Emergency Response to Radiological Releases: Have We Communicated Effectively to the First Responder Communities to Prepare Them to Safely Manage These Incidents?

The emergency responder community trains for and responds to many types of incidents on a daily basis and has done so for years. This experience with fires, emergency medical calls, chemical spills, confined spaces, and other common calls for assistance has helped responders develop an understanding of the problems and a confidence in solving them. Radiation from an accidental release in a facility or during transportation, or from a terrorist incident that causes radioactive materials to be released from their containment vessel, remains a cause of concern and fear. Emergency responders are a segment of the general population and share some of the same fears of radioactive materials as the whole population. Radioactive material incidents are not a common 911 call type. Radiation training has been included in emergency responder training standards for several decades and covers a broad range of topics from simple awareness and recognition to technical knowledge of the materials, detection and identification capabilities, self-protection, medical effects, and countermeasures to overall public and environmental safety and health. The safety factor of the radiation community has been very good, but without the actual response confidence in handling previous incident releases, many responders remain fearful of radiation. A single source site where responders can post and read after-action reports on actual radiation incidents may help communicate health and safety information, building responder confidence. Competencies in standards do not always translate into compliance in training curriculum and exercises. The fire service has been the key local response agency to radiation accidents for many years and has developed training programs that meet the competencies found in 29 CFR 1910.120 [q], How to Determine What Training is Required for Emergency Response Team Members, and the National Fire Protection Associations Standard 472: Competence of Responders to Hazardous Materials/Weapons of Mass Destruction Incidents. The majority of fire service responders in the United States are volunteers who often make decisions on what they train for based on the time available and their areas' hazard assessment. This has often caused radiation training to be limited at best. Communicating timely and accurate hazards and risks associated with radiation threats and incidents may increase the amount and level of training in response to these types of incidents. Many law enforcement and emergency medical services and other key disciplines did not address these standards requirements prior to 9/11, as they were considered outside their "normal" mission space. The change in the mission space caused by the new threat of radiological terrorism has required additional training and equipment. This training has started but will take time to impact the entire responder community, it will require funding for the training and equipment, and most of all, sustainment. Communicating the broad scope of capabilities necessary to safely manage a radiation incident and the requirement for all agencies to be involved may support the effort to train these disciplines in their new mission space. The serious and much publicized radiological incidents that have occurred during the lifetime of many of today's responder community (Chernobyl, Fukushima, and Three Mile Island) have added to this fear within the responder community. The majority of today's responder communities are between 21 and 50 y of age. In studies conducted in recent years by federal agencies, it was identified that this group did not receive the basics of nuclear information provided to the U.S. population at the start of the Cold War and the fear of a nuclear war. These studies have identified the gap that exists in understanding basic radiation terminology, protective actions including sheltering-in-place, informed evacuation, public messaging, and others. Despite studies like this, federal, state, and local public officials have been slow to communicate emergency action plans to the public for radiological and nuclear incidents. Emergency management agencies at all levels have action plans for natural events such as hurricanes, tornadoes, and coastal storms, and now they are including biological incidents and active shooters. Nuclear and radiological incident plans and protective actions need to be included and communicated to members of the public (and responders) in all media streams. Several federal agencies have been tasked with radiological and nuclear mission space, but this appears to remain fragmented without an organizing agency. The Domestic Nuclear Detection Office (U.S. Department of Homeland Security) remains in a detection and prevention mission and has provided a good amount of equipment, training, and coordination, but primarily among law enforcement organizations. The Federal Emergency Management Agency remains in the response mission but has limited outreach to the majority of response organizations. The U.S. Department of Health and Human Services (Assistant Secretary for Preparedness and Response) has stepped up its efforts in medical countermeasures, surge capabilities, and support services. All of this information and support comes to the responder community separately, and it is left to the local-level planners to piece it together. It needs to be coordinated and communicated as one source. Communications remains the top challenge for the responder community as we look to the new administration for a plan for radiological and nuclear preparedness: communicating public messaging on radiation terminology, how members of the public can protect themselves and expected public agency actions; communicating a coordinated response plan that includes all levels and agencies; communicating the necessary training; andcommunicating the recovery actions that will have to take place.

Visual outcome in 879 children treated for strabismus: insufficient accommodation and vision deprivation, deficient emmetropisation and anisometropia.

PURPOSE: To identify the effect of infant hypermetropia on residual amblyopia in children remaining after treatment. MATERIALS AND METHODS: 879 strabismic children had cycloplegic retinoscopy at the age of 6 months and later when strabismus was diagnosed. A total of 26 hypermetropes consistently wore glasses from the age of 6 months, and 305 other hypermetropes had their accommodation periodically assessed by dynamic retinoscopy before strabismus was diagnosed. The relation between the last known visual acuity after treatment and all other clinical findings was analysed using t-tests and regression analysis. RESULTS: Vision less than 6/12 in nonfixing eyes was associated with infantile hypermetropia > +5.0D, and in rare instances in excess of -3.0D of myopia. In hypermetropes only, anisometropia was associated with worse amblyopia. Astigmatism was associated with myopia and low levels of hypermetropia but not with worse vision. The vision of fixing eyes that were hypermetropic was significantly worse than that of emmetropic or myopic eyes. Wearing spectacles from the age of 6 months was associated with better vision in the nonfixing eye. Vision in the nonfixing eye of 19 hypermetropic heterotropes who started wearing glasses between 6 and 18 months of age also was better than that of those who started wearing glasses after 18 months of age. Insufficiency of accommodation was related to the degree of infantile hypermetropia, to worse vision and to failure to emmetropise. Difference in amplitude of accommodation between the eyes was largest in hypermetropes with anisometropia > +1.50 D and was marginally associated with worse vision in microtropes who became anisometropic after infancy. Hypermetropia decreased more in fixing eyes than in nonfixing eyes, thereby causing anisohypermetropia to increase after infancy. This change was most pronounced in hypermetropic microtropes. Conversely, failure of fixing eyes to emmetropise was associated with an increase in their inability to accommodate and heterotropia. CONCLUSIONS: On the basis of these findings, severe residual amblyopia in children remaining after treatment could be explained by additional vision deprivation. It can be reduced by starting spectacle correction of hypermetropia before the age of 18 months. Anisometropia seemed the result of deficient emmetropisation.

Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes.

The imprinted gene cluster at the telomeric end of mouse chromosome 7 contains a differentially methylated CpG island, KvDMR, that is required for the imprinting of multiple genes, including the genes encoding the maternally expressed placental-specific transcription factor ASCL2, the cyclin-dependent kinase CDKN1C, and the potassium channel KCNQ1. The KvDMR, which maps within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1. A 244-base-pair deletion of the promoter on the paternal allele leads to the derepression of all silent genes tested. To distinguish between the loss of silencing as the consequence of the absence of transcription or the transcript itself, we prematurely truncated the Kcnq1ot1 transcript by inserting a transcriptional stop signal downstream of the promoter. We show that the lack of a full-length Kcnq1ot1 transcript on the paternal chromosome leads to the expression of genes that are normally paternally repressed. Finally, we demonstrate that five highly conserved repeats residing at the 5' end of the Kcnq1ot1 transcript are not required for imprinting at this locus.

Functional characterization of a testis-specific DNA binding activity at the H19/Igf2 imprinting control region.

The DNA methylation state of the H19/Igf2 imprinting control region (ICR) is differentially set during gametogenesis. To identify factors responsible for the paternally specific DNA methylation of the ICR, germ line and somatic extracts were screened for proteins that bind to the ICR in a germ line-specific manner. A specific DNA binding activity that was restricted to the male germ line and enriched in neonatal testis was identified. Its three binding sites within the ICR are very similar to the consensus sequence for nuclear receptor extended half sites. To determine if these binding sites are required for establishment of the paternal epigenetic state, a mouse strain in which the three sites were mutated was generated. The mutated ICR was able to establish a male-specific epigenetic state in sperm that was indistinguishable from that established by the wild-type ICR, indicating that these sequences are either redundant or have no function. An analysis of the methylated state of the mutant ICR in the soma revealed no differences from the wild-type ICR but did uncover in both mutant and wild-type chromosomes a significant relaxation in the stringency of the methylated state of the paternal allele and the unmethylated state of the maternal allele in neonatal and adult tissues.

Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta.

To increase our understanding of imprinting and epigenetic gene regulation, we undertook a search for new imprinted genes. We identified Gatm, a gene that encodes l-arginine:glycine amidinotransferase, which catalyzes the rate-limiting step in the synthesis of creatine. In mouse, Gatm is expressed during development and is imprinted in the placenta and yolk sac, but not in embryonic tissues. The Gatm gene maps to mouse chromosome 2 in a region not previously shown to contain imprinted genes. To determine whether Gatm is located in a cluster of imprinted genes, we investigated the expression pattern of genes located near Gatm: Duox1-2, Slc28a2, Slc30a4 and a transcript corresponding to LOC214616. We found no evidence that any of these genes is imprinted in placenta. We show that a CpG island associated with Gatm is unmethylated, as is a large CpG island associated with a neighboring gene. This genomic screen for novel imprinted genes has elucidated a new connection between imprinting and creatine metabolism during embryonic development in mammals.

A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer.

The imprinted gene cluster on mouse distal chromosome 7 contains a differentially methylated CpG island that maps within the Kcnq1 gene that has been shown to be required for the imprinting of multiple genes. To evaluate models for how this imprinting control region (ICR) regulates imprinting, we have characterized it structurally and functionally. We show that the region contains a promoter for a paternally expressed anti-sense transcript, Kcnq1ot1, and we define the extent of the minimal promoter. We describe three paternal-specific nuclease hypersensitive sites immediately upstream from the start site and show that they are required for full promoter activity. The expression of Kcnq1ot1 during pre- and postnatal development is compared to that of other imprinted genes in its vicinity, Cdnkn1c and Kcnq1. The lack of coordination in their expression tends to rule out an enhancer competition model for the action of the ICR in imprinting control. Using a stable transfection assay we show that the region contains a position-independent and orientation-independent silencer. We propose, on the basis of these findings, that the Kcnq1 ICR functions as a silencer on the paternal chromosome to effect the repression of neighboring genes.

Candidate genes required for embryonic development: a comparative analysis of distal mouse chromosome 14 and human chromosome 13q22.

Mice homozygous for the Ednrb(s-1Acrg) deletion arrest at embryonic day 8.5 from defects associated with mesoderm development. To determine the molecular basis of this phenotype, we initiated a positional cloning of the Acrg minimal region. This region was predicted to be gene-poor by several criteria. From comparative analysis with the syntenic human locus at 13q22 and gene prediction program analysis, we found a single cluster of four genes within the 1.4-to 2-Mb contig over the Acrg minimal region that is flanked by a gene desert. We also found 130 highly conserved nonexonic sequences that were distributed over the gene cluster and desert. The four genes encode the TBC (Tre-2, BUB2, CDC16) domain-containing protein KIAA0603, the ubiquitin carboxy-terminal hydrolase L3 (UCHL3), the F-box/PDZ/LIM domain protein LMO7,and a novel gene. On the basis of their expression profile during development, all four genes are candidates for the Ednrb(s-1Acrg) embryonic lethality. Because we determined that a mutant of Uchl3 was viable, three candidate genes remain within the region.