text:
The focus of this session of the workshop was an assessment of known threats. Anthrax is a proven risk and of immediate concern. Smallpox is equally urgent because of its capability for person-to-person transmission and the large number of completely susceptible individuals in the United States and around the world. Presenters discussed details of the bioweapons potential and treatments available for each of these threats along with those of three other "high-priority" potential bioterrorist agents: plague, tularemia, and botulinum toxin. However, these are not the only credible bioterrorist agents out there. For example, the former Soviet Union is known to have weaponized at least thirty biological agents, including several vaccine- or drug-resistant strains.
There are many imaginable bioterrorist scenarios, but if the goal is to induce mass casualties, an aerosol attack is probably most likely. Aerosols exhibit wide-area coverage, and their small particle size allows them to deposit very deeply in the lung tissue which is where many agents, including anthrax, induce maximal damage. A large amount of agent disseminated under good meteorological conditions over a substantially sized city could have considerable downwind reach, resulting in large numbers of casualties.
Food-borne bioterrorism, which could encompass a variety of agents, must also be considered an equally likely threat. Agents that cause foodborne illness are easy to obtain from the environment and often have very low-dose requirements. Foodborne pathogens may in fact be the easiest bioterrorism agent to disseminate. In addition to public health risks, there are several important agri-
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Biological Threats and Terrorism: Assessing the Science and Response Capabilities - Workshop Summary
Assessing Our Understanding of the Threats
The focus of this session of the workshop was an assessment of known threats. Anthrax is a proven risk and of immediate concern. Smallpox is equally urgent because of its capability for person-to-person transmission and the large number of completely susceptible individuals in the United States and around the world. Presenters discussed details of the bioweapons potential and treatments available for each of these threats along with those of three other "high-priority" potential bioterrorist agents: plague, tularemia, and botulinum toxin. However, these are not the only credible bioterrorist agents out there. For example, the former Soviet Union is known to have weaponized at least thirty biological agents, including several vaccine- or drug-resistant strains.
There are many imaginable bioterrorist scenarios, but if the goal is to induce mass casualties, an aerosol attack is probably most likely. Aerosols exhibit wide-area coverage, and their small particle size allows them to deposit very deeply in the lung tissue which is where many agents, including anthrax, induce maximal damage. A large amount of agent disseminated under good meteorological conditions over a substantially sized city could have considerable downwind reach, resulting in large numbers of casualties.
Food-borne bioterrorism, which could encompass a variety of agents, must also be considered an equally likely threat. Agents that cause foodborne illness are easy to obtain from the environment and often have very low-dose requirements. Foodborne pathogens may in fact be the easiest bioterrorism agent to disseminate. In addition to public health risks, there are several important agri-
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Biological Threats and Terrorism: Assessing the Science and Response Capabilities - Workshop Summary
cultural risks which were mentioned briefly but not discussed in detail during this workshop.
B. anthracis is a very stable organism because of its ability to sporulate. Most naturally occurring anthrax cases are cutaneous and are transmitted from agricultural exposure. The incidence of infection is unknown; most cases occur in underdeveloped countries. Throughout the world, since the late 1930s, attenuated strains have been used as live veterinary spore vaccines and have proven to be highly effective in controlling disease in domesticated animals. Since the 1950s, one of these strains has been used as a live attenuated strain in humans in countries of the former Soviet Union. The molecular pathogenesis of anthrax, including the exact target of its lethal factor, is largely unknown. However, enough is known that we can begin to predict where second-generation vaccines and various antitoxin modalities might work.
Currently, there are three types of preventative or therapeutic countermeasures against anthrax: vaccination, antibiotics, and various adjunctive anti-toxin treatments. In terms of developing new therapeutics, initial immediate efforts should be to evaluate already licensed antibiotics. Longer-term efforts should include identifying protective antigens that are effective against modified strains; developing vaccines that act more quickly and would be more useful in a post-exposure scenario; exploring the combined use of vaccines and antibiotics; and exploring new antitoxin treatments. Critical to all of these efforts is the need for a large-scale central animal testing facility.
Smallpox has several features that make it an attractive bioterrorist agent: it is highly stable; it is infectious by aerosol; it is highly contagious; most clinicians lack experience recognizing the disease; and, because vaccination against smallpox ceased after eradication, most of the world's population is highly susceptible to infection.
Even though a smallpox vaccine exists, there are several unresolved bioterrorism-related issues regarding smallpox vaccination:
It is not clear which health care providers should be immunized preceding any potential outbreak versus immediately following an outbreak.
The current supply of vaccinia immune globulin is insufficient for treating all of the expected adverse effects associated with vaccinia immunization, should all 300 million doses of cell-cultured vaccinia that are currently being produced be administered.
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The cell-cultured vaccine that is currently being produced is considered only a stop gap measure since it cannot be used in immunocompromised individuals or children.
It is unclear whether the available vaccine would protect against aerosol exposure of the type and magnitude that would be expected in a bioterrorist event. Although monkey/monkeypox studies have shown that yes, the vaccine does provide adequate protection, it is unclear how applicable these studies are to smallpox in humans.
Currently, most research and development efforts for smallpox therapeutics are focused on antiviral drugs. Thus far, the leading candidate is cidofovir, which has been approved under an IND for treating disseminated vaccinia but has not been approved for treating smallpox. Despite its promise, however, cidofovir is unsuitable for mass casualty use. More effort needs to be directed toward other therapeutics, such as immunomodulators.
Plague—a deadly and highly contagious disease—was weaponized in the former Soviet Union for aerosol delivery and engineered for antimicrobial resistance and possibly enhanced virulence. In the WHO modeling scenario that was developed in 1970, a 50-kilogram release over a city of five million would cause about 150,000 cases, or 36,000 deaths, in the first wave. A secondary spread would cause a further 500,000 cases, or 100,000 deaths. Plague requires intensive medical and nursing support and isolation for at least the first fortyeight hours, followed by two to three weeks of slow convalescence. The hospitalization and isolation that would be required for this many people in a single city is nearly unimaginable.
Currently in the U.S., there is no available plague vaccine. The live vaccines that are sometimes used in other countries have unacceptable adverse effects. There are, however, a number of laboratories trying to develop a new generation vaccine, as well as new delivery methods. Several different types of antibiotics that can be used to treat plague are included in the national pharmaceutical stockpile. Antibiotic treatment must be instituted early during the course of infection, otherwise death occurs in three to six days.
Tularemia was weaponized as an aerosol both in the U.S. and the former Soviet Union where it was also engineered for vaccine-resistance. In the WHO modeling scenario of 1970, 50 kg over a city of 5 million would incapacitate 250,000 people and cause 19,000 deaths. Tularemia is highly infectious but not contagious. Treatment is similar to that for plague but more extensive, as is the post-prophylaxis to prevent relapses of disease. The tularemia vaccine is a live
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attenuated vaccine that was previously available as an investigational drug through DoD and is now being investigated by the Joint Vaccine Acquisition Program. However, it does not offer full protection against inhalational transmission, and it takes about fourteen days for protection to develop. The vaccine has been recommended for use in people who work routinely with the organism in the laboratory, but it is unknown whether it would be useful in first responders at high risk for exposure.
Botulinum Toxin
Botulinum toxin has several features that make it an attractive bioweapon, including its extreme potency and lethality; the ease of its production, transport and misuse; and its profound impact on its victims as well as the health care infrastructure. Like tularemia, it has a very diverse mode of transmission: it can spread through foods, beverages or as an aerosol. Botulinum toxin, of which there are seven serotypes, kills by paralytic ability and is one of the most poisonous substances known.
Although an investigational vaccine exists, immunization is really not a viable option for bioweapons defense: the vaccine is still only investigational even after ten years; its components are aging and losing potency; it only protects against toxins A, B, C, D, and E, not serotypes F and G; it is very painful to receive; it requires a booster at one year; and the use of it would deprive the recipient for life of access to medicinal botulinum toxin.
The army has developed an equine antitoxin that provides coverage against all seven toxin serotypes, but the supply is limited and the drug carries the risk of serious allergic reaction. However, equine antitoxin is inexpensive to produce and could be made in large quantities if a specialized facility were available. A human-derived botulinum antitoxin has been developed as an orphan drug but is very difficult to produce in large quantities and is of limited use because it protects against only five serotypes.
DoD is developing a recombinant vaccine which is not expected to become a licensed product, however, for at least another ten years. Researchers are also developing recombinant human antibodies as an alternative therapeutic option. Antibodies have several distinct advantages as bioweapons defense agents: they induce immediate immunity; they can be produced in unlimited quantities; and they are highly potent. In fact, an unlimited supply of human recombinant antitoxin is probably the best defensive measure against botulinum toxin.
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Biological Threats and Terrorism: Assessing the Science and Response Capabilities - Workshop Summary
Colonel Arthur M. Friedlander*
Senior Military Research Scientist, United States Army
Medical Research Institute of Infectious Diseases
"It has now prevailed and been recognized in this neighborhood about forty years, and notwithstanding all that has been done to prevent it, by ventilation, the use of respirators and other means, it still continues, as severe and frequent as it ever was, overclouding the life of the sorter." (Bell, 1880)
Anthrax has a long history: apocryphal accounts describe it as the fifth and sixth plagues in Exodus, when dust was cast into Pharaoh's eyes; it was the first disease for which a microbial etiology was determined by Robert Koch; and the anthrax vaccine was one of the first live vaccines, developed by Pasteur and one of the first examples of attenuation of a fully virulent organism for use as a vaccine. Physicians in the latter part of the 19th century, particularly in England, were well aware of the clinical and pathological aspects of anthrax. It is now incumbent upon a new generation of physicians to become intimately familiar with this disease.
There are several characteristics of B. anthracis that make it a potentially very lethal bioweapon, most importantly its stability and infectivity as an aerosol and its large footprint after aerosol release. An aerosol release of anthrax could potentially affect millions of individuals.
The organism's stability stems from its ability to sporulate. Dormant spores are estimated to have survived in some archaeological sites for hundreds of years. The spores occur in soils worldwide and infect grazing herbivores. After they enter their mammalian host, they germinate into actively replicating vegetative cells. When the mammalian host dies and its carcass is exposed to the air, the bacteria sporulate. It is unknown whether spores go through a germination-replication-sporulation cycle in the soil, or whether amplification of bacterial numbers occurs only within the host.
Under natural circumstances, humans become infected only via contact with infected animals or contaminated animal products. Anthrax is primarily a developing world disease associated with agricultural exposure causing cutaneous or gastrointestinal infection. However it emerged as "woolsorter's disease" in the industrial world in the latter half of the 19th century. With the rise of the industrial revolution, the large quantities of contaminated animal products being processed in enclosed rooms generated aerosols of anthrax spores which caused the first known cases of inhalational anthrax. Today, inhalational anthrax is extraordinarily rare.
This statement reflects the professional view of the author and should not be construed as an official position of the U.S. Army Medical Research Institute of Infectious Diseases.
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The incidence of all forms of anthrax is unknown because reporting is unreliable. Large anthrax outbreaks tend to occur during breakdowns of the public health structure, for example during war. Ten thousand human cases occurred in Zimbabwe during the 1970's and early 1980's; only eight of these cases were reported to be inhalational anthrax although no autopsies were performed.
B. anthracis is a large gram-positive, sporeforming, non-hemolytic, non-motile bacillus. Its known virulence factors include a polyglutamic acid capsule, which is antiphagocytic and without which the organism is attenuated; and the well-known lethal and edema toxins. Like most bacterial pathogens, the virulence determinants are encoded on plasmids. The two toxins are encoded on one plasmid, and the genes responsible for synthesis of the capsule are on a smaller plasmid. It is possible, under specific laboratory conditions, to eliminate the smaller plasmid and produce an unencapsulated, attenuated strain of bacteria that still produces both toxins. Since the late 1930's and early 1940's, the Sterne strain and others similar to it have been used throughout the world as live veterinary spore vaccines that have proven to be highly effective in controlling disease in domesticated animals. Since the 1950's, a similar strain has been used as a live attenuated vaccine for humans in the former Soviet Union. It is also possible to delete the toxin plasmid, resulting in an avirulent organism that produces only capsule.
Inhalational anthrax is characterized by lymphadenitis of the tracheobronchial and mediastinal lymph nodes and mediastinitis. On chest x-ray, the lungs are usually clear while there is usually mediastinal widening and often pleural effusions. The incubation period is usually a week or less. The initial symptoms are mild and non-specific and include fatigue, which can be very profound, headache, fever, chills, and sweats. There may or may not be a cough, usually non-productive. Because the disease is centered in the mediastinum, patients sometimes experience a sense of precordial discomfort. Abdominal pain has been prominent in some cases. As the infection progresses, symptoms include the abrupt onset of dyspnea, tachycardia, increased chest pain, and occasionally stridor. Pneumonia may occur but is usually absent. There is a rapid progression to cyanosis, shock, and death.
An early diagnosis is enormously important. The definitive criterion for establishing a diagnosis is isolation of the bacteria from blood, pleural or cerebral spinal fluid, or other tissue. Since there is no other gram-positive bacillus that causes sepsis in healthy individuals, the isolation of a bacillus from the blood should alert every clinical microbiology department to the diagnosis of anthrax. A chest x-ray or CT scan should also show the characteristically enlarged mediastinum. An outbreak would be characterized by large numbers of previously healthy people with these symptoms appearing in emergency rooms and physician offices.
Our knowledge of the gross pathogenesis of this disease is good but, as with many infectious diseases, we know very little about its molecular pathogenesis. The infectious spore enters the body either through a break in the skin, the GI
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tract, or by the respiratory route. In the skin and GI tract, the spore germinates locally. After entry through the respiratory tract, the spore is transported from the lung via macrophages to the regional lymph nodes. It spreads from node to node producing hemorrhagic necrosis and then extending into the mediastinum. From the lymph it spreads into the systemic circulation. About fifty percent of individuals with inhalational anthrax have evidence of meningitis. Impairment of respiratory function due to interference with lymphatic and vascular outflow associated with mediastinitis and pleural effusions is likely the primary mechanism of death.
The anthrax toxin, which causes edema and cell necrosis, probably contributes to death as well. Although the anthrax toxin is similar to many other bacterial and plant toxins, it is unusual in the sense that the functional domains reside on separate proteins. The individual proteins by themselves are inactive and have no biological function. Only when protective antigen combines with lethal factor does it constitute lethal toxin, and only when it binds with edema factor does it constitute edema toxin.
From cell culture studies, it appears that the anthrax toxins function as outlined in Figure 2-1. Protective antigen binds to a cellular receptor where a cell surface protease cleaves it, releasing a small 20 kD fragment and exposing a cryptic site on the molecule; it then forms a heptamer and subsequently binds to either edema or lethal factor. This whole complex is then internalized by receptormediated endocytosis into an acidic vesicle. Under conditions of low pH, the complex inserts into the membrane and, like other toxins, the enzymatic toxin components are delivered to the cytosol. Edema factor raises cyclic AMP levels to pharmacological levels, which is clearly responsible for some of its biological effects. The exact target of lethal factor, a zinc protease, remains, to date, unknown.
As follows from this model there are several potential targets for antitoxin therapeutics (see Collier's discussion of the most promising). The recent identification of a motor protein that controls sensitivity, or resistance to lethal toxin, will hopefully lead to additional antitoxin strategies. The current human vaccine is thought to act predominantly by inducing antibodies that block the binding of protective antigen to the cell surface receptor and block the binding of edema and lethal factor to the cell-bound protective antigen although the antibodies may also act on the organism itself.
It is unclear whether anthrax pathogenesis involves a cytokine cascade. If so, the recent licensure of activated protein C for use in sepsis could have important ramifications for anti-anthrax therapy. The possible role of cytokines in anthrax warrants further evaluation. The multiple studies that have tested adjunctive treatment for sepsis should be used to guide this effort.
There are many unresolved issues with regards to prophylaxis and treatment. For example, which antibiotics should be used? Do we need adjunctive treatments? What if the B. anthracis strain is antibiotic- or vaccine-resistant?
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About ten years ago, Russian investigators reportedly produced both multidrugresistant and vaccine-resistant B. anthracis strains.
In terms of therapy, there are several points to be emphasized. First, it should be remembered that antibiotics affect only the bacillus, not the spore. Thus it is possible that sufficient numbers of ungerminated spores may persist in an exposed individual after completion of a course of antibiotics, only to cause disease upon subsequent germination when antibiotics are no longer present. The conditions which govern the germination of spores in vivo remain obscure. Secondly, the notion that inhalational anthrax is invariably fatal once symptoms occur is likely untrue as evidenced by the survival of some of the current cases. Indeed, there is experimental evidence supporting the efficacy of late-stage intensive treatment in non-human primates showing signs of bacteremia or even mediastinitis. Lastly, there are many other antibiotics that show activity in vitro that may extend the therapeutic options for prophylaxis and treatment. These need to be evaluated in animal models before consideration for human use.
The Department of Health and Human Services, with input from the Department of Defense, is currently focusing on three therapeutic issues: testing licensed antibiotics that could be used to treat anthrax; developing human antibodies against the current vaccine, which has been administered to about 500,000 individuals; and assessing combined vaccine and antibiotic use. Other issues that need to be addressed include: identifying near-term, mid-term, and long-term research goals; identifying new protective antigens that are effective against modified strains; producing vaccines that work more quickly, particularly from the perspective of a post-exposure scenario; and, critical to all of these efforts, developing a large-scale central animal testing facility as evaluation of new treatments in humans will likely be extremely difficult.
FIGURE 2-1 Anthrax Toxin Function with Protective Antigens
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Biological Threats and Terrorism: Assessing the Science and Response Capabilities - Workshop Summary
Peter B. Jahrling,* Ph.D.
Senior Research Scientist, United States Army Medical
Research Institute of Infectious Diseases
The recent bioterrorist attacks involving anthrax have increased awareness that biological agents are truly weapons of mass destruction. Unlike anthrax, the smallpox virus is a contagious disease with fairly high rates of human to human transmission. As such, the use of smallpox as a bioterrorist agent is considered to pose an even greater threat than anthrax.Following publication of the Institute of Medicine report Assessment of the Future Scientific Needs for Live Variola Virus in 1999, collaborative research involving the Department of Defense (DoD) and the Department of Health and Human Services (DHHS) was initiated to address the recommendations suggested by the Report. The subject of today's presentation focuses on the recent research and our development of an animal model for Variola (smallpox) virus infection.
The desirability of animal model development is driven by the proposed Food and Drug Administration Animal Efficacy Rule, which was written to facilitate approval of countermeasures for infectious diseases, such as smallpox, which do not occur naturally in human populations. The Rule requires that pathophysiology of the animal model disease be faithful to the human disease course, and that the efficacy study endpoint must be based on reduced morbidity or mortality. Insight into the "toxemia" of human smallpox might be achieved by application of modern tools of virology and immunology to the model infection. Conventional wisdom holds that variola does not produce smallpox-like disease in any species other than humans; however, cynomolgus monkeys infected parenterally with variola strain were reported to develop non-specific, febrile disease. In studies conducted by the DoD in collaboration with the Centers for Disease Control, we tested four variola strains for virulence in monkeys exposed to high infectious doses delivered by aerosol, intravenous, or a combination of routes. Eventually, we identified a virus strain that produced a lethal disease process resembling rapidly progressive, human smallpox.
Initially, two variola strains (Yamada and Lee) were used to expose monkeys to aerosolized doses of 108 plaque-forming units (PFU). Results were disappointing, since the disease courses were mild and nondescript. Subsequent studies used different variola strains (Harper & India 7124), higher doses (109 PFU), and included intravenous inoculation, which may be critical. Summary data are shown in Table 2-1.
This statement reflects the professional view of the author and should not be construed as an official position of the U.S. Army Medical Research Institute of Infectious Diseases.
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TABLE 2-1 Results of primate exposures to smallpox virus
intended dose
Day death
VAR Harper
Aerosol + IV
VAR Harper
Aerosol + IV
VAR Harper
Aerosol + IV
VAR Harper
Aerosol + IV
Aerosol + IV
Aerosol + IV
Aerosol + IV
Aerosol + IV
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Three of four monkeys exposed to the Harper strain by a combination of aerosol and intravenous routes died rapidly, three to six days after exposure. Likewise, all four monkeys exposed to the India strain died, although one developed a more protracted disease course and died on day 13. Subsequent inoculation of four monkeys with 109 PFU India 7124 via the intravenous route alone yielded uniform rapid lethality. In subsequent attempts to obtain a more slowly evolving disease course, lower doses produced systemic infections and more protracted disease courses, but no deaths.
Hematologic evaluation of lethally infected primates revealed profound leukocytosis, with WBC > 50,000/mm3 (20% monocytes) in acutely ill animals. Platelet counts dropped to an average of 125,000, consistent with coagulation factor perturbations and fibrin deposition associated with evolving disseminated intravascular coagulation (DIC). Serum chemistry evaluations revealed profound increases in serum creatinine and blood urea nitrogen consistent with kidney lesions as well as elevations in AST and ALT consistent with hepatic damage. Infectious virus at concentrations > 108 PFU/g were retrieved from all visceral tissues obtained from acutely moribund or terminal monkeys at necropsy. This is consistent with the demonstration of viral antigens by immunohistochemistry in association with pathological lesions in these same tissues. Infectious viral burdens in monkey # C-713 (which died on day 13) were lower. Infectious virus was also retrieved from throat swabs of iv-inoculated animals within 48 hours of exposure, before the evolution of skin lesions or fevers. It is probably that these animals are contagious at this early stage of infection; isolation of virus from throat swabs of human smallpox-infected patients was never systematically attempted. Detection of viral genomes in the blood of inoculated monkeys as early as one day after inoculation was achieved using TaqMan PCR. This assay, which requires less than one hour to run, promises to detect infection during the asymptomatic prodrome, when countermeasures such as antiviral drugs are predicted to be most effective.
Additional insight into the pathogenesis of variola in lethally infected primates is being obtained by evaluation of high-density cDNA microarray data, which measures and classifies gene expression in peripheral blood cells obtained sequentially. RNA was prepared from isolated peripheral blood leukocytes, labeled as fluorescent cDNA for microarray analysis, and hybridized to arrays which include >10,000 uniquely named genes. Using a two- color comparative hybridization format, expression patterns were analyzed according to biological themes. Gene expression analysis identified dramatic response patterns that correlated with lethality and gave insight into pathogenesis. Several relevant biological themes included interference with interferon, IL-18, and TNF-alpha, inhibition of interleukin-1 beta and apoptosis. Activation of coagulation cascade factors, and down regulation of immunoglobulin response and cell mediated immunity-related genes were also related to lethality. Microarray evaluations will be extended to include tissue expression patterns, comparisons with other
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aerosols in this situation is thought to be small, but application of high energy sources or the presence of physical clumps of particles could be problematic.
The risk of aerosol infection to an exposed human would depend on the amount of material aerosolized and the infectious dose for humans. The actual amount of tularemia or Q fever required to infect 50% of exposed humans is known and is on the order of 1–10 organisms. For other organisms such as anthrax it is necessary to extrapolate from cynomolgus monkeys or other experimental animals. In this case the lethal dose for 50% of animals is 8,000 spores by aerosol. The LD50 is determined by exposing animals to graded doses of the infectious agent and calculating the linear relationship between the logarithm of the dose increment and the increase in response of the target animals (Finney, 1964). This is usually done between 20–80% lethality and the LD50 calculated. In fact the linearity can probably be extrapolated further to furnish at least an approximation of the risk from lower doses; in the case of anthrax, published values for the slope (Glassman et al., 1965; Chinn et al., 1990) suggest that inhaling a dozen spores could be risky in a small percentage of the population.
These concepts are important to the practical management of situations in which a suspicious powder is involved. The physical properties of a readily aerosolized powder will be recognized by an experienced observer or by laboratory analysis. An ordinary dried culture of, for example, anthrax will not pose a great hazard beyond the readily recognized and treated cutaneous anthrax. Decontamination of a building needs to address the dangerous states of the contaminating organism. Safety is the goal, not "sterility". In the case of anthrax spores, significant quantities of aerosolizable particles is the criterion. Sterility is less important than being certain that any residual infectivity is earth bound.
Relative Importance of Different Agents
Consideration of the different bioterrorism agents and some of their properties is the first step to prioritize defenses against them. Each has different properties as we see them today and thus each presents different threats and different opportunities for control. This discussion has been cast in terms of the worst case scenarios (effective broad-scale aerosol dissemination) but we must recognize that, although protection against this situation is important, the most likely eventuality is a less extensive or less successful attack. Fortunately, attention to the worst case is a step toward the more general solution, although the lesser eventuality should also be in the mind of planners.
It is also important to note that biodefense efforts meld with the general struggle against infectious diseases. For example, strengthening the public health system will provide benefits regardless of whether a bioterrorist attack occurs. Money spent on communications within the public health system is long overdue. Planning will help in disaster response, regardless of the nature of the event. Perhaps much of the money spent on increasing smallpox vaccine stocks
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will eventually be "sunk costs" but we should not regard research and vaccine development on other agents as anything other than an benefit for human-kind.
Smallpox provides a threat whose consequences are simply unacceptable, regardless of the probability of its use. Therefore we must develop clinician awareness, diagnostic systems, and stockpiles of existing vaccine that give us a validated countermeasure to deploy in case of attack. Whether additional antiviral drug and vaccine development is justified is a matter of prioritization against other threats.
Anthrax also is a special case. It is widely distributed in nature and thus readily available to terrorists in virulent form. The spores are extraordinarily stable on storage and in aerosols obviating many of the terrorist's research needs to develop an effective weapon. Inhalation anthrax is a fearsome disease if not treated early with effective antibiotics, and production of antibiotic-resistant anthrax is readily achieved.
Plague and tularemia are both severe diseases but they require another level of sophistication in weaponization. Their cultivation in virulent form and their dissemination in stable aerosols is more difficult than for anthrax. The viral hemorrhagic fevers are essentially without therapy, have severe psychological impact, and carry a high mortality. Their production is still more difficult, but the technology is readily accessible to an experienced microbiologist (Peters, 2000).
When considering the impact of limited or massive dissemination of the agents in tables 2-4 and 2-5, one must factor in the disruption of the health care system, the role of antibiotic resistance, the fear-factor in the population and medical staff, as well as the state of defensive preparations. One element that is often neglected is the influence of a communicable disease on travel and commerce. Any of these diseases could lead to severe disruptions in the free travel of U.S. citizens and others within the US and in international air transport systems. If the agent is also an agricultural pathogen, then internal movement of animals would be frozen and exports would be stopped, resulting in even more severe economic consequences.
Strategies to Confront the Problem
Any attempt to deal with BT should consider the entire spectrum of responses, including state and local organization supported by a comprehensive federal plan. The public health system will be the back-bone, but there will have to be participation of the entire society. Recognition by the clinician, laboratory diagnosis, and mobilization of countermeasures will all play a part. As noted above, the strategy should be tailored to each agent or group of agents.
It must be emphasized that environmental detection and patient diagnosis of the specific agent employed are keystones of an improved response to the threat. Detection suffers from the need to be active at the time and site of an attack, so economics will probably limit its future usefulness to selected high risk venues.
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Diagnostics are, in principle, more focused and also require the suspicions of informed clinicians; widely deployed they are a very significant expense. An additional demand on detection and diagnostics is the recognition of subversion of our defenses by inducing resistance to anti-infectives or other protective modalities.
Vaccine approaches are suitable for selected at-risk groups, particularly for specific high-priority BT agents. However, specific vaccines are not general remedies for the threat to the civilian population. The expense and difficulty of administration and the inevitable side effects will limit their widespread use. They remain important elements of our response in selected populations and specific circumstances.
Anti-infective drugs could be a very effective response if problems of drugdevelopment, drug-resistance, safety and efficacy testing, stockpiling, and distribution can be solved. Other supportive measures directed to bacterial toxins or the over-exuberant inflammatory responses induced by some viruses could be useful, as well. Further definition of the Toll-like receptor family could open the way to broadly protective remedies that could be used in the event of BT attacks.
Some agents pose sufficient problems to demand immediate and thorough attention. Smallpox, because of its track record of interhuman transmissibility and high case fatality, is clearly a first-echelon target. Anthrax, because of its ease of weaponization, deserves attention to the development of more effective therapy beyond antibiotics. Antitoxic strategies at the level of the toxin molecules as well as their down-stream effects should be developed in a very short time frame. Furthermore, the terrorist use of antibiotic-resistant strains should be anticipated.
Plague and tularemia might seem to be resolved in principle because of the existence of effective antibiotics, but their relatively short incubation periods place high demands on availability of effective antimicrobials and the facility with which antibiotic resistance can be induced has important implications for defensive strategies. This is complicated because the log-normal distribution of incubation periods is "front-loaded" (Sartwell, 1950) and because late treatment can fail even though the bacteria are eradicated.
The viral hemorrhagic fever agents would induce widespread fear and even panic among the both general population and health-care providers. The arenavirus drug ribavirin should be stockpiled in modest amounts in the mean while, but more general strategies against the arenaviruses and other viral threat pathogens should be pursued.
Of course intelligence information and any dissuasion afforded by international agreements would be most welcome. We clearly cannot depend on these modalities to protect us completely. Many of the agents are widely available and so measures designed to limit their access are illusory in their effectiveness; anthrax is a case in point. However, limiting access to certain agents such as Ebola, Marburg, and smallpox viruses should be pursued. The equipment needed to produce limited amounts of biological agents is readily available and
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we cannot control or monitor access, but perhaps we can develop measures to track high output equipment and the movement of particularly sensitive expertise and genetic material.
A strong research program and the industrial base to develop promising research leads into practical human countermeasures will be the best defense. One of the impediments, in addition to the perennial need for funding, is the lack of suitable containment laboratories. Furthermore, the diminution of expertise and suitable laboratories to study infectious aerosols is alarming. Another variable in play is the concern for limiting dissemination of research results; we have to be very careful not to suffocate our defensive effort with excessive secrecy unless the controls can be shown to add to our safety.
Susan E. Maslanka,* Jeremy Sobel,* and Bala Swaminathan*
Foodborne and Diarrheal Diseases Branch Division of Bacterial and Mycotic Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Estimates of Foodborne Illness in the United States
The spectrum of illnesses caused by consumption of contaminated foods may range from self-limiting mild gastroenteritis to life-threatening neurologic, hepatic and renal syndromes (Mead et al., 1999). recently estimated the number of illnesses, hospitalizations and deaths in the United States using data from various national surveillance systems. Their estimates indicate that contaminated foods cause approximately 76 million illnesses, 325,000 hospitalizations and 5,000 deaths in the United States each year. The economic burden is estimated to be 9 to 32 billion U.S. dollars. More than 200 known diseases are transmitted through foods; the agents of foodborne illnesses include viruses, bacteria and their toxins, fungi and their toxins, parasites, poisonous plant components, marine biotoxins, heavy metals and possibly, prions. However in 82% of foodborne illnesses the identity of the pathogen is unknown. Of 1,500 deaths each year due to known pathogens, 75% are caused by Salmonella, Listeria monocytogenes and Toxoplasma.
The information provided in this paper reflects the professional view of the authors and should not be construed as an official position of the U.S. Department of Health and Human Services or the Centers for Disease Control and Prevention.
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Changes in the Foodborne Disease Outbreak Scenario
The epidemiology of foodborne diseases has undergone profound changes in the last 2 decades. Some factors influencing this change are the global distribution of food supplies to meet increasing consumer demands for greater diversity of foods, centralization of food production, processing and distribution to improve efficiencies and reduce costs, demographic changes occurring in industrialized nations that have resulted in increases in the proportion of the population with heightened susceptibility to severe foodborne infections, changes in food-related behavior of consumers and dramatic increases in world travel (Kaferstein et al., 1997; Swerdlow and Altekruse, 1998). One negative effect of high-degree consolidation of food production, processing and distribution is that food safety-related failures may affect large numbers of people over large geographic areas and may have disastrous public health consequences. Because of the explosive increases in international travel, new and emerging pathogens from one corner of the world are able to arrive at a location thousands of miles away in a matter of hours. The transcontinental flights themselves offer ample opportunities for transmission of foodborne disease during travel (Tauxe et al., 1987). In addition, the manufacturers and/or the distributors of the contaminated food are likely to encounter dire financial and public relations consequences following the implication of their products as a source of widespread illness.
These changes in food diversity and consumer demands have changed the way outbreaks are investigated. In the past, the majority of foodborne outbreaks occurred locally and could be readily detected by epidemiologic surveillance methods. An outbreak could be detected by an acute increase in foodborne illness and local food handling mistakes could be identified and controlled following epidemiology investigations. The "New Scenario" foodborne outbreak may involve a complex multistate investigation that may also be separated by time of onset of illness. While epidemiology investigations still provide needed information; laboratory data, particularly subtyping data, is now critical to implicate a food source and to link cases which may be geographically unrelated. A new level of quality (validation and standardization) of laboratory methods is required because of the potential adverse effects on a manufacturer of an implicated product. A once local problem, managed locally, now requires extensive resources to investigate and control.
Large Foodborne Disease Outbreaks
Examples illustrating large-scale (several thousands of cases) foodborne outbreaks are listed in Table 2-6.
The 1985 outbreak of Salmonella ser. Typhimurium infections was most likely caused by improper switching of the stainless-steel pipes in the milk processing facility, which resulted in raw milk coming in contact with pasteurized
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TABLE 2-6 Foodborne outbreaks
Etiologic agent
Food vehicle
Number of persons affected
Midwestern U.S.A.
Salmonella serotype Typhimurium
2% pasteurized milk produced by a large dairy
Nationwide, U.S.A.
Salmonella ser. Enteritidis
Ice cream
Sakai city, Japan
E. coli O157:H7
School lunch, radish sprouts
milk (Ryan et al., 1987). Interestingly, the outbreak was first recognized as a potentially large one when clinical laboratories in the region ran out of laboratory supplies for culturing Salmonella from ill persons. The ice cream-associated outbreak of Salmonella enteritidis infections in 1994 was caused by improper cleaning and sanitation of the ice cream premix tanker that was used previously to transport raw liquid eggs (Hennessy et al., 1996). The Japanese outbreak of E. coli O157:H7 infections was most likely caused by contamination of seeds used for sprouting or contamination of water used in the sprouting process (Michino et al., 1999).
Foodborne Pathogen/Toxins as Agents for Bioterrorism
Intentional contamination of our food and water supply is a real threat. Before this year, the only acts of bioterrorism in the U.S. involved foodborne agents. In 1984, members of a religious commune in Oregon attempted to influence the outcome of a local election by intentionally contaminating salad bars in several restaurants with Salmonella ser. Typhimurium. The outbreak affected at least 750 persons and S. Typhimurium was cultured from stool specimens of 388 persons (Török et al., 1997). In 1996, 12 of 45 laboratory workers at a large medical center in Texas became infected with Shigella dysenteriae type 2; the outbreak was associated with eating pastries or doughnuts that had been placed in the staff break room on a specific day. Epidemiologic and laboratory investigations strongly suggested intentional contamination of pastries by someone who had access to the bacterial stock cultures in the medical center's laboratory and who was familiar with the methods of culturing the bacteria (Kolavic et al., 1997).
Unlike some potential threat agents (i.e., smallpox) for which the sources are limited, many foodborne agents such as Salmonella, E. coli O157, and even botulinum toxin are relatively easy to obtain or produce. Many of the agents are stable under a variety of conditions and so could easily be added to food and
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water supplies before consumption. Although there was no reason to suspect foul play in any of the three foodborne outbreaks listed above, each could have easily been caused by intentional contamination by one or more persons involved in some way in food processing, preparation or transport.
Some foodborne disease agents require only a small inoculum to cause disease. Shigellosis can be caused by as few as a few hundred organisms; the infective dose of E. coli O157:H7 is thought to be even less (Hornick, 1998). Botulinum toxin is one of the most potent toxins known; it has been estimated that 1 gram of botulinum toxin is enough to kill 1.5 million people. Introduction of botulinum toxin into a food source would severely strain the resources of the health care system (e.g. antitoxin, hospital support, mechanical ventilators, etc) to adequately respond.
Although perhaps less deadly, other pathogens intentionally introduced into food and/or water supplies could also negatively affect the ability of a community to respond to the disease. Widespread disease could easily overburden the health-care system (hospitals, doctors, medical supplies), the public health system (epidemiologists, diagnostic testing laboratories), and emergency response teams (police, paramedics, decontamination crews). In addition, lack of consumer confidence in the quality of the food and water supply would be an additional burden on community governments. Capacity for early detection of intentional contamination of the nation's food and water supply is vital to minimize the impact on community health.
Challenges to Rapid Response
There are a number of challenges to providing a rapid response to intentional or unintentional widespread foodborne outbreaks (Mead et al., 1999).
Specimen collection. Although a mundane and easily overlooked aspect of response, a standard protocol for specimen collection is needed. Different foodborne agents (bacterial, viral, parasitic, etc) have different requirements for preservation to ensure efficient recovery for laboratory detection (Kaferstein et al., 1997).
Cost-reduction initiatives in healthcare. There is a move toward non-culture diagnostic and anti-microbial susceptibility tests to reduce healthcare costs. In some cases, tests for certain agents are not performed unless specifically requested by the physician (Swerdlow and Altekruse, 1998).
Need to differentiate between sporadic and outbreak cases. Foodborne illness occurs daily in the United States. Subtyping methods are needed which can rapidly and accurately separate sporadic cases from outbreak cases (Tauxe et al., 1987).
Lack of monetary incentives for commercial companies. The development, validation, and standardization requirements needed to produce a test kit that can be used for clinical specimens are time consuming and expensive. The
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lack of potential for profit prevents commercial companies from developing the required subtyping methods (Ryan et al., 1987).
Demand for real-time data. Currently there is no standardized computer system that will allow real-time data exchange between laboratories. The lack of real-time data exchange increases the time for establishing interventions to disease.
PulseNet as a Model
The National Molecular Subtyping Network for Foodborne Disease Surveillance (PulseNet) is CDC's network of public health and food regulatory agency laboratories. As a model, this network fulfills some of the needs for rapid response to outbreaks. Each state health department has the capacity to perform DNA "fingerprinting" of foodborne pathogens using CDC's standardized pulsed-field gel electrophoresis protocols. DNA patterns are analyzed using a standard software package using parameters set by CDC. Testing laboratories are able to communicate electronically via the Internet. CDC maintains a national database of DNA "fingerprint" patterns which is updated as new patterns are confirmed. This database has allowed state health departments to have early recognition of case clusters and helps to identify or confirm potential sources of disease. PulseNet is a rapid, effective means of communication between public health laboratories.
Integrated Approach to Foodborne Diagnostics
An integrated approach is needed to respond to intentional and nonintentional outbreaks of foodborne disease. (1) Sample collection, (2) improved diagnostics (including pathogen identification without isolation, rapid characterization and subtyping without isolation, and preservation of samples for subsequent pathogen recovery if needed), and (3) implementation of a real-time communication network must be seamlessly interconnected in order to effectively apply intervention measures during widespread outbreaks.
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text:
For me I love the kimonos, the traditions, and exspecially the food... overall i like almost everything about Japan, mostly their fasion, too.
Firstly the history is awesome. I did a paper on it at uni and it was so awesome. Secondly there is so much culture and history within the country, just look at the temples and stuff. I Live in New Zealand and the oldest thing we have is captain cooks watch. Yay not and thirdly. Japanese chicks are hot
Thanks alot Sasurihell and Kedar for the sigs and thanks Sammy 65 for the changing pics
(just remove the "x" from the [x/img] tag!
For me I love the kimonos, the traditions, and exspecially the food... overall i like almost everything about Japan, mostly their fasion, too.
Japan.. (^.^)
I like the peace, and the shy way they live. Like, when they travel, they sit down, play their tune and.. that's it. No one tlaks to anyone.. so, no one is anoyed. Like me. I like to sit down, play my mp3, and shut off from the world. But, no. They talk, they pull my hand, ask me questions.. Why? Can't they see im "offline"? Sitting by the window on a bus (i take a bus everyday), looking how the terrain changes, and just.. dream away..
Beside that.. it's thae way they talk, that shy manners they have. We make too much noise on the streets and with each oter.. they are.. Here I go daydreaming again.. they are so closed and low profile.. Me, when I used to go in highschool.. it was all noise, all the time. You had to be the "bitch" just to make it. One day at a time. Hated it.. 'cause I was shy one.. I used to have name "philosopher": always had my nose stuck in a book or something.
What else.. gardens. Cherries. Colors that make you become peacefull and calm. Geishas, of corse.. Their way to "catsh" te man, without one single touch.. is poetic..Also the way the spend their entire life walking slow, caring about nothig.. nad just.. fluing around.
At the end (maybe not, but I cant remember anything else) there are those small things.. not origami.. Bosai. Always wanted one.. (^.^)
With high honor to please.. Ana
There are many things about Japan that I adore, but I like Japanese cuisine most of all. Japanese cooking proves that you can have a meal that's both sumptuous and healthy, and not just one or the other, as some of us are inclined to believe.
Plus ça change, plus c'est la même chose.
Besides anime, I love almost everything about Japan.
I love their food (besides Sashimi), they're culture, and their perfectly staright hair...-.- I love the kimonos, too! I own one, and I really enjoy whearing it, and I really wish one day I could actually buy one from a real Japanese store, instaed of through Disney World...
And I love their art, most of all. Their way of making paintings is so beutiful! I could look at one all day! In conclusion, I love almost EVERYTHING about Japan. ^^
I like what the Japanese value,the environment, movies, people,style, the way they express art,food, basically Culture and History
i also like TV serial XD like My Boss My Hero this serial is the best one i like , and this is another thing that i like in Japan except anime XD ... =^_^=
♥♥♥My Dreams Become Like The Rainbow♥♥♥
Love Like the Wind You Can't See It But You Can Feel It
Well I like there food...
But also the sakura trees and the
Japanese Gardens..
They are so beautiful..
And I think the nature over there..
Sometimes the culture too..
But that depends on it...
Bye Bye..^_^
We are affraid of losing controle...But why should you be affraid of losing it...While you didnt have it...

subset: commoncrawl


text:
30. Doppler22
5:01 PM GMT on August 31, 2013I want him to come back to being a full time blog member lol He made some great graphics p |
By: Astrometeor , 7:16 PM GMT on July 16, 2013
I would like to make an appeal to the general assembly blogging community.
As some of you know, trHUrrIXC5MMX (Max) has abruptly left WU for an undetermined amount of time. GOOD BYE EVERYONE Me and him talk via e-mail quite regularly, and this is what he sent me today:
But about the rest of your email. .. it comes down to a simple question. ..
Am I "that" important on wu...? Why the scare? Im not a featured or have special distinction on wu...
Just being real.
I answered him, but I would like to hear from the general community how they feel about him leaving us like this.
If you don't know who he is or don't remember, he is the creator of the Hurricane Chart:
Community Hurricane Prediction Chart
One more thing, I know he doesn't like me sharing his e-mails to the world, but I think it's important for him to hear from all of his WU friends.
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I want him to come back to being a full time blog member lol He made some great graphics p |
Quoting 28. Astrometeor: indeed, I check up often your blogs... |
Quoting 27. trHUrrIXC5MMX: Oh? Really? Didn't think you kept up with my blogs... |
Quoting 26. Astrometeor: Im aware of that post she made |
Quoting 25. AETHOMAS: If Max sees this bump... *cough* |
I really enjoy his blogs, and I am sad to hear that he left. :( |
Astrometeor has created a new entry. |
Quoting 21. hydrus: Oh man, my dad's funny. He sends first child to college and buys himself a 48 inch TV and a 20 inch reflector telescope. Second one goes to college and he buys several cameras, hardware, and another 20 inch refractor scope. I'm the third child, who knows what he'll buy when I leave for college. |
Just a look at the last three days of storms here in the states: Two days ago: Yesterday: Today: This one will update periodically, and I shall have to get the URL fixed when the day changes over, this is the URL for the "current reports" map. |
I Will visit the Science Adventure Center next time I am in Nashville..20 inch tele is the bomb..:) |
Quoting 19. auburn:I completely agree with auburn here, and with originalLT #10 above as to Max. And I'm glad to hear Max is just taking a break. Astro, you are showing what a good heart you have. Kudos to you. |
Quoting 11. Patrap: The best I have seen it said. "No one blogger is more important than any other. We are a Community, and to that end we care for our members like family." |
Just checking my blog, looked at the little MapLoco counter. Interesting little thing, it is. One note: There is an AOI in the Central Pacific to the south-east of Hawaii. 0% chance of development, but it reminds me to check the Central Pac every once in a while as well. Otherwise quiet around the world in all basins, there is a tropical wave approaching the edge of Africa and set to emerge into the Atlantic that the GFS has been hinting at for possible development. Be back in the evening, thanks for visiting my blog everyone! |
Quoting 13. trHUrrIXC5MMX: Have a good vacation. Take some pics if you see anything worth while for us Max. Also, I checked my e-mail then noticed that part there, lol. Guess I did things backwards. |
Quoting 15. originalLT: No problem. |
Max E-Mailed me so I have it again! Thanks Astro and Max! |
Astro, regarding your question in post #12, he may have but I don't know where it is. I do have his mailing address in Norwalk CT. So I could always send something there. I'm sure his Mom could get anything I send him in Norwalk, to where he is in Marietta Ga. I could also send Max a WU E-Mail, hopefully he'll check his WU mail once in a while.---Thanks for all you are doing here. LT |
Well Im here (people can say what not.... whatever) Just typing this up in regards to Astro's deeds... appeal & abruptly - how should I take this? I have not been the only one going idle here... fyi There is no cause as to why Im doing this unlike others who get banned-angry or have other time consuming issues. trying to vacation peacefully for a little while... expect me back! yes, Im the creator of such chart please, let me rest and thanks to all for such responses about myself here and in my blog. check your email Astro. Bye. |
Quoting 10. originalLT: Max said he had given you his e-mail address. Do you not have it anymore? |
I took a 7 month sabbatical from Blogging to focus on a Health issue. Trust me, it does one a lot of good. No one blogger is more important than any other. We are a Community, and to that end we care for our members like family. I for one,hope to see the blogger return. Patrick |
Astro, if I could talk to Max, I would try to explain, it's not about , "importance" , it's about the sharing of ideas, opinions, information, discussions etc. That is what Max helped facilitate on WU and certainly on his blog. I feel we are all grateful for that. And that is why we all miss him. He was (and hopefully will be again) an important contributor to WU., You don't have to be a "Featured Blogger" for that. I hope he will see what we are all missing now.-- If you talk to him or E-Mail him, keep his spirits up. |
Quoting 8. originalLT: No problem. |
Hi Astro, thanks for sharing some info. And thanks on that post about 97L. I will include it on my chart, but of course with notation--with that information you supplied, thanks again. LT. |
"But about the rest of your email. .. it comes down to a simple question. .. Am I "that" important on wu...? Why the scare? Im not a featured or have special distinction on wu... Just being real." Please pardon the expression but, I can see that Max definitely has a good head on his shoulders. He'll be fine. For the better, sometimes folks from every side of the equation just need to let things go for a little while. It always makes us stronger in the end. I for one learned this the hard way a few years ago and I paid the consequences for my actions. |
Reminder for me:Quoting 509. ricderr: |
Quoting 4. Astrometeor: No Problem Astro ... He is one of the good guys . |
Thanks you guys for posting, VR, I saw that post, but thanks for re-posting here. |
Don't leave us Max!! I enjoy our discussions during the "Off Season" about severe weather and you diagrams are friggin awesome!! I've been around here for quite some time (a lot longer than my join date says. I'm on my second profile.) I've seen way to many good bloggers leave for various reasons, and would hate to lose another. Well, hope you do make it back around, but if you don't, I won't hold it against you. |
Astro I posted this in Max blog ! I had not been on much recently ... Max I am so sorry you are quitting . you did a wonderful job with your charts and you are a good person ... I know, I sometimes take time away from here it does me good . Swearing I am never coming back(usually once a month) but then my anger or hurt eases And I come back . I hope the same will be for you .. If not Take Care |
One more thing, P.S. TropicalAnalystwx13, I would most appreciate you giving your thoughts, you know why. |


text:
The Community of Disc Golfers and About All Things Disc Golf
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Update -09/12/2009. Looks like the good folks of New York suffered another terrorist attack on 9/11 –
Original Post –
Facing 5 weeks of political stalemate and vicious gridlock in the NY Senate which has brought the state of New York nearly to it's knees –
Governor Paterson drops the hammer. And no, it isn't the appointment of the new Lt. Governor…
He's suspended the Senator's paychecks and expense vouchers!
Since they can't pass any legislation – they can't even get a bribe. Continue reading
Filed under: You Know It's Bad When... | Tagged: democrat, Governor David Paterson, Governor of New York, Governor Paterson, Gridlock New York, New York, New York Senate, Republican, Senate Meltdown | 1 Comment »


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Whiplash walking Frog Records. CD. Composed 2000. Published by C.L. Barnhouse (CL.WFR558).
The O-Zone Percussion Group An eclectic collection of 13 entertaining percussion pieces vigorously performed by the outstanding O-Zone Percussion Group. Great listening and an invaluable way to inspire your budding percussionists, this delightful recording should be in the CD library of every serious percussion student or teacher. VERY NICE! Bouree, J.S. Bach Greensleeves, traditional Scherzo from Symphony #4, Peter Tchaikovsky Prelude XXII, J.S. Bach La Fille Aux Cheveaux De Lin, Claude Debussy Farandole, George Bizet Daybreak, Jack Stamp Rainbow Ripples, G.H. Green Log Cabin Blues, G.H. Green The Graceful Ghost, William Bolcom The Whistler, G.H. Green Root Beer Rag, Billy Joel Whiplash, Hank Levy.
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Defying Gravity $14.95
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Source: FOOTYMAD
Barrett: 'If we don't beat Brighton we could find ourselves cut adrift at the bottom'
Blues skipper Adam Barrett's hamstring strain saw him pull out of the Bees match during the warm-up and is unlikely to face the Seagulls at the weekend. Barrett: 'I should be back for the Oldham game' Shrimpers skipper Adam Barrett's absence on Tuesday evening was a major blow as it happened just before kick-off.Luckily, the form on the night of replacement Jean-Yves Mvoto helped paper the cracks, still the Blues legend will be missed in the vital clash at the weekend against Brighton, themselves not 100% clear of relegation just yet.Barrett told www.southendunited.co.uk: "I've slightly strained my hamstring and, unfortunately, I think Saturday's game is going to come too soon for me. It was sore and tight (in the Bees warm-up) and was very uncomfortable, especially when I had to run a bit faster. There was just no way I could've played, but I think I should be back for the Oldham game and hopefully we can go into that with a win over Brighton because that's definitely what we need." The Southend legend felt the side played well in the second half against Brentford, showing great spirit, but knows it really is 'last saloon' time now, that draws are no good and a win will do with the team stuck in the bottom four five points from safety and only four games remaining. Captain Adam continued: "We need all three points and we're fully aware of that. If we don't then we could find ourselves really cut adrift at the bottom if other results don't go our way. This pressure is on, but it will be difficult because Brighton have been in good form lately."


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Summary: | Previous Session open tabs closed in last session. | ||
Creator: | desga2 | Date: | 2008-12-06 19:20:05 |
Project: | Plugin - Sessions | Owner: | .Nobody |
Status: | Open | Severity: | RFE |
Version: | 1.5.0 | Target Version: | Unknow |
User-agent: Firefox/188.8.131.52
This happen because "Previous Session" is updated only when a new tab is open.
If you close some tabs and close K-Meleon, when you start K-Meleon again and Load Previous Session closed tabs in previous session are opened.
This problem happen in 1.5.X (X include 0, 1 and 2RC)
happens here too, 1.5.1 and 1.5.2 (nt and w9x versions: same issue)
That's because sessions can't know if you closed the tabs or if they were closed because you exited kmeleon.
Workaround: Reload one of the tab before exiting, to force writing the session.
I continue thinking this is a bug or feature needed in Sessions plugin.
Sessions must know when a tab is closed similar that it know when this is opened or reloaded.
Session can hook to CloseTab event identically that OpenTab/LoadTab event.
And Session plugin can know similar way than K-Meleon know when a tab is closed or K-Meleon is closed.
CloseTab is always sent, even at exit. There is no easy way to make a difference between both currently.
Would a "reload Tab No.1" event triggered by, and deferring, the exit command, be able to help?
If yes, would the resulting lag be a problem?
Could the reloading be cancelled as soon as the refreshed session has been written?
[Changed Severity from "Minor" to "RFE"]
[Changed Status from "Unconfirmed" to "Open"]


text:
September 1999
They worked hard, overcame obstacles, bucked conventional wisdom, and touched our lives. Meet the most impressive, intriguing, and influential Texans of 1999.
Once upon a time, you went to a museum to see what was inside. Now you go to see the museum itself—and nowhere is this trend more in evidence than in Texas.
After years of not much brewing, Houston's Duncan Coffee Company is piping hot all over again.
What do gossipeuse Liz Smith, politico Paul Begala, and Hollywood hotshot Robert Rodriguez have in common? They all worked—and networked—at the hundred-year-old Daily Texan.
Ricky Martin? Jennifer Lopez? The real Spanish-language stars of the moment are the Monterrey punk, funk, jazz, and hip-hop duo Plastilina Mosh.
Jailhouse Chili is a gastronomic pleasure for the Kinkster—and the rest of us.


text:
News Archive
Little Falls Man Charged In Death Of Teens
LITTLE FALLS, Minn. (AP) -A Little Falls man has been charged with two counts of second-degree murder in the shooting deaths of two teenager he said broke into his home.
64-year-old Byron David Smith was charged in a criminal complain filed Monday.
The complaint quote Smith telling investigators he shot 17-year-old Nicholas Brady Schaeffel and 18-year-old Haile Kifer as they came down into his basement.
The complain says Smith told investigators he fired "more shots than I needed to" he told them he was afraid the teens might have a weapon.
School officials say the victims were cousins.
Kifer was a senior at Little Falls High School. Superintendent Stephen Jones said Sunday he was notified of her death by investigators.
Schaeffel was a student at Pillager High School. The Star Tribune identified him after interviewing his principal.
The sheriff's department says police visited his home near Little Falls on Friday afternoon. Officers say 64-year-old Byron David Smith immediately confessed to killing two people the previous day about noon.
Morrison County Sheriff Michel Wetzel says people have every right to defend themselves and their homes, but circumstances suggest Smith went beyond that point.
Latest News
Man Seriously Injured After Accident On Highway 55 Near Buffalo
Powerhouse Outdoor Equipment In St. Cloud Burglarized Early Tuesday Morning
Cigarette Butt Believed to Have Started Grass Fire in St. Wendel Township
Stearns County Sheriff's Office Warns Of Phone Scam Involving IRS Employee
Coon Rapids Man Sent Airborne In Car Collision On Highway 10
MnDOT To Reduce Eastbound I-94 Between St. Michael And Monticello To Single Lane Overnights
Supporters Of Convicted Killer Byron Smith Meet To Discuss Reversing The Jury's Verdict
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Will iBank support user profiles for each member of a family of 4?
- Asked by Marcela S from Virginia Beach
iBank 4
Product No Longer Available
1 Answer from the Community
You can create multiple documents in iBank, with the accounts for every member of the family in a separate one. Then, if you'd like to keep each person's finances private, those documents can each have their own password.
Put another way, two parents might want to share one password-protected document that includes credit card accounts, a mortgage account, an IRA and salary and tax-related data, while teens in the house might want to track wages, savings and a car loan in their own private documents - all using one copy of iBank.
Also worth noting is that each document can be synced separately to iBank Mobile on each person's iPhone or iPod touch.- Answered by Scott B from Putney


text:
SBCustomIcon is a MobileSubstrate-based extension that allows iPhone applications to easily change their icon in SpringBoard.
- Jailbroken iPhone or iPod touch (OS 2.0 to 3.1.2)
- MobileSubstrate
How it Works
SBCustomIcon adds the following methods to the UIApplication class for customizing the app icon:
- (BOOL)hasCustomIcon;
if the application currently has a custom icon,NO
otherwise- (BOOL)setCustomIcon:(UIImage*)customIcon;
sets the app's icon to customIcon
on success,NO
on failure- (BOOL)setCustomIconFile:(NSString*)customIconPath;
sets the app's icon to the file at customIconPath, that should be a PNG file
on success,NO
on failure- (void)removeCustomIcon;
removes the custom icon for the application, turning it back to the default
The app will also need the following keys in it's Info.plist
- SBWillUseCustomIcon (boolean)
set toYES
if your application uses SBCustomIcon functionality - SBCustomIconIsPersistent (boolean)
By default, the icon turns back to normal when the app terminates. If you want it to persist, add this key and set it toYES
You can determine if SBCustomIcon is available before calling any of its methods with the SBCustomIconAvailable
macro, or check if the methods exists with respondsToSelector:
. Like that your application can work even if the extension isn't installed.
To use SBCustomIcon in your project, include this header file:
#import <UIKit/UIKit.h> #import <objc/runtime.h> #define SBCustomIconAvailable (class_respondsToSelector(objc_getClass("UIApplication"), @selector(hasCustomIcon))) @interface UIApplication (SBCustomIcon) - (BOOL)hasCustomIcon; - (BOOL)setCustomIcon:(UIImage*)customIcon; - (BOOL)setCustomIconFile:(NSString*)customIconPath; - (void)removeCustomIcon; @end
You can find SBCustomIcon in the BigBoss & Planet-iPhones repository in Cydia, or download the deb here and install it manually:
SBCustomIcon | sbcustomicon-1.0.deb (13 KiB) | SHA1 c187a6663913cbf7746605376259d6813b748afa |
This program is distributed in the hope that it will be useful, but WITHOUT
ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS
You are free to use the functionality of SBCustomIcon in your own software.
The source code is provided as reference, but distribution of modified versions
is not allowed, since it could create conflicts.
Source Code
- You can check out the source code from subversion:
svn checkout svn:/
- Or browse and download it with WebSVN:


text:
On Sun, Jul 31, 2011 at 6:39 AM, JonnyDrummer said:
i have not an i-phone D:
On Mon, Jul 25, 2011 at 10:41 PM, kornchino said:
app for a blackberry please!!
On Sat, Jul 23, 2011 at 11:03 PM, I_h8_you said:
Yes..I have symbian((( What should i do? Fuck :!
On Fri, Jul 22, 2011 at 9:37 PM, kornhivgurl said:
one for the android more like it lol
On Thu, Jul 21, 2011 at 9:54 PM, Kaiowas said:
Fuck the iPhone, what about an app for BlackBerry!? Please!
On Wed, Jul 20, 2011 at 6:19 PM, Chellie said:
Something to look forward to when my contract runs out... :)
On Mon, Jul 18, 2011 at 10:28 AM, kornhivgurl said:
damn i dont have the iphone =/
On Sat, Jul 16, 2011 at 12:06 AM, preyforbeg4484 said:
I'll pass
On Thu, Jul 14, 2011 at 1:03 PM, lrgrogg said:
Or Android????
On Thu, Jul 14, 2011 at 12:31 AM, mateusz said:
Another iPhone app.. maybe something on symbian? huh?
12 Results Found


text:
Common words appear frequently in written and spoken language across many genres from radio to academic journals.
Informal words should be reserved for casual, colloquial communication.
in a zealous manner
Synonyms for zealously
in a zealous manner
More words related to zealously
adv. actively; intently
- indefatigably
- industriously
- laboriously
- like all get out
- like the devil
- like the dickens
- nimbly
- painstakingly
adv. not humorously
adv. anxiously
adv. tenderly
Roget's 21st Century Thesaurus, Third Edition Copyright © 2013 by the Philip Lief Group.
Cite This Source


text:
Related Artists
In This Moment
Birth Place: Los Angeles, California
Years Active: 2005–present
Genres: Metalcore, Alternative Metal
Years Active: 2005–present
Genres: Metalcore, Alternative Metal
In This Moment is a heavy metal band that hail from Los Angeles, California, and came together in 2005 when lead singer Maria Brink and guitarist Chris Howorth decided to form a band. The duo recruited drummer Jeff Fabb and started out as a trio called, Dying Star. Eventually the trio changed their name to, In This Moment, and added two more members to the fold: guitarist Blake Bunzel and bassist Josh Newell. 2005 saw a series of steady line-up changes begin with the band's bass player: Newell left and was replaced by Pascual Romero, who in turn was replaced by Jesse Landry; Landry by Kyle Konkiel in 2009, and Konkiel by Travis Johnson in 2010. 2011 also saw Fabb and Bunzel part ways with th... Continue Bio >>
Listen to In This Moment
and similar artists - Play Now
All Albums >>and similar artists - Play Now
Latest Tracks:
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text:
Duel Masters #6 The Winners
| ||||
The winners of Duel Masters Sex!
(That's Latin for six, I guess) We congratulate the top 3 contestors:
JohnnyGambler, HellRaiser and Ian
The Final Round Video: Final Round ESL:JKA on Youtube Previous Finals The Hall of Fame will soon contain your names. We also like to thank the teams for their server support: We hope you enjoyed this cup and hope to meet again next Sunday! Do not forget; we hope to hear from you about the custom maps. Your Jedi Knight: Jedi Academy – Admin Team
Monday, 23/01/12 00:38
| ||||
| ||||
Someone pls call inactive oldsqlers to spit on the winners cuz we're in 2012.
Setting that aside.
Gratz great cup!
Setting that aside.
Gratz great cup!
Noctis wrote:
hacher you have the potential to shove my snow, please contact me :-)
You have the potential to wash my dick. (:-


text:
Asia Risk awards 2011 winner: Citi Private Bank – Private Bank of the Year
Citi Private Bank retained this award in large part due to its fine-tuning of business activities following an overhaul of its sales and compensation models during the previous awards period. This enabled the private bank to grow its assets under management (AUM) in the region to $193 billion by the end of the second quarter of this year, up from $179 billion at the end of 2010, and up from $165 billion in 2009.
One of Citi Private Bank's big new initiatives included the roll-out of hedge fund and mutual fund platforms in Asia during the past year. Citi distributes a large number of funds: for example, there are 1,500 listed on the bank's mutual funds platform, all offered by third parties. The new platforms streamline the buying of positions and execution of trades, but most innovative is the amount of research that goes into rating best-of-breed funds, and using this information to form the basis of portfolios for clients.
Debashish Dutta Gupta, investments head for Asia in Singapore at Citi Private Bank, says clients previously did not receive advice on "high conviction" funds from private banks. Although it is common to offer such investment outlooks for other asset classes, such as equities or commodities, advice for funds has generally been ad hoc. Citi Private Bank's new approach poses some risks – for example, the removal of a recommendation for a hedge fund could cause tensions with prime brokerage – but Gupta says discussions within Citi are "mature enough" that "they respect and understand our decisions".
Fee structure
Gupta adds that the private bank only charges on an advisory basis, meaning there is no conflict of interest as might occur if the bank was actively managing the client's money. "Therefore, we're judged by the client purely on the basis of the performance of this portfolio, as opposed to anything else," Gupta says. "Asians trade mutual funds much more than anyone else, so for them this is particularly attractive, especially not having to pay switching costs, plus in general in this region investors are loath to pay inception fees."
One of the biggest successes of the ties between the investment bank and the private bank is in the area of initial public offerings (IPOs), which is of particular relevance in Asia where many family businesses are conducting their first IPOs. "The private bank probably already has a relationship with the client, and the manager gets involved in that dialogue when the client is hatching their plans and brings the investment bank into the discussion," says Bassam Salem (below), Asia-Pacific CEO.
Citi Private Bank also acts as a powerful distribution channel for IPOs to its own client base and has been involved in several of this year's major IPOs in Asia – both for wealth structures and distribution – including a major commodities company that went public globally.
Though Citi Private Bank declined to name its clients, the biggest commodities IPO of the year was the listing of Glencore in the London and Hong Kong bourses, with Citi as a lead arranger. The listing was tipped to make several of Glencore's executives and traders billionaires, with corresponding wealth management needs. Citi Private Bank did say it teamed up with its investment bank on a $500 million Asian transport IPO, securing a mandate to manage the owner's wealth post-IPO, and another transaction involving the IPO of a Chinese industrials company, with the private bank partnering the investment bank to help the owners secure more capital for growth and develop their personal wealth legacies.
Citi also appointed Ted Teo at the end of March this year to co-ordinate activities between the investment bank and private bank, or act as a "traffic warden" according to Gupta.
The private bank also helped clients look at portfolios with risk-return in mind. The bank offered a trade mixing global equity index protection with a contingency on gold price increases to make the put cheaper – a worst-of Standard & Poor's 500 index put/gold ETF call. "Buying a put on, for example, the S&P index, contingent on an increase in the gold price, would not normally make the option any cheaper because they are so correlated negatively, but we've noticed in the current environment it can actually make the put over 50% cheaper," says Gupta. "From mid-Q4 last year we've been telling clients to go underweight equity and gold and buy long-duration government bonds. It seemed like a crazy trade at the time, but it has turned out to be most prescient."
Topics: Awards and rankings, Asia, Citi
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