Walt Disney Company’s Yen Financing Case Essay - 4601 Words

Introduction: The Walt Disney Company is the largest media conglomerate in the world and is headquartered in Burbank, California, USA. It was established by Walt and Roy Disney in 1923. Since its inception, Disney has grown vastly so that operational areas now include theme parks, motion pictures, television dramas and consumer products. In 1955, the most charming place in the world was ‘Disneyland’ was open for the public. The idea was to create a magical place for the whole family. Ever since then, Disneyland theme parks have been growing and today Walt Disney Company owns 14 theme parks in the world. In Film Industry, Disney mainly focused on children; however the films produced by Disney under touchstone label were focused†¦show more content†¦And the ratio of debt to total capitalization jumped from 20% to 43%. Japanese Royalties Situation With the opening of Tokyo Disneyland in April 1983 and the inflow of yen royalty receipts, the Walt Disney want to increase the assets and decrease debt, they realized they had an opportunity to use the yen royalties from Japan to pay down some of their debt: * In 1984 the average exchange rate is 347.30 JPY/US$ * The royalties of Disneyland Tokyo of JPY 8 billion was equivalent to US $ 33,712,600 * This represents 11.58% (=33,712,600 / 291,033,000) of 1984 operating income before corporate expenses, a percentage which is more common to grow, since Disney itself will probably not grow as rapidly as its JPY royalties * In Figure 5, only 21.47% of all debts has a maturity greater than 2 years * The JPY has also depreciated to disrupt Disney’s financial plan for its large, long-term construction, expansion, production, and development. * Disney transferred Yen to USD from the 2nd quarter of 1984 through the first quarter of 1985, because the JPY recei pts are a huge amount of money. * However, it has appreciated in the quarter since then. Issues: TheShow MoreRelatedThe Walt Disney Companys Yen Financing, Harvard Case Study1352 Words   |  6 Pagesthat it becomes more expensive to buy  ¥ and more expensive to buy the foreign import. Risk can work both ways: if the ex-rate is 125 ¥ / $ (dollar appreciates, Yen depreciates) in 6 months, the cost is only $800. In this case, the dollar got stronger, so it became cheaper to buy Yen, and the foreign product (priced in a fixed amount of Yen) became cheaper. Ex-rate volatility (currency risk) means the cost of parts could range between $800-1250 over the next 6 months for the U.S. manufacturer. ImagineRead MoreWalt disney companys yen financing1838 Words   |  8 PagesCASE STUDY THE WALT DISNEY COMPANYS YEN FINANCING Alexandra Molnà ¡r Laure Vigneron Manuel Aguilee Pimprapai Lertamornkitti Pranav Goyal EXECUTIVE SUMMARY Walt Disney, an American leisure and entertainment company, receives royalty payment from Tokyo Disneyland every year. The royalties were denominated in yen and were constantly growing and becoming significant for the company (8 billion Yen in 1984, with 10-20% projected growth). However, the depreciation of the yen against the dollar couldRead MoreWalt Disney Case2290 Words   |  10 PagesThe Walt Disney Company’s Yen Financing International Financial Economics Universiteit van Amsterdam Question 1 Should Walt Disney Company hedge its yen exposure? Why? On April 1983 Tokyo Disneyland started to operate. The Japanese company that operated this park paid royalties on certain revenues to Walt Disney Productions. The Yen royalties receipts in 1984 already reached a height of 8 billion Yen. The director of finance of the Walt Disney Company expected a further growth of 10% toRead MoreAccounting 1-4 Chapter100452 Words   |  402 Pagesknow how to read financial statements, you can’t really know your business. 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In some cases, other firms may acquire the firm if they observe the firm is underperforming (market discipline). III. Clients of the financial system 1. Household sector: a. Tax concerns: people in different tax brackets need different financial assets with Read MoreContemporary Issues in Management Accounting211377 Words   |  846 Pagesfrom a UK perspective Robert W. Scapens 16. Strategic cost management: upsizing, downsizing, and right(?) sizing John K. Shank 17. Environmental management accounting Kazbi Soonawalla 18. Organization control and management accounting in context: a case study of the US motion picture industry S. Mark Young, Wim A. Van der Stede, and James J. 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string(132) " potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours\." Dementia Dementia  has become an all-important  disease  because the population is aging rapidly and the cost of health care associated with  dementia  is ever increasing. In addition to cognitive function impairment, associated behavioral and psychological symptoms of  dementia  (BPSD) worsen patient’s quality of life and increase caregiver’s burden. Alzheimer’s  disease  is the most common type of  dementia  and both behavioral disturbance and cognitive impairment of  Alzheimer’s  disease  are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline in  Alzheimer’s  disease. We will write a custom essay sample on Dementia or any similar topic only for you Order Now We  reviewthe literature regarding  dementia  (especially  Alzheimer’s  disease), BPSD and relevant findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine. Literatures suggest that behavioral disturbance and cognitive impairment of  Alzheimer’s  disease  may be associated with excitatory neurotoxic effects which result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition, function, agitation/aggression and delusion in  Alzheimer’s  disease. On the other hand, some NMDA modulators which enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic symptoms. We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological symptoms of  Alzheimer’s  disease. Prospective study using NMDA enhancers in patients with  Alzheimer’sdisease  and associated behavioral disturbance is needed to verify this hypothesis. Mental disorders constitute a huge social and economic burden for health care systems worldwide [1], raising the question of effective and lasting treatments. Physical activity (PA) and exercise (EX) continue to gain the attention of practitioners and researchers with regard to prevention and treatment of different psychopathological abnormalities. In the general population, several epidemiological studies have found significant cross-sectional correlations between mental health and PA levels. In an adult US population, regular PA is associated with a significantly decreased prevalence of current major depression, panic disorder, agoraphobia, social phobia, and specific phobia [2]. A study from Norway confirmed this negative cross-sectional association between depression and leisure-time PA of any intensity (not work-related PA), and pointed out that social factors such as social support, rather than biological markers, play an important role [3]. Recently, a Dutch study replicated this finding, reporting lower rates of any affective, anxiety, or substance use disorder in subjects who exercised at least 1 h/wk, without finding a linear dose-response relationship [4]. Prospectively, the overall incidence of mental disorders and co-morbid mental disorders, as well as the incidence of anxiety, somatoform, and dysthymic disorder, decreases by PA [5]. Furthermore, a four-year prospective study revealed that PA decreases the incidence rates of depressive and anxiety disorders in older adults [6]. Finally, ten Have et al. reported in their epidemiological study that patients engaging in regular PA were more likely to recover from their mental illness at a three-year follow-up In psychiatric patients, different mechanisms of action for PA and EX have been discussed: On a neurochemical and physiological level, a number of acute changes occur during and following bouts of EX, and several long-term adaptations are related to regular EX training. For instance, EX has been found to normalize reduced levels of brain-derived neurotrophic factor (BDNF) and therefore has neuroprotective or even neurotrophic effects [7-9]. Animal studies found EX-induced changes in different neurotransmitters such as serotonin and endorphins [10,11], which relate to mood, and positive effects of EX on stress reactivity (e. g. , the hypothalamus-pituitary-adrenal axis [12,13]). Finally, anxiolytic effects of EX mediated by atrial natriuretic peptide have been reported [14]. Potential psychological mechanisms of action include learning and extinction, changes in body scheme and health attitudes/behaviors, social reinforcement, experience of mastery, shift of external to more internal locus of control, improved coping strategies, or simple distraction Several prospective studies have found that a high level of PA seems to delay the onset of dementia (see [74] for a review). Since improvements in strength and endurance after training were found in cognitively impaired patients as well as healthy controls [75], PA interventions are generally feasible in this population. For Alzheimer’s disease (AD), preliminary evidence suggests that EX interventions may improve communication performance [78], Mini Mental State Examination scores and verbal fluency [79], and disruptive behavior [80]. Four studies [81-84] found that PA slowed down and partially reversed the decline in performance of activities of daily living and progression of the cognitive symptoms related to dementia, in contrast to an older study, which did not find improvements in functional ability [85]. Zschucke , E. and Gaudlitz, K. Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence Zschucke , E. and Gaudlitz, K. (2013) Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence. Journal of Preventative Medicine and Public Health  , 46 (1), p. 12-21. Available at: http://www. ncbi. nlm. nih. gov/pmc/articles/PMC3567313/ [Accessed: 6th Mar 13]. Leptin, an adipocytokine produced in the peripheral system as well as in the brain, is implicated in obesity, food intake, glucose homeostasis, and energy expenditure. Leptin expression levels and signaling pathways may also be linked to the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. Epidemiological studies have demonstrated that higher circulating leptin levels are associated with lower risk of dementia including Alzheimer’s disease, and lower circulating levels of leptin have been reported in patients with Alzheimer’s disease. Leptin receptors are highly expressed in the hippocampus, a brain area involved in learning and memory and severely affected during the course of Alzheimer’s disease. In laboratory studies, several in vivo and in vitro studies have shown that leptin supplementation decreases amyloid-? (A? ) production and tau phosphorylation, two major biochemical events that play a key role in the pathogenesis of Alzheimer’s disease. In this review, we will review the structure of leptin, the type of receptors of leptin in the brain, the various biological functions attributed to this adipocytokine, the signaling pathways that govern leptin actions, and the potential role of leptin in the pathophysiology of Alzheimer’s disease. Leptin exerts its functions by binding to the leptin receptor (ObR). This binding can involve several signaling pathways including JAK/STAT pathway, ERK pathway and the PI3K/Akt/mTOR Pathway. Modulation of these pathways leads to the regulation of a multitude of functions that define the intricate involvement of leptin in various physiological tasks. In this review, we will specifically relate the potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours. You read "Dementia" in category "Papers" All this work points to leptin as a possible target for developing supplementation therapies for reducing the progression of Alzheimer’s disease. Leptin is a 146 amino acid protein with a molecular weight of 16 kDa encoded by the  ob  gene and primarily, but not exclusively, expressed by the white adipose tissue (WAT) and is implicated in obesity, food intake, and energy homeostasis. Leptin protein was discovered by the molecular geneticist Jeffrey Friedman in 1994 at Rockefeller University and the work was published in a landmark  Nature  paper in December 1994 [1]. The human  ob  gene has been mapped to chromosome 7q31. 3 [2] and encodes a 4. 5 kb mRNA transcript that is translated into a 167 amino acid peptide and subsequently processed in the ER into the 146 amino acid mature leptin protein [1]. Antecedent to the discovery of the leptin protein and positional cloning of the  ob  gene in 1994, the  ob/ob  mouse characterized by hyperphagia and a marked obese phenotype was serendipitously discovered by animal caretakers in 1950 at Jackson Laboratories [3]. It was the general consensus that the  ob/ob  mouse possessed a mutation in the  obgene, but this was not elucidated and unequivocally established until the discovery of the leptin protein and mapping of the  ob  gene by Friedman and colleagues in 1994 who showed that the mutation resulted in the loss of leptin production. In 1966, the  db/db  mouse was discovered, again at Jackson Laboratories, which not only exhibited a similar hyperphagic, obese phenotype, but also hyperglycemia [4]. Tartaglia and colleagues in 1995 showed that the  db/db  mouse phenotype can be attributed to the mutation in the  db  gene that codes for the long-form of the leptin receptor obRb [5]. However, it was the seminal work of Doug Coleman and colleagues who demonstrated by a series of parabiosis experiments using  ob/ob  mice and  db/db  mice pairs and established that the  ob/ob  mice lacked a circulating factor whereas the  db/db  mice produced the circulating factor but were not able to respond to it [6,7]. The validity of these breakthroughs was affirmed by subsequent discovery of the leptin protein and cloning of the  ob  gene [1] as well as the cloning of the  db  gene which coded for the long-form leptin receptor obRb [5]. Further corroboration emanated from the finding that the  db  mice produced the truncated form of obRb that was incapable of transducing leptin-mediated intracellular signal transduction [8-12] and administration of exogenous leptin obviated the obese, hyperphagic, hypothermic, and hypometabolic phenotype in  ob/ob  mice [13-15]. Go to: ————————————————- Leptin – structure, expression, and secretion The crystal structure of leptin has revealed the secondary and tertiary structure of the leptin molecule. The three dimensional crystal structure of leptin depicts the presence of four antiparallel ? -helices (A, B, C, and D) [16]. Two long crossover loops connect the A-B and C-D ? -helices, while a short loop connects the B-C ? -helices [16]. The entire leptin molecule is oblong shaped with the dimensions of 20x25x45 A0[16]. The entire molecule comprising of the bundle of four ? -helical loops adopts a bilayered stratified structure with ? helices A-D in one layer contiguous with ? -helices B-C in the other layer [16]. The conformation adopted by the leptin molecule results in the surface emergence of a few key hydrophobic residues like Phe41, Phe92, Trp100, Trp138, and Leu142  which not only play an indispensable role in the regulation of solubility and aggregation kinetics of the leptin protein, but are also critically requisi te for as well as modulate the binding of leptin to the leptin receptor and determine the binding kinetics of the leptin-leptin receptor interaction [16]. The three dimensional four-helical bundle crystal structure of leptin exhibits an overt, conspicuous congruence with other cytokines such as growth hormone (GH) [17], leukemia inhibitory factor (LIF) [18], and G-CSF (G-colony stimulating factor) [19], despite lack of primary sequence homology with these proteins or other proteins [1]. Leptin is expressed primarily by the white adipose tissue [1,20] and circulating leptin levels are proportional to the white adipose tissue mass [21,22]. In humans, leptin expression in the subcutaneous adipose tissue is significantly more in magnitude than omental adipose tissue [23-26]. Other studies have demonstrated no difference in leptin expression between the subcutaneous and omental adipose tissue [27]. Leptin expression in humans also exhibits sexual dimorphism with circulating leptin levels about 3-fold greater in females than males [25,28,29]. It is now certain that other tissues also produce leptin, including stomach [30,31], mammary gland [32], human placenta [33], ovaries [34], heart [35], skeletal muscle [36], pituitary gland [37], and the brain [37-39]. In the brain leptin mRNA expression and immunoreactivity has been seen in the hypothalamus, cortex, dentate gyrus and the hippocampus of the rat [38,39]. Leptin immunoreactivity has also been reported in the mouse and hamster brain [40]. Leptin expression and circulating leptin levels are primarily contingent on the white adipose tissue mass [21,22] and are significantly elevated in obesity [21,22,41,42]. Consistent with this observation, weight loss is associated with a decrease in leptin levels in the plasma [22]. Leptin levels in the plasma also fluctuate in an ultradian manner and exhibit diurnal rhythm [43,44]. Leptin secretion occurs in a pulsatile rhythm with ~30 pulses of leptin secretion in a 24-hour cycle [43,45]. Acute caloric restriction reduces leptin levels by ~30% within 24 hours [46-48] whereas caloric excess elevates leptin levels in the plasma by ~35% within 5-8 hours [47]. Therefore, nutritional intake regulates leptin expression in an acute as well as chronic fashion. The physiological and hormonal parameters that increase leptin expression include obesity [21,22,41], overfeeding or excess caloric intake [49,50], insulin [51-55], glucocorticoids [51,52,56,57], glucose [58], tumor necrosis factor ? (TNF? ) [54,59], estradiol [60-62], and IL1 [63,64] among others. The physiological and hormonal factors that decrease leptin expression include androgens [61,65], acute caloric restriction [49,50], growth hormone [66-69], somatostatin [68,70], exposure to cold temperatures [50,71,72], ? 3  adrenergic agonists [70,73-76], long-term exercise [77,78], cAMP (51, 57), PPAR? agonists such as thizolidinediones Pioglitazone, Troglitazone, and Rosiglitazone [79], and free fatty acids [80] among others. Go to: ————————————————- Leptin receptors Leptin receptors (obR) are encoded by the  db  gene [5]. The obR are transmembrane spanning proteins that transduce and mediate leptin signaling. The obR exhibit structural and functional homology to the class I cytokine receptors [81,82]. The obR along with other class I cytokine receptors are typified by the characteristic presence of four cysteine residues and a â€Å"WSXWS† motif [81,83] which are a part of multiple fibronectin Type III subdomains in their extracellular domains [84]. The obR transcript undergoes alternate splicing to generate six different receptor isoforms (obRa – ob-Rf) [11]. The six isoforms of obR are distinguished by and exhibit very little homology in their intracellular domain [85]. However, all the six isoforms have the same extracellular domain of over 800 amino acids and a transmembrane domain that spans 34 amino acid residues [85]. The six isoforms of obR are pigeonholed into three different groups, namely – short form, long form, and secreted obR [85]. The short-form of obR subsuming obRa (894 amino acids), obRc (892 amino acids), obRd (901 amino acids), and obRf (896 amino acids) possess a short 30-40 amino acid residue intracellular domain [85]. bRb (1162 amino acids) is the only functionally active leptin receptor isoform capable of transducing leptin signaling as it contains an intracellular domain that spans ~280 amino acid residues [5]. The obRe isoform (805 amino acids) lacks the intracellular domain and is therefore classified as a secreted soluble receptor and functions as a buffering system involved in the transport of leptin an d bioavailibility of free circulating leptin [86,87]. The short isoforms obRa, obRc, obRd, and obRf are abundantly expressed in the choroid plexus and endothelial cells of the brain microvasculature that form the BBB and may therefore regulate the flux of leptin across the BBB [88,89]. obRb is pervasively expressed in the human and rodent brain with the highest density in the ventromedial, arcuate, and dorsomedial hypothalamic nuclei [90-93]. obRb is termed the long-form leptin receptor and is solely responsible for propagating signal transduction mechanisms initiated by leptin [5,94]. The short forms of the leptin receptor ob-Ra, ob-Rc, obRd, and obRf are devoid of intracellular signaling motifs that are obligatory for signal transduction [5]. However the short form receptors obRa and obRc are highly expressed in the choroid plexus and it is speculated that they mediate the uptake of leptin across the BBB (88, 89). obRb expression has been reported in several regions of the rodent and human brain including the hypothalamus [90,92,93], hippocampus, brain stem (nucleus of the solitary tract and the dorsal motor nucleus of the vagus), amygdala and the substantia nigra [92,93,95,96]. In the hippocampus leptin receptor immunoreactivity is observed in the CA1/ CA3 region and the dentate gyrus [95,97]. Furthermore, axonal and somato-dendritic regions and hippocampal synapses exhibit leptin receptor immunolabeling in primary hippocampal cultures [97]. Go to: ————————————————- Biological and physiological functions Leptin was discovered as the endogenous hormone that precludes obesity and regulates energy homeostasis [1]. Antecedent to the discovery of leptin in 1994, about two decades ago, Doug Coleman had posited the role of a circulating hormone that thwarted obesity via its action in the brain to regulate food intake and energy homeostasis and in the peripheral tissues to regulate energy catabolism, thermogenesis as well as basal metabolism [7]. This was corroborated in the mid 1990s after the discovery of leptin by studies that demonstrated in rodents that administration of exogenous leptin decreased food intake and augmented energy expenditure [13-15,98,99]. Leptin administration augments energy expenditure by actuating the ? -oxidation of fatty acids in the mitochondria and also inducing the expression of enzymes involved in ? -oxidation [100]. However, the notion that high levels of leptin augment weight loss and circumvent obesity must be tempered with the fact that high endogenous leptin levels have been effete in thwarting obesity in humans and other mammals [21,22,41]. This can be ascribed to a phenomenon termed â€Å"leptin resistance† [101-103]. Leptin plays a pivotal role in the induction of puberty and fertility. Leptin reinstates puberty, restores fertility in  ob/ob  mice, escalates puberty and fosters reproductive behavior in wildtype rodents [104-107]. Leptin directly regulates the hypothalamic-pituitary-gonadal (HPG) axis by inducing gonadotropin release and modulating estradiol production in the ovarian follicles [108,109]. Leptin also regulates the hypothalamic-pituitary-adrenal (HPA) axis by attenuating corticotrophin releasing hormone (CRH) production and release [110,111] as well as directly inhibiting ACTH (adrenocorticotropic hormone)-induced glucocorticoid release from the adrenal cortex [111-113]. Leptin is also integrally involved in the physiological homeostasis of the circulatory system. Emerging evidence implicates leptin in hematopoeisis as leptin is involved in proliferation and differentiation hematopoietic precursors [114-116]. Higher plasma levels of leptin (~100ng/mL), suchas those observed in obese individuals, foster and promote platelet aggregation [117]. Leptin is also one of the most potent inducers of vascular epithelial cell growth and angiogenesis and the short forms and the long-form of the leptin receptor is abundantly expressed in the vasculature [117-119]. Go to: ————————————————- Leptin function in the brain Hypothalamus Leptin signaling in the hypothalamus regulates food intake and energy homeostasis in mammals. The arcuate nucleus (ARC), dorsomedial nucleus (DMH), and the ventromedial nucleus (VMH) of the hypothalamus express the obRb in the greatest density. In the ARC, the obRb is abundantly expressed in two disparate neuronal cell types, ones that express neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the others that express pro-opiomelanocortin (POMC) [92,120-122]. Leptin induced activation of the obRb in the POMC neurons results in depolarization and increased biosynthesis of ? -melanocyte-stimulating hormone (? -MSH) which signals downstream by actuating the melanocortin system comprising of melanocortin-3-receptors (MC3R) and melanocortin-4-receptors (MC4R) expressed by the second order neurons downstream to evoke an anorexiogenic (decreased appetite) response [122-127]. Activation of the melanocortin pathway not only suppresses appetite but also increases energy expenditure by increasing sympathetic tone resulting in ? oxidation of fatty acids in skeletal and adipose tissue. While leptin activates the POMC-expressing neurons, the actuation of obRb by leptin in the NPY/AgRP neurons results in the decreased genesis of NPY and AgRP peptides which are orexiogenic (increase appetite) in nature [122,128]. Therefore, in conspectus, leptin signaling in the hypothalamus results in the decreased expression of orexiogenic peptides (NPY, AgRP) and incr eased expression of anorexiogenic peptides (? -MSH) as well as increased energy expenditure in the adipose tissue and skeletal muscle tissue. Hippocampus Leptin receptors are abundantly expressed in the CA1 and CA3 regions of the hippocampus as well as the dentate gyrus [95,97]. Leptin regulates the excitability and firing of hippocampal neurons via the modulation of BK potassium channels [97]. Leptin also improves memory processing and retention when administered directly into the CA1 region in mice [129] and rodents that are deficient in the leptin receptor (db/db  mice and  fa/fa  rats) exhibit profound deficits in spatial learning and memory [129-131]. Treatment of acute hippocampal slices with leptin results in the conversion of short-term potentiation (STP) to long term potentiation (LTP) by enhancing Ca2+  influx through NMDA receptors [132]. Leptin increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin also increases neurogenesis in the dentate gyrus of adult mice [134]. Leptin also plays a critical role in hippocampal neuronal survival by activating the PI3K-Akt and JAK2/STAT3 signal transduction pathways [135]. Leptin upregulates the expression of potent endogenous antioxidant enzyme Mn-SOD (manganese superoxide dismutase) and the anti-apoptotic protein Bcl-xL (B-cell lymphoma xL) in a STAT3-dependent manner in the hippocampus [135]. Leptin stabilizes mitochondrial membrane potential and attenuates the glutamate-induced mitigation in mitochondrial membrane potential and also extenuates the free iron-induced augmentation in mitochondrial ROS [135]. Go to: ————————————————- Leptin signaling Leptin binding to its long-form receptor obRb actuates four major signal transduction pathways that are coupled to obRb – JAK/STAT pathway, ERK pathway, PI3K/Akt/mTOR pathway, as well as the AMPK/SIRT1 signal transduction pathways. JAK/STAT pathway Leptin signaling via the obRb is integrally coupled to the JAK2/STAT3, JAK2/STAT5 and JAK2/STAT6 pathways [10]. The long-form of the leptin receptor obRb is constitutively coupled to Janus kinase 2 (JAK2) via the evolutionary conserved domains proximal to the membrane [136]. The binding of leptin to obRb evokes a conformational change in the receptor that actuates JAK2 by phosphorylation at Tyr1007/1008  residues [136]. Activated phosphorylated JAK2 subsequently phosphorylates evolutionary conserved tyrosine residues of obRb [94] at Tyr985, Tyr1077  and Tyr1138  [137,138]. The obRb phosphorylated at Tyr1077  and Tyr1138  serves as a docking site and recruits Srchomology 2 (SH2)- and Src-homology 3 (SH3)-domain comprising roteins that subsume proteins such as Signal Transducer and Activator of Transcription 3 (STAT3), Signal Transducer and Activator of Transcription 5 (STAT5), and Src homology region 2 domain-containing phosphatase 2 (SHP2) [139]. The phosphorylated Tyr1138  residue of obRb recruits STAT3 and STAT5 which are subsequently phosphorylated by JAK2 at Tyr705  and Tyr694  respectively. The phosphorylation STAT3 and STAT5 causes their disengagement from the leptin receptor, results in the dimerization of STAT proteins via their p hosphotyrosine residues in the SH2 domains [140-142], and culminates in their nuclear translocation [142]. In the nucleus, STAT dimers bind to distinct motifs or elements in the DNA called ? -IFN-activated site (GAS) in the enhancer regions of target genes and thereby modulate and regulate gene expression of target genes [142-146]. In the nucleus, the STAT signaling is abrogated by dephosphorylation and subsequent export of STAT proteins from the nucleus to the cytosol [142,144,147] or by targeted degradation of the STAT proteins via the Ubiquitin Proteasomal System (UPS) [148]. The JAK/STAT pathway is negatively regulated by three classes of proteins, namely – suppressors of cytokine signaling (SOCS), protein inhibitors of activated STATs (PIAS), and protein tyrosine phosphatases (PTP) [149]. There are eight members of the SOCS family and their expression is induced by JAK/STAT signaling (STAT3 in particular) thereby suggesting the existence of a negative feedback loop that abrogates JAK/STAT signaling [150]. The SOCS proteins negatively regulate the JAK/STAT pathway by competitively engaging and occupying the phosphotyrosine residues in obRb via their SH2 domains and obviating the recruitment of STAT proteins to obRb, thereby precluding STAT activation [150,151]. SOCS proteins via their SH2 domains also directly bind to JAK2 and extenuate the kinase activity of JAK2 [150,151]. The PIAS proteins negatively regulate the JAK/STAT signaling pathway by impeding the binding of STAT proteins to the response elements in the DNA by physically interacting and binding with STAT proteins via their zinc-binding RING-finger domains [151]. SHP1 and SHP2 are most well characterized protein tyrosine phosphatases implicated in the negative regulation of the JAK/STAT pathway [149]. SHP1 and SHP2 possess two SH2 domains and therefore bind to phosphotyrosines of JAK2 and obRb and effectuate the dephosphorylation of JAK2 and obRb thereby terminating the JAK/STAT signaling [149]. ERK pathway The extracellular regulated kinase (ERK) pathway is an integral part of a larger signaling network called mitogen activated protein kinase (MAPK) pathway that is activated by leptin signaling via the leptin receptor (obRb). While phosphorylation of Tyr1138  and Tyr1077  are both requisite and mediate the activation of STAT3 and STAT5 respectively, the phosphorylation of Tyr985  of obRb mediates the activation of ERK pathway [138]. Leptin signaling via the obRb evokes the actuation of ERK pathway, both centrally and peripherally, as well as in  in vivo  and  in vitro  experimental paradigms [85]. Leptin evokes the activation of ERK pathway by both JAK2-mediated and JAK2-independent signaling effects [94,152]. Contemporary evidence has implicated the protein tyrosine phosphatase SHP2 and the adaptor protein Grb2 (growth receptor bound 2) as the requisite mediators in the leptin-induced activation of ERK signaling pathway [153]. Leptin signaling also activates other members and signaling cascades subsumed under the MAPK signaling pathway, namely p38 [154-157] and JNK pathways [156]. PI3K/Akt/mTOR pathway Leptin signaling also induces the activation of the ubiquitous, pervasive, nutrient-sensitive anabolic, and the broad spectrum PI3K/Akt/mTOR pathway [152,158-161]. Empirical evidence has demonstrated that the adaptor proteins IRS1 (insulin receptor substrate 1) and IRS2 (insulin receptor substrate 2) mediate the leptin-obRb induced activation of PI3K-Akt pathway [94,158,162]. A multitude of studies have demonstrated that leptin induces the activation of Akt via phosphorylation of Akt at Ser473[163,164]. As a consequence, Akt activation is ensued upon leptin signaling which results in inhibition of GSK3? through phosphorylation at Ser9  residue [165-167]. Evidently leptin also activates the serine/threonine kinase mammalian target of Rapamycin (mTOR) in the hypothalamus and macrophages [168,169] through the PI3K-Akt pathway [170]. mTOR is an evolutionary conserved kinase that modulates translation of several mRNA transcripts involved in cell growth and proliferation. mTOR regulates translation by phosphorylation and attenuation of the inhibitor of mRNA translation, eukaryotic initiation factor 4E-binding protein (4E-BP) [171-175], as well as through the phosphorylation and activation of S6 kinase (p70S6K1) [176,177]. TOR is autophosphorylated at Ser2481  and exhibits spontaneous intrinsic kinase activity under the activation of Akt [178,179]. mTOR phosphorylation and activation is negatively regulated by the TSC1/TSC2 protein complex [170]. Akt phosphorylates TSC2 causing disintegration of the TSC1/TSC2 complex which consequently results in mTOR activation [180]. Furthermore, Akt has been shown to directly phosphorylate mTOR at Ser2 448residues and consequently activate mTOR [181,182]. Therefore, Akt positively regulates mTOR activation by direct phosphorylation at Ser2448  as well as by indirect means which involves relieving the repressive effects of the upstream inhibitor TSC1/2 complex. Thus leptin, by virtue of its inherent ability to activate Akt, is expected to increase mTOR phosphorylation and activity. AMPK-SIRT1 pathway The 5’AMP activated protein kinase (AMPK) is the master regulatory kinase termed the â€Å"fuel gauge† that integrates signals from upstream mediators and effectors of hormones and cytokines to maintain metabolic homeostasis [183]. AMPK activation leads to increase ? -oxidation of fatty acids in the mitochondria and inhibition of lipogenesis [184,185]. Multiple lines of evidence have cogently demonstrated that leptin activates AMPK and consequently increases fatty acid oxidation [186-188]. One exception to this is the hypothalamic neurons, where leptin inhibits AMPK activation to evoke satiety and other hypothalamic effects of leptin [189-191]. In general, AMPK plays a catabolic role and engenders energy production via effects on glucose and lipid metabolism. AMPK activation also effectuates the induction of the NAD+  Ã¢â‚¬â€œ dependent deacetylase SIRT1 (silent mating type information regulation 2 homolog) [192,193], a metabolic master regulator unequivocally implicated in ageing and the regulation of lifespan [194-198] as well as regulating metabolism [199,200]. The anorexic effect of leptin mediated by the activation of POMC neurons in the hypothalamus is contingent on SIRT1 expression and activation in the neurons of the arcuate nucleus of the hypothalamus [201]. Go to: ————————————————- Role of leptin in Alzheimer disease Alzheimer Disease (AD) is a progressive, debilitating and the most prevalent neurodegenerative disorder typified by memory impairment and cognitive dysfunction eventually leading to fatality. The gross pathologic hallmarks of autopsied brains of patients with AD include atrophy with widened sulci and narrowed gyri in the temporal, parietal, and frontal lobes as well as the neocortex and cingulated gyrus areas of the cerebral cortex. The entorhinal cortex, amygdala, hippocampus and the para-hippocampal gyrus also exhibit pronounced atrophy due to neuronal loss [202,203]. There is a decrease in gross weight of brain by 10-15% in AD patients [202]. The thickness of the six cortical layers (cortical ribbon) is usually reduced by 10-20% in AD [202] and ventricular dilation is apparent prominently in the temporal horn as a consequence of the atrophy of the amygdala and the hippocampus. Furthermore, there is a propensity for the loss of larger neurons than the loss of smaller neurons or glial cells in AD [202]. Microscopically, AD is characterized by two most common and distinct â€Å"hallmark† microscopic lesions namely senile plaques and neurofibrillary tangles (NFT). Senile plaques are extraneuronal deposits of accumulated and aggregated amyloid-? (A? ) protein in the brain parenchyma, while the NFT are intraneuronal aggregates of protein tau in the hyperphosphorylated state. Other pathological features of the AD brain include synaptic loss, neuronal and dendritic loss, neuropil threads, granulovacuolar degeneration, dystrophic neurites, Hirano bodies, and cerebrovascular amyloid deposition. There is substantial evidence that leptin modulates A? production and metabolism. Chronic peripheral leptin administration in Tg2576 mice has been reported to reduce the brain A? evels [204]. Moreover leptin also decreases the BACE1 activity in SH-SY5Y cell line [204]. Leptin decreases tau phosphorylation explicitly at residues Ser202, Ser396, and Ser404  in retinoic acidinduced differentiated SH-SY5Y cells, differentiated human NT2 cells (NT2N), and rat primary cortical neurons [205-207]. Leptin also increases synaptogenesis and aids in memory formation in the hippocampus and is purported to be a cognitive enhancer [133]. Leptin has been shown to convert STP into LTP in hippocampal cultures and hippocampal slices [132]. Recent evidence suggests that leptin facilitates spatial learning and memory [130] and also increases neurogenesis in the dentate gyrus of adult mice [134]. Recent epidemiological studies have also unequivocally implicated decreased leptin levels in the pathogenesis of AD. In the Framingham prospective study, 785 subjects were followed between 1990 and 1994 from the original Framingham cohort [208]. The study concluded that leptin levels were inversely related to the risk of developing dementia of the Alzheimer type [208]. A year preceding the findings of Lieb and colleagues, a morphometric study in Japan conducted by Narita and group found higher leptin levels were positively correlated with higher hippocampal volumes [209]. Leptin decreases Amyloid-? (A? ) levels by attenuating the genesis and augmenting the clearance of the peptide The A? peptide is derived from a two-step successive proteolytic cleavage of Amyloid-? precursor protein (A? PP) [210]. In the first step, A? PP is cleaved by the membrane-bound protease BACE1 (? -site APP cleaving enzyme 1) (also called ? secretase) to generate CTF? (carboxy terminal fragment ? ) (also known as C99 fragment) [211-215] which in the second step is subsequently cleaved by the ? -secretase complex to generate A? peptide [216-218]. According to the â€Å"amyloid cascade hypothesis†, A? is considered as the culpable factor in the instigation and progression of all the neurodegenerative events that characterize AD [219]. A plethora of studies have demons trated that leptin decreases A? levels in several  in vivo  and  in vitro  paradigms [204,220-223]. Leptin has been shown to mitigate A? roduction by extenuating BACE1 activity in neural cultures [204]. Recent studies have implicated the AMPK/SIRT1 pathway in the leptin-induced modulation of A? levels [222]. Emerging data from our unpublished work has not only corroborated the finding that leptin regulates A? metabolism via SIRT1, but also implicated the ubiquitous transcription factor NF-? B as a SIRT1 target downstream in the modulation of A? genesis (unpublished). Leptin decreases A? levels by targeting all facets of A? metabolism, namely – production, clearance, and degradation. We have shown that leptin increases the expression levels of insulin degrading enzyme (IDE) putatively by activating the Akt pathway [223], thus augmenting the degradation of A?. Furthermore, leptin also increases the expression levels of LRP1 [223], suggesting that leptin may foster the uptake of A? by astrocytes and microglia or reuptake of A? by neurons and therefore target A? for intracellular degradation or for clearance across the blood-brain-barrier (BBB). Leptin also effectuates the ApoE-mediated clearance of A? [204]. Specifically, leptin dose-dependently increased the LRP1-mediated uptake of ApoE-bound A? , therefore committing A? toward the endosomal/lysosomal degradation pathway [204]. Leptin attenuates BACE1 expression and activity The first line of evidence linking leptin signaling dyshomeostasis in the pathogenesis of Alzheimer disease emanated from the work of Tezapsidis and colleagues [204], who demonstrated in neural cultures from transgenic mice that leptin mitigates BACE1 activity by evoking changes in lipid composition of lipid rafts of cell membranes. Furthermore, the study also demonstrated that the lipolytic ability of leptin as a consequence of increased ? -oxidation of fatty acids and decrease  de novo  synthesis of fatty acids and triglycerides underlies the mechanistic link between the effects of leptin on lipid composition of membranes and BACE1 activity. Recent data from our studies [223] and other laboratories [221] cogently demonstrate that leptin negatively regulates BACE1 expression, both  in vitroand  in vitro  paradigms. Moreover, Greco and colleagues have attributed this effect of reduced BACE1 expression on the ability of leptin to induce PPAR? expression and activation [221]. Indeed, leptin is a well characterized inducer of PPAR? expression and activity [220,224]. In light of this, it is important to reiterate that multiple lines of evidence exist in current literature demonstrating the role of PPAR? as a negative regulator of BACE1 expression [225]. Another mediator of leptin induced modulation of BACE1 expression may be the transcription factor STAT3. The BACE1 promoter contains a multitude of STAT3 binding sites [226]. Multiple lines of evidence have implicated STAT3 in the regulation of BACE1 expression [226-228]. Leptin may also modulate BACE1 activity via the activation of the PI3K/Akt and ERK signaling pathways [229]. BACE1 expression is also modulated by the master transcription factor NF-? B [230]. We have found that leptin represses NF-? B transcriptional activity via induction of SIRT1 expression and activity and thereby attenuates BACE1 expression (unpublished). Furthermore, inhibition of SIRT1 activity significantly compromised the mitigating effect of leptin on BACE1 expression (unpublished). Therefore, the entire range of discrete signal transduction pathways activated by leptin may be implicated in the modulation of BACE1 expression. Leptin mitigates tau phosphorylation It is now the consensus that tau hyperphosphorylation precedes and leads to PHF formation in NFT [231] and aberrant tau hyperphosphorylation is implicated in neurodegeneration in AD [232-236]. Recent studies by Tezapsidis and colleagues as well as our work has cogently demonstrated that leptin decreases hyperphosphorylation of tau, primarily by the activation of known canonical signal transduction pathway coupled to leptin receptors. Firstly, Greco  et al. demonstrated  in vitro, in SH-SY5Y and NTera-2 human neuronal cell lines, that leptin reduces the phosphorylation of tau at Ser202, Ser396, and Ser404  residues [205]. In the same study, it was shown that leptin was ~300-fold more potent than insulin at mitigating tau phosphorylation and the activation of AMPK pathway was implicated in mediating this effect [205]. The following year, the same group systematically investigated the involvement of other signal transduction pathways activated by leptin that may contribute to the attenuation of tau phosphorylation and concluded that leptin-induced activation of Akt, p38 MAPK, as well as AMPK were all intricately involved [206]. Notably, of great mechanistic importance, was the revelation that all the three aforementioned pathways activated by leptin, culminated in the phosphorylation of the tau kinase GSK3? at Ser9  residue leading to the inhibition of its kinase activity. Therefore, leptin-induced activation of Akt, p38 MAPK, and AMPK signal transduction pathways converged at the focal point – GSK3? , a bona fide tau kinase [206,207]. Data from our studies carried out in organotypic slices from the hippocampi of adult rabbits has also cogently demonstrated that leptin inhibits GSK3? -induced tau phosphorylation at AT8 (Ser202, Thr205) and PHF1 (Ser396, Ser404) epitopes via the activation of Akt [223,237]. Of greater importance and relevance, was the finding that 8-weeks of leptin treatment in CRND8 transgenic mice resulted in a ~2-fold decrease in tau phosphorylation at AT8 and PHF1 epitopes [221]. Leptin fosters synaptogenesis and synaptic plasticity Several studies have shown that synaptic dysfunction and synaptic loss are the cardinal hallmarks of incipient AD [238-244]. Electron microscopy [238,241,245-248], immunohistochemical and biochemical studies [240,249-251] have demonstrated that synaptic loss in the neocortex and the hippocampus is an early episode in Alzheimer’s disease [252,253]. Synaptic loss is also the most important structural correlate of cognitive impairment in AD [250,254-260]. Synaptic dysfunction can be detected in patients diagnosed ith mild cognitive impairment (MCI), a condition which may or may not progress to AD and characterized by many as a prodromal state of AD [247,261]. Leptin plays an indispensable role in learning, memory, and maintenance of synaptic plasticity [262]. Leptin receptor mutant  db/db  mice and  fa/fa  rats have deficits in spatial memory and inadequate short term memory processing as assessed by the Morris water m aze [130] and T-maze footshock avoidance test paradigms [129]. In the CA1 region of the hippocampus, leptin exclusively enhances the NMDA receptor-mediated synaptic transmission [132]. Leptin facilitates the trafficking of NMDA receptors to the plasma membrane and this may contribute to the effect of leptin on enhancing the NMDA receptor-mediated current [133]. This was also corroborated in a  Xenopus  oocyte model system expressing recombinant NMDA receptors [132]. Leptin evokes the conversion of STP to LTP in acute hippocampal slices. Further delving into the molecular mechanism underlying this effect has implicated the PI3K/Akt and ERK signaling cascades at the nexus as the inhibitors of these signaling pathways mitigated this effect of leptin [132]. Furthermore, in the CA1 region of the hippocampus, leptin also fosters the induction of a novel form of LTD and this effect was attributed to NMDA receptor activation [263]. The study by Durakoglugil also examined the signal transduction cascades involved in the induction of this novel LTD by leptin and concluded that this effect was contingent on the PI3K signaling cascade, but independent of the ERK signaling pathway [263]. In addition to regulating synaptic strength by modulation of LTP and LTD, leptin also fosters synaptogenesis. The leptin deficient  ob/ob  mice have decreased synapse density and exogenous leptin corrects this deficit in these mice [264,265]. Leptin also induces the expression of a multitude of pre- and postsynaptic proteins such as synapsin2A and synaptophysin in the hippocampus [266]. Leptin also has a profound effect on dendritic morphology. Leptin augments filopodial stabilization, fosters mobility and boosts their density, thus promoting synapse formation [267]. Interestingly, this effect of leptin on filopodial stability and density is contingent on ERK signaling pathway and not on the PI3K signaling pathway [267]. Leptin increases neuronal survival and mitigates cell death There is growing consensus that leptin is a growth and survival factor in the CNS. Leptin increases the viability of SH-SY5Y cells and suppresses apoptosis by down-regulation of caspase-10 and TRAIL and this effect is contingent on the ability of leptin to activate the JAK-STAT, PI3K-Akt, as well as ERK signaling pathways [268]. Leptin has been shown to exert neuroprotective properties in cultured MN9D rat dopaminergic cells against 6-OHDA. Leptin also averted the 6-OHDA-induced dopaminergic cell loss in the substantia nigra of mice when administered intracranially [269]. This pro-survival effect of leptin on dopaminergic neurons was attributed to the JAK2-dependent activation of the ERK signaling pathway resulting in increased levels of survival factors p-CREB and BDNF [269]. Our recent work has unequivocally demonstrated that leptin upregulates the expression of Insulin-like Growth Factor – 1 (IGF-1), a known neurotrophic and survival factor in the brain [270]. Leptin has also been shown to attenuate apoptotic cell death of cultured cortical neurons in an  in vitro  oxygen-glucose deprivation model of global ischemia [271]. Furthermore, the study by Zhang  et al. , also cogently showed that intraperitoneal administration of leptin in mice reduced the infarct volume and significantly improved behavioral parameters in a middle cerebral artery occlusion (MCAO) model of global ischemia [271]. This effect of leptin was attributed to the activation of ERK signaling pathway as the general inhibitor of ERK signaling abolished this effect of leptin, both  in vitro  and  in vivo  [271]. Another study employing hippocampal cultures has demonstrated that leptin inhibits neuronal cell loss in response to growth factor withdrawal and oxidative insult by evoking JAK-STAT activation leading to enhanced expression Mn-SOD and Bcl-xL and stabilizing the mitochondrial membrane potential [135]. Leptin also mitigated neuronal loss in response to excitotoxic insult evoked by glutamate in hippocampal cultures by the aforementioned molecular mechanism [135]. Leptin also protected the hippocampal neurons from kainite-induced damage in response to excitotoxicity evoked seizures in a mice model of temporal lobe epilepsy [135]. A recent study found that leptin also attenuates MPP+-induced cell death in neuronal cultures via the activation of STAT3 and inducing the expression of UCP-2 that culminates in the obviation of mitochondrial dysfunction by MPP+  [272]. Of particular interest is the finding that cultured cortical neurons secrete prodigious amounts of leptin in response to oxygen-glucose-serum deprivation that results in enhanced expression of IL-1? and increased intransigence to apoptotic cell death [273]. Moreover, neutralization of this endogenous leptin with an antibody resulted in increased susceptibility of these cultured cortical neurons to oxygen-glucose-serum deprivation – induced cell death [273]. The salutary effects of leptin on neuronal viability and function have also been corroborated by electrophysiological studies. One such study has cogently demonstrated that leptin combats the hypoxia-induced inhibition of spontaneously firing hippocampal neurons by activating the BK channels (large conductance Ca2+  activated K+  channels) [274]. Leptin induces proliferation of neuronal progenitors – evokes neurogenesis As Alzheimer disease is typified with selective neuronal loss in the hippocampus and other regions of the brain, the debunking of the dogma that neurogenesis occurs exclusively prenatally and the revelation that neurogenesis persists in the adult mammalian brain has opened novel therapeutic avenues to combat the neuronal loss in AD. Chronic leptin treatment increases hippocampal neurogenesis in mice and induces proliferation of adult hippocampal progenitor cultures [134]. This effect of leptin on adult hippocampal neurogenesis is attributed to increased cell proliferation in the dentate gyrus and not enhanced cell differentiation or cell survival [134]. The study by Garza and colleagues unequivocally implicated the JAK2-STAT3 and PI3K-Akt signal transduction pathways in the leptin induced enhancement of hippocampal neurogenesis [134]. Furthermore, leptin rescues the attenuation in adult hippocampal neurogenesis in a mouse model of chronic unpredictable stress-evoked depression via the inhibition of GSK3? nd subsequent stabilization of ? -catenin [275]. Leptin has also been documented to evoke neurogenesis and angiogenesis in a mouse stroke model (Avraham  et al. , 2011). Go to: ————————————————- Conclusion Here we have reviewed the contemporary knowledge on the protective role of the adipokine leptin and its signaling in Alzheimer’s disease. In conspectus, leptin impinges on all facets of Alzheimer’s disease pathophysiology (Figure 1). These attributes of leptin such as the decrease in A? production and increase of A? learance, reduction in tau hyperphosphorylation as well as increased synaptogenesis, increased memory, increased spatial learning, and increased neurogenesis catapult leptin treatment as a unique therapeutic intervention and an indispensable tool in the elucidation of biochemical mechanisms involved in the etiology of the sporadic form of Alzheimer’s disease. Marwarha , G. and Ghribi, O. Leptin signaling and Alzheimer’s disease Marwarha , G. and Ghribi, O. (2012) Leptin signaling and Alzheimer’s disease. American Journal of Neurodegenerative Disease, 1 (3), p. 45-265. Lifestyle nonpharmacological interventions can have a deep effect on cognitive aging. We have reviewed the available literature on the effectiveness of physical activity, intellectual stimulation, and soc ialization on the incidence of dementia and on the course of dementia itself. Even though physical activity appears to be beneficial in both delaying dementia onset and in the course of the disease, more research is needed before intellectual stimulation and socialization can be considered as treatments and prevention of the disease. Through our paper, we found that all three nonpharmacological treatments provide benefits to cognition and overall well-being in patients with age-related cognitive impairments. These interventions may be beneficial in the management of dementia. Alzheimer’s disease (AD) is a neurodegenerative disorder with devastating consequences [1]. Despite being the most common cause of dementia, affecting approximately 5. 4 million Americans [2] and almost 50% of people over the age 85 [3], no cure has yet been discovered. Efforts are also focusing on the development of more effective strategies to slow the progression of AD to increase the quality of life of those affected. Even a two-year delay in disease onset would reduce the prevalence of AD among Americans by two million people within fifty years [4]. If an intervention that delayed the onset of AD by five years had been applied back in 1997, we would have seen a 50% reduction in AD incidence [4]. Research on strategies to slow the development and progression of AD is arguably more important now than ever before, since the number of people with AD is expected to nearly triple over he next forty years [4], and dementia is the most important contributor to disability in the elderly [5]. Among others, three nonpharmacological interventions are particularly relevant as they might positively influence cognition, general functioning, and overall quality of life. These three strategies arephysical exercise,  intellectual stimulation,  and  social interaction. While there are studies that evaluate the role of individual and multimodal interventions on AD, there is a lack of literature on the combination of all three. The purpose of this paper is to review key areas of the literature that focus on the effects of physical exercise, intellectual stimulation, and socialization strategies on AD evolution, as they collectively play an important role in the management of Alzheimer’s disease. Physical exercise encapsulates both aerobic exercises (e. g. , walking and cycling) and nonaerobic exercises (e. g. , strength and resistance training; flexibility and balance exercises). For intellectual stimulation, we examine studies that have evaluated the prognostic effects of either cognitive hobbies (e. g. reading, word puzzles, and card games) or cognitive training (e. g. , computer training games/paradigms that target specific cognitive domains such as memory and attention). Social interaction is defined as the participation of an AD patient in group-related activities, such as mealtime conversations, support groups, or other forms of social engagement. The health benefits attributed to physical acti vity are numerous and well known. Exercise has been associated with a lower incidence in many chronic diseases, such as coronary heart disease [6], type 2 diabetes [7], obesity [8], cancer [9], bone loss [10], and high blood pressure [11]. We have reviewed the effects of physical exercise on cognition. Higher cardiorespiratory fitness has been related to higher scores on tests of cognitive function [12]. A meta-analysis of randomized controlled trials examining the relationship between exercise and cognition showed modest improvements in attention, processing speed, executive function, and memory among older adults in the treatment arms [13]. This is highly relevant for the elderly population, as it suggests that physical activity can serve as a preventative measure against age-related cognitive decline [14]. Several large longitudinal studies followed older adults without cognitive impairments at baseline and measured rate of incident dementia to clarify the relationship between physical activity and incident cognitive loss. A large prospective study by Podewils et al. identified an inverse relationship between physical activity and dementia risk [15]. Compared to no exercise, physical activity has been linked with reduced risks of developing cognitive impairment and dementia [16] with the risk for dementia being further reduced with increasing levels of physical activity. Larson and colleagues found that persons who exercised three or more times per week had a reduced risk of developing dementia compared to those who exercised less, and the reduction was more marked among those with the poorest physical function at baseline [17]. These results were corroborated by Buchman et al. who found that participants in the lowest percentiles of physical activity had more than twice the risk of developing dementia than those in the highest percentiles of physical activity [18]. Furthermore, Lautenschlager et al. demonstrated that these results might be transferable to adults with mild cognitive impairment (MCI), and, thus, at high risk for dementia; participants who underwent exercise training showed modest improvements in cognition after six months [19]. Physical exercise has, therefore, been recommended as a preventative measure of mild cognitive impairment and dementia [20,  21]. There is much less research focusing on the effect of physical activity in AD patients. This may be due to the challenges of implementing an exercise regime while managing the behavioral and emotional disturbances in AD patients, particularly in the later stages of the disease. However, the results in the available literature are promising. Early research involving AD patients in nonrandomized controlled trials showed significant cognitive improvements among participants who underwent cycling training and somatic and isotonic-relaxation exercises [22,  23]. Physical exercise may have beneficial effects in AD patients beyond cognition as well. A meta-analysis on 30 randomized controlled trials that employed exercise, behavioral and environmental manipulations in patients with cognitive impairment found exercise had positive effects on strength and cardiovascular fitness in addition to improvements in behavior and cognition [24–26]. Further evidence supporting multifaceted positive effects of exercise on AD can be traced to recent randomized controlled trials of physical exercise regimes on AD patients (Table 1). Compared to controls, patients in the intervention programs showed better physical functioning (functional reach, walking, and mobility). After treatment, these patients also showed improved performance of activities of daily living (ADLs), and less cognitive decline and cognitive improvement in some cases. Physical exercise, therefore, appears to be beneficial for AD patients. While the majority of the studies did not find any differences in depression, one study by Steinberg found increased depression and decreased quality of life in patients who underwent the exercise intervention [31]. Further research into the effect of physical exercise on mood and quality of life in AD patients is, therefore, required. When considering the role of exercise on AD, it is important to note that any positive results may be due to a placebo effect, even in randomized controlled trials. However, due to the varied nature of the outcome measures used in these studies, it is unlikely that every intervention group demonstrated significant gains over the controls due to a placebo effect alone. Furthermore, control group members never appeared to show any improvement and often showed higher rates of functional and cognitive decline. Enhanced neuroplasticity might be underlying the improvements seen. Colcombe and colleagues demonstrated that older adults without dementia who performed aerobic exercises had greater grey and white matter volumes compared to adults who engaged in stretching and toning exercises [38]. Exercise has also been associated with functional connectivity between brain networks often affected by age, such as the default mode, frontal parietal, and frontal executive networks, in older adults without dementia [39]. While randomized controlled trials in AD patients examining the relationship between neuroplasticity and exercise are underway, correlational studies examining brain volumes and cardiorespiratory fitness have been done. In AD patients, cardiorespiratory fitness has been associated with brain volume. VO2peak, peak oxygen consumption, has been positively correlated with greater whole brain volume and white matter volume [40], notably in the inferior parietal lobule, hippocampal, and parahippocampal regions [41]. Future results of randomized controlled trials will improve our knowledge in this field of research. Overall, physical activity offers promising outcomes for cognition and physical health in the elderly population and AD patients. Engagement in intellectually stimulating activities has been linked with reduced risk of developing AD and intellectual stimulation has been widely explored as a nonpharmacological treatment option for dementia [42]. Among cognitively ormal older persons, randomized control trials employing intellectual training concluded that cognitive interventions produce protective and potentially long lasting positive effects in various cognitive domains as well as activities of daily living [43]. There is also evidence that frequent engagement in hobbies, including reading, puzzles, and games, for at least six hours per week reduces the risk of incident dementia [44]. The concept of intellectual stimulation as a preventative measure for dementia in healthy older adult s can be parallel to the notion of building a â€Å"compensatory mechanism† or â€Å"cognitive reserve† [45–48]. Cognitive reserve refers to the hypothesis that individual differences shaped by inherent characteristics and external sources including intelligence, years of education, occupation, and intellectual activities, may provide neural protective support against dementia [45–47]. It has been argued that these collective life experiences may contribute to building cognitive reserve and, thus, provide skills to compensate for AD pathology [45–47]. In other words, a greater cognitive reserve might delay the appearance of dementia despite the presence of neuropathology, after which a rapid progression of cognitive decline may ensue once pathology is significant enough to result in AD diagnosis. Thus, AD patients with higher education and occupation accomplishments suffer more rapid decline in cognitive abilities when compared to AD patients with less education and occupational attainment following diagnosis [49]. Another study by Helzner and colleagues [50] investigated the relationship between premorbid leisure activity and rate of cognitive decline in AD patients. Leisure activities were classified into four categories: intellectual, social, physical, and other. Higher-frequency participation in intellectual leisure activities prior to AD diagnosis was associated with delayed AD onset followed by faster cognitive decline. The study by Helzner and colleagues [50] provides evidence for the benefits of intellectual stimulation on slowing down AD development. Besides reducing the risk of dementia, cognitive interventions later in life may affect functional decline in AD. Treiber and colleagues [51] explored the association between engaging in cognitively stimulating activities in late life and the rate of cognitive decline in incident AD. This study included a wide range of intellectual activities that required varying levels of cognitive demand, for example, completing puzzles, reading, watching television, listening to music, and cooking. The results suggested that higher-frequency participation in stimulating activities in early stages of dementia resulted in slower cognitive decline. However, as time progressed there was an overall decrease in participation in activities, which might reflect the nature of AD in terms of functional abilities. Intellectual stimulation can be divided into several categories including cognitive stimulation, cognitive t How to cite Dementia, Papers

Supervision Concepts and Skill Building †Free Samples to Students

Question: Discuss about the Supervision Concepts and Skill Building. Answer: Introduction: Before applying any strategy, it is important to look at the issue from different perspectives and to know who was wrong and who was right(Johnson, R, Clark, G, 2008). One of the most important questions to ask is, was the receptionist honest with the customers? If she was not, then the burden is on her. The most effective strategies, in this case, are the following. In any business environment, it is important to make sure that there is an understanding before making any judgment. In this case, the person who is in the middle of the issue is the receptionist. Therefore, as a manager, I must be just, and fear and that calls for me to hear her side of the story. I would ask her if she tried to call the landscaper herself(Helo, P, Gunasekaran, A, Rymaszewska, 2017). The reason for asking the question is because if she knew that the landscaper was not available on the phone, why did she refer the customer to a person who is not reachable? As a manager, it is important to know more about stakeholders. Though the problem here revolves around the receptionist, the landscaper has his fair share of the blame. Reliability of an employee is crucial to an employer(Dabholkar, 2015). An employee who cannot be found when he or she is needed ought not to work for an organization. With this in mind, it is important to make sure that I get to know about the behaviors of the landscaper. Knowing the behaviors of the landscaper would help me to deal with the issue with all fairness. Though it would be important to know about the landscaper from himself, I would make sure that I get information from different people in the Association as well as look for more information about him from his past customers. The best way to make sure that a tree never grows again is but digging out its roots. The same strategy would be very effective in this case.(Cummings, T, Christopher, G, 2014) To make sure that the problem does not emerge again, I would make sure to deal with the person who is at the center of the issue, and that is the landscaper. He ought to give his side of the story if the problem is to be dealt with once and for all. The most appropriate way of doing so is by inviting the landscaper and having a one on one session with him. During the session, there are some questions that I would ask him. One of them is if the allegations of him not picking the phone are true, second is why does he not get back to the customers, and the third and most harsh but must be asked if he is tired of working(Mitra, 2016). The receptionist cannot be followed up if there is no way to prove if she is doing her job well. The only way to do so is by having the contacts of the customer. This is to make sure that the information provided by the receptionist can be verified(Coghlan, D, Teresa, B, 2014). Asking for the landscapers number The number of the landscaper will be used in proving if he is on voicemail as the customer claims. At the same time, I would be taking the number so as to make sure that it is a genuine number which is owned by one of the landscapers from the Association(Certo, 2015). The customer might have been provided with the wrong number mistakenly. The receptionist must be given a chance to give her side of the story. I would ask her if the services she provided to the customer are of good quality. To prove if the information provided by the receptionist is true, I would make a call to the customer. The customer has the right to good services, and for this reason, I must hear her side of the story. The whole case must be followed up in a way that every party that is affecting the work of the receptionist must be consulted. The landscaper must give reasons why his phone is on voicemail and why he does not receive or answer the calls of the customers. If it is true he does that; then the receptionist is suffering because of his negligence and unreliability. Therefore, the landscaper ought to make things clear so as the whole issue can be dealt with. Enquiring if there are more available landscapers The receptionist stated that there were no other landscapers and that the customer had no choice than to keep on waiting on the unreliable landscaper(Zurich, 2017). Therefore, to make sure that the information provided to the customer is true and reliable, I would take the initiative of finding out if it is true that there are no more free landscapers. The truth about the issue will dictate the type of action that should be taken(Woodside, R Tricia, M, 2016). The last and most important step would be taking action. If it is true that the landscaper has been ignoring the customers, I believe he is of no use to the association and that he should reform or be fired(Moore, 2014). If it is a lie that there are no freer landscapers, the receptionist will face a disciplinary action because she failed in providing quality services to the customer. Steps to determine how LNA Masters Landscapers Association could deliver better service to the customers seeking referrals The following flow chart looks at all aspects of how the Association can take its services to a higher level. Bibliography Certo, S., 2015. Supervision: Concepts and Skill-Building. New York: McGraw-Hill Higher Education. Coghlan, D, Teresa, B, 2014. Doing Action Research in your Organization. Boston: SAGE. Cummings, T, Christopher, G, 2014. Organization Development and Change. Boston: Cencage Learning. Dabholkar, P., 2015. How to Improve Perceived Service Quality by Increasing Customer Participation. Proceedings of the 1990 Academy of Marketing Science (AMS) Annual Conference. Berlin: Springer International. Helo, P, Gunasekaran, A, Rymaszewska, 2017. Managing Service Delivery. In Designing and Managing Industrial Product-Service Systems (pp. 49-56). New York: Springer International Publishing. Johnson, R, Clark, G, 2008. Service Operations Management: Improving Service Delivery. New York: Pearson. Mitra, A., 2016. Fundamentals of Quality Control and Improvement. New York: John Wiley and Sons. Moore, S., 2014. The Mediation Process: Practical Strategies for Resolving Conflict. New York: John Wiley and Sons. Woodside, R Tricia, M, 2016. Generalist Case Management: A Method of Human Delivery. Boston: Cencage Learning. Zurich, L., 2017. Service Operations and Management.

Role of Women in the Odyssey free essay sample

These ones can be seen as women in power because they use these tools in order to control men. Mothers portrayed in this epic poem are seen as the givers of â€Å"pity and sorrow† rather than true supporters of their sons and husbands when in war. In most cases, these are women who need to be guided and supported by males, whether it be a son or a husband. An example of this would be when Telemachus ordered Penelope from the room, in order to show the suitors of his intention to claim to his father’s throne. Another example would be Anticlea, Odysseus’ mother. She committed suicide because she missed Odysseus and believed he was dead. Mothers need to look after, nurture, and protect their sons and husbands. I’d say Penelope is the most complex woman I have ever read about. She is both a mother and sometimes a seductress. We will write a custom essay sample on Role of Women in the Odyssey or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page She leads the suitors on and makes them wait. She is not ready to marry again. â€Å"It is your mother’s fault not ours, for she is a very artful woman. This three years past, and close on four, she has been driving us out of our minds, by encouraging each one of us, and sending him messages without meaning one word of what she says† (Book II). Penelope mourns her lost love, and at first is completely oblivious to the attention from the suitors. She reminds me of a Siren, (seen in book 11) always singing to encourage men but not intending to fulfill any promise of love or sex. Penelope is the perfect example of a woman in the novel that is a mother, and sometimes a seductress. During the absence of her son Telemachus, she begins singing about the deadly battles where she assumes Odysseus has perished and falls to weeping. When Telemachus returns, he knocks some sense into Penelope. Odysseus is not the only man who never came back from Troy, but many another went down as well as he. Go, then, within the house and busy yourself with your daily duties, your loom, your distaff, and the ordering of your servants; for speech is man’s matter, and mine above all others- for it is I who am master here† (Book 1). The sirens and Circe are the ultimate seductresses in the epic poem. Circe turns Odysseus’ men into pi gs and tells him she will change them back only if he goes into bed with her. Odysseus does not realize that he stays in bed with her for about a year or so. Sirens sing to men at sea and make them fall in love with them and then eat them. These are great examples of seductresses. However, I believe Clytemnestra is another good example. She is Agamemnon’s wife and during his absence, suitors too surround her. Clytemnestra also went through a deep mourning and shows that women who are mothers and are devoted to their husbands, sons, and family, are prone to look for other men, in their absence. Clytemnestra falls in love with Aegisthus and they plot to kill Agamemnon when he returns. At first she would have nothing to do with his wicked scheme, for she was of a good natural disposition; moreover there was a bard with her, to whom Agamemnon had given strict orders on setting out for Troy, that he was to keep guard over his wife† (Book 3) but he was gone too long and she fell in love with someone else. In â€Å"The Odyssey† by Homer, Homer really describes women as people who are weak and fragile. He depicts women to be p rone to find another male figure in their absence (a long absence). Women in this story need men in order to feel like they are fulfilling their destiny by looking after, nurturing, and protecting their sons and/or husbands. Penelope and Circe are good examples of women in power in â€Å"The Odyssey† because Penelope uses her mother figure to in a way control Telemachus and uses seduction to control the suitors and keep them in the palace and Circe tells Odysseus she will change his men back to humans IF and only IF he goes to bed with her. I think women really do play a large role in â€Å"The Odyssey. †

Horace Boigraphy essays

Horace Boigraphy essays Quintus Horatius Flaccus was born at Venusia, Italy, Dec. 8 65 B.C.E and died in Nov. 27 8 B.C.E (Crystal, crystalinks.com/horace.html). He is recognized as one of historys greatest poets. Horace was a humble person, for this he was loved by all his friends. He had very few enemies. His favorite subjects for poetry were love and nature. Later in his life he went from writing poetry to writing philosophy (Gilleland, kirjasto.sci.fi/horatius.htm). There were many things that affected Horace in his youth which influenced his adulthood. Horaces father was a freed slave and found employment in the areas of tax collecting and as an auction broker. Horace lived a modest childhood (Crystal, crystalinks.com/horace.html). Even though his family was barely getting by, Horaces father made sure that Horace got the best education possible. At a young age, Horace was sent to Athens to study, and after went to Rome to find a career. Horace always expressed his gratitude towards his father for getting him a good education and teaching him deep-rooted morals. Horace joined the army at the age of nineteen. He fought on the side of the conspirators, Brutus and Cassius, as a military tribune, which was exceptional for a freemans son. When the war was lost, all his assets were seized and he was forced to return home penniless. Along with living a modest childhood, war greatly humbled Horace. By the age of twenty he had already experien ced loss, death, and tragedy, which made him want no more excitement in his life (Gilleland, kirjasto.sci.fi/horatius.htm). Horace was a renowned writer. He was known mostly for his poems. Earlier in his career, his poems were about love, pleasure, wine, friendship, and the beauty of a simple life. Later in his life, his subjects turned more serous, involving the race for power and position, the folly of extremes, the desirability of ...

Julissa Brisman and the Craigslist Killer

Julissa Brisman and the Craigslist Killer On April 14, 2009, Julissa Brisman, 25, was meeting a man named Andy who had answered a masseuse ad that she had placed in the Exotic Services section of Craigslist. The two had emailed back and forth to arrange the time and agreed on 10 p.m. that night. Julissa had an arrangement with her friend, Beth Salomonis. It was a security system of sorts. When someone would call the number Julissa had listed on Craigslist, Beth would answer the call. She would then text Julissa that he was on the way. Julissa would then text Beth back when the man left. At around 9:45 p.m. Andy called and Beth told him to go to Julissas room at 10 p.m. She sent a text to Julissa, with a reminder to text her when it was over, but she never heard back from her friend. From Robbery to Murder of  Julissa Brisman At 10:10 p.m. the police were called to the Marriott Copley Place hotel in Boston after hotel guests heard screams coming from a hotel room. The hotel security found Julissa Brisman in her underwear, lying in the doorway of her hotel room. She was covered in blood with a plastic zip-tie around one wrist. EMS rushed her to Boston Medical Center, but she died within minutes of her arrival. At the same time, the investigators were looking at hotel surveillance photos. One showed a young, tall, blond man wearing a cap on an escalator at 10:06 p.m. The man looked familiar. One of the detectives recognized him as the same man who Trisha Leffler had identified as her attacker just four days earlier. Only this time his victim was beaten and shot to death. The medical examiner said Julissa Brisman had suffered a fractured skull in multiple places from being hit with a gun. She was shot three times- one shot to her chest, one to her stomach and one into her heart. She had bruises and welts on her wrists. She had also managed to scratch her attacker. The skin under her nails would provide the DNA of her killer. Beth called Marriott security early the next morning. She had not been able to get in touch with Julissa. Her call was routed to the police and she received the details of what had happened. She hoped by providing the investigators with Andys email address and his cell phone information that it would be of some help. As it turned out, the email address proved to be the most valuable clue to the investigation. The Craigslist Killer Brismans murder was picked up by the news media and the suspect was dubbed the Craigslist Killer (although he is not the only one that has been given this moniker). By the end of the day following the murder, several news organizations  were aggressively reporting on the murder along with copies of the surveillance photos that the police had provided. Two days later the suspect emerged again. This time he attacked Cynthia Melton in a hotel room in Rhode Island, but he was interrupted by the victims husband. Fortunately, he did not use the gun that he had pointed at the couple. He opted to run instead. Clues left behind at each attack led the Boston detectives to the arrest of 22-year-old Philip Markoff. He was in his second year of medical school, engaged and he had never been arrested. Markoff was charged with armed robbery, kidnapping, and murder. Those close to Markoff knew the police had made a mistake and arrested the wrong man. However, over 100 pieces of evidence had turned up, all pointing to Markoff as the right man. Death Before there was a chance for a jury to decide on who was right, Markoff took his own life in his cell at Bostons Nashua Street Jail. The Craigslist Killer case ended abruptly and without the victims or their loved ones feeling like justice had been served.

Homosexual Parents and Capability of Providing Care and Guidance Research Paper

Homosexual Parents and Capability of Providing Care and Guidance Needed by the Children - Research Paper Example Since gay parenting has a significant influence over the sexual orientation of the children, many people are prejudice with regards to lesbian and gay parents. As part of protecting the best interests of the children, gay parents often loss physical custody or being prohibited over the right to adopt children (Appell, 2003). On the contrary, Tobin and Mcnair (2009) argued that empirical evidence proves that there is really no concrete evidence for considering the sexual orientation of parents in assessing their capability to adopt a child. There are some studies revealing that lesbians and gays are not allowed to foster care or adopt children for the reason that gays are considered mentally ill making lesbians less maternal as compared to women who are heterosexual. It is also possible that the type of sexual relationship that gays and lesbians have usually allowed them little time to be involved in the actual parent-child interaction. On the contrary, the study of Vanfraussen, Ponja ert-Kristofferson, & Brewaeys (2003) revealed that the parent-child interaction among lesbian couples is fairly the same as compared with the heterosexual parents. In reality, there is no single empirical study that can prove that lesbians and gays are not capable of becoming a good parent. In line with this, there are several studies showing no significant difference between the way lesbians and heterosexual women could rear a child nor there was any difference in the mental health condition of the two groups of individuals.

Argument analysis Essay Example | Topics and Well Written Essays - 750 words - 2

Argument analysis - Essay Example out the themes and concepts of passive objectification of women, asexuality as a foil, vigilant heterosexuality and athleticism as a sexual performance. The paper analyses the movie Catwoman (Pitof 2004) by discussing the themes that have been discussed by Helene Shugart in her article. The movie Catwoman stars Patience Phillips (Halle Berry), who is a graphic designer working for an organization called Hedare Beauty. This is a very large cosmetic company that has realized considerable market success, and is about to release into the market a product that combats the effects of aging. Patience later discovers that Hedare’s operations are riddled in conspiracy and secrecy. She discovers deep secrets concerning the about to be released beauty product, but just as she is about to leave the premises, security personnel starts pursuing her. Patience is forced to run for her life. Dramatic events follow, and later we see her being transformed into a woman with cat-like traits; elusive, dangerous, untamed, fast and with senses of her cat. Therefore, Patience is changed to Catwoman. However, she has a double personality; on one side she is Patience, and on the other she is Catwoman. Catwoman’s starts fighting crime in the city and also helps the helpless. She is accused by the Hedare family for murder, but this does not deter her from soldiering on. The authorities chase her day and night for murder charges, and this search is led by Tom Lone, who is in a relationship with Patience. At the end, Patience becomes the hero. She manages to get her revenge on the Hedare family and she still continues to be the people savior. Therefore, from the movie Catwoman, the producer portrays women as the suppressed gender by the society. Society considers the woman as the weaker sex, and the producer of the movie is using the case of Patience to empower women. In the movie, Patience is faced with very many problems and challenges. At the end, she defies all odds and she becomes

Supply Chain Strategy Essay Example for Free

Supply Chain Strategy Essay What recent changes have caused supply chain management to gain importance? 2. With so much productive capacity and room for expansion in the United States, why would a company based in the United States choose to purchase items from foreign firm? Discuss the pros and cons. The use of foreign firms can provide a U. S. firm more alternatives in selecting a supplier. The pros are more choices, potentially reduced costs in the areas of materials, transportation, production, and distribution, and potentially moving closer to a foreign market. The cons are the distance is generally increased, communications problems are increased due to distance, culture, and technology. There may be problems with customs, government regulations, political stability, etc. 3. Describe the differences between functional and innovative products. Functional products are staples that people buy in a wide range of retail outlets. Typically, they do not change much over time, have low profit margins, stable predictable demand and long life cycles. Innovative products, on the other hand, give customers additional reasons to buy. Fashionable clothes and personal computers are examples of innovative products. Innovative products have short life cycles, high profit margins, and volatile demand. 4. What are characteristics of efficient, responsive, risk-hedging and agile supply chains? Can a supply chain be both efficient and responsive? Risk-hedging and Agile? Why or Why not? As a supplier, which factors would you consider about a buyer (your potential customer) to be important in setting up a long-term relationship? The financial stability and credit worthiness of the company is of primary importance. The reputation of the company visavis their supplier is also very important. For example, is this a company that is fair with its suppliers and honors its payables in a timely fashion? Is the technological match between supplier and customer sufficient? Will delivery schedules and quantities be stable, facilitating smooth operations? For the value density example in Exhibit 10. 9, what would the effect be if a competing firm offers you a similar service for 10 percent less than Federal Express’s rates? 7. What are the advantages of using the postponement strategy? Process postponement delays the process step that differentiate the product to as late in the supply chain as possible. The advantages of this approach are that lower levels of inventory, and fewer models are needed to match customer requirements. This results in higher levels of customer satisfaction at a lower cost.

Andina Bottling Company Case Essay -- Business Cola Products Latin Ame

Andina Bottling Company Case Andina is a major distributor of Coca-Cola products in Latin America. The market for soft drinks is very competitive in Latin America. The dominate brands are not necessarily Coca-Cola or Pepsi brands. For a company to succeed in the distribution and manufacturing of soft drinks in Latin America, they need to be efficient. The plants need to work at capacity or close to it. The distribution also has to be logical. It is not worth it for them to sell to less populated mountain areas. The point of the new system that Andina is introducing is going to make sales, distribution, and manufacturing easier. The three countries are going to share their information with each other. Control panel and the rest of the system will be successful if Andina can convince each country that they can trust it. Andina is doing a good job of trying to unite the three subsidiaries through Control Panel. For Andina to succeed in the bottled drinks manufacturing and distribution business, they need to be the most efficient that they can be. There are many bottled drinks in Latin America. There are many knock-offs of Coca-Cola as well. Andina is facing a lot of competition. They need to make sure that they are selling to a larger audience and not to a smaller one. There is no point in concentrating a large amount of your sales force on a mountain area or one that is spread out over some distance unless there is a large population that the drink is marketed to. If the mountain region makes up less than 5% of the company’s sales, they should try to focus on a more populated area with more of a target market. In the case, it talks about how this happened in Argentina. They had 25,000 clients that accounted for only 3% of their sales, (10). The distribution costs were incredibly high on these customers. The smaller clients were raising their distribution costs because deliverin g a case here and a case there adds up. When it comes to manufacturing, the company needs to make sure that they have enough outputs for the demand. Also the sales force needs to target the correct market. If the sales force focuses on a market with low consumption, their sales are not going to be as good as a market with high consumption. With the implementation of the new system and control panel, Andina is trying to bring their company together. T... ...elped solve. In order for Control Panel to work fully, Andina corporate needs to convince their Brazilian subsidiary that the Control Panel is here to help not hurt them. Also it seems like a case of the managers being afraid of losing their jobs to other managers such as one from Chile. The corporate headquarters needs to reassure them that Control Panel is not a way to fire the employee but there to help them do their job more effectively and efficiently. Maybe a training session with the employees could help boast their confidence in the system. For the managers in Brazil, they could hold like a managers retreat and inform them of how useful the whole system and it components are. They could also try to reassure them that they will not be losing their jobs because of the implementation of the new system. Andina is making a very good effort to combine their company. They seem to be willing to work with each subsidiary to try and make the manufacturing and distribution processes easier. They need to continue to take the path they are currently on. They also need to keep reassuring their subsidiaries that this new system and all it components are there to help not destroy.

History of education Essay

â€Å"Education is the most powerful weapon which you can use to change the world. † –Nelson Mandela The importance of learning is to enable the individual to put his potentials to optimal use. Education makes man a right thinker and a correct decision-maker. It achieves this by bringing him knowledge from the external world, teaching him to reason and acquainting him with past history, so that he can be a better judge of the present. With education, he finds himself in a room with all its windows open to the outside world. A well educated man is a more dependable worker, a better citizen, a centre of wholesome influence, pride to his community and honour to his country. A nation is great only in proportion of its advancement in education. Education is Self Empowerment. Receiving a good education makes a person strong enough to look after himself in any given situation. It keeps him aware of the given surrounding as well as the rules and regulations of the society. It’s only through knowledge that one can question authority for its negligence or discrepancies and only then that can a person avail his rights as a citizen and seek improvement in the structural functioning of governance and economy. As a whole, people can bring about development only when they know where improvement is necessary for the greater good of mankind. Education gives a better understanding to the person, it helps realize potential and qualities one possesses as a human being. It helps tap into latent talent, so that people can sharpen their skills. Education teaches what man lives and struggles for. It cultivates an integrated life. By so doing, it gives significance of life. It helps restores financial stability and dignity of life. It is the essential basis of a good life. Education enlightens and lifts a nation to heights of progress. The problem in India is that it has adopted democracy without preparing the ground for it by educating population. But its never too late to undertake mass programmes of Adult education or Social education. Adult education is the education of grown up men and women. In the complex modern times, people must be knowledgeable and be aware of what they are doing and what is being done to them. To create such sentience every responsible citizen should take up this social cause and educate the knowledge deprived people. Teaching a daily worker for just an hour daily can change their lives in propitious ways as it was rightly quoted by Neil Armstrong, ‘One small step is a giant leap for mankind’. In recent history our country has taken up good measures to ensure a high educated population by taking up several social causes and concentrating on the rural areas, since they comprise a majority but the system has been laid back due the restraints imposed by old cultural ethics. For the past few centuries in India, the girl has been completely neglected even as a human being, her sole purpose of life has been to feed the family and bear a child. Good education has been denied to women. It is argued that women have their domestic duties to perform and that, if they were educated, they would bury themselves in their books and have little time for attending to the management of their households. But what people fail to understand is education involves knowledge of the means by which health may be preserved and enable a mother to consult such modern books as will tell her how to rear up her children into healthy men and women and skilfully nurse them and her husband, when disease attacks her household. The purpose of education is not just earning a livelihood but education makes an individual into a good human being, which is passed on to the next the kith and kin. It is true that, the education of girls has lately taken a slight leap but this is only in a very small segment of Indian society. Unless the motion is fast and continuous, and includes more of poor urban and rural girls in the field of education, there can be no hope of having a developed and first world country status for India. â€Å"When a man is educated, only he is educated but, when a woman is educated, a family is educated. † – Indira Gandhi â€Å"Education is the great engine of personal development. It is through education that the daughter of a peasant can become a doctor, that the son of a mineworker can become the head of the mine, that a child of farworkers can become the president of a great nation. It is what we make out of what we have, not what we are given, that separates one person from another. † – Nelson Mandela.