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There is growing public urgency to close equity gaps in health and development by addressing inequities at multiple levels of children's developmental ecosystems. Current measurement strategies obscure the dynamic structural and relational patterns of oppression, adversity, and disadvantage that children can experience in their local intimate developmental ecosystem, as well as the leverage points that are necessary to change them. The purpose of this study is to examine the relationship between a universally available measure of neighborhood socio-economic context, the National Neighborhood Equity Index (NNEI), and a population measure of early child development and well-being, the Early Development Instrument (EDI). Data from a convenience sample of 144,957 kindergarteners in neighborhoods across the US demonstrate that children living in neighborhoods with more equity barriers are more likely to be on vulnerable developmental trajectories than those who reside in neighborhoods without any equity barriers. A multi-dimensional measurement approach that incorporates both the EDI and the NNEI can be used to quantify ethnoracialized patterns of structural disadvantage during critical periods of health development. These measures can inform community action to intervene early in the lifecourse to optimize children's health development trajectories at a population level., Competing Interests: None., (© 2023 Published by Elsevier Ltd.)

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.

ABSTRACTOne of the biggest medical challenges after the detonation of a nuclear device will be implementing a strategy to assess the severity of radiation exposure among survivors and to triage them appropriately. Those found to be at significant risk for radiation injury can be prioritized to receive potentially lifesaving myeloid cytokines and to be evacuated to other communities with intact health care infrastructure prior to the onset of severe complications of bone marrow suppression. Currently, the most efficient and accessible triage method is the use of sequential complete blood counts to assess lymphocyte depletion kinetics that correlate with estimated whole-body dose radiation exposure. However, even this simple test will likely not be available initially on the scale required to assess the at-risk population. Additional variables such as geographic location of exposure, sheltering, and signs and symptoms may be useful for initial sorting. An interdisciplinary working group composed of federal, state, and local public health experts proposes an Exposure And Symptom Triage (EAST) tool combining estimates of exposure from maps with clinical assessments and single lymphocyte counts if available. The proposed tool may help sort survivors efficiently at assembly centers near the damage and fallout zones and enable rapid prioritization for appropriate treatment and transport. (Disaster Med Public Health Preparedness. 2018; 12: 386-395).

Research has shown linkages between environmental exposures and population health metrics such as low birth weight and incidence of congenital anomalies. While the exact causal relationship between specific environmental teratogens and suspected corresponding congenital anomalies has largely not been established, spatial analysis of anomaly incidence can identify potential locations of increased risk. This study uses the Vital Statistics Birth Master File to map and analyze the rates of congenital anomalies of births from non-smoking mothers 15-35 years old within Los Angeles County. Hot spot analysis shows that the distribution of congenital anomalies is not randomly distributed throughout the county and identified the Antelope Valley and San Gabriel Foothills as two areas with elevated incidence rates. These results are not explained by potential confounders such as maternal age, race, smoking status, or socioeconomic status and seem to correlate well with the concentration of atmospheric ozone. This approach demonstrates the value of using spatial techniques to inform future research efforts and the need to establish and maintain a comprehensive reproductive health surveillance system.

All large-scale emergencies and disaster incidents, including the detonation of an improvised nuclear device (IND), have life and death medical consequences. Responders must have realistic plans to save lives and reduce physical and psychological morbidity. Fifteen years after 9/11, considerable progress toward developing and implementing such plans has been made, but gaps in the management of response to an IND loom large. Another paper in this series reviewed gaps for first responders; this paper reviews gaps for first receivers and public health. Closing gaps requires the implementation of complex systems including.

Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multi-faceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided.

The detonation of a nuclear device in a US city would be catastrophic. Enormous loss of life and injuries would characterize an incident with profound human, political, social, and economic implications. Nevertheless, most responders have not received sufficient training about ionizing radiation, principles of radiation safety, or managing, diagnosing, and treating radiation-related injuries and illnesses. Members throughout the health care delivery system, including medical first responders, hospital first receivers, and health care institution support personnel such as janitors, hospital administrators, and security personnel, lack radiation-related training. This lack of knowledge can lead to failure of these groups to respond appropriately after a nuclear detonation or other major radiation incident and limit the effectiveness of the medical response and recovery effort. Efficacy of the response can be improved by getting each group the information it needs to do its job. This paper proposes a sustainable training strategy for spreading curricula throughout the necessary communities. It classifies the members of the health care delivery system into four tiers and identifies tasks for each tier and the radiation-relevant knowledge needed to perform these tasks. By providing education through additional modules to existing training structures, connecting radioactive contamination control to daily professional practices, and augmenting these systems with just-in-time training, the strategy creates a sustainable mechanism for giving members of the health care community improved ability to respond during a radiological or nuclear crisis, reducing fatalities, mitigating injuries, and improving the resiliency of the community.

This article summarizes major points from a newly released guide published online by the Office of the Assistant Secretary for Preparedness and Response (ASPR). The article reviews basic principles about radiation and its measurement, short-term and long-term effects of radiation, and medical countermeasures as well as essential information about how to prepare for and respond to a nuclear detonation. A link is provided to the manual itself, which in turn is heavily referenced for readers who wish to have more detail.

Following the attacks of 11 September 2001, emergency preparedness within the U.S. Department of Health and Human Services, as well as at the Department of Defense and other federal agencies, received higher visibility, new mandates and increased funding. Emergency deployment teams increased the frequency of drills to enable better response to the health consequences of mass-casualty incidents. Interagency coordination has also continued to increase to more efficiently and effectively leverage federal resources toward emergency medical preparedness for both civilian and military populations.

The hallmark of a successful response to a nuclear detonation will be the resilience of the community, region, and nation. An incident of this magnitude will rapidly become a national incident; however, the initial critical steps to reduce lives lost, save the lives that can be saved with the resources available, and understand and apply resources available to a complex and dynamic situation will be the responsibility of the local and regional responders and planners. Expectations of the public health and health care systems will be met to the extent possible by coordination, cooperation, and an effort to produce as consistent a response as possible for the victims. Responders will face extraordinarily stressful situations, and their own physical and psychological health is of great importance to optimizing the response. This article illustrates through vignettes and supporting text how the incident may unfold for the various components of the health and medical systems and provides additional context for the discipline-related actions outlined in the state and local planners' playbook.

The purpose of this article is to set the context for this special issue of Disaster Medicine and Public Health Preparedness on the allocation of scarce resources in an improvised nuclear device incident. A nuclear detonation occurs when a sufficient amount of fissile material is brought suddenly together to reach critical mass and cause an explosion. Although the chance of a nuclear detonation is thought to be small, the consequences are potentially catastrophic, so planning for an effective medical response is necessary, albeit complex. A substantial nuclear detonation will result in physical effects and a great number of casualties that will require an organized medical response to save lives. With this type of incident, the demand for resources to treat casualties will far exceed what is available. To meet the goal of providing medical care (including symptomatic/palliative care) with fairness as the underlying ethical principle, planning for allocation of scarce resources among all involved sectors needs to be integrated and practiced. With thoughtful and realistic planning, the medical response in the chaotic environment may be made more effective and efficient for both victims and medical responders.

A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network.

Based on background information in this special issue of the journal, possible triage recommendations for the first 4 days following a nuclear detonation, when response resources will be limited, are provided. The series includes: modeling for physical infrastructure damage; severity and number of injuries; expected outcome of triage to immediate, delayed, or expectant management; resources required for treating injuries of varying severity; and how resource scarcity (particularly medical personnel) worsens outcome. Four key underlying considerations are: 1.) resource adequacy will vary greatly across the response areas by time and location; 2.) to achieve fairness in resource allocation, a common triage approach is important; 3.) at some times and locations, it will be necessary to change from "conventional" to "contingency" or "crisis" standards of medical care (with a resulting change in triage approach from treating the "sickest first" to treating those "most likely to survive" first); and 4.) clinical reassessment and repeat triage are critical, as resource scarcity worsens or improves. Changing triage order and conserving and allocating resources for both lifesaving and palliative care can maintain fairness, support symptomatic care, and save more lives. Included in this article are printable triage cards that reflect our recommendations. These are not formal guidelines. With new research, data, and discussion, these recommendations will undoubtedly evolve.

For efficient and effective medical responses to mass casualty events, detailed advanced planning is required. For federal responders, this is an ongoing responsibility. The US Department of Health and Human Services (DHHS) prepares playbooks with formal, written plans that are reviewed, updated, and exercised regularly. Recognizing that state and local responders with fewer resources may be helped in creating their own event-specific response plans, subject matter experts from the range of sectors comprising the Scarce Resources for a Nuclear Detonation Project, provided for this first time a state and local planner's playbook template for responding to a nuclear detonation. The playbook elements are adapted from DHHS playbooks with appropriate modification for state and local planners. Individualization by venue is expected, reflecting specific assets, populations, geography, preferences, and expertise. This playbook template is designed to be a practical tool with sufficient background information and options for step-by-step individualized planning and response.

The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.S./European Consultation Workshop addressing approaches to radiation emergency preparedness and assistance, which was held recently at Ulm University, Ulm, Germany. Discussions dealt with the assessment of the extent of damage after total body exposure and, in particular, the quantity and quality of the damage to the hematopoietic stem cell pool. Secondly, the pathogenesis of the multiorgan failure was considered because of the organ-to-organ interactions. Thirdly, approaches were considered to harmonize the "triage-methods" used on an international level using the "Response Category" approach as developed for the European Communities. These discussions lead to the conclusion that there is a strong need for continuing education of physicians, nurses, and support personnel to address the issues posed by the management of patients suffering from radiation syndromes. Finally, the discussions expressed the need for more international cooperation in research and development of more refined methods to treat patients with any type of radiation syndromes.

The end of the Cold War led to a reduced concern for a major nuclear event. However, the current threats from terrorism make a radiologic (dispersal or use of radioactive material) or nuclear (improvised nuclear device) event a possibility. The specter and enormousness of the catastrophe resulting from a state-sponsored nuclear attack and a sense of nihilism about the effectiveness of a response were such that there had been limited civilian medical response planning. Although the consequences of a radiologic dispersal device are substantial, and the detonation of a modest-sized (10 kiloton) improvised nuclear device is catastrophic, it is both possible and imperative that a medical response be planned. To meet this need, the Office of the Assistant Secretary for Preparedness and Response in the Department of Health and Human Services, in collaboration within government and with nongovernment partners, has developed a scientifically based comprehensive planning framework and Web-based "just-in-time" medical response information called Radiation Event Medical Management (available at http://www.remm.nlm.gov). The response plan includes (1) underpinnings from basic radiation biology, (2) tailored medical responses, (3) delivery of medical countermeasures for postevent mitigation and treatment, (4) referral to expert centers for acute treatment, and (5) long-term follow-up. Although continuing to evolve and increase in scope and capacity, current response planning is sufficiently mature that planners and responders should be aware of the basic premises, tools, and resources available. An effective response will require coordination, communication, and cooperation at an unprecedented level. The logic behind and components of this response are presented to allow for active collaboration among emergency planners and responders and federal, state, local, and tribal governments.

Untoward events involving radioactive material, either accidental or intentional, are potentially devastating. Hematologists and oncologists are uniquely suited to help manage radiation victims, as myelosuppression is a frequent complication of radiation exposure. In the aftermath of a large event, such as a nuclear detonation, there may be a national call for surge capacity that involves hematologists/oncologists across the country in the disaster response. In preparation, the National Marrow Donor Program and American Society for Blood and Marrow Transplantation have established the Radiation Injury Treatment Network (RITN), a voluntary consortium of transplant centers, donor centers, and umbilical cord blood banks. RITN is partnered with the Office of the Assistant Secretary for Preparedness and Response in the United States Department of Health and Human Services to develop treatment guidelines, educate healthcare professionals, coordinate situation response, and provide comprehensive evaluation and care for radiation injury victims. We outline the current plans for event response and describe scenarios, including catastrophic events that would require extensive support from hematologists/oncologists across the country. In addition, we highlight important reference resources and discuss current efforts to develop medical countermeasures against radiation toxicity. Practitioners and institutions across the country are encouraged to become involved and participate in the planning.

Planning for and exercising the medical response to potential chemical, biological, radiological, nuclear, and explosive (CBRNE) terrorist events are new responsibilities for most health care providers. Among potential CBRNE events, radiological and/or nuclear (rad/nuc) events are thought to have received the least attention from health care providers and planners. To assist clinicians, the U.S. Department of Health and Human Services (HHS) has created a new, innovative tool kit, the Radiation Event Medical Management (REMM) web portal (http://remm.nlm.gov). Goals of REMM include providing (1) algorithm-style, evidence-based, guidance about clinical diagnosis and treatment during mass casualty rad/nuc events; (2) just-in-time, peer-reviewed, usable information supported by sufficient background material and context to make complex diagnosis and management issues understandable to those without formal radiation medicine expertise; (3) a zip-file of complete web portal files downloadable in advance so the site would be available offline without an Internet connection; (4) a concise collection of the printable, key documents that can be taken into the field during an event; (5) a framework for medical teams and individuals to initiate rad/nuc planning and training; and (6) an extensive bibliography of key, peer-reviewed, and official guidance documents relevant to rad/nuc responses. Since its launch, REMM has been well received by individual responders and teams across the country and internationally. It has been accessed extensively, particularly during training exercises. Regular content updates and addition of new features are ongoing. The article reviews the development of REMM and some of its key content areas, features, and plans for future development.

Background: Searching for health information is one of the most-common tasks performed by Internet users. Many users begin searching on popular search engines rather than on prominent health information sites. We know that many visitors to our (National Cancer Institute) Web site, cancer.gov, arrive via links in search engine result., Objective: To learn more about the specific needs of our general-public users, we wanted to understand what lay users really wanted to know about cancer, how they phrased their questions, and how much detail they used., Methods: The National Cancer Institute partnered with AskJeeves, Inc to develop a methodology to capture, sample, and analyze 3 months of cancer-related queries on the Ask.com Web site, a prominent United States consumer search engine, which receives over 35 million queries per week. Using a benchmark set of 500 terms and word roots supplied by the National Cancer Institute, AskJeeves identified a test sample of cancer queries for 1 week in August 2001. From these 500 terms only 37 appeared >or= 5 times/day over the trial test week in 17208 queries. Using these 37 terms, 204165 instances of cancer queries were found in the Ask.com query logs for the actual test period of June-August 2001. Of these, 7500 individual user questions were randomly selected for detailed analysis and assigned to appropriate categories. The exact language of sample queries is presented., Results: Considering multiples of the same questions, the sample of 7500 individual user queries represented 76077 queries (37% of the total 3-month pool). Overall 78.37% of sampled Cancer queries asked about 14 specific cancer types. Within each cancer type, queries were sorted into appropriate subcategories including at least the following: General Information, Symptoms, Diagnosis and Testing, Treatment, Statistics, Definition, and Cause/Risk/Link. The most-common specific cancer types mentioned in queries were Digestive/Gastrointestinal/Bowel (15.0%), Breast (11.7%), Skin (11.3%), and Genitourinary (10.5%). Additional subcategories of queries about specific cancer types varied, depending on user input. Queries that were not specific to a cancer type were also tracked and categorized., Conclusions: Natural-language searching affords users the opportunity to fully express their information needs and can aid users naïve to the content and vocabulary. The specific queries analyzed for this study reflect news and research studies reported during the study dates and would surely change with different study dates. Analyzing queries from search engines represents one way of knowing what kinds of content to provide to users of a given Web site. Users ask questions using whole sentences and keywords, often misspelling words. Providing the option for natural-language searching does not obviate the need for good information architecture, usability engineering, and user testing in order to optimize user experience.

Background: Providing quality, current cancer information to cancer patients and their families is a key function of the National Cancer Institute (NCI) Web site. This information is now provided in predominantly-text format, but could be provided in formats using multimedia, including animation and sound. Since users have many choices about where to get their information, it is important to provide the information in a format that is helpful and that they prefer., Objective: To pilot and evaluate multimedia strategies for future cancer-information program formats for lay users, the National Cancer Institute created new multimedia versions of existing text programs. We sought to evaluate user performance and preference on these 3 new formats and on the 2 existing text formats., Methods: The National Cancer Institute's "What You Need to Know About Lung Cancer" program was the test vehicle. There were 5 testing sessions, 1 dedicated to each format. Each session lasted about 1 hour, with 9 participants per session and 45 users overall. Users were exposed to the assigned cancer program from beginning to end in 1 of 5 formats: text paperback booklet, paperback booklet formatted in HTML on the Web, spoken audio alone, spoken audio synchronized with a text Web page, and Flash multimedia (animation, spoken audio, and text). Immediately thereafter, the features and design of the 4 alternative formats were demonstrated in detail. A multiple-choice pre-test and post-test quiz on the cancer content was used to assess user learning (performance) before and after experiencing the assigned program. The quiz was administered using an Authorware software interface writing to an Access database. Users were asked to rank from 1 to 5 their preference for the 5 program formats, and provide structured and open-ended comments about usability of the 5 formats., Results: Significant improvement in scores from pre-test to post-test was seen for the total study population. Average scores for users in each of the 5 format groups improved significantly. Increments in improvement, however, were not statistically different between any of the format groups. Significant improvements in quiz scores were seen irrespective of age group or education level. Of the users, 71.1% ranked the Flash program first among the 5 formats, and 84.4% rated Flash as their first or second choice. Audio was the least-preferred format, ranking fifth among 46.7% of users and first among none. Flash was ranked first among users regardless of education level, age group, or format group to which the user was assigned., Conclusions: Under the pilot study conditions, users overwhelmingly preferred the Flash format to the other 4 formats. Learning occurred equally in all formats. Use of multimedia should be considered as communication strategies are developed for updating cancer content and attracting new users.

One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.

This is a case of oesophageal penetration by dental prosthesis probably brought on by alcoholism. No other classical complication occurred for three weeks. It was increasing dysphagia that led the patient to hospital. Endoscopy revealed an unfamiliar object and its nature, but did not enable it to be extracted. The object was taken out afterwards by cervicotomy.

The authors report the first case of fetus in fetu situated in the adrenal gland where the diagnosis was suggested by prenatal ultrasound. The anatomo-pathology, the aetiology, the antenatal ultrasound picture and the treatment of this abnormality of embryonic development are described.

Etiology of malignant melanoma in persons younger than 20 years of age was examined using data from two sources: medical records of 78 patients with this diagnosis at six hospitals, and information on 101 individuals included in 10 U.S. population-based SEER cancer registry areas between 1973-1976. Annual melanoma incidence rate was 3.4 per million in boys, 3.9 per million in girls, and 10-fold greater in white children than in black children. Melanoma was seven times more frequent in the second decade of life than the first. Skin was the primary site of melanoma in approximately 90% of the children in the two study series. The predominant cutaneous sites were head, neck, and trunk among boys, and arms and legs among girls. These variations by age, race, and sex suggest the etiologic role of cumulative skin exposure to sunlight, particularly in two patients with xeroderma pigmentosum. In 14 patients in the hospital series, melanoma was reported to develop within pigmented nevi that were present at birth.

To investigate the role of oncogenes in malignancies characteristic of neurofibromatosis, oncogene transcripts were quantitated in a neurofibrosarcoma and in control tissue from a patient with hereditary neurofibromatosis. Sis and N-ras were moderately hyperexpressed, raf, Blym, and erbA were slightly hyperexpressed, and abl, erbB, fes/fps, fgr, fos, mos, myb, myc, N-myc, rasHarvey, rasKirsten, ros, src, and yes were not hyperexpressed in the tumor compared to the control tissue. Although additional tumors will be assayed before conclusions are possible, it may be significant that the two oncogenes most hyperexpressed are prior suspects for a pathogenetic role in tumors of the nervous system.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Based on the Third National Cancer Survey (1969 to 1971), the incidence of malignant neoplasms in the United States was 183.4 per million live births per year in infants younger than 1 year and 36.5 in newborns younger than 29 days. In both age groups, neuroblastoma was the most commonly diagnosed neoplasm. Overall, cancer incidence in infants younger than 1 year was almost 3.5 times greater than mortality determined from US death certificates from 1960 to 1969. For individual tumor types, the ratio between incidence and mortality varied between 159 for retinoblastoma and 1.5 for leukemia largely reflecting relative differences in survival due to treatment.

Twelve new cases of childhood leukemia and neurofibromatosis were ascertained and evaluated in conjunction with 17 previously well-documented cases. The ratio of ALL:nonlymphocytic leukemia was 9:20, markedly different from the 4:1 ratio in children without NF. Rarer subtypes predominated: 8 CML and 8 AMML. The peculiar distribution of leukemia by cell type and the number of cases observed in the United States indicate that the risk of childhood leukemia in NF is increased. Two possible variants were noted: NF with "transient leukemia," and multiple skin xanthomas with nonlymphocytic leukemia.

In 11 patients, bilateral retinoblastoma presented at a mean age of 6 months and pineoblastoma at 4 years. We suggest that the hereditary multicentric retinoblastoma arose in vestigeal photoreceptors in the pineal as well as in the hypothetical retinoblasts of the retina. In certain lower animals, the pineal functions as a photoreceptor organ, resembles the retina histologically, and is described as a "third eye." Hence, the patients we describe may be considered as having "trilateral retinoblastoma." Two possible variants of this entity were also noted: (1) three children without retinoblastoma with rosettes and photoreceptor differentiation characteristic of retinoblastoma, and (2) three additional cases involving children who presented with retinoblastoma-like tumors in the suprasellar or parasellar region 2 to 6 months before the discovery of intraocular retinoblastoma. These observations suggest that the retinoblastoma gene confers a previously unappreciated susceptibility to a narrow spectrum of neuroblastic tumors, which usually present in the retina but which can also occur ectopically.

Linkage analysis of 28 genetic markers was undertaken in 108 subjects from 11 families with well-documented, classic, peripheral neurofibromatosis. Fifty-four persons were affected in one four-generation family, seven three-generation families, and three two-generation families. Lod scores were calculated using the standard LIPED programme for 49 combinations of theta male and theta female from 0.01 to 0.50. Lod scores excluded close linkage with 16 markers, including most tested on chromosome 1 and HLA on chromosome 6, and were inconclusive for 12 markers, including the secretor locus, closely linked to myotonic dystrophy. Analysis of five informative families resulted in a lod score of +2.2 for close linkage with GC on chromosome 4. However, the lod score for GC in the one additional informative family was negative, so that the final interpolated maximum was Z = 0.89 for theta male = 0.03, theta female = 0.28. Further studies are needed to evaluate this suggestion of linkage and possible genetic heterogeneity.