed facilities beyond traditional scopes of practice and brought together numerous health care community response partners. Using lessons learned from this exercise coupled with subsequent real-world events and training exercises, participants have significantly enhanced preparedness levels and increased the metropolitan region’s medical surge capacity in the case of a multiple casualty disaster. (Disaster Med Public Health Preparedness. 2015;9:681–689)

Purpose: To identify druggable oncogenic fusions in invasive mucinous adenocarcinoma (IMA) of the lung, a malignant type of lung adenocarcinoma in which KRAS mutations frequently occur. Experimental Design: From an IMA cohort of 90 cases, consisting of 56 cases (62%) with KRAS mutations and 34 cases without (38%), we conducted whole-transcriptome sequencing of 32 IMAs, including 27 cases without KRAS mutations. We used the sequencing data to identify gene fusions, and then performed functional analyses of the fusion gene products. Results: We identified oncogenic fusions that occurred mutually exclusively with KRAS mutations: CD74-NRG1, SLC3A2-NRG1, EZR-ERBB4, TRIM24-BRAF, and KIAA1468-RET. NRG1 fusions were present in 17.6% (6/34) of KRAS-negative IMAs. The CD74-NRG1 fusion activated HER2:HER3 signaling, whereas the EZR-ERBB4 and TRIM24-BRAF fusions constitutively activated the ERBB4 and BRAF kinases, respectively. Signaling pathway activation and fusion-induced anchorage-independent growth/tumorigenicity of NIH3T3 cells expressing these fusions were suppressed by tyrosine kinase inhibitors approved for clinical use. Conclusions: Oncogenic fusions act as driver mutations in IMAs without KRAS mutations, and thus represent promising therapeutic targets for the treatment of such IMAs. Clin Cancer Res; 20(12); 3087–93. ©2014 AACR.

Radioactive iodide ((131)I-) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish (131)I- urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered (131)I- and 3 hours later dosed with either saline, 30 mg/kg of NH(4)ClO(4) or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH(4)ClO(4) treated animals excreted significantly more (131)I- compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T(4)) was administered daily over a 3 day period. During the first 6-12 hour after (131)I- dosing, rats administered NH(4)ClO(4) excreted significantly more (131)I- than the other treatment groups. T(4) treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after (131)I- administration. We speculate that the T(4) treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to (131)I- compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.

The case of a 57-year-old woman with no personal or family history of coagulopathy or blood dyscrasia who was found to be factor VII deficient by routine laboratory testing is reported. The patient was also found to have type 2 diabetes mellitus and adenocarcinoma of the uterus in the course of her hospitalization.

Biological adhesive fixation of skin grafts has been performed successfully on patients with facial burns and burns at difficult sites by using autologous human fibrin adhesive, which eliminates the danger of multidonor pool preparations. There are several distinct advantages to the use of fibrin glue: There is no danger of multidonor pool preparations. Wounds do not require any sutures or pressure dressings in the immediate postoperative period. Grafts demonstrate excellent take with minimal postoperative care. The patients can maintain normal ambulation. Fibrin glue seems to be an important factor in the application of skin grafts to burned areas in these two groups of patients.

A preliminary survey of HIV risk and service preferences among American Indians residing in the New York metropolitan area included 68 women and 32 men (M age=35.8 years). Overall, the sample was knowledgeable about the mechanisms of HIV transmission, and 58 percent reported having taken an HIV test. However, of the 63 percent who reported sexual activity in the last six months, 73 percent reported engaging in vaginal or anal sex without a condom with at least 1 partner, and 52 percent used condoms none of the time during vaginal and anal sex. Almost half (43 percent) reported alcohol or other drug (AOD) use for non-ceremonial purposes in the last six months. Alarmingly, 44 percent reported lifetime trauma, including domestic violence (20 percent) and physical (29 percent) or sexual (26 percent) assault by a family member or stranger. Bivariate and multivariate analyses indicated trauma and drug use were factors that may place respondents at risk for sexual transmission of HIV. Trauma variables were better predictors of HIV risk behaviors than social cognitive variables providing preliminary support for the use of a postcolonial framework in American Indian HIV studies.

• Medullary carcinoma of the thyroid is unique in that it can often be diagnosed solely on the basis of abnormally high basal serum thyrocalcitonin levels. Two brothers described in this report were found to have normal basal serum thyrocalcitonin levels when examined after another family member died from metastatic medullary carcinoma of the thyroid. Pentagastrin, a synthetic analog of gastrin, was subsequently administered to these two high-risk relatives and found to stimulate the release of thyrocalcitonin to abnormally high levels. They were found to have occult medullary carcinoma of the thyroid. Eight other first-degree relatives of the deceased patient with normal basal serum thyrocalcitonin levels were screened with pentagastrin and found to have normal stimulated levels of thyrocalcitonin. This report reinforces the need to recognize that medullary carcinoma of the thyroid can be familial and that physicians are obligated to screen asymptomatic kin who are at high risk. We recommend that all susceptible relatives, even if they have normal basal serum thyrocalcitonin levels, undergo the provocative pentagastrin test with repeat annual testing if necessary. In addition, the provocative pentagastrin test can be used to follow up patients who have undergone thyroidectomy. ( Arch Surg 113:241-243, 1978)