title: Jormungand (manga)

text: Scott Green, writing for Ain't It Cool News, summed up the series as being enjoyable, but underachieving. Matthew Warner feels that the story in the fourth volume is more focused on the business of trading weapons, describing it as a nice change of pace for the story, but Warner was disappointed that the violence and "dark, twisted plot points" of earlier volumes in the series were not present. Erica Friedman, organiser of Yuricon, noted the yuri potential of Valmet, but declared the manga to be "just a dumb manga that I really like". Karen Maeda enjoyed the action shown in the sixth volume, regarding the panels as being easy to follow, and hoped that "Jormungand" would be produced as an anime.


title: Jormungand (manga)

text: Anime News Network's review of "Jormungand" points out the "challenging ideas about war, peace, and world affairs—and throws in some whiz-bang military action for good measure."


title: Jormungand (manga)

text: In Japan, the manga's 9th Volume sold 41,712 copies in a week for a total of 42,337 in the 27th place out of 30. Jormungand's 11th Volume was in 10th place and had sold 70,593 copies. It later placed itself in the 20th place out of 30, selling 34,697 copies weekly for a total of 105,290.


title: Gianluigi Aponte

text: Gianluigi Aponte (; born 27 June 1940) is an Italian billionaire businessman, and the founder, owner and chairman of Mediterranean Shipping Company (MSC).


title: Gianluigi Aponte

text: Gianluigi Aponte was born in Sant'Agnello, Italy (near Sorrento, in the province of Naples) on 27 June 1940.


title: Gianluigi Aponte

text: Aponte is a Neapolitan captain, who entered the shipping industry in 1970 together with his spouse, Rafaela. At the time, the newly-formed company owned a single vessel that shipped cargo between Europe and Africa. With the growth of his business, he made a move into the cruise industry in 1988. As of 2014, he had retired from the position of CEO and president in favour of his son Diego Aponte, assuming the role of executive chairman within MSC.


title: Gianluigi Aponte

text: In 2009, at the Teatro di San Carlo of Naples, he received, along with Fabio Cannavaro, Ambra Vallo and others, a prize for "Neapolitan Excellence in the World" from then-Italian prime minister Silvio Berlusconi.


title: Gianluigi Aponte

text: In 2012, he won the Cruise International Lifetime Achievement Award in recognition of his long term activity in the industry.


title: Gianluigi Aponte

text: In October 2013, he received Containerisation International’s Lifetime Achievement Award, as well as a knighthood, the Order of Merit for Labour, from Italian President Giorgio Napolitano. The Aponte family have featured prominently in the Lloyd's List Top 100 most influential people in the shipping industry, named in the top 10 in 2014 and in position 16 in 2018.


title: Gianluigi Aponte

text: He is married to Rafaela Diamant Pinas, a Swiss woman of Israeli origin, and daughter of a Geneva banker, he met when she was a passenger on a boat of which he was the captain. They have two children, Diego Aponte and Alexa Aponte Vago, who serve respectively as CEO and CFO of MSC.


title: Chronic pain

text: Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between acute and chronic pain is sometimes determined by the amount of time since onset. Two commonly used markers are pain that continues at three months and six months since onset, but some theorists and researchers have placed the transition from acute to chronic pain at twelve months. Others apply the term "acute" to pain that lasts less than 30 days, "chronic" to pain of more than six months duration, and "subacute" to pain that lasts from one to six months. A popular alternative definition of "chronic pain", involving no fixed duration, is "pain that extends beyond the expected period of healing".


title: Chronic pain

text: Chronic pain may originate in the body, or in the brain or spinal cord. It is often difficult to treat. Epidemiological studies have found that 8–11.2% of people in various countries have chronic widespread pain. Various non-opioid medicines are initially recommended to treat chronic pain, depending on whether the pain is due to tissue damage or is neuropathic. Psychological treatments including cognitive behavioral therapy and acceptance and commitment therapy may be effective for improving quality of life in those with chronic pain. Some people with chronic pain may benefit from opioid treatment while others can be harmed by it. People with non-cancer pain who have not been helped by non-opioid medicines might be recommended to try opioids if there is no history of substance use disorder and no current mental illness.


title: Chronic pain

text: People with chronic pain tend to have higher rates of depression and although the exact connection between the comorbidities is unclear, a 2017 study on neuroplasticity found that "injury sensory pathways of body pains have been shown to share the same brain regions involved in mood management." Chronic pain can contribute to decreased physical activity due to fear of making the pain worse. Pain intensity, pain control, and resilience to pain can be influenced by different levels and types of social support that a person with chronic pain receives, and are also influenced by the person's socioeconomic status.


title: Chronic pain

text: One approach to predicting a person's experience of chronic pain is the biopsychosocial model, according to which an individual's experience of chronic pain may be affected by a complex mixture of their biology, psychology, and their social environment.


title: Chronic pain

text: The International Association for the Study of Pain defines chronic pain as pain with no biological value, that persists past normal tissue healing. The DSM-5 recognizes one chronic pain disorder, somatic symptom disorders. The criteria include pain lasting longer than six months.


title: Chronic pain

text: The International Classification of Disease, Eleventh Revision (ICD-11) suggests seven categories for chronic pain.


title: Chronic pain

text: Chronic pain may be divided into "nociceptive" (caused by inflamed or damaged tissue activating specialized pain sensors called nociceptors), and "neuropathic" (caused by damage to or malfunction of the nervous system).


title: Chronic pain

text: Nociceptive pain can be divided into "superficial" and "deep", and deep pain into "deep somatic" and "visceral". "Superficial" pain is initiated by activation of nociceptors in the skin or superficial tissues. "Deep somatic" pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is dull, aching, poorly-localized pain. "Visceral" pain originates in the viscera (organs). Visceral pain may be well-localized, but often it is extremely difficult to locate, and several visceral regions produce "referred" pain when damaged or inflamed, where the sensation is located in an area distant from the site of pathology or injury.


title: Chronic pain

text: Neuropathic pain is divided into "peripheral" (originating in the peripheral nervous system) and "central" (originating in the brain or spinal cord). Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles".


title: Chronic pain

text: Under persistent activation, the transmission of pain signals to the dorsal horn may produce a pain wind-up phenomenon. This triggers changes that lower the threshold for pain signals to be transmitted. In addition, it may cause nonnociceptive nerve fibers to respond to, generate, and transmit pain signals. The type of nerve fibers that are believed to generate the pain signals are the C-fibers, since they have a slow conductivity and give rise to a painful sensation that persists over a long time. In chronic pain, this process is difficult to reverse or stop once established. In some cases, chronic pain can be caused by genetic factors which interfere with neuronal differentiation, leading to a permanently lowered threshold for pain.


title: Chronic pain

text: Chronic pain of different causes has been characterized as a disease that affects brain structure and function. MRI studies have shown abnormal anatomical and functional connectivity, even during rest involving areas related to the processing of pain. Also, persistent pain has been shown to cause grey matter loss, which is reversible once the pain has resolved.


title: Chronic pain

text: These structural changes can be explained by neuroplasticity. In the case of chronic pain, the somatotopic representation of the body is inappropriately reorganized following peripheral and central sensitization. This can cause allodynia or hyperalgesia. In individuals with chronic pain, EEGs showed altered brain activity, suggesting pain-induced neuroplastic changes. More specifically, the relative beta activity (compared to the rest of the brain) was increased, the relative alpha activity was decreased, and the theta activity was diminished.


title: Chronic pain

text: Dysfunctional dopamine management in the brain could potentially act as a shared mechanism between chronic pain, insomnia and major depressive disorder. Astrocytes, microglia, and satellite glial cells have also been found to be dysfunctional in chronic pain. Increased activity of microglia, alterations of microglial networks, and increased production of chemokines and cytokines by microglia might aggravate chronic pain. Astrocytes have been observed to lose their ability to regulate the excitability of neurons, increasing spontaneous neural activity in pain circuits.


title: Chronic pain

text: Pain management is a branch of medicine that uses an interdisciplinary approach. The combined knowledge of various medical professions and allied health professions is used to ease pain and improve the quality of life of those living with pain. The typical pain management team includes medical practitioners (particularly anesthesiologists), rehabilitation psychologists, physiotherapists, occupational therapists, physician assistants, and nurse practitioners. Acute pain usually resolves with the efforts of one practitioner; however, the management of chronic pain frequently requires the coordinated efforts of a treatment team. Complete, longterm remission of many types of chronic pain is rare.


title: Chronic pain

text: Initially recommended efforts are non opioid based therapies. Non-opioid treatment of chronic pain with pharmaceutical medicines might include acetaminophen (paracetamol) or NSAIDs.


title: Chronic pain

text: Various other nonopioid medicines can be used, depending on whether the pain is a result of tissue damage or is neuropathic (pain caused by a damaged or dysfunctional nervous system). There is limited evidence that cancer pain or chronic pain from tissue damage as a result of a conditions (e.g. rheumatoid arthritis) is best treated with opioids. For neuropathic pain other drugs may be more effective than opioids, such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and anticonvulsants. Some atypical antipsychotics, such as olanzapine, may also be effective, but the evidence to support this is in very early stages. In women with chronic pain, hormonal medications such as oral contraceptive pills ("the pill") might be helpful. When there is no evidence of a single best fit, doctors may need to look for a treatment that works for the individual person. It is difficult for doctors to predict who will use opioids just for pain management and who will go on to develop an addiction. It is also challenging for doctors to know which patients ask for opioids because they are living with an opioid addiction. Withholding, interrupting or withdrawing opioid treatment in people who benefit from it can cause harm.


title: Chronic pain

text: Interventional pain management may be appropriate, including techniques such as trigger point injections, neurolytic blocks, and radiotherapy. While there is no high quality evidence to support ultrasound, it has been found to have a small effect on improving function in non-specific chronic low back pain.


title: Chronic pain

text: Psychological treatments, including cognitive behavioral therapy and acceptance and commitment therapy can be helpful for improving quality of life and reducing pain interference. Brief mindfulness-based treatment approaches have been used, but they are not yet recommended as a first-line treatment. The effectiveness of mindfulness-based pain management (MBPM) has been supported by a range of studies.


title: Chronic pain

text: Among older adults psychological interventions can help reduce pain and improve self-efficacy for pain management. Psychological treatments have also been shown to be effective in children and teens with chronic headache or mixed chronic pain conditions.


title: Chronic pain

text: While exercise has been offered as a method to lessen chronic pain and there is some evidence of benefit, this evidence is tentative. For people living with chronic pain, exercise results in few side effects.


title: Chronic pain

text: In those who have not benefited from other measures and have no history of either mental illness or substance use disorder treatment with opioids may be tried. If significant benefit does not occur it is recommended that they be stopped. In those on opioids, stopping or decreasing their use may improve outcomes including pain.


title: Chronic pain

text: Some people with chronic pain benefit from opioid treatment and others do not; some are harmed by the treatment. Possible harms include reduced sex hormone production, hypogonadism, infertility, impaired immune system, falls and fractures in older adults, neonatal abstinence syndrome, heart problems, sleep-disordered breathing, opioid-induced hyperalgesia, physical dependence, addiction, abuse, and overdose.


title: Chronic pain

text: Alternative medicine refers to health practices or products that are used to treat pain or illness that are not necessarily considered a part of conventional medicine. When dealing with chronic pain, these practices generally fall into the following four categories: biological, mind-body, manipulative body, and energy medicine.


title: Chronic pain

text: Implementing dietary changes, which is considered a biological-based alternative medicine practice, has been shown to help improve symptoms of chronic pain over time. Adding supplements to one's diet is a common dietary change when trying to relieve chronic pain, with some of the most studied supplements being: Acetyl-L-carnitine, alpha lipoic acid, and vitamin E. Vitamin E is perhaps the most studied out of the three, with strong evidence that it helps lower neurotoxicity in those with cancer, multiple sclerosis, and cardiovascular diseases.


title: Chronic pain

text: Hypnosis, including self-hypnosis, has tentative evidence. Hypnosis, specifically, can offer pain relief for most people and may be a safe alternative to pharmaceutical medication. Evidence does not support hypnosis for chronic pain due to a spinal cord injury.


title: Chronic pain

text: Preliminary studies have found medical marijuana to be beneficial in treating neuropathic pain, but not other kinds of long term pain. , the evidence for its efficacy in treating neuropathic pain or pain associated with rheumatic diseases is not strong for any benefit and further research is needed. For chronic non-cancer pain, a recent study concluded that it is unlikely that cannabinoids are highly effective. However, more rigorous research into cannabis or cannabis-based medicines is needed.


title: Chronic pain

text: Tai chi has been shown to improve pain, stiffness, and quality of life in chronic conditions such as osteoarthritis, low back pain, and osteoporosis. Acupuncture has also been found to be an effective and safe treatment in reducing pain and improving quality of life in chronic pain including chronic pelvic pain syndrome.


title: Chronic pain

text: Transcranial magnetic stimulation for reduction of chronic pain is not supported by high quality evidence, and the demonstrated effects are small and short-term.


title: Chronic pain

text: Spa therapy could potentially improve pain in patients with chronic lower back pain, but more studies are needed to provide stronger evidence of this.


title: Chronic pain

text: While some studies have investigated the efficacy of St John's Wort or nutmeg for treating neuropathic (nerve) pain, their findings have raised serious concerns about the accuracy of their results.


title: Chronic pain

text: Myofascial release has been used in some cases of fibromyalgia, chronic low back pain, and tennis elbow but there is not enough evidence to support this as method of treatment.


title: Chronic pain

text: Chronic pain varies in different countries affecting anywhere from 8% to 55.2% of the population. It affects women at a higher rate than men, and chronic pain uses a large amount of healthcare resources around the globe.


title: Chronic pain

text: A large-scale telephone survey of 15 European countries and Israel found that 19% of respondents over 18 years of age had suffered pain for more than 6 months, including the last month, and more than twice in the last week, with pain intensity of 5 or more for the last episode, on a scale of 1 (no pain) to 10 (worst imaginable). 4839 of these respondents with chronic pain were interviewed in-depth. Sixty-six percent scored their pain intensity at moderate (5–7), and 34% at severe (8–10); 46% had constant pain, 56% intermittent; 49% had suffered pain for 2–15 years; and 21% had been diagnosed with depression due to the pain. Sixty-one percent were unable or less able to work outside the home, 19% had lost a job, and 13% had changed jobs due to their pain. Forty percent had inadequate pain management and less than 2% were seeing a pain management specialist.


title: Chronic pain

text: In the United States, chronic pain has been estimated to occur in approximately 35% of the population, with approximately 50 million Americans experiencing partial or total disability as a consequence. According to the Institute of Medicine, there are about 116 million Americans living with chronic pain, which suggests that approximately half of American adults have some chronic pain condition. The Mayday Fund estimate of 70 million Americans with chronic pain is slightly more conservative. In an internet study, the prevalence of chronic pain in the United States was calculated to be 30.7% of the population: 34.3% for women and 26.7% for men.


title: Chronic pain

text: In Canada it is estimated that approximately 1 in 5 Canadians live with chronic pain and half of those people have lived with chronic pain for 10 years or longer. Chronic pain in Canada also occurs more and is more severe in women and Canada's Indigenous communities.


title: Chronic pain

text: Sleep disturbance, and insomnia due to medication and illness symptoms are often experienced by those with chronic pain. These conditions can be difficult to treat due to the high potential of medication interactions, especially when the conditions are treated by different doctors.


title: Chronic pain

text: Severe chronic pain is associated with increased risk of death over a ten-year period, particularly from heart disease and respiratory disease. Several mechanisms have been proposed for this increase, such as an abnormal stress response in the body's endocrine system. Additionally, chronic stress seems to affect risks to heart and lung (cardiovascular) health by increasing how quickly plaque can build up on artery walls (arteriosclerosis). However, further research is needed to clarify the relationship between severe chronic pain, stress and cardiovascular health.


title: Chronic pain

text: Two of the most frequent personality profiles found in people with chronic pain by the Minnesota Multiphasic Personality Inventory (MMPI) are the "conversion V" and the "neurotic triad". The conversion V personality expresses exaggerated concern over body feelings, develops bodily symptoms in response to stress, and often fails to recognize their own emotional state, including depression. The neurotic triad personality also expresses exaggerated concern over body feelings and develops bodily symptoms in response to stress, but is demanding and complaining.


title: Chronic pain

text: Some investigators have argued that it is this neuroticism that causes acute pain to turn chronic, but clinical evidence points the other way, to chronic pain causing neuroticism. When long term pain is relieved by therapeutic intervention, scores on the neurotic triad and anxiety fall, often to normal levels. Self-esteem, often low in people with chronic pain, also shows improvement once pain has resolved.


title: Chronic pain

text: It has been suggested that catastrophizing might play a role in the experience of pain. "Pain catastrophizing" is the tendency to describe a pain experience in more exaggerated terms than the average person, to think a great deal more about the pain when it occurs, or to feel more helpless about the experience. People who score highly on measures of catastrophization are likely to rate a pain experience as more intense than those who score low on such measures. It is often reasoned that the tendency to catastrophize "causes" the person to experience the pain as more intense. One suggestion is that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. However, at least some aspects of catastrophization may be the "product" of an intense pain experience, rather than its cause. That is, the more intense the pain feels to the person, the more likely they are to have thoughts about it that fit the definition of catastrophization.


title: Chronic pain

text: Individuals with posttraumatic stress disorder (PTSD) have a high comorbidity with chronic pain. Patients with both PTSD and chronic pain report higher severity of pain than those who do not have a PTSD comorbidity.


title: Chronic pain

text: Chronic pain's impact on cognition is an under-researched area, but several tentative conclusions have been published. Most people with chronic pain complain of cognitive impairment, such as forgetfulness, difficulty with attention, and difficulty completing tasks. Objective testing has found that people in chronic pain tend to experience impairment in attention, memory, mental flexibility, verbal ability, speed of response in a cognitive task, and speed in executing structured tasks. A review of studies in 2018 reports a relationship between people in chronic pain and abnormal results in test of memory, attention, and processing speed.


title: Chronic pain

text: Social support has important consequences for individuals with chronic pain. In particular, pain intensity, pain control, and resiliency to pain have been implicated as outcomes influenced by different levels and types of social support. Much of this research has focused on emotional, instrumental, tangible and informational social support. People with persistent pain conditions tend to rely on their social support as a coping mechanism and therefore have better outcomes when they are a part of larger more supportive social networks. Across a majority of studies investigated, there was a direct significant association between social activities or social support and pain. Higher levels of pain were associated with a decrease in social activities, lower levels of social support, and reduced social functioning.


title: Chronic pain

text: Evidence exists for unconscious biases and negative stereotyping against racial minorities requesting pain treatment, although clinical decision making was not affected, according to one 2017 review. Minorities may be denied diagnoses for pain and pain medications, and are more likely to go through substance abuse assessment, and are less likely to transfer for pain specialist referral. Preliminary research showed that health providers might have less empathy for black patients and underestimated their pain levels, resulting in treatment delays. Minorities may experience a language barrier, limiting the high level of engagement between the person with pain and health providers for treatment.


title: Chronic pain

text: Similar to the damaging effects seen with catastrophizing, perceived injustice is thought to contribute to the severity and duration of chronic pain. Pain-related injustice perception has been conceptualized as a cognitive appraisal reflecting the severity and irreparability of pain- or injury-related loss (e.g., "I just want my life back"), and externalizing blame and unfairness ("I am suffering because of someone else's negligence."). It has been suggested that understanding problems with top down processing/cognitive appraisals can be used to better understand and treat this problem.


title: Chronic pain

text: COVID-19 has disrupted the lives of many, leading to major physical, psychological and socioeconomic impacts in the general population. Social distancing practices defining the response to the pandemic alter familiar patterns of social interaction, creating the conditions for what some psychologists are describing as a period of collective grief. Individuals with chronic pain tend to embody an ambiguous status, at times expressing that their type of suffering places them between and outside of conventional medicine. With a large proportion of the global population enduring prolonged periods of social isolation and distress, one study found that people with chronic pain from COVID-19 experienced more empathy towards their suffering during the pandemic.


title: Chronic pain

text: In the workplace, chronic pain conditions are a significant problem for both the person with the condition and the organization; a problem only expected to increase in many countries due to an aging workforce. In light of this, it may be helpful for organizations to consider the social environment of their workplace, and how it may be working to ease or worsen chronic pain issues for employees. As an example of how the social environment can affect chronic pain, some research has found that high levels of socially prescribed perfectionism (perfectionism induced by external pressure from others, such as a supervisor) can interact with the guilt felt by a person with chronic pain, thereby increasing job tension, and decreasing job satisfaction.


title: Chronic pain

text: A 2022 systematic review found that chronic pain could increase crash risk among drivers. Chronic pain drivers report experiencing difficulties with safety maneuvers, such as shoulder checking for blind spots, merging with traffic, turning corners, and reversing the vehicle.


title: Long-term potentiation

text: In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.


title: Long-term potentiation

text: It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.


title: Long-term potentiation

text: LTP was discovered in the rabbit hippocampus by Terje Lømo in 1966 and has remained a popular subject of research since. Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still, others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of clinical research, for example, in the areas of Alzheimer's disease and addiction medicine.


title: Long-term potentiation

text: At the end of the 19th century, scientists generally recognized that the number of neurons in the adult brain (roughly 100 billion) did not increase significantly with age, giving neurobiologists good reason to believe that memories were generally not the result of new neuron production. With this realization came the need to explain how memories could form in the absence of new neurons.


title: Long-term potentiation

text: The Spanish neuroanatomist Santiago Ramón y Cajal was among the first to suggest a mechanism of learning that did not require the formation of new neurons. In his 1894 Croonian Lecture, he proposed that memories might instead be formed by strengthening the connections between existing neurons to improve the effectiveness of their communication. Hebbian theory, introduced by Donald Hebb in 1949, echoed Ramón y Cajal's ideas, further proposing that cells may grow new connections or undergo metabolic and synaptic changes that enhance their ability to communicate and create a neural network of experiences:


title: Long-term potentiation

text: Eric Kandel (1964) and associates were some of the first researchers to discover long-term potentiation during their work with sea slug Aplysia. They attempted to apply behavioral conditioning to different cells in the slug’s neural network. Their results showed synaptic strength changes and researchers suggested that this may be due to a basic form of learning occurring within the slug.


title: Long-term potentiation

text: Though these theories of memory formation are now well established, they were farsighted for their time: late 19th and early 20th century neuroscientists and psychologists were not equipped with the neurophysiological techniques necessary for elucidating the biological underpinnings of learning in animals. These skills would not come until the later half of the 20th century, at about the same time as the discovery of long-term potentiation.


title: Long-term potentiation

text: LTP was first observed by Terje Lømo in 1966 in the Oslo, Norway, laboratory of Per Andersen. There, Lømo conducted a series of neurophysiological experiments on anesthetized rabbits to explore the role of the hippocampus in short-term memory.


title: Long-term potentiation

text: Lømo's experiments focused on connections, or synapses, from the perforant pathway to the dentate gyrus. These experiments were carried out by stimulating presynaptic fibers of the perforant pathway and recording responses from a collection of postsynaptic cells of the dentate gyrus. As expected, a single pulse of electrical stimulation to fibers of the perforant pathway caused excitatory postsynaptic potentials (EPSPs) in cells of the dentate gyrus. What Lømo unexpectedly observed was that the postsynaptic cells' response to these single-pulse stimuli could be enhanced for a long period of time if he first delivered a high-frequency train of stimuli to the presynaptic fibers. When such a train of stimuli was applied, subsequent single-pulse stimuli elicited stronger, prolonged EPSPs in the postsynaptic cell population. This phenomenon, whereby a high-frequency stimulus could produce a long-lived enhancement in the postsynaptic cells' response to subsequent single-pulse stimuli, was initially called "long-lasting potentiation".


title: Long-term potentiation

text: Timothy Bliss, who joined the Andersen laboratory in 1968, collaborated with Lømo and in 1973 the two published the first characterization of long-lasting potentiation in the rabbit hippocampus. Bliss and Tony Gardner-Medwin published a similar report of long-lasting potentiation in the awake animal which appeared in the same issue as the Bliss and Lømo report. In 1975, Douglas and Goddard proposed "long-term potentiation" as a new name for the phenomenon of long-lasting potentiation. Andersen suggested that the authors chose "long-term potentiation" perhaps because of its easily pronounced acronym, "LTP".


title: Long-term potentiation

text: The physical and biological mechanism of LTP is still not understood, but some successful models have been developed. Studies of dendritic spines, protruding structures on dendrites that physically grow and retract over the course of minutes or hours, have suggested a relationship between the electrical resistance of the spine and the effective synapse strength, due to their relationship with intracellular calcium transients. Mathematical models such as BCM Theory, which depends also on intracellular calcium in relation to NMDA receptor voltage gates, have been developed since the 1980s and modify the traditional "a priori" Hebbian learning model with both biological and experimental justification. Still, others have proposed re-arranging or synchronizing the relationship between receptor regulation, LTP, and synaptic strength.


title: Long-term potentiation

text: Since its original discovery in the rabbit hippocampus, LTP has been observed in a variety of other neural structures, including the cerebral cortex, cerebellum, amygdala, and many others. Robert Malenka, a prominent LTP researcher, has suggested that LTP may even occur at all excitatory synapses in the mammalian brain.


title: Long-term potentiation

text: Different areas of the brain exhibit different forms of LTP. The specific type of LTP exhibited between neurons depends on a number of factors. One such factor is the age of the organism when LTP is observed. For example, the molecular mechanisms of LTP in the immature hippocampus differ from those mechanisms that underlie LTP of the adult hippocampus. The signalling pathways used by a particular cell also contribute to the specific type of LTP present. For example, some types of hippocampal LTP depend on the NMDA receptor, others may depend upon the metabotropic glutamate receptor (mGluR), while still others depend upon another molecule altogether. The variety of signaling pathways that contribute to LTP and the wide distribution of these various pathways in the brain are reasons that the type of LTP exhibited between neurons depends only in part upon the anatomic location in which LTP is observed. For example, LTP in the Schaffer collateral pathway of the hippocampus is NMDA receptor-dependent - this was proved by the application of AP5, an antagonist to the NMDA receptor, which prevented LTP in this pathway. Conversely, LTP in the mossy fiber pathway is NMDA receptor-independent, even though both pathways are in the hippocampus.


title: Long-term potentiation

text: The pre- and postsynaptic activity required to induce LTP are other criteria by which LTP is classified. Broadly, this allows classification of LTP into Hebbian, non-Hebbian, and anti-Hebbian mechanisms. Borrowing its name from Hebb's postulate, summarized by the maxim that "cells that fire together wire together," Hebbian LTP requires simultaneous pre- and postsynaptic depolarization for its induction. Non-Hebbian LTP is a type of LTP that does not require such simultaneous depolarization of pre- and postsynaptic cells; an example of this occurs in the mossy fiber hippocampal pathway. A special case of non-Hebbian LTP, anti-Hebbian LTP explicitly requires simultaneous presynaptic depolarization and relative postsynaptic hyperpolarization for its induction.


title: Long-term potentiation

text: Owing to its predictable organization and readily inducible LTP, the CA1 hippocampus has become the prototypical site of mammalian LTP study. In particular, NMDA receptor-dependent LTP in the adult CA1 hippocampus is the most widely studied type of LTP, and is therefore, the focus of this article.


title: Long-term potentiation

text: NMDA receptor-dependent LTP exhibits several properties, including input specificity, associativity, cooperativity, and persistence.


title: Long-term potentiation

text: While induction entails the "transient" activation of CaMKII and PKC, maintenance of E-LTP (early-form LTP) is characterized by their "persistent" activation. During this stage, PKMz (Protein kinase Mζ) which does not have dependence on calcium, become autonomously active. Consequently, they are able to carry out the phosphorylation events that underlie E-LTP expression.


title: Long-term potentiation

text: Phosphorylation is a chemical reaction in which a small phosphate group is added to another molecule to change that molecule's activity. Autonomously active CaMKII and PKC use phosphorylation to carry out the two major mechanisms underlying the expression of E-LTP. First, and most importantly, they phosphorylate existing AMPA receptors to increase their activity. Second, they mediate or modulate the insertion of additional AMPA receptors into the postsynaptic membrane. Importantly, the delivery of AMPA receptors to the synapse during E-LTP is independent of protein synthesis. This is achieved by having a nonsynaptic pool of AMPA receptors adjacent to the postsynaptic membrane. When the appropriate LTP-inducing stimulus arrives, nonsynaptic AMPA receptors are rapidly trafficked into the postsynaptic membrane under the influence of protein kinases. As mentioned previously, AMPA receptors are the brain's most abundant glutamate receptors and mediate the majority of its excitatory activity. By increasing the efficiency and number of AMPA receptors at the synapse, future excitatory stimuli generate larger postsynaptic responses.


title: Long-term potentiation

text: While the above model of E-LTP describes entirely postsynaptic mechanisms for induction, maintenance, and expression, an additional component of expression may occur presynaptically. One hypothesis of this presynaptic facilitation is that persistent CaMKII activity in the postsynaptic cell during E-LTP may lead to the synthesis of a "retrograde messenger", discussed later. According to this hypothesis, the newly synthesized messenger travels across the synaptic cleft from the postsynaptic to the presynaptic cell, leading to a chain of events that facilitate the presynaptic response to subsequent stimuli. Such events may include an increase in neurotransmitter vesicle number, probability of vesicle release, or both. In addition to the retrograde messenger underlying presynaptic expression in early LTP, the retrograde messenger may also play a role in the expression of late LTP.


title: Long-term potentiation

text: Late LTP (L-LTP) is the natural extension of E-LTP. Unlike E-LTP, which is independent of protein synthesis, L-LTP requires gene transcription and protein synthesis in the postsynaptic cell. Two phases of L-LTP exist: the first depends upon protein synthesis, while the second depends upon both gene transcription and protein synthesis. These phases are occasionally called LTP2 and LTP3, respectively, with E-LTP referred to as LTP1 under this nomenclature.


title: Long-term potentiation

text: Late LTP is induced by changes in gene expression and protein synthesis brought about by the persistent activation of protein kinases activated during E-LTP, such as MAPK. In fact, MAPK—specifically the extracellular signal-regulated kinase (ERK) subfamily of MAPKs—may be the molecular link between E-LTP and L-LTP, since many signaling cascades involved in E-LTP, including CaMKII and PKC, can converge on ERK. Recent research has shown that the induction of L-LTP can depend on coincident molecular events, namely PKA activation and calcium influx, that converge on CRTC1 (TORC1), a potent transcriptional coactivator for cAMP response element binding protein (CREB). This requirement for a molecular coincidence accounts perfectly for the associative nature of LTP, and, presumably, for that of learning.


title: Long-term potentiation

text: Upon activation, ERK may phosphorylate a number of cytoplasmic and nuclear molecules that ultimately result in the protein synthesis and morphological changes observed in L-LTP. These cytoplasmic and nuclear molecules may include transcription factors such as CREB. ERK-mediated changes in transcription factor activity may trigger the synthesis of proteins that underlie the maintenance of L-LTP. One such molecule may be protein kinase Mζ (PKMζ), a persistently active kinase whose synthesis increases following LTP induction. PKMζ is an atypical isoform of PKC that lacks a regulatory subunit and thus remains constitutively active. Unlike other kinases that mediate LTP, PKMζ is active not just in the first 30 minutes following LTP induction; rather, PKMζ becomes a requirement for LTP maintenance only during the late phase of LTP. PKMζ thus appears important for the persistence of memory and would be expected to be important in the maintenance of long-term memory. Indeed, administration of a PKMζ inhibitor into the hippocampus of the rat results in retrograde amnesia with intact short-term memory; PKMζ does not play a role in the establishment of short-term memory. PKMζ has recently been shown to underlie L-LTP maintenance by directing the trafficking and reorganization of proteins in the synaptic scaffolding that underlie the expression of L-LTP. Even more recently, transgenic mice lacking PKMζ demonstrate normal LTP, questioning the necessity of PKMζ.


title: Long-term potentiation

text: The long-term stabilization of synaptic changes is also determined by a parallel increase of pre- and postsynaptic structures such as axonal bouton, dendritic spine and postsynaptic density.


title: Long-term potentiation

text: On the molecular level, an increase of the postsynaptic scaffolding proteins PSD-95 and Homer1c has been shown to correlate with the stabilization of synaptic enlargement.


title: Long-term potentiation

text: The identities of only a few proteins synthesized during L-LTP are known. Regardless of their identities, it is thought that they contribute to the increase in dendritic spine number, surface area, and postsynaptic sensitivity to neurotransmitter associated with L-LTP expression. The latter may be brought about in part by the enhanced synthesis of AMPA receptors during L-LTP. Late LTP is also associated with the presynaptic synthesis of synaptotagmin and an increase in synaptic vesicle number, suggesting that L-LTP induces protein synthesis not only in postsynaptic cells, but in presynaptic cells as well. As mentioned previously, for postsynaptic LTP induction to result in presynaptic protein synthesis, there must be communication from the postsynaptic to the presynaptic cell. This may occur via the synthesis of a retrograde messenger, discussed later.


title: Long-term potentiation

text: Even in studies restricted to postsynaptic events, investigators have not determined the location of the protein synthesis that underlies L-LTP. Specifically, it is unclear whether protein synthesis takes place in the postsynaptic cell body or in its dendrites. Despite having observed ribosomes (the major components of the protein synthesis machinery) in dendrites as early as the 1960s, prevailing wisdom was that the cell body was the predominant site of protein synthesis in neurons. This reasoning was not seriously challenged until the 1980s, when investigators reported observing protein synthesis in dendrites whose connection to their cell body had been severed. More recently, investigators have demonstrated that this type of local protein synthesis is necessary for some types of LTP.


title: Long-term potentiation

text: One reason for the popularity of the local protein synthesis hypothesis is that it provides a possible mechanism for the specificity associated with LTP. Specifically, if indeed local protein synthesis underlies L-LTP, only dendritic spines receiving LTP-inducing stimuli will undergo LTP; the potentiation will not be propagated to adjacent synapses. By contrast, global protein synthesis that occurs in the cell body requires that proteins be shipped out to every area of the cell, including synapses that have not received LTP-inducing stimuli. Whereas local protein synthesis provides a mechanism for specificity, global protein synthesis would seem to directly compromise it. However, as discussed later, the synaptic tagging hypothesis successfully reconciles global protein synthesis, synapse specificity, and associativity.


title: Long-term potentiation

text: Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed postsynaptically, some evidence suggests that it is expressed presynaptically as well. The hypothesis gets its name because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell. For induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the postsynaptic cell to the presynaptic cell in a "retrograde" (reverse) direction. Once there, the message presumably initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of neurotransmitter vesicle release.


title: Long-term potentiation

text: Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell contributes at all to the expression of LTP. Even among proponents of the hypothesis there is controversy over the identity of the messenger. Early thoughts focused on nitric oxide, while most recent evidence points to cell adhesion proteins.


title: Long-term potentiation

text: Before the local protein synthesis hypothesis gained significant support, there was general agreement that the protein synthesis underlying L-LTP occurred in the cell body. Further, there was thought that the products of this synthesis were shipped cell-wide in a nonspecific manner. It thus became necessary to explain how protein synthesis could occur in the cell body without compromising LTP's input specificity. The synaptic tagging hypothesis attempts to solve the cell's difficult problem of synthesizing proteins in the cell body but ensuring they only reach synapses that have received LTP-inducing stimuli.


title: Long-term potentiation

text: The synaptic tagging hypothesis proposes that a "synaptic tag" is synthesized at synapses that have received LTP-inducing stimuli, and that this synaptic tag may serve to capture plasticity-related proteins shipped cell-wide from the cell body. Studies of LTP in the marine snail "Aplysia californica" have implicated synaptic tagging as a mechanism for the input-specificity of LTP. There is some evidence that given two widely separated synapses, an LTP-inducing stimulus at one synapse drives several signaling cascades (described previously) that initiates gene expression in the cell nucleus. At the same synapse (but not the unstimulated synapse), local protein synthesis creates a short-lived (less than three hours) synaptic tag. The products of gene expression are shipped globally throughout the cell, but are only captured by synapses that express the synaptic tag. Thus only the synapse receiving LTP-inducing stimuli is potentiated, demonstrating LTP's input specificity.


title: Long-term potentiation

text: The synaptic tag hypothesis may also account for LTP's associativity and cooperativity. Associativity ("see Properties") is observed when one synapse is excited with LTP-inducing stimulation while a separate synapse is only weakly stimulated. Whereas one might expect only the strongly stimulated synapse to undergo LTP (since weak stimulation alone is insufficient to induce LTP at either synapse), "both" synapses will in fact undergo LTP. While weak stimuli are unable to induce protein synthesis in the cell body, they may prompt the synthesis of a synaptic tag. Simultaneous strong stimulation of a separate pathway, capable of inducing cell body protein synthesis, then may prompt the production of plasticity-related proteins, which are shipped cell-wide. With both synapses expressing the synaptic tag, both would capture the protein products resulting in the expression of LTP in both the strongly stimulated and weakly stimulated pathways.


title: Long-term potentiation

text: Cooperativity is observed when two synapses are activated by weak stimuli incapable of inducing LTP when stimulated individually. But upon simultaneous weak stimulation, both synapses undergo LTP in a cooperative fashion. Synaptic tagging does not explain how multiple weak stimuli can result in a collective stimulus sufficient to induce LTP (this is explained by the postsynaptic summation of EPSPs described previously). Rather, synaptic tagging explains the ability of weakly stimulated synapses, none of which are capable of independently generating LTP, to receive the products of protein synthesis initiated collectively. As before, this may be accomplished through the synthesis of a local synaptic tag following weak synaptic stimulation.


title: Long-term potentiation

text: As described previously, the molecules that underlie LTP can be classified as mediators or modulators. A mediator of LTP is a molecule, such as the NMDA receptor or calcium, whose presence and activity is necessary for generating LTP under nearly all conditions. By contrast, a modulator is a molecule that can alter LTP but is not essential for its generation or expression.


title: Long-term potentiation

text: In addition to the signaling pathways described above, hippocampal LTP may be altered by a variety of modulators. For example, the steroid hormone estradiol may enhance LTP by driving CREB phosphorylation and subsequent dendritic spine growth. Additionally, β-adrenergic receptor agonists such as norepinephrine may alter the protein synthesis-dependent late phase of LTP. Nitric oxide synthase activity may also result in the subsequent activation of guanylyl cyclase and PKG. Similarly, activation of dopamine receptors may enhance LTP through the cAMP/PKA signaling pathway.


title: Long-term potentiation

text: While the long-term potentiation of synapses in cell culture seems to provide an elegant substrate for learning and memory, the contribution of LTP to behavioral learning — that is, learning at the level of the whole organism — cannot simply be extrapolated from "in vitro" studies. For this reason, considerable effort has been dedicated to establishing whether LTP is a requirement for learning and memory in living animals. Because of this, LTP also plays a crucial role in fear processing.


title: Long-term potentiation

text: In 1986, Richard Morris provided some of the first evidence that LTP was indeed required for the formation of memories "in vivo". He tested the spatial memory of rats by pharmacologically modifying their hippocampus, a brain structure whose role in spatial learning is well established. Rats were trained on the Morris water maze, a spatial memory task in which rats swim in a pool of murky water until they locate the platform hidden beneath its surface. During this exercise, normal rats are expected to associate the location of the hidden platform with salient cues placed at specific positions around the circumference of the maze. After training, one group of rats had their hippocampi bathed in the NMDA receptor blocker APV, while the other group served as the control. Both groups were then subjected to the water maze spatial memory task. Rats in the control group were able to locate the platform and escape from the pool, while the performance of APV-treated rats was significantly impaired. Moreover, when slices of the hippocampus were taken from both groups, LTP was easily induced in controls, but could not be induced in the brains of APV-treated rats. This provided early evidence that the NMDA receptor — and by extension, LTP — was required for at least some types of learning and memory.


title: Long-term potentiation

text: Similarly, Susumu Tonegawa demonstrated in 1996 that the CA1 area of the hippocampus is crucial to the formation of spatial memories in living mice. So-called "place cells" located in this region become active only when the rat is in a particular location — called a "place field" — in the environment. Since these place fields are distributed throughout the environment, one interpretation is that groups of place cells form maps in the hippocampus. The accuracy of these maps determines how well a rat learns about its environment and thus how well it can navigate it. Tonegawa found that by impairing the NMDA receptor, specifically by genetically removing the NR1 subunit in the CA1 region, the place fields generated were substantially less specific than those of controls. That is, mice produced faulty spatial maps when their NMDA receptors were impaired. As expected, these mice performed very poorly on spatial tasks compared to controls, further supporting the role of LTP in spatial learning.


title: Long-term potentiation

text: Enhanced NMDA receptor activity in the hippocampus has also been shown to produce enhanced LTP and an overall improvement in spatial learning. In 1999, Tang "et al". produced a line of mice with enhanced NMDA receptor function by overexpressing the NR2B subunit in the hippocampus. The resulting smart mice, nicknamed "Doogie mice" after the fictional prodigious doctor Doogie Howser, had larger LTP and excelled at spatial learning tasks, reinforcing LTP's importance in the formation of hippocampus-dependent memories.


title: Long-term potentiation

text: In 2006, Jonathan Whitlock and colleagues reported on a series of experiments that provided perhaps the strongest evidence of LTP's role in behavioral memory, arguing that to conclude that LTP underlies behavioral learning, the two processes must both mimic and occlude one another. Employing an inhibitory avoidance learning paradigm, researchers trained rats in a two-chambered apparatus with light and dark chambers, the latter being fitted with a device that delivered a foot shock to the rat upon entry. An analysis of CA1 hippocampal synapses revealed that inhibitory avoidance training induced "in vivo" AMPA receptor phosphorylation of the same type as that seen in LTP "in vitro"; that is, inhibitory avoidance training mimicked LTP. In addition, synapses potentiated during training could not be further potentiated by experimental manipulations that would have otherwise induced LTP; that is, inhibitory avoidance training occluded LTP. In a response to the article, Timothy Bliss and colleagues remarked that these and related experiments "substantially advance the case for LTP as a neural mechanism for memory."


title: Long-term potentiation

text: The role of LTP in disease is less clear than its role in basic mechanisms of synaptic plasticity. However, alterations in LTP may contribute to a number of neurological diseases, including depression, Parkinson's disease, epilepsy, and neuropathic pain. Impaired LTP may also have a role in Alzheimer's disease and drug addiction.


title: Long-term potentiation

text: LTP has received much attention among those who study Alzheimer's disease (AD), a neurodegenerative disease that causes marked cognitive decline and dementia. Much of this deterioration occurs in association with degenerative changes in the hippocampus and other medial temporal lobe structures. Because of the hippocampus' well established role in LTP, some have suggested that the cognitive decline seen in individuals with AD may result from impaired LTP.


title: Long-term potentiation

text: In a 2003 review of the literature, Rowan "et al." proposed one model for how LTP might be affected in AD. AD appears to result, at least in part, from misprocessing of amyloid precursor protein (APP). The result of this abnormal processing is the accumulation of fragments of this protein, called amyloid β (Aβ). Aβ exists in both soluble and fibrillar forms. Misprocessing of APP results in the accumulation of soluble Aβ that, according to Rowan's hypothesis, impairs hippocampal LTP and may lead to the cognitive decline seen early in AD.


title: Long-term potentiation

text: AD may also impair LTP through mechanisms distinct from Aβ. For example, one study demonstrated that the enzyme PKMζ accumulates in neurofibrillary tangles, which are a pathologic marker of AD. PKMζ is an enzyme with critical importance in the maintenance of late LTP.


title: Long-term potentiation

text: Research in the field of addiction medicine has also recently turned its focus to LTP, owing to the hypothesis that drug addiction represents a powerful form of learning and memory. Addiction is a complex neurobehavioral phenomenon involving various parts of the brain, such as the ventral tegmental area (VTA) and nucleus accumbens (NAc). Studies have demonstrated that VTA and NAc synapses are capable of undergoing LTP and that this LTP may be responsible for the behaviors that characterize addiction.


title: Rivellino

text: Roberto Rivellino (also Rivelino, ; ; born 1 January 1946) is a Brazilian football pundit and retired footballer. He was one of the stars of Brazil's 1970 FIFA World Cup winning team. Rivellino currently works as a pundit for Brazilian TV Cultura.


title: Rivellino

text: The son of Italian immigrants from Macchiagodena (Isernia), he was famous for his large moustache, bending free kicks, long range shooting, accurate long passing, vision, close ball control and dribbling skills. He also perfected a football move called the "flip flap", famously copied by Romário, Mágico González, Ronaldo, Ronaldinho and Cristiano Ronaldo in recent years. A former attacking midfielder, he is widely regarded as one of the most graceful football players ever, and one of the greatest players of all time. With the close control, feints and ability with his left foot, Diego Maradona named Rivellino among his greatest inspirations growing up. In 2004, he was named by Pelé in the FIFA 100 list of the world's greatest living players.


title: Rivellino

text: Rivellino was born in São Paulo, and started as a futebol de salao player at Clube Atletico Barcelona. After that, he tried his luck with Barcelona's biggest rival, Corinthians, where he moved on to professional football and quickly became a favourite of the fans—and was therefore nicknamed "O Rei do Parque" (King of the Park) (after the club's home ground, Parque São Jorge). However, the late 60s and early 70s were one of the most troubled periods in the history of the club, which did not win a single São Paulo state league title between 1954 and 1977.


title: Rivellino

text: In 1974, after Corinthians was defeated by arch-rivals Palmeiras in the São Paulo league finals, as the star player Rivellino was singled out by most fans as one of the most responsible for not winning. He moved on to Rio de Janeiro, where he defended Fluminense until the end of the 1970s. Rivellino was undoubtedly the greatest star in the excellent Fluminense of the mid 70s, dubbed "the tricolor machine", among Doval, Pintinho, Gil and Carlos Alberto Torres. He won the Rio de Janeiro league championship in 1975 and 1976. By the end of the decade, he moved on to play for Al Hilal in Saudi Arabia; he retired from professional football in 1981.


title: Rivellino

text: Rivellino was a key member of Brazil's 1970 FIFA World Cup winning team, which is often cited as the greatest-ever World Cup team. Wearing the number 11 jersey, Rivellino was deployed on the left side of midfield and scored 3 goals, including the powerful bending free-kick against Czechoslovakia, which earned him the nickname "Patada Atómica" (Atomic Kick) by Mexican fans. Rivellino also played in the 1974 and 1978 FIFA World Cups, finishing in fourth and third place respectively.


title: Rivellino

text: After his professional retirement, Rivellino started a career as a football commentator and coach (he has managed Shimizu S-Pulse in Japan's J. League). Rivellino further represented Brazil in the 1989 edition of the World Cup of Masters, scoring in the final against Uruguay. Rivellino is sometimes credited with scoring the fastest goal in football history when he supposedly scored a goal direct from the kick-off after noticing the opposition goalkeeper on his knees finishing off pre-match prayers.


title: Rivellino

text: Regarding the 2014 FIFA World Cup held in his country, Rivellino criticized the inclusion of the Amazonian city of Manaus with its stadium Arena da Amazônia in the hosting venues, saying "it’s absurd to play in Manaus. You start sweating the moment you leave the locker room".


title: Thug Behram

text: Thug Behram (c. 1765 – 1840), also known as Buhram Jamedar and the King of the Thugs, was a leader of the Thuggee cult active in Oudh in central India during the late 18th and early 19th century, and is often cited as one of the world's most prolific serial killers. He may have been involved in up to 931 murders by strangulation between 1790 and 1840 performed with a ceremonial rumāl, a handkerchief-like cloth used by his cult as a garrote. Only 125 were confirmed.


title: Thug Behram

text: While Behram is sometimes suspected of having committed 931 murders, James Paton, an East India Company officer working for the Thuggee and Dacoity Office in the 1830s who wrote a manuscript on Thuggee, quotes Behram as saying he had "been present" at 931 cases of murder, and "I may have strangled with my own hands about 125 men, and I may have seen strangled 150 more."


title: Thug Behram

text: The English word 'thug' is in fact borrowed from the Hindi word 'thag' (ठग). The thugs were covert members of a group, and the term 'Thugee' typically referred to an act of deceitful and organised robbery and murder.


title: Thug Behram

text: Buhram used his cummerbund or "rumāl", with a large medallion sewn into it, as a garrote to execute his killing. Through sheer skill, he could cast the "rumal" to cause the medallion to land at the adam's apple of his victims, adding pressure to the throat when he strangled them.


title: Rillettes

text: Rillettes (, , ) is a preservation method similar to confit where meat is seasoned then slow cooked submerged in fat and cooked at an extremely slow rate for several hours (4 to 10 hours). The meat is shredded and packed into sterile containers covered in fat. Rillettes are most commonly made with pork, but also made with other meats such as goose, duck, chicken, game birds, rabbit and sometimes with fish such as anchovies, tuna, pike or salmon. Rillettes are best served at room temperature spread thickly on toasted bread.


title: Rillettes

text: The term "rillette" can refer to the final product and its appearance when spread on sliced bread. Rillettes were traditionally made with fatty pork belly or pork shoulder. The meat was cubed, salted and cured, cooked slowly over low heat until very tender, then raked into small shreds and blended with the warm cooking fat to form a rustic paste. Rillettes could be stored in crocks for several months. In Anjou, rillaud was a speciality, plated in the shape of a pyramid and topped with the pig's tail; the rillettes were proudly displayed to the guest of honor. In time the rillette cooking style was applied to game birds, wild rabbit, and fish. Eventually several preparations for seafood rillettes were developed including an anchovy, tuna, and salmon version. Though the fish is not actually cooked in the fat, it is blended with fat to form the characteristic paste-spread. The soft, smooth texture is a deciding factor in determining a good rillette dish.


title: Rillettes

text: Like cassoulet or fondue, this French dish has its many regional definitions. In general most rillettes are served at room temperature, as a spread with toast points, much like a pâté. Pork rillettes from the northwestern regions of Tours and Anjou are famous for the rich texture and bronze color achieved during the cooking process. Rabelais called rillettes "brown pig jam" ("brune confiture de cochon"). Rillettes from the adjacent "département" of Sarthe are distinguished by a more rustic texture, complete with larger pieces of pork and less color.


title: Rillettes

text: The French word "rillettes" is first evidenced in 1845. It derives from the Old French "rille", meaning a slice of pork, which is first attested in 1480. This is a dialect variation of the Old French "reille", meaning a lath or strip of wood, from the Latin "regula".


title: Clockwise

text: Two-dimensional rotation can occur in two possible directions. Clockwise motion (abbreviated CW) proceeds in the same direction as a clock's hands: from the top to the right, then down and then to the left, and back up to the top. The opposite sense of rotation or revolution is (in Commonwealth English) anticlockwise (ACW) or (in North American English) counterclockwise (CCW).


title: Clockwise

text: Before clocks were commonplace, the terms "sunwise" and "deasil", "deiseil" and even "deocil" from the Scottish Gaelic language and from the same root as the Latin "dexter" ("right") were used for clockwise. "Widdershins" or "withershins" (from Middle Low German "weddersinnes", "opposite course") was used for counterclockwise.


title: Clockwise

text: The terms clockwise and counterclockwise can only be applied to a rotational motion once a side of the rotational plane is specified, from which the rotation is observed. For example, the daily rotation of the Earth is clockwise when viewed from above the South Pole, and counterclockwise when viewed from above the North Pole (considering "above a point" to be defined as "farther away from the center of earth and on the same ray").


title: Clockwise

text: Clocks traditionally follow this sense of rotation because of the clock's predecessor: the sundial. Clocks with hands were first built in the Northern Hemisphere (see "Clock"), and they were made to work like horizontal sundials. In order for such a sundial to work north of the equator during spring and summer, and north of the Tropic of Cancer the whole year, the noon-mark of the dial must be placed northward of the pole casting the shadow. Then, when the Sun moves in the sky (from east to south to west), the shadow, which is cast on the sundial in the opposite direction, moves with the same sense of rotation (from west to north to east). This is why hours must be drawn in horizontal sundials in that manner, and why modern clocks have their numbers set in the same way, and their hands moving accordingly. For a vertical sundial (such as those placed on the walls of buildings, the dial being "below" the post), the movement of the sun is from right to top to left, and, accordingly, the shadow moves from left to down to right, i.e., counterclockwise. This effect is caused by the plane of the dial having been rotated through the plane of the motion of the sun and thus the shadow is observed from the other side of the dial's plane and is observed as moving in the opposite direction. Some clocks were constructed to mimic this. The best-known surviving example is the Münster astronomical clock, whose hands move counterclockwise.


title: Clockwise

text: Occasionally, clocks whose hands revolve counterclockwise are sold as a novelty. One historic Jewish clock was built that way in the Jewish Town Hall in Prague in the 18th century, using right-to-left reading in the Hebrew language. In 2014 under Bolivian president Evo Morales, the clock outside the Legislative Assembly in Plaza Murillo, La Paz, was shifted to counterclockwise motion to promote indigenous values.


title: Clockwise

text: Typical nuts, screws, bolts, bottle caps, and jar lids are tightened (moved away from the observer) clockwise and loosened (moved towards the observer) counterclockwise in accordance with the right-hand rule.


title: Clockwise

text: To apply the right-hand rule, place one's loosely clenched right hand above the object with the thumb pointing in the direction one wants the screw, nut, bolt, or cap ultimately to move, and the curl of the fingers, from the palm to the tips, will indicate in which way one needs to turn the screw, nut, bolt or cap to achieve the desired result. Almost all threaded objects obey this rule except for a few left-handed exceptions described below.


title: Clockwise

text: The reason for the clockwise standard for most screws and bolts is that supination of the arm, which is used by a right-handed person to tighten a screw clockwise, is generally stronger than pronation used to loosen.


title: Clockwise

text: Sometimes the opposite (left-handed, counterclockwise, reverse) sense of threading is used for a special reason. A thread might need to be left-handed to prevent operational stresses from loosening it. For example, some older cars and trucks had right-handed lug nuts on the right wheels and left-handed lug nuts on the left wheels, so that, as the vehicle moved forward, the lug nuts tended to tighten rather than loosen. For bicycle pedals, the one on the left must be reverse-threaded to prevent it unscrewing during use. Similarly, the flyer whorl of a spinning wheel uses a left-hand thread to keep it from loosening. A turnbuckle has right-handed threads on one end and left-handed threads on the other. Some gas fittings are left-handed to prevent disastrous misconnections: oxygen fittings are right-handed, but acetylene, propane, and other flammable gases are unmistakably distinguished by left-handed fittings.


title: Clockwise

text: In trigonometry and mathematics in general, plane angles are conventionally measured counterclockwise, starting with 0° or 0 radians pointing directly to the right (or east), and 90° pointing straight up (or north). However, in navigation, compass headings increase clockwise around the compass face, starting with 0° at the top of the compass (the northerly direction), with 90° to the right (east).


title: Clockwise

text: A circle defined parametrically in a positive Cartesian plane by the equations and is traced counterclockwise as the angle "t" increases in value, from the right-most point at . An alternative formulation with sin and cos swapped gives a clockwise trace from the upper-most point.


title: Clockwise

text: In general, most card games, board games, parlor games, and multiple team sports play in a clockwise turn rotation in Western Countries and Latin America with a notable resistance to playing in the opposite direction (counterclockwise). Traditionally (and still continued for the most part) turns pass counterclockwise in many Asian countries. In Western countries, when speaking and discussion activities take part in a circle, turns tend to naturally pass in a clockwise motion even though there is no obligation to do so. Curiously, unlike with games, there is usually no objection when the activity uncharacteristically begins in a counterclockwise motion.


title: Clockwise

text: As an alternative to using a clock to describe the rotation of a body, it is possible to use the right/left hand rule to determine the rotation. The thumb shall point in the normal direction of the surface in question and the four remaining fingers in the direction of the rotation of the surface. The resulting direction of the rotation is thereby


title: Clockwise

text: Most left-handed people prefer to draw circles and circulate in buildings clockwise, while most right-handed people prefer to draw circles and circulate in buildings counterclockwise. While this was theorized to result from dominant brain hemispheres, research shows little correlation and instead attributes it to muscle mechanics.


title: Lee Boardman

text: Lee Boardman (born 2 July 1972) is an English actor and narrator. He has appeared in the films "Jack the Giant Slayer" and "Love's Kitchen", and the television series "Rome".


title: Lee Boardman

text: Boardman played Murray Priestman in "Drop Dead Gorgeous" as well as the drug dealer Jez Quigley in "Coronation Street". He appears as Timon the Jew in the television series "Rome". He also made an appearance in the fifth episode of the 2011 BBC crime-drama series "Death in Paradise". In 2013 he starred in the ITV1 comedy drama series "Great Night Out" as Hodge. In 2014 he played the recurring character of Amerigo Vespucci in "Da Vinci's Demons".


title: Lee Boardman

text: He was also the narrator of popular Sky 1 police documentary "Road Wars" and its spin off "Street Wars".


title: Lee Boardman

text: Born in Stockport, England, in 1972, Boardman studied at Stockport College prior to winning a scholarship to the Oxford School of Drama. In 2001 he married his former "Coronation Street" co-star Jennifer James. They have two children; a son born in 2004 and a daughter born 2010.


title: Lee Boardman

text: In 2013, Boardman and James launched Actor Tribe, an acting school for children and adults in Knutsford. The courses focus on the complexities of being a working actor through guest tutors who are professional actors themselves. Due to the success of the program, an additional school in Heaton Mersey was opened in 2016, with Boardman and his wife, Jennifer, dividing their time between the two locations.


title: Smoke + Mirrors

text: Smoke + Mirrors is the second studio album by American pop rock band Imagine Dragons. The album was recorded during 2014 at the band's home studio in Las Vegas, Nevada. Self-produced by members of the band along with English hip-hop producer Alexander Grant, known by his moniker Alex da Kid, the album was released by Interscope Records and Grant's Kidinakorner label on February 17, 2015, in the United States.


title: Smoke + Mirrors

text: The album received generally mixed reviews from music critics upon release. However, it debuted at number one on the "Billboard" 200 in the United States, moving more than 172,000 units (becoming their only album to date to debut at number one), and also debuted at number one on the UK Albums Chart and the Canadian Albums Chart. It has since been certified gold in the United States, United Kingdom, Mexico, and Brazil. Three official singles have been released from the standard version of the album: "I Bet My Life", "Gold" and "Shots". As of July 2017 the album has sold over 1,000,000 copies in the US.


title: Smoke + Mirrors

text: In 2012, Imagine Dragons released their debut studio album "Night Visions". The album, produced by the band along with Alexander Grant and Brandon Darner, launched the band into international mainstream commercial success, charting within the top ten of 14 national record charts, in addition to charting on eight others. Certified Platinum by seven national music associations, including 2× Platinum in the United States by the RIAA and 3× Platinum in Canada by Music Canada, the album was initially met with first week sales in excess of 83,000 copies, the highest charting for a debut rock album since 2006. The album was also nominated for the 2014 Juno Award for International Album of the Year.


title: Smoke + Mirrors

text: The band released six singles during the "Night Visions" album cycle in 2012 and 2013, five of which charted on the "Billboard" Hot 100. "Radioactive," a 2013 single, sold more than nine million singles in the United States, spending more than 1 year consecutively on the Billboard Hot 100. Peaking at no. 3 on the chart, it also broke the record for the longest run into the top five and is the best-selling rock single on the Nielsen SoundScan running list of best-selling rock tracks in digital history. "Billboard" listed the band as one of "2012's Brightest New Stars" and later "The Breakout Band of 2013."


title: Smoke + Mirrors

text: To further promote the already-successful "Night Visions", the band set out on a year-long concert tour beginning in early 2013 and ending in mid-2014, dubbed the "Night Visions Tour." The tour spanned for over 170 dates, and visited North America, South America, Europe and Oceania. An additional tour of North America, dubbed the "Into the Night Tour," was also executed. The conclusion of the Into the Night Tour signaled the end of the "Night Visions" album cycle, with "Night Visions Live", a live album, serving as the last release in the cycle. Lead singer Dan Reynolds joked about the end of the "Night Visions" cycle, saying that "We're always writing on the road, [so] that second album will come, unless we die at the age of 27 next year. Hopefully we don't die and there will be a second album. I don't know when it will be, but it may come." The band were also inspired greatly by their experiences on the Night Visions Tour. Dan Reynolds told New Orleans-based newspaper "The Times-Picayune" that the world tour had "a lot of inspiration to be drawn," and further stating, "You kind of realize that you’re a lot smaller than you think."


title: Smoke + Mirrors

text: The idea behind the second studio album, dubbed as their "new year's resolution," was to create music and finish it when the band feels that their work is done. Reynolds told MTV in 2014 that the band wanted to "put out an album that [they're] really happy with". He further said that "we tend to be perfectionists, too hard on ourselves at times, and we don't want to rush anything because we know how we are with things. We don't want to put a record out until we really feel good about it, you know, and who knows how long that will take."


title: Smoke + Mirrors

text: Reynolds stated to music magazine "Rolling Stone" that the next album will be "different" from "Night Visions", and that the band intends the album to be "stripped back quite a bit." He added that "we embraced a lot of hip-hop influences with "Night Visions", but I think the next record will be more rock-driven. It’s too early to say, but there is some weird stuff going on in these songs."


title: Smoke + Mirrors

text: The creative process for the album began long before the conclusion of the "Night Visions" cycle. Since the beginning of the Night Visions Tour in 2012, the band had been writing new material for an upcoming album, and, even as early as the start of the tour, had been recording demos for the album, before entering the studio. By the time that they entered the studio to work on the album, they had amassed 50 demos to work from. The demos had been described by Reynolds as "definitely different," but added that "it’s still Imagine Dragons, but we’ve got a lot of growth and maturing to do as a band. I think [the new material] is going to hopefully be a step in the right direction. We’re just trying to create and do what comes out and what feels right." The band also were self-critical throughout the sessions, with Drummer Daniel Platzman stating that there was "no room for external pressure" during the recording of the album.


title: Smoke + Mirrors

text: The "Smoke + Mirrors" album cycle featured three singles and two promotional singles. Regional releases from the album feature different track listings. Target has made available an exclusive deluxe version of the album featuring four bonus tracks, available online internationally.


title: Smoke + Mirrors

text: Target teamed with the band to air the first ever live commercial performance during the Grammy Awards. On February 8, 2015, the band performed "Shots" from Las Vegas' Freemont Street under the direction of Jonas Åkerlund. "Billboard" estimated the commercial cost $8 million in airtime.


title: Smoke + Mirrors

text: Hard Rock Cafe teamed with the band, granting them the first ever full access to take control of Hard Rock Cafe's internal video system (more than 20,000 screens at all 151 locations worldwide) on February 17, 2014. Also, autographed T-shirts will be hidden throughout the Hard Rock Cafe shops supporting the Tyler Robinson Foundation, benefiting the families of children with cancer.


title: Smoke + Mirrors

text: Preceding the release of lead single "I Bet My Life," Imagine Dragons posted on social media segments of the single's artwork imposed by lyrics from the song and mirrored letters that spelled the song's title in reverse.


title: Smoke + Mirrors

text: On December 12, 2014, Imagine Dragons posted on social media a request that fans look around Las Vegas Valley for hidden clues to upcoming songs. The band gave 13 fans puzzle pieces of the artwork for the album. When combined, the puzzle pieces revealed the cover art and album title. On December 15, 2014, "Gold" was released as a single with a video being released later. On the cover art for the album were a set of numbers that provided specific coordinates to prizes hidden in the Nevada desert, including an autographed guitar, drumsticks, Polaroid pictures, and a master pass for free concert tickets for the entire tour.


title: Smoke + Mirrors

text: On January 24, 2015, the band flew in 200 prize winning fans from around the world to attend a special listening event at the P3 Studio Art Gallery in the Cosmopolitan of Las Vegas. The event included an art exhibition of Tim Cantor's work for the album and attendees were allowed to listen to the full album through Beats headphones. Then the band arrived for an interview and private performance.


title: Smoke + Mirrors

text: February 20 through February 26, 2015, the band, partnering with Southwest Airlines, flew over 30 winners from all over the U.S. from coast to coast on what they called the "Destination Dragons" Tour. The Destination Dragons tour consisted of all the winners being flown from their hometowns, to small clubs in Los Angeles, Provo, Las Vegas, and Atlanta. This tour was a promotion for "Smoke + Mirrors", and a chance for the band to road test their new music live, in preparation for their "Smoke + Mirrors" World Tour. They paid homage to the clubs they got their start in by playing small, private shows for the Destination Dragons winners, as well as local winners in each city. They played The Troubadour in Los Angeles, Velour in Provo, Utah, Vinyl in Las Vegas, and wrapped up the tour at Terminal West in Atlanta, Georgia. During the Southwest flight from Las Vegas to Atlanta, fans were treated to an acoustic concert in what the airline calls "Live at 35" where artists play for airplane passengers after the airplane reaches 35,000 feet. All winners flew to all 4 cities, were given tickets to all 4 private shows, were able to attend the "Live at 35" event, and were given a meet and greet.


title: Smoke + Mirrors

text: The song "Friction" appeared in the trailer for "" and in the third and final season for "Crossing Lines".


title: Smoke + Mirrors

text: "I Bet My Life" was released as the lead single from "Smoke + Mirrors" and debuted at number 15 on the Canadian Hot 100, number 27 on the UK Singles Chart, and 28 on the "Billboard" Hot 100. It also topped the Billboard Adult Alternative Songs, a first for the band. The band performed the song live on "American Music Awards" (2014), "Good Morning America" (2015), "The Ellen DeGeneres Show" (2015), VH1's "Big Morning Buzz Live" (2015).


title: Smoke + Mirrors

text: "Gold" was released as the second single from "Smoke + Mirrors" on December 16, 2014, and peaked at number 12 on the "Billboard" Hot Rock Songs chart.


title: Smoke + Mirrors

text: "Shots" was released as the third and final single from "Smoke + Mirrors" and charted on the Billboard Hot 100 as well as reaching No. 3 on the Norway Singles chart. The band performed the song live during the "Grammy Awards" (2015), a first ever live commercial performance, directed by Jonas Åkerlund. They also performed the song live on "Good Morning America" (2015), "The Tonight Show Starring Jimmy Fallon" (2015), "The Howard Stern Show" (2015), "Jimmy Kimmel Live!", "The Ellen DeGeneres Show" (2015), and "Today" (2015).


title: Smoke + Mirrors

text: On February 5, 2015, the band played a live streaming concert for Live Nation and Yahoo! during which they announced the North American leg of the arena tour. The band embarked on a world tour, Smoke + Mirrors Tour, in promotion of the worldwide release of "Smoke + Mirrors". The tour began on began April 12, 2015 and concluded on February 5, 2016.


title: Smoke + Mirrors

text: The album overall received mixed reviews from critics. Metacritic gave a score of 60/100 from 12 critics. "Q" published a positive review of the album, calling it "[a] modern pop-rock gem" and also noting it as an improvement upon their debut album "Night Visions"." "Entertainment Weekly" published a positive review stating, "the group's sophomore effort scales back on the electronic frippery, revealing the tightly focused rock juggernaut they are on stage." "Illinois Entertainer" published an interview with Reynolds on February 2, 2015, saying the album is "an ambitious, rock-solid effort, with potential hits galore." "The Daily Telegraph" published a highly positive review of the album, calling it "thunderous" and saying its "songs are peppered with bright ideas and odd collisions, world music sounds percolating through R&B grooves, stuttering digital breaks interrupting solid rhythms. Lyrics and delivery suggest Imagine Dragons adhere to old-fashioned rock band idealism, but nothing is allowed to get in the way of a sparkling hook."


title: Smoke + Mirrors

text: Allison Stewart of "The Washington Post" wrote that the band "is very good at what it does, even if what it does isn't very good," having "effortlessly achieved" the album's one purpose, "to cram as many popular styles as possible into a mainstream rock album to appeal to as many people as it can." Dave DiMartino of Yahoo! Music wrote that "it is the band’s music, and not their faces, or personalities, that resonates with the mass audiences. And this is good. . . This is a pretty solid, surprisingly diverse sounding rock album—not a tuneless screech-fest by any means—and a record the band should be proud of. . . This could have been a shambles, and it's anything but." Stephen Thomas Erlewine of AllMusic described the album as "overblown" arena rock, with more style than substance, and an overemphasis on reverberation effects such that "the reverb nearly functions as a fifth instrument in the band".


title: Smoke + Mirrors

text: "Smoke + Mirrors" debuted at number one on the US "Billboard" 200 chart with 195,000 album-equivalent units (172,000 of which were pure album sales). It more than doubled the group's previous best sales week. The album remained in the chart's top twenty for the next several weeks, as of July 2017, the album has sold over 1,000,000 copies in the United States. In the United Kingdom, it became the final album to reach number one on sales alone as streaming became incorporated into the UK Albums Chart the following week.


title: Smoke + Mirrors

text: All songs written and produced by Imagine Dragons (Dan Reynolds, Wayne Sermon, Ben McKee and Daniel Platzman), except where noted.


title: American Kennel Club

text: The American Kennel Club (AKC) is a registry of purebred dog pedigrees in the United States. In addition to maintaining its pedigree registry, this kennel club also promotes and sanctions events for purebred dogs, including the Westminster Kennel Club Dog Show, an annual event which predates the official forming of the AKC, the National Dog Show and the AKC National Championship. The AKC is a non-member partner with the Fédération Cynologique Internationale. The AKC recognizes 200 dog breeds, as of 2022.


title: American Kennel Club

text: In the early 1800s, the English became concerned with the beauty of dogs as well as their function. This fad spread to North America, and in 1877, the Westminster Kennel Club Dog Show began. Soon after, the need for a regulating body became obvious. The National American Kennel Club, which had been founded in 1876, began to publish and make publicly available its studbook in 1879. This organization, however, had a more vested interest in field trials than in conformation shows, and eventually changed its name to the National Field Trial Association and stopped hosting conformation shows completely.


title: American Kennel Club

text: In 1884, a group of 13 breed clubs, 10 American clubs and three Canadian clubs founded the American Kennel Club. These 13 clubs pledged "to do everything to advance the study, breeding, exhibiting, running and maintenance of purity of thoroughbred dogs." The AKC differed from The Kennel Club in that individuals could not directly join the AKC; they became members of smaller, individual breed clubs, which were themselves members of the AKC. When arguments began to develop between the American and Canadian breed clubs in 1886, the Canadian clubs pulled out from the organization and established their own kennel club two years later, the Canadian Kennel Club.


title: American Kennel Club

text: In 1894, the American Kennel Club began to refuse to allow Canadian dogs without an American pedigree to participate in its shows, following the prevailing trends in American purebred cattle organizations. In 1906, the U.S. Department of Agriculture ruled that any dogs imported to America who were not registered with the AKC would have to pay a duty charge; this was later changed in 1911, allowing any dog registered with a kennel club in its home country duty-free entry into the country. Soon after the AKC, CKC, and KC produced agreements that made any dog eligible to be registered with the club in its home country, eligible for registration in the remaining two clubs as well. In 1909, the group moved to New York and became incorporated.


title: American Kennel Club

text: On July 1, 2012, the AKC began to recognize certain titles issued by the North American Flyball Association. These titles are Flyball Champion (FDCh), Flyball Master (FM), and the ONYX title.


title: American Kennel Club

text: The AKC is the largest registry of purebred dogs in the U.S. and is the only not-for profit registry, as well as the most well-known and the most influential. For a purebred dog to be registered with the AKC, the dog's parents must be registered with the AKC as the same breed, and the litter in which the dog is born must be registered with the AKC. If the dog's parents are not registered with the AKC or the litter is not registered, an exception may be made if the AKC determines, through special registry research, that the dog is eligible for AKC registration. Once a determination of eligibility is met, either by litter application or registry research, the dog can be registered as purebred by the AKC. Registration indicates only that the dog's parents were registered as one recognized breed; it does not necessarily indicate that the dog comes from healthy or show-quality bloodlines, nor is registration necessarily a reflection on the quality of the breeder or how the puppy was raised.


title: American Kennel Club

text: The AKC's Foundation Stock Service is an optional breed registry service the club provides for new purebred dog breeds that have been introduced to the US and are yet to be recognized by the AKC.


title: American Kennel Club

text: In AKC conformation shows dogs compete in different classes based on breed and sex, with breeds divided into hound, terrier, working, herding, sporting, non-sporting, toy and miscellaneous groups. The AKC's premier conformation shows are the Westminster Dog Show and the AKC National Championship.


title: American Kennel Club

text: The AKC organises a variety of field competitions they term performance dog sports, including herding and farm dog trials, scent work trials, earthdog trials, lure coursing trials and field trials for Bassets, Beagles, coonhounds, Dachshunds, pointing dogs, retrievers and spaniels.


title: American Kennel Club

text: The AKC also offers the Canine Good Citizen program. This program tests dogs of any breed (including mixed breed) or type, registered or not, for basic behavior and temperament suitable for appearing in public and living at home.


title: American Kennel Club

text: Another AKC affiliate is AKC Reunite, formerly AKC Companion Animal Recovery (AKC CAR), founded in 1995, which is North America's largest not-for-profit pet ID and recovery service.


title: American Kennel Club

text: Another AKC affiliate is the AKC Humane Fund, which supports breed rescue activities, assists shelters that permit domestic violence victims to bring their pets and educates dog lovers about responsible dog ownership.


title: American Kennel Club

text: The AKC also provides titles for therapy dogs, after the dogs have been certified by AKC recognized therapy dog organizations and have performed a required number of visits.


title: American Kennel Club

text: The AKC has been criticized for the prevalence of genetic disorders in their dogs. As many as 25% of purebred dogs registered by the AKC has at least one hereditary genetic problem. These problems cost breeders and owners almost $1 billion in vet bills and lost revenues from stillborn pups. Some breed clubs, such as the U.S. Border Collie Club, resisted applying for AKC breed acceptance due to fears that doing so would be detrimental to the genetics of the breed they represent.


title: American Kennel Club

text: These genetic issues have resulted in the emergence of "puppy lemon laws" in several U.S. states. These laws protect dog owners from genetic diseases that their breeder may have neglected to inform them of, allowing them to get a refund for the cost of the puppy or to force the breeder to pay their vet bills.


title: American Kennel Club

text: The AKC supports some canine health research and has run advertising campaigns implying that the AKC is committed to healthy dogs, but the AKC's role in furthering dog health is controversial. Temple Grandin maintains that the AKC's standards only regulate physical appearance, not emotional or behavioral health. The AKC itself states that "There is a widely held belief that 'AKC' or 'AKC papers' guarantee the quality of a dog. This is not the case. AKC is a registry body. A registration certificate ... in no way indicates the quality or state of health of the dog."


title: American Kennel Club

text: The AKC has no health standards for breeding; the only breeding restriction is age (a dog can be no younger than eight months). Though the majority of the 170 breed-specific parent clubs have a health committee devoted to their breed's specific concerns, the AKC prohibits clubs from imposing stricter regulations since the AKC Rules Applying to Registration and Discipline apply to all breed clubs and do not provide an option for breed clubs to extend or override them. Thus, an AKC breed club cannot require a higher breeding age, hip dysplasia ratings, genetic tests for heritable diseases, or any other restrictions. Parent clubs have the power to define the looks of the breed, or the breed standard, and may also restrict participation in non-regular events or classes such as futurities or maturities to only those dogs meeting their defined criteria. These non-regular events can require health testing, DNA sampling, instinct/ability testing, and other outlined requirements as established by the hosting club.


title: American Kennel Club

text: In summary, attention to health among breeders is voluntary and not mandated. By contrast, many dog clubs outside the U.S. do require health tests of breeding dogs. The German Shepherd Club of Germany, for example, requires hip and elbow X-rays in addition to other tests before a dog can be bred. Such breeding restrictions are not allowed in AKC member clubs. As a result, some U.S. breeders have established parallel registries or health databases outside of the AKC; for example, the Berner Garde established such a database in 1995 after genetic diseases reduced the average lifespan of a Bernese Mountain Dog to seven years. By comparison, the Swiss Bernese Mountain Dog Club introduced mandatory hip X-rays in 1971.


title: American Kennel Club

text: For these, and other reasons, a small number of breed clubs have not yet joined the AKC so they can maintain stringent health standards, but, in general, the breeders' desire to show their dogs at AKC shows such as the Westminster Kennel Club Dog Show has won out over these concerns. Concern surrounding the AKC's connections to low-quality breeders has resulted in some dog owners seeking to distance themselves from the organization. In October 2012, Hailey Parker, a longtime Coton de Tulear breeder, filed a lawsuit (that was settled) against the AKC and cited the AKC's connections with high-volume breeders among the reasons. The Coton's "reputation and business model is based on a disassociation from 'puppy mills' and similar commercial breeding operations", according to the complaint.


title: American Kennel Club

text: The club has also been criticized for courting large scale commercial breeders and for lax enforcement of breeding regulations. The AKC employs just nine field inspectors and critics argue that its inspections are ineffective. For example, the owner of a Montana Alaskan Malamute kennel approved by AKC inspectors in 2008 and 2009 was sentenced to five years in prison for animal cruelty in operating that kennel. Similarly, an AKC inspector found a North Carolina kennel "in compliance with AKC's Care Conditions Policy" three months before county officers raided the facility and found the dogs in "poor" condition, suffering from illnesses, injuries and living in "unhealthy conditions", according to court documents. A veterinarian told the court that the rescued dogs had ailments that ranged "from serious to severe" and that "most of the injuries appeared to be chronic, having been in existence for a substantial period of time."


title: American Kennel Club

text: Similarly, the Humane Society of the United States criticized the AKC for not taking a stand against puppy mills. According to the Humane Society's report, "over the past five years, AKC has opposed more than 80 different state bills and local ordinances designed to provide stronger protections for dogs in puppy mills".


title: American Kennel Club

text: The AKC does support several health research initiatives. The AKC Canine Health Foundation funded research that led to the mapping of the canine genome (DNA sequence) with grants totaling more than $2,000,000. Sequencing of the dog genome began in June 2003, funded in large part by the National Human Genome Research Institute (NHGRI) and finished the completed sequence of the entire dog genome at MIT's Broad Institute in 2005. Because people inherit many of the same diseases as dogs, humans can also benefit from health research funded for dogs.


title: American Kennel Club

text: The Orthopedic Foundation for Animals (OFA) and the AKC Canine Health Foundation have established the Canine Health Information Center (CHIC) to encourage health testing by breeders and provide breeders and researchers with information to improve breeding programs. More than 135 different breeds have specific health testing prerequisites required by their parent breed club.


title: American Kennel Club

text: The AKC tracks all dog-related legislation in the U.S., lobbies lawmakers and issues legislative alerts on the internet asking for citizens to contact public officials. They are particularly active in combating breed-specific legislation, such as bans on certain breeds considered dangerous.