This selective listening task highlights the power of attention to filter extraneous information from awareness while letting in only those elements of our world that we want to hear treatment zenkers diverticulum generic zyprexa 7.5 mg visa. Focused attention is crucial to our powers of observation medications valium zyprexa 2.5mg lowest price, making it possible for us to zero in on what we want to see or hear while filtering out irrelevant distractions symptoms zenkers diverticulum buy cheap zyprexa 5 mg line. But treatment 6th nerve palsy cheap zyprexa 5 mg line, it has consequences as well: We can miss what would otherwise be obvious and important signals medicine 852 zyprexa 20 mg visa. The video will begin playing at 30 minutes medicine 2 generic 2.5mg zyprexa amex, watch till 37:08 to understand the criteria for automaticity medications you should not take before surgery zyprexa 20mg fast delivery. For example medications quotes buy 20mg zyprexa overnight delivery, if I can achieve a match between the large red object I see in the street and my stored representation of a London bus, then I recognize a London bus. However, one difficulty for this theory is illustrated in the figure to the below. A second problem is that we continue to recognize most objects regardless of what perspective we see them from. This would suggest we have a nearly infinite store of templates, which hardly seems credible. Instead of comparing a visual array to a stored template, the array is compared to a stored prototype, the prototype being a kind of average of many other patterns. The perceived array does not need to exactly match the prototype in order for recognition to occur, so long as there is a family resemblance. For example, if I am looking down on a London bus from above its qualities of size and redness enable me to recognize it as a bus, even though the shape does not match my prototype. There is good evidence that people do form prototypes after exposure to a series of related stimuli. For instance, in one study people were shown a series of patterns that were related to a prototype, but not the prototype itself. When later shown a series of distractor patterns plus the prototype, the participants identified the prototype as a pattern they had seen previously. Feature Analysis: Feature-matching theories propose that we decompose visual patterns into a set of critical features, which we then try to match against features stored in memory. When I am presented with a letter of the alphabet, the process of recognition involves identifying the types of lines and angles and comparing these to stored information about all letters of the alphabet. If presented with a "Z", as long as I can identify the features then I should recognise it as a "Z", because no other letter of the alphabet shares this combination of features. In a paper titled Forest before trees David Navon suggested that "global" features are processed before "local" ones. He showed participants large letter "H"s or "S"s that were made up of smaller letters, either small Hs or small Ss. People were faster to identify the larger letter than the smaller ones, and the response time was the same regardless of whether the smaller letters (the local features) were Hs or Ss. However, when required to identify the smaller letters people responded more quickly when the large letter was of the same type as the smaller letters. One difficulty for feature-matching theory comes from the fact that we are normally able to read slanted handwriting that does not seem to conform to the feature description given above. For example, if I write a letter "L" in a slanted fashion, I cannot match this to a stored description that states that L must have a vertical line. Another difficulty arises from trying to generalise the theory to the natural objects that we encounter in our environment. Thus, the ability to recognize an individual just by looking at their face is crucial for human social interaction. Prosopagnosia is a cognitive condition characterized by a relatively selective impairment in face recognition. The disorder can be acquired or developmental in nature, with the latter also referred to as "congenital" or "hereditary" prosopagnosia. For instance, many people with prosopagnosia can identify people via voice, gait and general appearance and manner15. Subsequently, these individuals may not become aware of their difficulties for a long period of time. This may conceal the condition from other people, or even falsely indicate to oneself, that they are able to recognize others in the same manner as most others in the general population. Concepts and Categories Categories A category a set of objects that can be treated as equivalent in some way. For example, consider the following categories: trucks, wireless devices, weddings, psychopaths, and trout. Although the objects in a given category are different from one another, they have many commonalities. The psychology of categories concerns how people learn, remember, and use informative categories such as trucks or psychopaths. There is a category of trucks in the world, and you also have a concept of trucks in your head. This set of things can be considered a category, a set of objects that can be treated as equivalent in some way. But, most of our categories seem much more informative- they share many properties. There is a category of trucks in the world, and I also have a concept of trucks in my head. We expect people to be able to know what to do in new situations and when confronting new objects. If you go into a new classroom and see chairs, a blackboard, a projector, and a screen, you know what these things are and how they will be used. In short, concepts allow you to extend what you have learned about a limited number of objects to a potentially infinite set of entities. You know thousands of categories, most of which you have learned without careful study or instruction. If you teach a learning program that a robin, a swallow, and a duck are all birds, it may not recognize a cardinal or peacock as a bird. Simpler organisms, such as animals and human infants, also have concepts (Mareschal, Quinn, & Lea, 2010). Squirrels may have a concept of predators, for example, that is specific to their own lives and experiences. However, animals likely have many fewer concepts and cannot understand complex concepts such as mortgages or musical instruments. Here is a very good dog, but one that does not fit perfectly into a well-defined category where all dogs have four legs. This means that you can give a definition that specifies what is in and out of the category. Second, those features must be jointly sufficientfor membership: If an object has those features, then it is in the category. For example, if I defined a dog as a fourlegged animal that barks, this would mean that every dog is four-legged, an animal, and barks, and also that anything that has all those properties is a dog. Unfortunately, it has not been possible to find definitions for many familiar categories. I knew a dog that lost her bark with age (this was an improvement); no one doubted that she was still a dog. Even in domains where one might expect to find clear-cut definitions, such as science and law, there are often problems. For example, many people were upset when Pluto was downgraded from its status as a planet to a dwarf planet in 2006. After an astronomical organization tried to make a definition for planets, a number of astronomers complained that it might not include accepted planets such as Neptune and refused to use it. If everything looked like our Earth, our moon, and our sun, it would be easy to give definitions of planets, moons, and stars, but the universe has sadly not conformed to this ideal. Fuzzy Categories Borderline Items Experiments also showed that the psychological assumptions of well-defined categories were not correct. Hampton (1979) asked subjects to judge whether a number of items were in different categories. Instead, he found many items that were just barely considered category members and others that were just barely not members, with much disagreement among subjects. Sinks were barely considered as members of the kitchen utensil category, and sponges were barely excluded. People just included seaweed as a vegetable and just barely excluded tomatoes and gourds. Many studies since then have found such borderline members that are not clearly in or clearly out of the category. Examples of two categories, with members ordered by typicality (from Rosch & Mervis, 1975) McCloskey and Glucksberg (1978) found further evidence for borderline membership by asking people to judge category membership twice, separated by two weeks. They found that when people made repeated category judgments such as "Is an olive a fruit So, not only do people disagree with one another about borderline items, they disagree with themselves! As a result, researchers often say that categories are fuzzy, that is, they have unclear boundaries that can shift over time. Typicality A related finding that turns out to be most important is that even among items that clearly are in a category, some seem to be "better" members than others (Rosch, 1973). Typicality is perhaps the most important variable in predicting how people interact with categories. Think of the most typical category member: this is often called the category prototype. Items that are less and less similar to the prototype become less and less typical. At some point, these less typical items become so atypical that you start to doubt whether they are in the category at all. From day to day, you might change your mind as to whether this atypical example is in or out of the category. Typicality and Cognition Source of Typicality Intuitively, it is not surprising that robins are better examples of birds than penguins are,or that a table is a more typical kind of furniture than is a rug. But given that robins and penguins are known to be birds, why should one be more typical than the other One possible answer is the frequency with which we encounter the object: We see a lot more robins than penguins, so they must be more typical. Frequency does have some effect, but it is actually not the most important variable (Rosch, Simpson, & Miller, 1976). For example, I see both rugs and tables every single day, but one of them is much more typical as furniture than the other. They proposed that items are likely to be typical if they (a) have the features that are frequent in the category and (b) do not have features frequent in other categories. Robins are small flying birds that sing, live in nests in trees, migrate in winter, hop around on your lawn, and so on. Furthermore, they have properties that are common in other categories, such as swimming expertly and having wings that look and act like fins. When you think of "bird," how closely does the robin resemble your general figure Rather, it is because the robin has the shape, size, body parts, and behaviors that are very common among birds-and not common among fish, mammals, bugs, and so forth. In a classic experiment, Rosch and Mervis (1975) made up two new categories, with arbitrary features. Subjects viewed example after example and had to learn which example was in which category. Rosch and Mervis constructed some items that had features that were common in the category and other items that had features less common in the category. In another experiment, Rosch and Mervis constructed items that differed in how many features were shared with a different category. The more features were shared, the longer it took subjects to learn which category the item was in. These experiments, and many later studies, support both parts of the family resemblance theory. Category Hierarchies Many important categories fall into hierarchies, in which more concrete categories are nested inside larger, abstract categories. For example, consider the categories: brown bear, bear, mammal, vertebrate, animal, entity. Clearly, all brown bears are bears; all bears are mammals; all mammals are vertebrates; and so on. Examples of biological categories come to mind most easily, but within the realm of human artifacts, hierarchical structures can readily be found: desk chair, chair, furniture, artifact, object. Brown (1958), a child language researcher, was perhaps the first to note that there seems to be a preference for which category we use to label things. This is a highly simplified illustration of hierarchically organized categories, with the superordinate, basic, and subordinate levels labeled. The basic level represents a kind of Goldilocks effect, in which the category used for something is not too small (northern brown bear) and not too big (animal), but is just right (bear). They found that 1,595 names were at the basic level, with 14 more specific names (subordinates) used. Furthermore, in printed text, basic-level labels are much more frequent than most subordinate or superordinate labels. As Brown noted, children use these categories first in language learning, and superordinates are especially difficult for children to fully acquire. People are faster at identifying objects as members of basic-level categories (Rosch et al. North Americans are likely to use names like tree, fish, and bird to label natural objects. But people in less industrialized societies seldom use these labels and instead use more specific words, equivalent to elm, trout, and finch (Berlin, 1992). Because Americans and many other people living in industrialized societies know so much less than our ancestors did about the natural world, our basic level has "moved up" to what would have been the superordinate level a century ago. Furthermore, experts in a domain often have a preferred level that is more specific than that of non-experts. Birdwatchers see sparrows rather than just birds, and carpenters see roofing hammers rather than just hammers (Tanaka & Taylor, 1991). One explanation of the basic-level preference is that basic-level categories are more differentiated: the category members are similar to one another, but they are different from members of other categories (Murphy & Brownell, 1985; Rosch et al. Superordinate categories are not as useful because their members are not very similar to one another. As a result, it can be difficult to decide which subordinate category an object is in (Murphy & Brownell, 1985). Experts can differ from novices in which categories are the most differentiated, because they know different things about the categories, therefore changing how similar the categories are. This is a controversial claim, as some say that infants learn superordinates before anything else (Mandler, 2004). However, if true, then it is very puzzling that older children have great difficulty learning the correct meaning of words for superordinates, as well as in learning artificial superordinate categories (Horton & Markman, 1980; Mervis, 1987). However, it seems fair to say that the answer to this question is not yet fully known. It is closely related to the highly interdisciplinary cognitive science and influenced by artificial intelligence, computer science, philosophy, anthropology, linguistics, biology, physics, and neuroscience. Fundamentally, cognitive psychology studies how people acquire and apply knowledge or information. Scott Holmes Sharon Hu Francesca Iacopi Danielle Ilmeni Jean Anne Incorvia Engin Ipek Satoshi Kamiyama Kiyoshi Kawabata Asif Khan Hajime Kobayashi Suhas Kumar Ilya Krivorotov Xiuling Li Xiang (Shaun) Li Shy-Jay Lin Tsu-Jae King Liu Matthew Marinella Bicky A. Nahmias Emre Neftci Mike Niemier Dmitri Nikonov Yutaka Ohno Chenyun Pan Ferdinand Peper Shriram Ramanathan Mingyi Rao Shashi Paul Paul R. Prucnal Titash Rakshit Arijit Raychowdhury Sayeef Salahuddin Shintaro Sato Michael Schneider Bhavin J. Shastri Xia Sheng Takahiro Shinada Urmita Sikder Greg Snider John-Paul Strachan Dimitri Strukov Naoyuki Sugiyama Tarek Taha Alexander N. Tait Shinichi Takagi Norikatsu Takaura Tsutomu Teduka Yasuhide Tomioka Wilman Tsai Tohru Tsuruoka Zhongrui Wang R. Scaling has enabled many of these applications through increased performance and complexity. This is driving interest in new devices for information processing and memory, new technologies for heterogeneous integration of multiple functions, and new paradigms for system architecture. An overarching goal of this chapter is to survey, assess, and catalog viable emerging devices and novel architectures for their long-range potential and technological maturity and to identify the scientific/technological challenges gating their acceptance by the semiconductor industry as having acceptable risk for further development. These communities include universities, research institutes, and industrial research laboratories; tool suppliers; research funding agencies; and the semiconductor industry.
At low doses treatment quad strain cheap zyprexa 5 mg without prescription, intramuscular or subcutaneous injections may result in necrosis at the injection site possibly resulting in secondary infections medicine jobs zyprexa 5mg visa. Targosz and colleagues99 describe a suicide case in which an individual injected himself subcutaneously with a large dose of ricin extracted from castor beans medications hyperkalemia zyprexa 2.5 mg for sale. The patient was observed with hemorrhagic diathesis and liver medications that cause high blood pressure order zyprexa 20 mg without a prescription, kidney medicine joint pain buy cheap zyprexa 5 mg, cardiovascular medicine for stomach pain zyprexa 2.5 mg otc, and respiratory systems failure requiring endotracheal intubation and artificial ventilation medicine upset stomach order zyprexa 7.5 mg without a prescription. Although given maximal doses of pressor amines and treated for hemorrhagic diathesis symptoms mercury poisoning order zyprexa 20mg online, treatments were ineffective and the patient developed symptoms of multiorgan failure followed by asystolic cardiac arrest. A postmortem examination revealed hemorrhagic foci in the brain, myocardium, and pleura. Markov experienced severe local pain after the injection, which was followed by a general weakness 5 hours later. Fifteen to 24 hours later, he had an elevated temperature, felt nauseated, and vomited. While his blood pressure remained normal, lymph nodes in the affected groin were swollen and sore, and a 6-cm diameter area of induration was observed at the injection site. Just over 2 days after the attack, he suddenly became hypotensive and tachycardic with a pulse rate of 160 beats/minute and a white blood cell count of 26,300/mm. Shortly thereafter, Markov died from cardiac failure complicated by pulmonary edema; the time of death was 3 days after he was initially poisoned. Most of the human data comes from descriptions of workers being exposed to castor bean dust in or around castor bean processing plants. Unlike other routes of intoxication, damage caused by an aerosol exposure is greatly dependent on particle size, and to a lesser extent on the dose and cultivar from which ricin was obtained. Most of the toxin was found in the trachea, and little lung damage was observed in histological sections of lung tissue taken 48 hours postexposure. Three days post-exposure, there was significant diffuse alveolar edema, and severe capillary congestion and macrophage infiltration of the alveolar interstitium. By day four, there was a rapidly resolving pulmonary edema and renewal of the bronchial epithelium, even though severe pas-sive venous congestion existed in all solid peripheral organs. Examination of tissue sections from sacrificed animals were similar to control tissues, except for focal areas of intraalveolar macrophage infiltration. Thirty hours after challenge, alveolar flooding was apparent, along with arterial hypoxemia and acidosis. Histopathology showed lesions throughout the respiratory tract, spleen, and thymus. As with other laboratory animal models, investigations in which nonhuman primates were challenged with an aerosolized dose of ricin indicate that disease progression is proportional to particle size. At 16 hours, progression of pulmonary tissue damage continued, and by 24 hours, there was edema, pulmonary congestion, necrotic alveolar septa, and necrotic bronchiolar epithelium (Figure 16-5). Thirty-two hours later, there was marked perivascular and peribronchiolar interstitial edema and alveoli contained fluid (edema) mixed with fibrin and viable or degenerate neutrophils and macrophages. The bronchiolar epithelium was necrotic and often sloughed into the lumen, whereas lymphatics surrounding the airways were moderately dilated and the endothelium of many small vessels had atrophied. In the tracheal mucosa, there was epithelial degeneration with scattered areas of necrosis and subacute inflammation. The cortex of adrenal glands showed mild degeneration and necrosis, and there 383 Medical Aspects of Biological Warfare a b c Figure 16-5. Cause of Death Although the exact cause of death from ricin toxicity is not known, clinical symptoms of individuals exposed to lethal doses of the toxin suggest that death results from a severe inflammatory response and 384 multiorgan failure. More investigations are necessary to understand how ricin activates severe inflammatory responses that lead to multiorgan failure, shock, and death. The cellular uptake of ricin is rapid and thus limits the diagnosis of ricin in blood and other fluid samples. Additionally, the ricin concentration may be below the current levels of detection, making diagnosis more difficult. Ricin does not replicate, so detection relies on the ability to identify physical attributes of the toxin within the sample. The most common method for toxin identification uses antiricin antibodies to which ricin would bind. In recent years, several variations of antigen (toxin)antibody assays have been developed. The sample is added to one end of the bed, and capillary action causes the sample to flow across the matrix. If ricin is present, then the detecting antibody causes color development at the line. The magnet is set on an electrode that delivers the proper amount of electrical potential resulting in the emission of light identifying that the sample contains ricin. The combination of liquid chromatography and mass spectrometry allows for the separation of mixtures in a sample while being able to identify specific substances based on their molecular mass via their mass to charge ratio (m/z). Picogram amounts of ricin can be detected within a 5-hour timeframe allowing for fast, reliable detection. For example, a highly pure form of the toxin might indicate that an organized terrorist group, such as Al Qaeda, produced the ricin while a less pure form may indicate fewer organized groups or individuals acting alone. The amount of luminescence, produced when the luciferin substrate is added to luciferase, is proportional to the amount of luciferase produced in the in vitro translation system. Diagnosis Diagnosis of ricin intoxication is challenging because the cellular uptake of ricin is extremely rapid and limits the availability of ricin for diagnosis in blood and other fluid samples to 24 hours postintoxication. The biphasic half-life suggests rapid distribution and uptake of the toxin followed by the slow clearance of excess toxin. Evaluation of handheld assays for the detection of ricin and staphylococcal enterotoxin B in disinfected waters. Forensic identification of neat ricin and of ricin from crude castor bean extracts by mass spectrometry. However, these antibodies are not present until approximately 2 weeks postintoxication and, therefore, could not be used in the initial diagnosis. Given that ricin does not have cell specific selectivity, treatment of ricin intoxication is dependent on the site or route of entry, is largely symptomatic, and basically supportive to minimize the poisoning effects of the toxin. Medical countermeasures that have demonstrated capability to disrupt the ricin intoxication process include vaccines and antibody therapy. Both rely on the ability of antibody to prevent the binding of ricin to cell receptors. To ensure maximum protection, the vaccine must be given before exposure, and sufficient antibody must be produced. Additionally, ricin is not completely inactivated by formalin and may retain some of its enzymatic activ ity (albeit approximately 1,000-fold lower than native ricin). Thus, other approaches to vaccine development have been investigated to develop a safe and efficacious candidate. Results of these studies showed that RiVax appeared to be immunogenic and well tolerated in humans. An end of clinical use stability testing to include the 54-month time point was initiated in October 2013 for both the final drug product and the diluent. In mice, pretreatment of nebulized antiricin IgG protected against aerosol exposure to ricin. In a recent study, four chimeric toxin-neutralizing monoclonal antibodies were produced and evaluated for their ability to passively protect mice from a lethal-dose ricin challenge. Introduction of a disulfide bond leads to stabilization and crystallization of a ricin immunogen. Identification and characterization of a monoclonal antibody that neutralizes ricin toxicity in vitro and in vivo. Supportive and Specific Therapy the route of exposure for any agent is an important consideration in determining prophylaxis and therapy. For oral intoxication, supportive therapy includes intravenous fluid and electrolyte replacement and monitoring of liver and renal functions. Because of the necrotizing action of ricin, gastric lavage or induced emesis should be used cautiously. An aerosol-exposed patient may require the use of positive-pressure ventilator therapy, fluid and electrolyte replacement, antiinflammatory agents, and analgesics. Development of Ricin Small Molecule Inhibitors Reaching intracellular space with a ricin inhibitor provides an ideal pre- and postexposure therapeutic. At a minimum, small molecule inhibitors must pos- sess sufficient safety and efficacy to enable a pathway to licensure. A strong safety profile is critical since no diagnostic capability exists to identify personnel who have received a clinically significant dose of ricin. Ideally, the inhibitor is also self-administered, which would greatly reduce the burden on the healthcare system and allow the provider to focus on patients who require more intensive care and medical resources. A variety of approaches have been used to identify suitable small molecule ricin therapeutics. Although the large, open, and polar nature of the active site makes it a difficult drug target,151,152 high-resolution X-ray structures of the active site can help in the design of inhibitors. Virtual screening uses computational methods to evaluate large numbers of compounds for possible activity against ricin but requires careful consideration of molecular parameters to ensure optimal results, access to libraries of appropriate chemicals,154,155 and structural data, such as high resolution crystal structures of the target molecule. For cellbased assays the tested compounds should be soluble in cell culture media or with an excipient compatible with cellular growth. The solubility requirement significantly reduces the number of compounds that can be tested in cell-based assays. Furthermore, poor solubility may mask an otherwise useful molecule because it cannot be delivered to the cells in a high enough concentration to have an observable effect. Similar approaches have been used to 390 identify small molecule inhibitors of shigatoxin, a prokaryotic enzyme with related enzymatic activity but limited structural homology to ricin, suggesting pharmacophore discovery is broadly applicable. This approach to inhibitor design was designated as the "door-stop" approach because it prevents Tyr80 from undergoing the necessary conformational change for enzymatic activity. Pang et al161 screened more than 200,000 molecules with molecular weights lower than 300 Da and 226 were predicted to block the movement of Tyr80. Furthermore, these results demonstrated that direct competition with the ricin active site, a difficult target, was not essential to achieve inhibition of the ricin catalytic activity. Compounds ranked highly by both programs were selected for further study, and they revealed a variety of new chemical entities for further development. Although many of the compounds were cytotoxic, two were identified that protected vero cells exposed to ricin. The best performing compound showed little cytotoxicity and protected about 90% of cells exposed to ricin. Transport Inhibitors the second category of inhibitors, transport inhibitors, blocks the retrograde movement of ricin through the cell and may have its greatest utility as preexposure treatments. Compounds that inhibit the retrograde transport of ricin have substantial efficacy in animal models when used in a preexposure setting. Of more than 16,000 compounds, they identified two that were inhibitors of retrograde transport. Despite functionally blocking retrograde movement, these compounds exhibited no effect on the architecture of the Golgi complex or on cellular transport pathways such as endocytosis, vesicle recycling, degradation, or secretion. The compounds completely protected challenged animals when treatment was given 1 hour before ricin exposure; no acute toxicity was observed in animals that received only the test compounds. When ricin depurinates ribosomes in target cells, these cells enter a condition known as ribotoxic stress response. The other compound acted as an inhibitor of caspase 3 and 7 activation, thus blocking a critical step in the induction of apoptosis. Because of its potency, stability, wide availability of its source plants, and popularity on the Internet, ricin is considered a significant biological warfare or terrorism threat. As a biological weapon, ricin has not been considered as useful in comparison with other biological agents such as anthrax or botulinum neurotoxin. Nevertheless, its popularity and its track record in actually being exploited by extremist groups and individuals accentuate the need to be vigilant of its surreptitious misuse. Clinical manifestations of ricin poisoning vary depending on the routes of exposure. Aerosol exposure represents the greatest threat posed by ricin and can lead to death via hy- poxia. Diagnosis of ricin exposure is based on both epidemiological and clinical parameters. No Food and Drug Administration-approved drug or vaccine against ricin intoxication exists; treatment is mainly symptomatic and supportive. Since vaccination offers a practical prophylactic strategy against ricin exposure, considerable efforts have been devoted to develop a safe and effective ricin vaccine to protect humans, in particular soldiers and first responders. Recombinant candidate ricin vaccines are currently in advanced development in clinical trials. Efforts are also underway to develop small molecule inhibitors for the treatment of ricin intoxication. Recent findings suggest that refinement of the newly identified ricin inhibitors will yield improved compounds suitable for continued evaluation in clinical trials. North Georgia Men Arrested, Charged in Plots to Purchase Explosives, Silencers and to Manufacture a Biological Toxin. Carbohydrate-specifically polyethylene glycol-modified ricin A-chain with improved therapeutic potential. Ricin and ricin-containing immunotoxins: insights into intracellular transport and mechanism of action in vitro. Weapons of Mass Destruction: An Encyclopedia of Worldwide Policy, Technology, and History. Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals. Ricin suspect was tracked via mail scanners feds: Postal Service photographs every piece of mail. Kinetics of the binding of the toxic lectins abrin and ricin to the surface receptors of human cells. Mannose receptor-mediated uptake of ricin toxin and ricin A chain by macrophages: multiple intracellular pathways for a chain translocation. Protein disulphide isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. An interaction between ricin and calreticulin that may have implications for toxin trafficking. The low lysine content of ricin A chain reduces the risk of proteolytic degradation after translocation from the endoplasmic reticulum to the cytosol. Entry of protein toxins into mammalian cells by crossing the endoplasmic reticulum membrane: co-opting basic mechanisms of endoplasmic reticulum-associated degradation. Retrotranslocation of the chaperone calreticulin from the endoplasmic reticulum lumen to the cytosol. Dual effects of the ricin A chain on protein synthesis in rabbit reticulocyte lysate: inhibition of initiation and translocation. Ribosome inactivation by the toxic lectins abrin and ricin: kinetics of the enzymic activity of the toxin A-chains. Inhibition of ricin A-chain with pyrrolidine mimics of the oxacarbenium ion transition state. Ribocation transition state capture and rebound in human purine nucleoside phosphorylase. Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory and glomerular damage. Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice. Ricinus communis intoxications in human and veterinary medicine: a summary of real cases. Infectious and toxic cellulitis due to suicide attempt by subcutaneous injection of ricin. Suicidal poisoning with castor bean (Ricinus communis) extract injected subcutaneously: case report. Pollinosis to Ricinus communis (castor bean): an aerobiological, clinical and immunochemical study. Respiratory anaphylaxis (asthma) and ricin poisoning induced with castor bean dust. The acute toxicity, tissue distribution, and histopathology of inhaled ricin in Sprague Dawley rats and Balb/c mice.
In addition medications causing thrombocytopenia cheap zyprexa 10mg otc, building this 21 type of capital can have a positive effect on the pathways through which stress tends to affect individual and firm performance schedule 9 medications zyprexa 2.5mg with mastercard. Despite its popularity in clinical psychology literature symptoms 10 weeks pregnant generic zyprexa 5mg without prescription, mindfulness has only been recently being identified as an important construct in the fields of management and firm productivity (Altizer 2017; Brown and Ryan 2003; and Brown shinee symptoms mp3 purchase zyprexa 20mg with visa, Ryan symptoms for hiv cheap zyprexa 20 mg visa, and Creswell 2007) medications that cause high blood pressure generic 7.5mg zyprexa otc. A mindful person is defined as someone who has heightened awareness of the present reality and is able to view situations "for what they really are" without worrying about the past or the future (Andrea and others 2009) 606 treatment syphilis buy cheap zyprexa 20 mg. When one practices mindfulness treatment programs discount zyprexa 20mg fast delivery, one is able to achieve a sense of separation between the self and events that facilitates the working of the elements of psychological capital. Altizer (2017) reviewed the current literature on mindfulness to find that it improved overall health and stress management for individuals. It was also positively correlated with productivity and performance of individuals, teams, as well as leaders. Across all groups, mindfulness was negatively associated with dysfunctional outcomes such as anxiety, depression, and negative effect of the managerial leaders and burnout of entrepreneurs. Similarly, psychological capital was found to be positively associated with mindfulness, whereas for measures of dysfunctional mental well being, this association moves in different directions (Roche and others 2014). Summary (Section 3): Overall, these factors highlight two key aspects of psychological capital. Building psychological capital with mindfulness is linked to significant improvements in wellbeing at both the individual and organizational levels. The next section will explore various existing training curricula utilized in the field of psychology to cultivate and grow psychological capital. Although the field of psychology has developed various outcome measurement assessments, these have been traditionally used for mental health assessments. Typical entrepreneurship training curricula focus on developing hard skills, such as financial literacy, marketing, and accounting - or soft skills, such a teamwork, punctuality, and so on. Limited work has been done within the field of entrepreneurship to build the psychological capital of entrepreneurs, although this is changing. Most of these have been tested with a variety of populations (for example, atrisk youth, refugee populations, pregnant mothers, and others). A review of their purpose is then provided, including mechanisms in which psychological capital is built. A summary of the impact of such interventions on any population and entrepreneurs will be provided. If there are some recent studies that focus on developing soft skills or that use behavioral interventions for entrepreneurs, these will also be captured as they can be just as effective when it comes to improving business performance. A recent study on the cost effectiveness of 44 lowintensity psychological interventions in SubSaharan Africa shows that the most costeffective interventions to treat mental disorders (in this case, schizophrenia, bipolar disorder, depression, epilepsy, and heavy alcohol use) cost as low as $3. Each of these curricula has been tried across various contexts with distinct target groups. Instead, they are taught to engage in slower, more deliberative thinking that can potentially lead to better decisionmaking (and prosocial behavior). Studies show the latter approach tends to be both cost effective and therapeutically equivalent to the former in terms of impact (Oei and Dingle 2008; Tucker and Oei 2007). The program succeeded in significantly reducing violent crime arrests, and in improving school engagement and graduation rates among participants through a reduction of automatic thinking (Heller and others 2017). It succeeded in dramatically decreasing crime and violence (especially when followed by a cash grant). This study suggests that interventions with entrepreneurs do not necessarily need to be overly complex to be successful (Blonk and others 2006). KabatZinn (1991) originally developed it to treat recurrent depression (Segal, Williams and Teasdale 2013). The sessions utilize various mindfulnessbased tools, which are taught through direct experience and practice, and guided by an instructor. Indeed, it can be just as 25 effective as antidepressants if not more so (Freeman and Freeman 2015). Patients also demonstrate a significant increase in mindfulness and a reduction in rumination and cognitive reactivity (Winnebeck and others 2017). People can then rationalize to dispute and replace them with healthier, more productive beliefs (Ellis 2002; Psychology Today n. Once identified and understood, these irrational beliefs can be challenged and replaced with positive beliefs that instill better emotional wellbeing. The first three steps identify and diagnose the negative thoughts and feelings experienced by people; the latter two focus on challenging and replacing them with more positive and effective ones. It is also efficient for clinical and nonclinical populations across both gender groups and for a large agerange. It is 26 transdiagnostic in the sense that it applies "the same underlying principles across mental disorders, without tailoring the protocol to specific diagnoses" (McEnvoy, Nathan, and Norton 2009). More recently, the original design has been adapted to be administered in group settings (using longer, threehour sessions and group activities), and across various geographic and socio cultural contexts (Dawson and others 2015). As such, it focuses on developing a mindset of selfstarting behavior, innovation, identifying and exploiting new opportunities, goalsetting, planning and feedback cycles, and overcoming obstacles. In this regard, it involves a willingness and readiness to "act as a result of cognitive, affective, and motivational orientation and organization that is in tune with solving entrepreneurial challenges" (Campos and others 2017). It teaches entrepreneurs to look for ways to make their businesses stand out (relative to others), overcome adversities and/or setbacks, and plan effectively for opportunities and the future of the business. Classroom instruction is completed with inperson mentoring and business visits by trainers to ensure that the skills acquired in the classroom are being adequately incorporated into practice. As a result, firm profits increased by 30 percent (relative to an 11 percent increase with traditional business training), or around $60/month on average (Campos and others 2017). These approaches also highlight the importance of a mutually respectful relationship between the trainer and the adult student, whereby the trainer is learning while teaching to build trusting relationships during the course of the training (Freire 1968). Broadly speaking, the first four focus on recognizing and dealing with negative thought patterns, emotions or actions, either by cultivating acceptance, ameliorating their effects, or modifying behavior in a more positive way. In terms of their structure, most psychosocial support curricula (especially in nonmental health contexts) utilize facetoface interactions. Facetoface sessions can be both group or oneonone in nature, with the latter being more commonly used for mental healthrelated illnesses. However, almost all can and have been adapted to be administered in group settings. Table 3 (below) summarizes the standard modules, themes, structures, and delivery of each of these curricula in more detail. Social connectedness (community connections, how actions affect others; decisionmaking scenarios). Recognizing automatic thoughts (understanding and identifying thoughts/ beliefs and subsequent reactions etc. Thinking of new ways to respond (slowing down automatic thoughts, devising alternative responses, responding to conflict rational selfanalysis). Recognizing aversion 29 Structure & Delivery Group or individual; repeated longterm sessions (34 months), also utilizing feedback and homework; delivered in person, in groups, over the phone, internet, videos, and so on; mostly delivered by trained facilitators of varying levels of expertise. Allowing/letting be Thoughts are not facts Taking care of self Maintaining and extending new learning. World Bank 2018) $750/person in Togo (Campos and others 2017) Adaptable: individuals, couples, families or groups; facilitated by trained therapists; higher number of sessions is better. However, the absence of a relevant, offtheshelf psychosocial support intervention for entrepreneurs in developing countries means that any intervention for this specific population needs to be locally adapted to ensure suitability to the local context, and especially to the needs of the target population (Bernal 2006; Castro, Barrera, and Holleran Steiker 2010). The objective is to provide a rational basis and approach for local programming, while also generating information and lessons learned that can inform future services. According to the literature, entrepreneurship is arguably one of the most stressful occupational choices because entrepreneurs typically operate in competitive environments with high levels of risk and uncertainty. In other words, the psychological price of being an entrepreneur is high compared to other professions. Mindfulness is another positive psychological resource that can significantly contribute to well being and stress management in entrepreneurs. Khyber Pakhtunkhwa and Federally Administered Tribal Areas: Postcrisis Needs Assessment. Psychosocial Needs Assessment of Communities Affected by the Conflict in the Districts of Pidie, Bireuen and Aceh Utara. Stress and Job Performance: Theory, Research and Implications for Managerial Practice. Full catastrophe living: Using the wisdom of your body and mind to face stress, pain and illness. Association of torture and other potentially traumatic events with mental health outcomes among populations exposed to mass conflict and displacement: a systematic review and meta analysis. This area faced severe crises due to the activities of militants, particularly in 20072009, and mostly along the border with Afghanistan (Khalily 2011). The conflict has exacerbated the vulnerability of the region, which is already one of the poorest regions of Pakistan. Due to the crisis, firms have faced an unprecedented loss of buildings, machinery, equipment, and stocks that have been damaged. Forthcoming; World Bank Group Country Partnership Strategy for Pakistan (20152019); Field interviews (2018). Sudden Cardiac Arrest: Meeting the Challenge Foreword About 295,000 people suffer sudden cardiac arrest each year in the United States. In fact, the number of people who die each year from sudden cardiac arrest is seven times the number who die from breast cancer. A thickened heart muscle (cardiomyopathy) from any cause (typically high blood pressure or valvular heart disease)-especially coupled with heart failure Heart medications: Under certain conditions, various heart medications can set the stage for arrhythmias that cause sudden cardiac arrest. Paradoxically, antiarrhythmic drugs used to treat arrhythmias can sometimes produce lethal ventricular arrhythmias even at normally prescribed doses (a "proarrhythmic" effect). Blood vessel abnormalities: Less often, inborn blood vessel abnormalities, particularly in the coronary arteries and aorta, may be present in young sudden death victims. Adrenaline released during intense physical or athletic activity often acts as a trigger for sudden cardiac arrest when these abnormalities are present. Recreational drug use: In people without organic heart disease, recreational drug use is an important cause of sudden cardiac arrest. Cardiac arrest is the abrupt loss of heart function in a person who may or may not have diagnosed heart disease. Each year about 295,000 emergency medical services-treated out-of-hospital cardiac arrests occur in the United States. Prevention of arrest among those known to be at risk is a significant cornerstone in saving lives. Intended for physician reference, Part I of this v Sudden Cardiac Arrest: Meeting the Challenge publication presents the condensed, evidence-based guidelines of the American College of Cardiology/ American Heart Association/European Society of Cardiology formulated in 2006, and the guidelines of the American College of Cardiology/American Heart Association/Heart Rhythm Society formulated in 2008. Prompt care at the time arrest occurs, whether in the hospital or in the community, has significant impact on the outcome of sudden cardiac arrest. Placement of automated external defibrillators, and training in their use, has been shown to save lives. Those who are successfully resuscitated from sudden cardiac arrest require excellence in care from hospitals and from supportive entities in the community. This publication is not intended to offer medical advice; it is intended as a reference and resource for health professionals. Prevention 1 Sudden Cardiac Arrest: Meeting the Challenge 2 Sudden Cardiac Arrest: Meeting the Challenge Sudden Cardiac Arrest Prevention Note: this material was originally developed and published in the American College of Cardiology/American Heart Association/European Society of Cardiology. Little has been added to the original content; additions may be found in the accompanying list of selected references. We recognize that, in the general sense, all cardiac care has a goal of prevention of sudden cardiac arrest. Cardiac arrest is characterized by an abrupt loss of effective blood flow, sufficient to cause immediate loss of consciousness, leading immediately to death if untreated. The variation is based, in part, on the inclusion criteria used in individual studies. Selected examples range from 0% in Detroit and 3% in Chicago to 46% in Seattle and King County, Washington. Two studies published in the February 2002 New England Journal of Medicine demonstrated improved survival and neurological outcomes with induction of mild therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest. Bernard examined endpoint of survival to hospital discharge to home or a rehabilitation facility (good outcome) in 77 patients and demonstrated 49% in the hypothermia group compared with 26% in the normothermic group. Recent literature reports indicate that, increasingly, cities such as Boston, Seattle, and New York are requiring rescue personnel to take cardiac arrest victims to hospitals with cooling capabilities, rather than to the nearest hospital. However, as the population is sub-grouped by known risk, the event incidence is greater but the number of events smaller. The incidence is 100fold less in those 30 and younger than for those older than 35, but the proportion of coronary deaths and of all cardiac deaths that are sudden is highest in the younger age group. Hereditary factors influencing plaque destabilization, thrombosis, and arrhythmogenesis have been identified. Maintenance dose of cardiac medications may be skipped by those with limited economic resources, as access to care may be limited for the same population. Obesity, hypertension, lipid abnormalities, and diabetes are important risk factors. Right ventricular cardiomyopathy and hypertrophic cardiomyopathy are the major substrates found in the sudden deaths of pre-coronary age groups. There is no reason to treat asymptomatic ventricular arrhythmias in the absence of such potential benefit. Hemodynamically Unstable Ventricular Tachycardia: the term hemodynamically unstable has not been rigidly defined but connotes a tachycardia associated with hypotension and poor tissue perfusion that is considered to have the imminent potential to lead to cardiac arrest or shock if left untreated. Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies. Level of Evidence C: Only consensus opinion of experts, case studies, or standard-of-care. Other symptoms related to underlying structural heart disease may also be present, especially chest discomfort, dyspnea, and fatigue. A thorough drug history including dosages used must be included in the evaluation of patients suspected of having ventricular arrhythmias. Physical examination is often unrevealing in patients suspected of having ventricular arrhythmias unless the arrhythmia occurs while the patient is being examined. Although the safety of supervised exercise testing is well established, less data are available in patients at risk for serious ventricular arrhythmias. In one series, exercise testing in patients with life-threatening ventricular arrhythmias was associated with a 2. Such an exercise study may still be warranted because it is better to expose arrhythmias and risk under controlled circumstances. Exercise testing should be performed where resuscitation equipment and trained personnel are immediately available. A 24- to 48-hour continuous Holter recording is appropriate whenever the arrhythmia is known or suspected to occur at least once a day. For sporadic episodes producing palpitations, dizziness, or syncope, conventional event monitors are more appropriate because they can record over extended periods of time. Its most common application is for detection of silent ischemia in 7 Sudden Cardiac Arrest: Meeting the Challenge New implantable recorders are capable of monitoring the rhythm and can record on patient activation or automatically for prespecified criteria. Although these devices require surgical implantation, they have been shown to be extremely useful in diagnosing serious tachyarrhythmias and bradyarrhythmias in patients with life-threatening symptoms such as syncope. Persistent inducibility while receiving antiarrhythmic drugs predicts a worse prognosis. Management of the manifest arrhythmia may involve discontinuation of offending proarrhythmic drugs, specific antiarrhythmic therapy with drugs, implantable devices, ablation, and surgery. As a general rule, antiarrhythmic agents may be effective as adjunctive therapy in the management of arrhythmia-prone patients under 10 Sudden Cardiac Arrest: Meeting the Challenge special circumstances. Because of potential adverse side effects of the available antiarrhythmic drugs, these agents must be used with caution. Many marketed cardiac and noncardiac drugs prolong ventricular repolarization and have the potential to precipitate life-threatening ventricular tachyarrhythmias. Sotalol, like amiodarone, is effective in suppressing ventricular arrhythmias, but it has greater proarrhythmic effects and has not been shown to provide a clear increase in survival; worsening ventricular arrhythmias occur in 2% to 4% of treated patients. The efficacy of non-beta-blocker antiarrhythmic drugs is equivocal at best, and each drug has significant potential for adverse events including proarrhythmia. Beta blockers are safe and effective antiarrhythmic agents that can be considered the mainstay of antiarrhythmic drug therapy. The mechanism of antiarrhythmic efficacy of this class of drugs involves competitive adrenergicreceptor blockade of sympathetically mediated triggering mechanisms, slowing of the sinus rate, and possibly inhibition of excess calcium release by the ryanodine receptor. Amiodarone and Sotalol: Amiodarone has a spectrum of actions that includes block of potassium repolarization currents that can inhibit or terminate ventricular arrhythmias by increasing the wavelength for reentry. The overall long-term survival benefit from amiodarone is controversial, with most studies showing no clear advantage over placebo. Sotalol is effective in suppressing atrial and ventricular arrhythmias; the combination of beta blockers and amiodarone is an alternative approach. Amiodarone has been used off-label for rate control if other therapies are contraindicated, not tolerated, or ineffective. Eight percent of cardiac arrests occur in the home, and home placement may be of value for those with certain genetic arrhythmias. Findings indicate that statins reduce the occurrence of life-threatening ventricular arrhythmias in high-risk cardiac patients with electrical instability. Because of the severity of underlying heart disease and the high prevalence of conduction abnormalities, adjunct device therapy should be strongly considered in these patients. Surgery and Revascularization Procedures: Surgical therapy for the management of ventricular arrhythmias may involve ablation or surgical resection of an arrhythmogenic focus, cardiac sympathectomy, or aneurysm resection. Surgical or percutaneous coro- nary revascularization with improved coronary blood flow and reduction in myocardial ischemia has favorable antiarrhythmic effects. Revascularization for Arrhythmia Management: In patients with ventricular arrhythmias, assessment for the presence of obstructive coronary disease and active ischemia is essential.
