Tango - In Spanish Essays - DraftViviana Castrillon,

Tango - In Spanish "El tango tiene el poder de fundir a dos extra?os en uno solo, expresando a trav?s del baile sus deseos? los convierte en grandes amantes y h?roes, aunque sea por un breve momento. El tango es el susurro de la sensualidad que surge del ligero aroma de perfume. El tango es la glamour de un sal?n de baile y tambi?n el misterio de ese mundo que se encuentra debajo. Es la opulencia de Par?s y la obscura cortina humeante de un caf? de Buenos Aires. Es el mundo de met?foras sutiles que captura la melancol?a del coraz?n".

ElectroMagnetic Radiation essays

ElectroMagnetic Radiation essays Electromagnetic radiation is defined as the emission and transmission of energy in the form of electromagnetic waves (Chang, pp. 246). An electromagnetic wave consists of two waves at perpendicular planes, on representing the electrical field while the other represents the magnetic field. This spectrum is split up into about 81 octaves, much like the octaves of sound, which scientists have categorized in order to depict the usefulness of the different properties. Theoretically electromagnetic waves can be as long as the expansive width of the universe in one wave, to a wavelength the size of a quanta (the smallest amount of energy that can be transmitted). That, however, is at this point in time negligible because we either cannot detect wavelengths so extremely large or infinitesimally small. So generally the spectrum is regarded to be set between 30,000,000 km and .0001 angstroms (1 km is equal to 1 X 10^13 angstroms). The longest and least energetic of the accepted wavelengths are radio waves. Their wavelengths range from 300,000 km to 30 cm and a frequency of 30 kHz to 3,000,000 kHz. The waves are used in the transmission of radio and television signals. AM and FM radio signals fall in the long-wave radio range, while TV signals use the short-wave radio range, somewhere in the 3 m wavelength. Radio waves take up about 30 of the 81 octaves. The next slightly more energetic and shorter wavelength is microwaves. Obviously, most are familiar with microwaves since they are always being used to cook food, but microwaves are also used in radiotelescopes and radar, even the radiation from a neutral hydrogen atom falls in this range. Microwave range extends from wavelengths of 30 cm to .3 cm and frequencies of 1-100 billion cycles per second. This corresponds to 6 1/2 octaves. Then comes the infrared range. While much of the radio spectrum passes easily through our atmosphere, in ...

Environment assessment of Apple Inc Research Paper

Environment assessment of Apple Inc - Research Paper Example According to Porter, the threat of substitutes shapes competition within an industry and unless there is demand for a particular product, substitutes may not have any specific impact (Grundy, 2006). It was observed that although Apple is the most favored company as a retail vendor of tablets, its market shares have gone down significantly due to launch of low cost tablets by the competitors such as, Samsung, Asus and Blackberry. In addition, consumers are shifting towards budget phones with similar software and outlook owing to their declining disposable income (The Wall Street Journal, 2014). Previously, Apple faced low competition level as that of innovation was low; but presently, almost all companies are competing at the same level in terms of software and hardware superiority. There is little product differentiation that Apple can incorporate regarding software, but it can utilize the same strategy that the competitors are applying for hardware. Apple needs to upgrade the hardware features offered within a specific price range; in other words, the consumers must be provided with better product related services without increasing the cost. Bargaining power of buyers According to the Porter’s model, the bargaining power of buyers is determined by the concentration of consumers in an industry, product differentiation, brand identity and price sensitivity (Miller, 1988). The major opportunity lying ahead of Apple is that of capturing the market of emerging economies.

Ambiguilty and meaning in the Heart of Darkness by Joseph Conrad Essay

Ambiguilty and meaning in the Heart of Darkness by Joseph Conrad - Essay Example No, not very clear" (21). There are several sub-meanings in the novel that can be interpreted in several ways. The story in itself was narrated in a non-conventional way that there was a story within a story adding to the ambiguity of the narrative. But the most prominent ambiguity in the novel is moral ambiguity because its standard and application in the novel was uncertain that it is difficult to tell what constitutes right and wrong, good and evil because these standards were unclear and not easily understood in the novel. One of the most prominent ambiguity in the novel is Kurtz and the circumstances about him. Marlow first heard about Kurtz during a meeting with the accountant of the Company on his way to Congo making him a subject of a subject in a novel or a story of a story as Marlow, the protagonist of the story narrates about him. At first Marlow was somewhat impressed by the reputation Kurtz as he was described as â€Å"very remarkable person† (37) in the novel. Bu t as the novel progresses and as more information was revealed about him, his character becomes blurry that it is difficult to describe his circumstances. ... And perhaps being a novel, maybe device some unusual way to extract vengeance from him for his brutality. But no, he was strangely revered by the natives and was even treated like a god. In his deathbed, natives even surrounded him when Marlow paid Kurtz a visit. And even he felt kinship with the natives that the attack on Marlow’s boat was made with the prodding of Kurtz as revealed by the Russian trader so that Kurtz will not be found and perhaps, to be left alone with the natives. These circumstances blur the logical sequence of morality that you will be hated if you harm people. Instead, Kurtz seemed to be adored by the natives whom he used to slaughter for ivory. The use of words and description of places is also ambiguous that made the novel quite difficult to understand. Congo which is a part of Africa and Africa in general was referred to as the real heart of darkness as the title of the novel suggests but it is also described to be not as dark and gloomy as the coloni sts place such as London and Belgium. This run counters to the common view that we are accustomed with that Africa was supposed to be uncivilized and therefore darker and the Europeans which were supposed to be educated and civilize were supposed to be the bearer of light. But this was negated in the narrative because it was Europe that was darker and not the heart of darkness which was Congo. Here, the standard of what is morally desirable is blurred because the place that was assigned to be the heart of darkness was not after all darker but in fact better than Europe which we used to think as civilized. The ending of the novel was also ambiguous.

Nature, Nurture and Personality Essay Example | Topics and Well Written Essays - 500 words

Nature, Nurture and Personality - Essay Example I believe that it is this base personality that is genetically determined and is the most important factor in determining the true nature of personality. While there remains a number of external factors that contribute to the development and change of an individual’s personality, my personal understanding is that ultimately personality is most closely linked to these genetic factors that are affected upon in a variety of ways by external cultural and environmental factors. Personality is related to culture in a number of prominent ways. Indeed, this question can be considered on a micro and macro level. On a micro level, immediate social relations affect personality as individuals must tailor their personality and demeanor to fit into a variety of social situations. While this is not directly considered an element of culture, it is culture that determines the social structures in which human beings interact. As culture is a learned phenomenon and has evolved over the centuries there are many such elements that influence personality. It’s important in these regards to consider what constitutes personality. While the outward expression of an individual’s actions has become the accepted definition of personality, can one more accurately identify personality as an entity that is more highly personal? In terms of the first definition, culture greatly determines how a person acts in nearly all situations. In this understanding, personality is also an evolving thing that is directly connected to the evolution of culture. As social mores and appropriateness change with the progression of time, or even with the change of one’s culture surroundings (poor New Orleans vs the Hamptons, for instance) personality continues to be strongly linked to culture. While psychoanalytic thinkers believed that personality was greatly affected by early childhood events that become rooted in unconscious desires and impulses (some of which can be

Kappa Agonists in Management of Pain and Opioid Addiction

Kappa Agonists in Management of Pain and Opioid Addiction Joseph Nguyen Abstract Hypothesis: Opiates mediate pain via opioid receptors, which consist of several subtypes. One subtype, the kappa opioid receptors (KOR), has also been shown to prevent addictive behaviour. Potential novel therapeutic compounds acting on KOR include U50488, CR665, and CR845. It is hypothesized that selective kappa opioid receptor agonists are effective at controlling pain while managing opioid addiction. Methods: Studies for this review were obtained through the PubMed database using a keyword search strategy. Only articles in English published from December 2006 until December 2016 were considered. Results: Kappa agonists are able to decrease inflammatory, visceral, and surgical pain, but are unable to inhibit behaviour-depressing aspects of pain. Kappa agonists also decrease field potential and long-term potentiation in the basolateral amygdala. Additive anti-nociception with mu opioids has been observed as well as decreased fentanyl use, morphine tolerance development, and morphine withdrawal symptoms. Conclusions: Kappa agonists can be effective analgesics while also preventing abuse and addiction to mu opioids. Some evidence also suggests kappa agonist activity in the basolateral amygdala can inhibit affective components of pain. Abstract Word Count: 175 Keywords: kappa agonist, pain, analgesia, anti-nociception, tolerance, dependence, withdrawal, addiction Ultramini Abstract: This study reviewed current research on the analgesic and anti-addictive properties of selective kappa agonists for their use in pain management while preventing addiction. Introduction Opioids are one of the most powerful analgesics available with an increasing trend of prescription in the United States. Prescriptions per capita increased 7.3% from 2007-2012 with 259 million prescriptions in 2012, enough for one bottle of opioids per adult (Dowell et al., 2016). On the other hand, use of opioids presents risks including dependence, abuse, addiction, and overdose which lead to negative health, social and economically impacts. From 1999 to 2014, over 165,000 people have died from opioid overdose and in 2013; an estimated 1.9 million people abused or were dependent on prescribed opioids (Dowell, Haegerich Chou, 2016). However, pain treatment should not be ignored as there are clinical, psychological, and social consequences associated with chronic pain including limitations in complex activities, lost work productivity, reduced quality of life, and stigma, emphasizing the importance of appropriate and compassionate patient care (Dowell et al., 2016). The CDC has recently released a guideline, aimed at primary care settings, suggesting prescriptive protocols as well as methods to evaluate risk of patient substance abuse and addiction. However, the majority of evidence reviewed by the guideline had significant limitations. Although the CDC guideline still has value in preventing exacerbation of pre-existing risk of abuse, results and implementation remain to be seen. Efforts have been made to deter abuse through novel drug formulations, barriers, and pharmacokinetics. Nevertheless, nothing can prevent an addicted person from taking multiple doses at once. This may be a result of the inherent nature of the drugs to activate reward pathways in the brain along with its analgesic effects though mu receptors. Another opioid receptor, kappa-opioid receptor (KOR), has been shown to limit motivational properties of drug abuse (Lalanne, Ayranci, Keiffer Lutz, 2014). This has sparked interest in development of kappa agonists as novel analgesics with low abuse potential. Examples of known selective kappa agonists include U50488, CR665, and CR845 among many others including those continuing to be developed. However, questions still remain about analgesic efficacy and complications for patients already addicted to mu opioids transitioning to kappa agonists. This literature review explores the anti-nociceptive efficacy of kappa agonists and their ability to m anage opioid addicted patients. Balancing adequate pain control with risk of future abuse has been a difficult endeavour for physicians as well as patients. This topic was chosen to investigate the possibility of a potent pain medication without addictive properties as an alternative to traditional mu opioids. Surely, this would be a major instrument in the treatment of chronic pain. This study will be done under the hypothesis that kappa agonists are effective in management of pain and opioid addiction. Methods A search was performed for published literature on PubMed. Search terms were selected to assess analgesic properties and anti-addiction properties of kappa agonists on opiate use (Table 1). The search terms used included: pain, chronic pain, kappa opioid, kappa agonist, pain control, anti-nociception, withdrawal, dependence, addiction, and tolerance. This study looked at articles in English published between December 2006 and December 2016. Articles of all levels of evidence were considered and included review, preclinical, and clinical data. The initial search produced 574 results. These resources were then screened with the following exclusion criteria: articles not involving kappa agonists/receptors, articles on opioids without kappa receptor selectivity, articles on opioids with dual agonist activity, articles on kappa agonist interaction with drugs that were not analgesics. Abstract reviews of the remaining articles were performed to select for articles on analgesic efficacy or anti-addictive properties of selective kappa agonists. The resulting collection of evidence was organized into an evidence table (Appendix). Table 1-Keyword Search Strategy Population Intervention Comparison Outcome Pain OR Chronic Pain Kappa opioid OR Kappa agonist Analgesia OR Analgesic OR Pain control OR Antinociception OR Anti-nociception OR Withdrawal OR Dependence OR Addiction OR Tolerance Results A final total of 11 articles were included in this study, the majority being animal studies on mice or rats. One study involved rhesus monkeys. There was one study that involved a human clinical trial. Also, there was one review using human clinical trials focused only on peripherally selective kappa agonists. Table 2-Summary of Study Designs Reviewed Study Design # of Studies Animal Models 9 Clinical Trials 1 Review 1 Analgesic Efficacy An animal study by Auh and Ro (2012) induced inflammation in rat hindpaws with injections of complete Freunds adjuvant. After 3 days, when mechanical hyperalgesia was well developed, local injections of kappa agonist U50488 were given at different doses and mechanical threshold for hindpaw withdraw response was measured. The results showed dose-dependent increase in mechanical threshold by local injections of U50488 (Auh Ro, 2012). A time effect was also observed where increasing doses of U50488 prolonged the anti-hyperalgesia effect. The role of kappa opioids in inflammatory pain was also studied by Moon et al. (2016) in a research on the effects of peripheral kappa opioid receptors and arthritic pain. Arthritis was induced in rats using 1% ÃŽÂ »-carrageenan injected into the knee. After nociceptive behaviour was maximally expressed (reduced weight-bearing in ipsilateral joint), U50488 was injected into affected joints. A two-way repeated-measure ANOVA showed significant recovery of reduced weight-bearing in the affected limb in comparison to saline. In addition to inhibited nociceptive behaviour, U50488 was also found to reduce mechanosensitive afferent nerve fibre activity in the carrageenan-induced inflamed knee using nerve recording techniques. Aside from inflammatory pain relief by U50488, the peripheral kappa opioid CR665 was found to significantly increase pain threshold to esophageal distension in a study by Arendt-Nielsen et al. (2009). This randomized, double blinded, controlled study compared the effects of CR665 against oxycodone on skin, muscle, and visceral pain stimulation in healthy males. Although CR665 increased pain threshold to esophageal distension, oxycodone had the same effect with addition to increased pain threshold to cutaneous pinch pain, cuff pressure pain, and thermal stimulation. A number of other clinical trials, on peripheral kappa agonist CR845, were reviewed by Albert-Vartanian et al. (2016). A randomized, double-blinded, placebo-controlled study was conducted on elective hysterectomy patients for analgesic efficacy before and after the procedure, using a 10 cm visual analog scale for measurement of pain intensity. If pain persisted after 24 hours, rescue medication (IV morphine) was given. Significant differences were observed in comparison to patients who only received placebo. Less use of rescue medication as well as a 2-fold decrease in pain intensity was found in patients that received CR845 before and after the surgery. Albert-Vartanian et al. (2016) also discussed a phase 2, randomized, double-blinded, placebo-controlled clinical trial in patients electing bunionectomy surgery with fentanyl as rescue medication. Over a 48 hour period, pain was measured regularly using a visual analog scale. The study used a sum of pain intensity difference from baseline levels over 24 hours (SPID ­0-24) as a measurement for efficacy along with SPID0-36 and SPID0-48. In patients who completed the study, there was a statistically significant reduction in SPID0-24 and SPID0-48 in those treated with CR845 compared to placebo. However, there was no significant difference in the modified intent-to-treat group. In another phase 2 trial, patients with moderate to severe osteoarthritis pain (>4 out of an 11 point scale) were given an oral form of CR845 with acetaminophen as a rescue drug over 2 weeks (Albert-Vartanian, 2016). A dose-dependent reduction in average pain score of 25-34% was observed. Among patients receiving the highest dose of CR845, 50% had a reduction of †°Ã‚ ¥30% in their reported pain score at the end of the 2 weeks with an 80% reduction in requirement for acetaminophen. Analgesic Efficacy with Other Measures of Pain Aside from sensory components of pain, there are affective and behavioural components of pain as well. An electrophysiological experiment conducted by Huge, Rammes, Beyer, Zieglgansberger, Azad (2009) looked at the effects of kappa opioid receptors activation on mice basolateral amygdala, an area of the brain that is involved in pain processing and pain memory formation. The field potential amplitudes were measured at baseline and under induced long-term potentiation using high frequency stimulation and the effects of kappa agonist U50488H were studied.   The experiment found that U50488H decreased baseline levels of field potential amplitude as seen in Figure 1, while these effects were inhibited by kappa receptor antagonist norbinaltorphimine (nor-BNI). Figure 1. Effects of Kappa Agonist and Antagonist on Field Potential Amplitude of Mice Amygdala. Baseline (BL): 100 ±0.5%; U50488H: 86.3 ±2.4%, nor-BNI: 100 ±4.2%. Data points show average field potential (FP)  ± Standard Error. Reproduced from Huge et al., 2009, p. 125. Prior application of U50488H before high frequency stimulation was also found to inhibit induction of long term potentiation (Figure 2) in comparison to long term potentiation induction with no drug (Figure 3). Figure 2. Effect of Kappa Agonist Pre-treatment on High Frequency Stimulated Long Term Potentiation of Mice Amygdala. U50488H: 100 ±4.1%; High Frequency Stimulation (HFS): 102.6 ±7%. Data points show average field potential (FP)  ± Standard Error. Reproduced from Huge et al., 2009, p. 126. Figure 3. Long Term Potentiation Produced by High Frequency Stimulation. Baseline (BL): 100 ±2%, High Frequency Stimulation (HFS): 119 ±4%. Data points show average field potential (FP)  ± Standard Error. Reproduced from Huge et al., 2009, p. 126. Although pain-stimulated behaviours are often used as a measure of pain, such as a withdrawal or writhing response, complementary measures are behaviours that diminish in the presence of pain stimuli (Negus, OConnell, Morrissey, Cheng Rice, 2011, p. 506-507). An experiment by Negus et al. (2011) studied the effects of peripheral and central kappa agonists compared to ketoprofen on rats trained to evoke intracranial self-stimulation using a lever, a behaviour that is depressed by pain. Intraperitoneal lactic acid injection acted as a pain-inducing stimulus, with a stretch response being a pain-stimulated behaviour to contrast with the pain-depressed behaviour of intracranial self-stimulation. It was found that the central kappa agonist (salvinorin A), peripheral kappa agonists (ffir and ICI204448), and ketoprofen all inhibited lactic acid induced stretching. However, only ketoprofen inhibited lactic acid induced depression of intracranial self-stimulation. Salvinorin A had actually i ncreased depression of intracranial self-stimulation while ffir and ICI204448 had no appreciable effect. Similar results were found when Negus et al. used depression of nesting in mice as a measure of pain (2015). Kappa agonist U69593 failed to both inhibit and reverse depression of nesting induced by intraperitoneal lactic acid and intraplantar complete Freunds adjuvant (Figure 4A 4B). However, 1-way ANOVA analysis (pFigure 4A 4B). U69593 was shown to actually depress nesting when administered independently (Figure 4C) and this effect was not able to be reversed by neither ketoprofen nor morphine (Figure 4D). Figure 4. Effects of Ketoprofen, Morphine, and U69593 on Nesting under Different Conditions. Panel A: Nesting depressed by intraperitoneal administration of 0.32% lactic acid. Panel B: Nesting depressed by intraplantar administration of complete Freunds adjuvant. Panel C: Nesting under no treatment. Panel D: Nesting depressed by U69593. Nesting represented as the number of zones cleared of nesting material. V represents drug vehicle only. Darkened points represent significant difference from drug vehicle under given condition. Reproduced from Negus et al., 2015, p. 18.       Interactions with Mu Opioids There is evidence suggesting kappa agonists have anti-addictive effects (Lalanne et al., 2014). However, it is important to evaluate the effects of kappa opioids in concurrent use with mu opioids. A study on interactions of fentanyl and U69593 in rhesus monkeys showed a decrease in the rate of drug self-administration when the kappa agonist was added to fentanyl compared to fentanyl alone (Negus, Schrode Stevenson, 2008). This effect increased with greater proportions of U69593 in the mixture (Figure 5). Using a conditioned response for food as a measurement for activity, both fentanyl and U69593 alone depressed the behaviour while mixtures showed a less than additive effect. Furthermore, at the lowest proportion tested (0.22:1 U69593/fentanyl), U69593 reduced the behaviour depressing effects of fentanyl. Figure 5. Rate of Self-Administration of Fentanyl vs. Dose of Fentanyl, U69593, or Mixture. Reproduced from Negus et al., 2008. Negus et al. also demonstrated additive thermal anti-nociception, using tail withdrawal threshold from heated water, with the fentanyl/U69593 mixtures at all proportions tested (2008). More evidence of additive effects of kappa and mu opioids was shown by Sakakihara, Imamachi, Saito using a similar method in mice (2016). Intrathecal injection of kappa agonist TRK-820 combined with morphine resulted in a stronger anti-nociceptive effect compared to morphine alone. Compared to morphine alone, kappa agonists also have benefits regarding the development of tolerance. It is well known that repeated use of mu opioids quickly develops tolerance. The addition of a kappa agonist has been shown to inhibit the development of tolerance to morphine (Hamabe, Yamane, Harada Tokuyama, 2008). Mice treated daily with subcutaneous morphine for 5 days developed reduced analgesia from morphine from days 3 to 5. However, daily administration of kappa agonist U50488H 5 minutes after injection of morphine attenuated the onset of tolerance (Figure 6). Additionally, pre-treatment of kappa receptor antagonist nor-BNI inhibited the tolerance-blocking activity of U50488H. Figure 6. Effect of Kappa Agonist U50488H on Morphine Tolerance. Each point show means  ± standard error. AUC: Area under curve. #: P Although U50488H inhibited the development of tolerance it was unable to inhibit morphine withdrawal (Tao et al., 2008). However, Tao et al. demonstrated that another kappa agonist, LPK-26, may be able to. Chronic doses of morphine, kappa agonist (LPK-26 or U50488H), or both were administered to mice over 5 days and induction of withdrawal was achieved by subcutaneous injection of naloxone 2 hours after the final dose of morphine. Chronic treatment with LPK-26 did not produce a withdrawal response. However, chronic treatment with morphine produced a strong withdrawal response in the form of withdrawal jumping. Furthermore, chronic treatment with morphine along with pre-treatment with LPK-26 had a significant reduction in withdrawal response in a dose dependent manner (Figure 7A). Body weight was also measured before and after naloxone withdrawal induction (Figure 7B). Only LPK-26 showed significant reduction of morphine-induced weight loss. Figure 7. Effects of LPK-26 and U50488H on Withdrawal Jumping and Weight Loss. Data set shown as mean  ± standard error. Reproduced from Tao et al., 2008, p.310. Discussion Analgesic Efficacy of Kappa Opioids Side effects of selective kappa agonists mainly stem from its activity in the central nervous system. These side effects are the main hindrance for pharmacologic use of kappa opioids and include dizziness, dysphoria, confusion, sedation, hallucinations, diuresis, and even psychotic symptoms at high doses (Walsh, Strain, Abreu, Bigelow, 2001). Strategies to minimize these unwanted effects revolve around limiting the activity of kappa agonists to peripheral sites of action. Local injections have been shown to reduce inflammatory pain in animal models through reduced activity of afferent nerve fibres (Auh Ro, 2012; Moon et al., 2016). Although the analgesic results mentioned were limited to animal models, in humans, intravenous administration of peripherally selective formulation CR665 also shows evidence of analgesia for visceral and surgical pain (Arendt-Nielsen et al., 2009; Albert-Vartanian et al., 2016). Furthermore, oral formulations CR665 have been shown to reduce inflammatory osteoarthritic pain in humans (Albert-Vartanian et al., 2016). Continued pain treatment is required if kappa opioids are to be considered as an alternative to mu opioids and research shows viability of kappa opioids in different formulations and routes of administration for the treatment of pain in traditional measures. The components of pain include affective elements as well, which is especially important in chronic pain. Pain affect is comprised of the unpleasant emotions associated with pain as well the emotions towards future implications of having chronic pain. The latter is based on reflections of pain memory and is known as secondary pain affect. As a consequence, chronic pain states can lead to depression and anxiety, which lowers well-being and quality of life (Price, 2000). The amygdala is a crucial structure in the brain involved in emotional learning, pain processing, and constructing of pain memories (Huge et al., 2009). Kappa opioids are able to reduce the activity and inhibit long-term potentiation in the basolateral amygdala. As long-term potentiation is considered a cellular model for learning and memory formation, kappa opioids may be able to prevent or extinguish pain memory and treat affective components of pain. However, this experiment, at the moment, is limited to mice and fu rther study is required to assess whether the results can be translated to human.   Furthermore, these results may be due to structurally specific central actions on the amygdala as other studies show evidence of dysphoric effects from central kappa opioid receptor activation (Lalanne et al., 2014). Although kappa agonists have regularly been shown to provide analgesia in assays using pain-stimulated behaviours as measurements of pain, there is contrast when pain-depressed behaviours are observed instead. Pain-depressed behaviours are behaviours that are decreased due to pain. Some examples that have been tested in animal models are feeding, movement, and reinforced behaviours. In humans, it is analogous to mood or functionality. When pain-depressed behaviours are studied, not only do centrally active kappa agonists fail to relieve pain of this aspect, they may worsen it (Negus et al., 2012; Negus et al., 2015). It should be noted that peripherally active kappa agonists relieve pain in pain-stimulated assays without affecting pain in pain-depressed assays and may be safer than centrally active kappa agonists (Negus et al., 2011). In comparison to kappa opioids, conventional analgesics such as mu opioids and nonsteroidal anti-inflammatory drugs do relieve such components of pain in addition to pain-stimulated behaviours (Negus et al., 2011; Negus et al., 2015). Even so, kappa agonist still have value as they have been shown to reduce pain in human trials as discussed previously. The studies on pain-depressed behaviours have limitations to animal models and further studies are needed to understand how clinically relevant the effects may be for humans. Managing Addiction Some of the major problems of using mu opioids for pain control are the development of tolerance, dependence, and drug abuse, which may all contribute to addiction. Although there are many other drugs that also relieve pain, the difficulty lies in managing addiction at the same time. Kappa agonists, aside from having low abuse potential, have been shown to decrease self-administration of fentanyl in animal models (Negus et al., 2008). These results are promising evidence for kappa agonists being agents to prevent opioid abuse. Also, kappa agonists have additive analgesic effects with mu opioids (Negus et al., 2008; Sakakihara et al., 2016). This possibly reduces the amount of mu opioid required for effective pain management while also reducing addiction and abuse liability due to less use. Increased usage of mu opioids may be due to the development of tolerance, requiring increased dosage to maintain analgesia. The high addictive potential of mu opioids makes this a concerning issue. However, addition of kappa agonists during administration of mu opioids may be able to significantly inhibit the development of tolerance (Hamabe et al., 2008). It may be possible to prevent the development of physical dependence and addiction to mu opioids by adding kappa agonists to drug regimens of chronic pain patients. As for those who are already affected by physical dependence on mu opioids, there is evidence that kappa opioids can inhibit withdrawal symptoms and reduce dependence (Tao et al., 2008). However, some kappa agonists, such as U50488H, do not have any significant effect. It has been suggested that the inconsistency may be due to varying affinities for different subtypes of kappa opioid receptors. Nonetheless, this study demonstrates potential for kappa agonists in managing opioid addiction through modulating dependence and withdrawal. Future studies may provide better understanding on subtype functions and improve designs for desired effects while minimize side effects. Also, as the studies regarding kappa agonist interaction with mu opioids are mainly done on animal models, further investigation is required to see whether results can be extended to humans. One important point to distinguish is non-selective versus peripherally selective kappa agonists. As mentioned previously, activation of kappa receptors in the central nervous system can lead to many side effects. Peripherally selective kappa agonists still produces analgesia, but it is uncertain whether the effects of the kappa agonists on abuse, tolerance, and dependence are due to central or peripheral activity. If these effects are due to central activity, the benefits of kappa agonists for addiction management will be limited by their undesired side effects. Still, in a study involving a peripherally selective kappa agonist and its effects on nicotine, there is some evidence suggesting that activation of peripheral kappa receptors do inhibit symptoms of withdrawal and dependence by inhibiting activity of central kappa receptors. Conclusion In conclusion, this study found that selective kappa agonists provide analgesia to inflammatory, visceral, and surgical pain. In contrast, they were not effective inhibitors of behaviour-depressing effects of pain. Specific activities of kappa receptors in the basolateral amygdala, however, may inhibit affective components of pain.   In managing addiction, kappa agonists may able to prevent mu opioid abuse, prevent the development of tolerance, inhibit the symptoms of withdrawal, and reduce physical dependence. The additive effect with mu opioids and the inhibition of tolerance development can reduce the required amount of mu opioids for effective analgesia, thus reducing abuse and addiction likelihood. Overall, selective kappa agonists are a good prospect for managing pain while combating opioid abuse and addiction. Appendix Evidence Table First Author Date of Publication Study Design Level of Evidence Study Population Therapy or Exposure Outcome/Results Albert-Vartanian 2016 Review 1 Human CR845 CR845 reduced pain with less abuse potential Arendt-Nielsen 2009 Clinical trial 1 Healthy males CR665, Oxycodone CR665 is effective on visceral pain Auh 2012 Animal model 0 Rats U-50488 Local kappa agonist attenuated inflammatory mechanical hyperalgesia Hamabe 2008 Animal model 0 Mice Morphine, U-50488H Analgesic tolerance to morphine is prevented by U-50488H through suppression of PKC Huge 2009 Animal model 0 Mice U-50488H Activation of kappa receptors decrease synaptic transmission and long term potentiation in the amygdala Moon 2016 Animal model 0 Rats U-50488, Nor-BNI U-50488 inhibits nociception in arthritic knee joints of rats Negus 2008 Animal Model 0 Rhesus Monkey Fentanyl, U69593 Addition of kappa agonist to fentanyl demonstrated additive anti-nociception and decreased drug self administration Negus 2011 Animal Model 0 Rats Ffir, ICI204448, Salvinorin A Kappa agonists do not inhibit pain-depressed behaviours Negus 2015 Animal model 0 Mice Morphine, Ketoprofen, U69593 Morphine/Ketoprofen inhibited pain-depressed behaviours whereas U69593 failed to do so Sakakihara 2016 Animal Model 0 Mice Morphine, TRK-820, Nor-BNI Addition of kappa agonist to morphine may have additive anti-nociceptive effects Tao 2008 Animal Model 0 Mice Morphine, LPK-26, U50488H LPK-26 is a potent analgesic with low dependence and inhibits morphine withdrawal

Eamon De Valera :: essays research papers fc

Eamon de Valera, although born in New York City, in the United States of America, devoted his life to help the people of Ireland. As he once said it, â€Å"If I wish to know what the Irish want, I look into my own heart.† De Valera loved Ireland and its people with a deep and lasting passion. It was he, probably more than any other person in their history, who helped that country win freedom from British rule and then shaped its history well into the twentieth century.   Ã‚  Ã‚  Ã‚  Ã‚  De Valera’s mother, Catherine Coll, usually known as Kate, came to the states in 1879, at the young age of twenty-three. Like so many other Irish immigrants of that time, she had suffered from poverty, and even hunger, in her native land and saw America as a place where she could go to try and get a fresh start. She first took a job with a wealthy French family that was living in Manhattan. This is where and when she met Vivion Juan de Valera. He was a Spanish sculptor who came to the home of her employers to give music lessons to the children.   Ã‚  Ã‚  Ã‚  Ã‚  In 1881, the couple married. A little over a year later, while living at 61 east 41st Street, Kate Coll de Valera gave birth to the couple’s only child. His name was Edward, called by Eddie at first, but would become known to the world by the Irish variation of that name, Eamon.   Ã‚  Ã‚  Ã‚  Ã‚  Always in poor health, Vivion de Valera left his young family behind him and traveled to Colorado, hoping that perhaps the healthier air would help him out. Within a few months he died. Now a widow, Kate went back to work, leaving Eamon in the care of another woman who also had come from the tiny village of Bruree, in County Limerick. Later in his life, Eamon would remember occasional visits from, as he knew her, a woman in black, which ended up being his true mother. Kate de Valera decided that Eamon would be better cared for by her family back in Ireland. Before long he found himself away from noise of Manhattan, living in Bruree in a one-room house with mud walls and a thatched roof. Living with him were his grandmother, his twenty-one-year-old uncle, Pat, and young Hannie, his fifteen-year-old aunt. Shortly after Eamon arrived, the family moved to a cottage, built by the Irish government for farm workers, but it was only a little bit larger.

People v. Sisuphan Essay

Appellant Lou Surivan Sisuphan took $22,600 in cash and $7,275.51 from (Toyota Marin [the dealership] defendant) his employer’s safe on July 3, 2007. He did this in hopes that a coworker would be held responsible for the disappearance of the money and would be terminated. Sisuphan was convicted of embezzlement on April 15, 2008. In June 2008 he appeals from the judgment of conviction, contending that the trial court made a mistake when it failed to instruct the jury that at the time he took the money, he intended to return it before criminal charges were filed. He also states that the trial court excluded evidence on that he restored the money to the company, claiming this evidence proved he never intended to keep it and therefore lacked the requisite intent for the crime. Issue â€Å"The question, before us, therefore, is whether evidence that Sisuphan returned the money reasonably tends to prove he lacked the requisite intent at the time of the taking.† Was his the Fifth Amendment right to present defense and â€Å"all pertinent evidence of significance value to that defense† violated? Rule of Law The Fifth Amendment right to present defense and â€Å"all pertinent evidence of significant value to that defense† was not violated because the â€Å"return of the property is not a defense to embezzlement. Fraudulent intent is an essential element of embezzlement. Although restoration of the property is not a defense, evidence of repayment may be relevant to the extent it shows that a defendant’s intent at the time of the taking was not fraudulent.† Analysis Since Martin Sisuphan was authorized to manage the financing contracts and obtain payments from lenders on behalf of the defendant the lawsuit was effective. It does not matter that there was no intent of stealing the money because Section 508 (of the California Penal Code) states: â€Å"Every clerk, agent, or servant of any person who fraudulently appropriates to his own  use, or secretes with a fraudulent intent to appropriate to his own use, any property of another which has come into his control or care by virtue of his employment is guilty of embezzlement.† Holding The issue is that Susuiphan intended to use the money for a purpose other than to which the dealership entrusted it to him, therefore the evidence that he returned the money before criminal charges were filed is irrelevant. The judgment is affirmed. Plaintiff was sentenced to 120 days in custody and 3 years of probation.

Assassination Of JFK essays

Assassination Of JFK essays When I first approached the topic of the death of John F. Kennedy, one of our countrys most famous presidents a lot of questions came to mind, one of them being, was Oswald the only man involved? Or was his death one big conspiracy? That was the question I intended to answer. On our first day of research I went online and simply typed in the assassination of JFK and was amazed on the results I received. Well over twenty sites were related to the assassination and the conspiracy of Kennedys death. As I continued to research, I found a website containing some interesting documents on the detail of events leading up to the assassination. I also found pictures and diagrams showing the area, which is called Dealey Plaza, where the shooting actually took place. These pictures really interested me and helped me get more involved with the research and helped me make my own predictions on the course of events. I must have obtained over twenty pages of information on that one day alone. That night I sat down and read over everything at least twice to get a clear depiction on what happened since there were so many accounts and opinions of what and how it happened. This is a general overview of what happened that day. On November 22, 1963 John F. Kennedy arrived at Dallas, Texas around 11:45am, on his electoral battle tour of the southern states. By all accounts the people at the airport welcomed him positively. Governor John Connally, his wife and Jackie Kennedy, accompanied him to the limousine, which led the motorcade through the town. When the motorcade arrived at the Dealey Plaza at 12:30 it turned right from Main Street to Houston Street, then turned onto Elm passing the Schoolbook Depository Building. As the motorcade headed down Elm three gunshots rang out (the exact number was never determined but evidence showed three shots, possibly four) and everyone standing on the street ducked down for cover. Kenne...

Free Essays on Summary Of Elisabeth Kubler-Ross’s

Death: The Final Stage of Growth. Summary What could possible define quality of death? Death and dying are often perceived as the antithesis of quality of life, completely opposed to overarching philosophies of health consciousness, that focus on tapping every possible resource to prolong healthy, active living, and which accepts death as a last resort, whose destination must be cloaked with as much pharmacology (both literal and figurative) as possible, in order to obtund and dull its links with suffering. Death therefore seems to resemble a dark and ominous cave. To transform such attitudes to accept death as a natural process, and to consider entry into this territory as a quality, empowering experience seems a tremendous challenge, yet this is exactly the task that psychiatrist/author Elisabeth Kubler-Ross achieves in her book Death: The Final Stage of Growth. Through multiple experiential and cultural lenses, Kubler-Ross exposes the fears that shape human perspectives of death, and simultaneously reveals new hopefulness through a model that embraces death as the epitome of human opportunity for transformation and growth. Death comes to us all. Yet as Kubler-Ross observes in her introduction to this work, acceptance of death does not come to as many as it should. All at its door seem to find tremendous fear, anxiety and revulsion at the entrance to this cave. Clearly, the general conditions of death have remained constant throughout time, though perhaps they are better documented and empirically validated today than they were in ancient history. An anonymous student nurse, enduring the end-stage of terminal illness, found himself in a unique position to comment on the institutionalization of death as it existed in 1975, as he revealed it to Kubler-Ross in Death: The Final Stage of Growth: Nursing must be advancing. I wish it would hurry. We’re taught not to be overly cheery now, to omit the ‘Everything’s fine,’ rou... Free Essays on Summary Of Elisabeth Kubler-Ross’s Free Essays on Summary Of Elisabeth Kubler-Ross’s Death: The Final Stage of Growth. Summary What could possible define quality of death? Death and dying are often perceived as the antithesis of quality of life, completely opposed to overarching philosophies of health consciousness, that focus on tapping every possible resource to prolong healthy, active living, and which accepts death as a last resort, whose destination must be cloaked with as much pharmacology (both literal and figurative) as possible, in order to obtund and dull its links with suffering. Death therefore seems to resemble a dark and ominous cave. To transform such attitudes to accept death as a natural process, and to consider entry into this territory as a quality, empowering experience seems a tremendous challenge, yet this is exactly the task that psychiatrist/author Elisabeth Kubler-Ross achieves in her book Death: The Final Stage of Growth. Through multiple experiential and cultural lenses, Kubler-Ross exposes the fears that shape human perspectives of death, and simultaneously reveals new hopefulness through a model that embraces death as the epitome of human opportunity for transformation and growth. Death comes to us all. Yet as Kubler-Ross observes in her introduction to this work, acceptance of death does not come to as many as it should. All at its door seem to find tremendous fear, anxiety and revulsion at the entrance to this cave. Clearly, the general conditions of death have remained constant throughout time, though perhaps they are better documented and empirically validated today than they were in ancient history. An anonymous student nurse, enduring the end-stage of terminal illness, found himself in a unique position to comment on the institutionalization of death as it existed in 1975, as he revealed it to Kubler-Ross in Death: The Final Stage of Growth: Nursing must be advancing. I wish it would hurry. We’re taught not to be overly cheery now, to omit the ‘Everything’s fine,’ rou...

Biology Article Example | Topics and Well Written Essays - 500 words - 1

Biology - Article Example The study of microbiology also highlights the problems with regard to the biodegrading of toxic and other minerals present in the environment that are harmful to the plants, animals, apart from human beings. While biotechnology seeks to solve the problems faced in medicine, agriculture etc., and the microbiology is its branch that helps in the identification of the virus or fungie responsible for such problems. The study of microbes helps us to study the reactions that occur in higher organisms. Therefore, while studying the molecular level genetic engineering, the contribution of microbes in research for biochemical and molecular genetics has been increasing remarkably....(microbiology) This pertains to the study of cells and the method of interaction of cellular components that are responsible to promote life processes. While the study of this topic would include the synthesizing of DNA and RNA, it also helps in the research to find the mechanism for differentiation of a single-celled egg into a complex multi-cellular organism. For studying the concepts of biotechnology or genetic engineering, the detailed knowledge of cell and molecular biology is very important. The biologists concerned with this relevant topic use its results and findings to study the principals of protein synthesis, enzymology, organelle structure and function and cell ultra-structure, among other areas. Speaking in simpler terms the molecular biology is the science that transcribes the genetic material into RNA and then translates it into protein, as this helps us to know the mysteries surrounding this field in a better manner. As most of the work in microbiology can be quantified, we are now witnessing the off-shoot of this in bioinformatics and computational biology as some call these as the interface of this particular topic and the computers....(molecular) Biological techniques have been taken to such heights that

Experience Assignment Essay Example | Topics and Well Written Essays - 1250 words

Experience Assignment - Essay Example Since the far-reaching economic reforms from the late 1960s, growth has fuelled a remarkable increase in per capita income and at the same time, however, income disparities have increased. The growing income inequality is illustrated clearly by the living standards between the urban and the rural areas. The last three decades have seen unprecedented progress when it comes to reducing extreme poverty around the world, but there is still an awful lot more to be done. However, as the World Bank still points out, there are still roughly 1.3 billion people completely destitute, including about 400 million children. People around the world in â€Å"extreme poverty† tend to lack enough food to meet basic physical and mental needs. Judging from the daily incomes of the extremely poor around the world, extreme poverty is getting less deep. Poverty for middle and high income countries fell more than 50 percent since 1982. When one looks closely st the recent progress in the developing world, much of it is mostly attributed to countries like China, and to a lesser extent, India, whose amped up economic growth in recent years reduced their poverty rates. By contrast, extreme poverty in the 35 â€Å"low-income† countries fell by less than 33 percent. Aside from China and India, In dividuals living in extreme poverty in the developing world, today appear to be as poor as those living in extreme poverty thirty years ago, as the World bank puts it. Instead of asking myself which car should I buy, or what clothes should I wear or which different restaurant should I visit next, living on less than t $5 forces one to really have a tight budget as you cannot afford the luxuries that some of us do take for granted at times. When money is tight, we have to make whatever we have to stretch and lesser money means smaller, simpler meals. In this day and era, it is impossible to live without a