Medtronics Strategies

Description of the Situation Medtronic was established in 1957 by Earl Bakken who made a great contribution in the development of pacemakers (Christensen, 2002). The company became the leader in the sphere of pacemaker production.Advertising We will write a custom case study sample on Medtronic’s Strategies specifically for you for only $16.05 $11/page Learn More There were two major factors that secured the company’s leading position. In the first place, the company had a few competitors at that time. Medtronic came up with really helpful products which met consumers’ requirements and expectations. The company had a considerable portion (about 70 per cent) of the market share in 1960s. However, the company faced a lot of difficulties in 1970s up to 1986. First, many competitors entered the market. Secondly, many talented employees left the company as the company’s competitors offered more favorable conditions and were regarde d as more promising. The quality of Medtronic’s product decreased. The company failed to develop new products which could fit rapidly changing demands of consumers. More so, employees argued that one of the major problems was that there were far too many ideas and projects which led to many failures (Christensen, 2002, p. 4). Finally, inappropriate communication within the company negatively affected the company’s performance. In 1986, however, the things changed. Ken Anderson managed to obtain the support of executive to launch a new product which proved to be very successful.Advertising Looking for case study on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Activitrax, the new product developed, was one of a kind as it paced patients’ hearts to â€Å"beat more rapidly when they were working hard† and, at the same time, it paced â€Å"their hearts to beat more slowly when they were asleepâ €  (Christensen, 2002, p. 4). This made the patients feel stronger. This product made Medtronic a leader again. However, it is important to note that it is not about the product itself. Mike Stevens reshaped the company’s strategies to make it one of the world leaders. Thus, Stevens managed to improve communication within the company. He also reshaped the process of decision making. He outlined several key processes which optimized the process of product development. The major principles Stevens pursued were: speed, platform strategy, project documentation, phase definition, rhythm, and market inputs. Stevens’ actions proved to be successful as Medtronic is now one of the world leaders in the sphere. However, now the company faces a great challenge as it needs to hold the high position, which can be rather difficult. Evaluation Criteria When analyzing challenges the company faces, it is important to focus on such factors as product development strategies, communicat ion within the company, human resources management and marketing strategies. These factors can considerably affect the development of the company. It is important to provide an in-depth analysis of these factors as it will help to work out the most successful strategies which will help the company to maintain its leading position. Evaluation of the Situation In the first place, it is important to analyze communication within Medtronic. Stevenson has changed it considerably. In the first place, it is important to note that oral-based patterns were largely changed into written-based ones.Advertising We will write a custom case study sample on Medtronic’s Strategies specifically for you for only $16.05 $11/page Learn More In other words, when some important decisions are made, certain written reports are made where all the major points are revealed. Thus, employees involved in this or that project have an opportunity to stick to the plan. Of course, there can hardly be misunderstanding when departments have such reports on most important projects. Apart from this, there is proper communication between departments which eliminates (or at least minimizes) any delays. As far as product development strategies are concerned, the company’s platform strategy enables the company to develop products at lower costs and in a shorter period of time. Thus, the company does not need to develop new platforms for new products very often as they develop the platform that can be adjusted in different directions according to certain parameters. Admittedly, this reduces the time span which, in its turn, enables the company to introduce new products which meet various requirements of the rapidly changing market. Besides, the company focuses on patients’ needs when developing new products. For instance, there is a need to develop a pacemaker which is safe in MRI environment and Medtronic has been working on such kind of product (Sutto n et al., 2008). Thus, the company develops products which are potentially successful as they meet specific requirements of consumers. Furthermore, the marketing strategy of the company is also winning. For instance, the company has worked out a consumer-oriented marketing strategy. Thus, the company focuses on customers’ needs. The company also collaborates with healthcare institutions to raise awareness about the advantages of pacemakers.Advertising Looking for case study on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More It is also important to note that the company has reshaped its pricing policy. Now the company provides low cost pacemakers at low prices while setting fair prices on other models. As far as human resources management is concerned, it is important to note that the company invests in its staff. The company keeps coaching and training its employees. However, there is rather high rate of turnover: many highly skilled employees tend to leave the company. Therefore, it is important to focus on these issues. Structured Discussion of the Strength, Weaknesses, Risks and Opportunities Strength One of the company’s strengths is its platform strategy. This strategy has enabled the company to become one of the world leading pacemaker manufacturers. Thus, Medtronic introduces more new products at a shorter period of time. The company’s new marketing strategy is also a winning one. It enables the company to successfully market new products. The company has also chosen a customer-ori ented strategy. Therefore, Medtronic tries to understand real needs of pacemaker users to come up with ideas to meet those requirements. Finally, the company’s project management has also been improved drastically. The projects are carried out in accordance with specific plans and particular deadlines. Weaknesses One of the weaknesses of the company is that it still loses employees. Thus, people who have been trained are leaving to join other companies. This negatively influences the company’s performance. Of course, this trend should be changed so that the company’s investments into its employees can be repaid. Risks Though the company has become one of the leading pacemaker producers, there are still several challenges. In the first place, the company has come up with really successful products. Thus, there are concerns that there will be no opportunity for further development (Christensen, 2002). Thus, the company’s engineers will need to be really pre cise and far-seeing. Medtronic â€Å"brings into fashion† new products which are highly valued. Therefore, it is extremely important to maintain high quality of products and unique approach of the company. Opportunities Nonetheless, there are a lot of opportunities to develop the business. In the first place, the pacemakers still need improvements to meet specific need of the patients. The company is now working on new models to meet these requirements. Sutton et al. (2008) report on one of such projects. Apart from opportunities concerning product development, the company has many opportunities in the sphere of marketing. In the first place, the demand of pacemakers is now increasing in developed countries as ‘baby boomers’ are reaching the age when pacemakers are necessary. At that, the number of competitors has drastically decreased over the past decade. More so, economic growth in many developing countries of Asia, Eastern Europe and South America has made pa cemakers affordable for many citizens of those countries. It goes without saying that this market offers many opportunities for Medtronic. Qualifications It is important to note that the company has developed effective project management strategies. Thus, all projects are planned in detail. Employees have to report about the work completed at certain stages (or phases). This helps to meet the deadlines and, as a result, to introduce new products on time. Evaluation Action Plan Strength The company’s platform strategy has proved to be effective. Therefore, it is important to keep to it. Thus, the company will continue developing platforms which can be adjusted in accordance with numerous parameters. However, it is also important to keep working on creation of new platforms which can meet consumers’ requirements that constantly appear. As for the company’s marketing strategy, it also needs special attention. The company should work out successful strategies to ent er the market of developing countries. However, the company should work out specific programs for each country. It is essential to make sure that strategies chosen can be effective in this or that region. This is quite a great challenge the company has to face. As has been mentioned above the company has chosen a consumer-oriented approach which is winning in present-day environment. Of course, the company will need to carry out surveys and some research to define the features which can be valued by patients as well as cardiologists. Finally, the new project management strategies exploited have enabled the company to regain its leading position. However, the company has to make sure the phase strategy remains effective. Thus, it is always important to make sure that the plans worked out are executable and deadlines are realistic. At the same time, the plans should be rather flexible to be effective in the rapidly changing market. Finally, the company should pay special attention to communication strategies. Many companies are often overwhelmed by bureaucratic trends. Thus, written and oral communication should be balanced in Medtronic. Weaknesses It is also important to deal with human resources management strategies. Thus, Stevenson claims that they pay much attention to their employees’ development (Christensen, 2002). However, the company still loses employees. Therefore, it is important to work out a new system of values to make employees more loyal. Apparently, coaching and training are not enough. It is necessary to provide more opportunities for promotion. Apart from this, the employees should have more freedom to bring their ideas to life. For instance, Christensen (2002) states that some employees have left the company to be able to realize their ideas, which was impossible within Medtronic. Thus, the company should address this issue to make the employees more loyal. In this way, the company’s investments into the staff will be repaid. Reference List Christensen, C.M. (2002). We’ve got rhythm! Medtronic Corporation’s cardiac pacemaker business. Harvard Business School, Case 698-004. Sutton, R., Kanal, E., Wilkoff, B.L., Bello, D., Luechinger, R., Jenniskens, I., Hull, M. Sommer, T. (2008). Safety of magnetic resonance imaging of patients with a new Medtronic EnRythm MRI SureScan pacing system: Clinical study design. Trials, 9(68), 1-8. This case study on Medtronic’s Strategies was written and submitted by user Maleah Pate to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Learning and Personal Development Plan Essay Example

Learning and Personal Development Plan Essay Example Learning and Personal Development Plan Essay Learning and Personal Development Plan Essay Assessment 1: Developing Yourself as an Effective HR/LD Practitioner Core Unit for CHRP and CLDP Learning outcomes: 1. Understand the knowledge, skills and behaviours required to be an effective HR or LD practitioner. 2. Know how to deliver timely and effective HR services to meet users’ needs. 3. Be able to reflect on own practice and development needs and maintain a plan for personal development. All activities below should be undertaken: Activity A – 600 Words Write a short report on: . the concept and importance of Continuous Professional Development (CPD), 2. the knowledge, skills and behaviour required to be effective in an HR or LD role as per the CIPD HR Map. In your report you should present the CIPDs HR Profession Map, discussing: 1. at least 3 professional areas, two of which must be Strategies, Insights and Solutions and Leading, and Managing the Human Resources function and 2. all eight behaviours. Activity B – 900 Words Write a report that: 1. Identifies at least 3 users of HR services within an organisation and for each user list at least 2 key needs and explain how conflicting needs can be prioritised effectively. 2. Identify at least 3 methods of communication appropriate to employees at different levels 3. Describes the key components of effective service delivery including: a. building and maintaining good relationships, b. handling and resolving complaints, c. dealing with difficult customers, d. timely service delivery, e. budget implications and f. continuous improvement Activity C – PERSONAL DEVELOPMENT PLAN (Final assessment) No Word Limit At the beginning of the course you are required to undertake a self-assessment of capabilities as an HR or LD practitioner against the CIPD Associate Membership requirements to: 1. Identify your professional development needs. 2. Evaluate at least 3 options to meet the development needs identified, 3. Produce a Personal Development Plan to meet set objectives, At the end of the course you will be required to: 1. Reflect on performance against the plan, 2. Identify learning points for the future and, 3. Revise the plan by reviewing what you have learnt from each unit against the plan and adjusting development needs accordingly. Please note: You will need to submit a draft of Activity C to be marked at the beginning of the course. The deadline for this is the same as the one set for Activity A and Activity B. Furthermore, at the end of the course you will receive a second deadline in order to submit your final version of Activity C. Please discuss this with your tutor if you have any questions.

Empowerment and innovation change in workplace Essay

Empowerment and innovation change in workplace - Essay Example While performing the employee empowerment program care should be taken to provide maximum satisfaction to the employees. This will result production hike and thereby the customer satisfaction can be maximized. If there are technical difficulties in implementing empowerment program, then a cultural change is essential for the whole organization. The authorities must try to learn the requirements of the employees for dedicating themselves to promote result oriented work. People have different views regarding the nature of empowerment programs to be implemented. For different organization the structure of empowerment will be different. These variations are according to the requirements of each organization. The developmental background and the processing of procedures for empowerment implementation are entirely different with respect to organizational point of view. Moreover the working media, the type of work carrying out and the time frame of work are the various aspects which are to be considered before designing and implementing employee empowerment programs. The need of empowerment in an organization is a kind of work redesigning process. Before redesigning is carried out in an organization the authorities must make sure decisions regarding the innovations to be employed in the work front. They must make a confirmative effort to find out the section of the organization which needs the innovation. The organization expects well cooperated performance from the employee side. For achieving this feat the working environment of the natural work group should be enhanced considerably. Since the concept behind the working classes is highly complicated it should be dealt with utmost care. The very important part that we can observe in social work group empowerment is social interaction. These enable employees to socialize on works entrusted to them. The interaction should be purely task based. If

Bilingual Education for Americans Research Paper

Bilingual Education for Americans - Research Paper Example In the United States, Bilingual education focuses on the learners of English. The United States Department of Education notes that a bilingual educational program is an education program for limited English proficient students (ed.gov/). It is this definition that has remained in the federal government but there are several areas where it has fallen out of favor. This is because such a definition more or less shows that the student needs or requires support in the English language for him or her to succeed academically. In almost all, if not in all the states, there is a general feeling by the groups pushing for bilingual education system that it does not help to have this idea and they also do not find a justification for such a definition. History has it that the earliest instance of bilingual education in the United States occurred with the immigrants from Poland who first permanently settled in an English speaking area of Virginia. At this time it was only the rights of the Engli sh people that were recognized. It was as a result of the need that the English had for the skills of the Poles that got similar rights to the Englishmen and managed to establish a bilingual school (Seidner, p.72). In this school, the subjects were taught in both Polish and English, and this continued in other places in one form or system or another. It expanded to Native Americas, the Dutch, the Czech, the Germans, French, Spanish and Norwegians in the century that followed. Several states developed laws to address this issue depending on the demands of the foreigners. There are groups that believe that a bilingual education should be necessary, even if temporarily so as not to discriminate against foreign-born students, or bring them up to speed. On the other hand, there those who claim that English should be the national language, and until every student is proficient in English, the fact that they have the ability to speak another language hinders their development in the Englis h language and slows down the overall process of learning in America. Although most initiatives against bilingual education have always had a majority lead when it comes to this issue, I hold the opinion that the world has become a global village. As such, I believe that a bilingual education should be mandatory for Americans, starting in Elementary school, through secondary school and even in the collegiate levels as the need may require. This position is highly based on the fact the number of immigrants whose children are at the age of attending school but speak very little or no English, are denied the benefits of being able to attend school at the appropriate age. In most cases there is usually a sort of remedial classes that they have to attend where they are taught only English before they get the opportunity to become part and parcel of the main school curriculum. In a system of Bilingual education, the necessity of such classes would not be fundamental and the children will be able to learn without any regard of the language that they speak at home or with which they grew up. This is because the curriculum would include their language too. The Advantages of Having a Bilingual Education System They hold the opinion that it does not help to keep non-English speaking children out school for them to master the English langu

Rat Temple in India Essay Example | Topics and Well Written Essays - 1000 words

Rat Temple in India - Essay Example Considering the norm with Hindu temples, one must remove their shoes when they enter this temple. In addition, one must be careful not to step on them as that would be considered unholy; and if a rat dies because of being stepped on, it is expected that whoever killed it should replace the rat with a gold or silver statue of the same weight as the rat, for atonement. There are chains and grills positioned all around the enclosure of the temple, to protect the rats from predators such as birds. Inside the temple also, there are caretakers and priests that reside with their families and clean away the excrements of the rats, whilst ensuring they are fed. Foodstuffs such as coconut shells are scattered around the temple for the rats to feed on and milk to drink served in pots (Kaushik). Karni Mata’s rats are treated as deities due to the Hindu’s belief in samsara which is the cycle of transmigration that one undergoes when they die and are reincarnated. The legend’s origins can be traced to the goddess of influence and victory, Durga who was reborn as Karni Mata that came to be a spiritual matriarch of the 14th century. In her life, one of members of her tribe lost their child and Karni Mata attempted to bring him back to life, only to be informed by Yama, the goddess of death, that he had by then been reincarnated. Following this, Karni Mata made an agreement with Yama whereby everyone from the tribe would be reincarnated as rats until the entire clan was reborn. This is in accordance with the Hindu belief that death signifies the end of one stage and start of another (Kaushik). Karni Mata temple completed at the beginning of the 20th century was designed in the late Mughal style, and Maharaja Ganga Singh of Bikaner was responsible for its completion and in 1999, Kundanlal Verma undertook further renovation. Born in October 1387, Karni Mata was the seventh daughter of Mehoji Charan and Deval Devi and they resided in Rajasthan; considered an h onorific name, Karni got it when she cured her aunt at the tender age of six years. Even though they did not live an ordinary matrimonial life, Karni Mata was married to Dipoji Charan. She had four sons who were reincarnated as white rats and are believed to bring luck if one spots them out of the other tens of thousands found within the temple this is because they are believed to be holy above all the rest (Karni Temple). The sophisticated, artistic sense of Indians can be noted with the intricate marble panels that line the entrance and floors of the Karti Mana Temple, and features silver and gold decorations all over. Linked to the royal family that ruled Bikaner, the nearby city, the Temple was established to provide greater power and protection to the family, as goddesses are believed to be directly involved in people’s personal lives. Thus, where a Hindu royal family seeking more power would establish a cult in favour of a goddess as is the case with Karni Mata and the worshipping of rats. Also deemed to be a blessing or sign of good luck, is sampling on food and water that has previously been nibbled on by the rats within the temple. In a bid to gain luck from sighting of the ‘special’ white rats, visitors of the temple offer Prasad, a sweet-tasting type of food. Proof of the holiness of these rats has been the fact that there has never been an outbreak of any

Staphylococcus Aureus: Structure and Functions

Staphylococcus Aureus: Structure and Functions Introduction 1.1 Staphylococcus aureus Staphylococcus aureus is an opportunistic yet versatile pathogen that can infect almost all types of tissue in the human body. 33-50% of healthy individuals were reported to be S. aureus carriers. The diseases resulting from S. aureus infection range from superficial infections; invasive infections such as endocarditis to the life threatening septic shock and toxic shock. The presence of foreign material greatly increases the risk of infection by providing a base for attachment and biofilm formation. S. aureus appears as clustered gram positive cocci under the microscope. Criteria used to identify this organism include the production of golden pigment on nutrient agar; being positive for coagulase; mannitol fermentation and the production of deoxyribonuclease. The virulence of the infecting strain and the nature of the host immune response are important determinants for the outcome of severe S. aureus infection . 1.1.1 S. aureus genome and regulation of gene expression S. aureus has a 2.8-2.9 Mbp circular genome. House-keeping genes and genes associated with central metabolism and some virulence determinants (e.g. protein A) are highly conserved among strains and make up the majority of S. aureus genome. The rest more variable regions mainly consists of mobile elements such as pathogenicity islands (SaPI, 7 identified), genomic islands (ÃŽ ½SaÃŽ ± and ÃŽ ½SaÃŽ ²), Staphylococcal chromosomal cassettes (SCC) and bacteriophages. S. aureus expresses an array of adhesins, immunomodulatory molecules; anti-inflammatory proteins and as many as 30 toxins to invade, evade and cause host tissue damage. Many of the virulence factors discussed below are encoded by genes located in the variable region. Their expression is under the control of a complicated and interconnected regulatory network . Four main gene regulators have been identified, including the two component regulatory system (agr, sae); the transcription factors (SarA and its homologous); the nutrient regulated CodY regulator and alternative transcription factor ÏÆ'B. agr is an auto-inducible quorum-sensing system, promoting expression of extracellular virulence factors and down-regulating cell surface proteins. ÏÆ'B has been shown to participate in the general stress response, and may be involved in antibiotic resistance; pigmentation; biofilm and micro-colony formation (referenced in ). Many surface proteins/adhesin have been shown to be positively influenced by ÏÆ'B, while the expression of most exoproteins and toxins were down-regulated. Activity ofthe agr system is influenced by other gene regulators and may be regulated by cell density. The transcription of agr components were found to be promoted by SarA and gene products of the sar locus and repressed by CodY. To add up the complexity, transcription o f the Sar locus was controlled by three promoters that can be differently activated during in vitro growth. One of these promoters was demonstrated to be ÏÆ'B dependent . It is generally regarded that exponential growth in vitro is correlated with the colonization phase of infection. Correspondingly, genes encoding surface proteins were found to be expressed earlier, starting during the transition from stationary to exponential growth while the expression of secreted proteins started at late-exponential growth phase. The in vivo situation of infection is likely to be more dynamic. Different stimuli trigger combined and coordinated action of the regulatory network, reflecting the particular state of bacterial growth, host defense and environmental nutrition. For example, phagocytosis by neutrophil triggered differential expression of 21.8-39.1% of S. aureus genes â€Å"at any time† following the event. The suppressive effect of CodY on S. aureus virulence factors lead to the possible suggestion that S. aureus may maintain its virulence factor to low level to ‘co-exist harmlessly with the host until a invading opportunity arise. In any case , it would be interesting to see how host immunological activity ‘feedback on S. aureus regulation of its virulence factors, especially immune evasion molecules. 1.1.2 Antibiotic resistance The rapid spreading of antibiotic resistant S. aureus strains through human communities presents a major challenge for conventional treatment. In 2005, it was reported that methicillin-resistant S. aureus (MRSA) infection caused more death than AIDS in USA. S. aureus demonstrated amazing ability to â€Å"co-evolve† with the development of antibiotics. The first generation penicillin uses ÃŽ ²-lactam to bind penicillin-binding proteins (PBP, bacterial transpeptidase) and inhibits bacterial cell wall synthesis. S. aureus resists this class of antibiotics by producing ÃŽ ²-lactamases (aka penicillinase) that cleaves ÃŽ ²-lactam. Second generation of penicillin, such as methicillin was developed. The structure of their ÃŽ ²-lactam has been modified to resist ÃŽ ²-lactamases. S. aureus soon acquired the mecA operon that encodes a modified PBP (PBP 2a), which showed reduced susceptibility for ÃŽ ²-lactam and thus granted resistance to all ÃŽ ²-lactam containing antibiotics. mecA is located on the staphylococcal chromosome cassette mec (SCCmec), a mobile genetic element that allows horizontal transfer of mecA between strains. MRSA infection shows increasing prevalence in all continents, primarily in healthcare-environments (HA-MRSA). Alarmingly, these strains have been shown to exhibit resistance to other types of commonly used non-lactam antibiotics such as ciprofloxacin and erythromycin. Vancomycin, a peptidoglycan polymerization inhibitor, is now considered as the last-line antibiotics for MRSA treatment. However, strains of vancomycin-intermediate S. aureus (VISA) have emerged. Notably, these strains have developed thicker cell walls that require higher concentrations of vancomycin to be effective (minimal inhibitory concentration MIC over 4ug/ml). A vancomycin resistant S. aureus (VRSA) strain has been reported recently (MIC >32 ÃŽ ¼g/ml). This complete resistance is most likely due to the horizontal transfer of the vancomycin resistant gene (VanA) from En terococcus faecalis. Development of effective new antibiotics against S. aureus has met with only limited success, urging the development of alternative therapies based on better understanding of the pathogenicityof S. aureus . 1.2 Adhesin / ECM interaction as key to S. aureus colonization/invasion Colonization is always the first step in bacterial infection and is an important component in pathogenesis. The wide range of tissues that S. aureus can infect reflects its ability to adhere and therefore colonize many different biological niches. S. aureus is now recognized as an invasive organism, targeting non-professional phagocytes such as keratinocytes, epithelial cells, endothelial cells and osteoblasts. The tasks of initial colonization and invasion are assisted by S. aureus surface anchored and secreted adhesive molecules known as MSCRAMM, microbial surface components recognizing adhesive matrix molecules and SERAM, secretable expanded repertoire adhesive molecules. The majority of MSCRAMM and SERAM bind extracellular matrix (ECM) proteins such as fibrinogen and fibronectin. In general, the interaction with ECM proteins is regarded as providing a ‘foothold for S. aureus to establish and to exacerbate infection. However, it has been reported that in some animal models l oss of fibronectin binding proteins (FnBPs) led to an increase in bacterial virulence, indicating a role of the ECM protein in limiting bacterial dissemination or enhancing bacterial clearance. Due to overlap in target specificity; functional redundancy and the difference in experiment settings, the exact contribution of each isolated staphylococcal adhensin protein remains ambiguous. Nevertheless, fibronectin (Fn) and fibrinogen (Fg) are the most popular targets of known S. aureus adhesins. The interaction between FnBPs and Fn is thought to play a key role in S. aureus internalization by non-phagocytic cells, as FnBP-coated latex beads and non-invasive bacteria expressing FnBPs were readily taken into the human cells (293 cells). Internalization provides several benefits for the bacterium: firstly, protection from host serum defense mechanisms and antibiotics ; secondly, access to nutrient-rich environments after escape from phagocytic vessels; thirdly, facilitating the crossing of the endothelial/epithelial layer and spreading of the infection; and lastly, establishing intracellular bacterial reservoirs for recurrent infection. S. aureus produces two related FnBPs (namely A and B) that contain almost identical Fn-binding domains in the close proximity to their cell-wall-spanning domain. The Fn-binding repeats of FnBPA were crystallized in complex with the N-terminal F1 modules of Fn. FnBPA peptide is inserted along the triple-stranded ÃŽ ² sheets of the Fn F1 module to form an antiparallel tandem ÃŽ ² zipper. Since the C-terminus of Fn interacts with ÃŽ ±5ÃŽ ²1 integrin that are expressed on most host cell surfaces, S. aureus can attach to the host cell through a Fn bridge. The attachment was shown to trigger the accumulation of actin and focal-contact-associated proteins (e.g. tensin) at the bacteria contact site and initiate internalization in a protein tyrosin kinase FAK-dependent manner. It was predicted that one FnBP can bind six to nine Fn molecules. This multivalent interaction was suggested to be important in mediating internalization . The bindings of Fg by the clumping factors (ClfA and ClfB) and FnBPA are mediated by a shared protein structure called the A domain and by a â€Å"dock, lock and latch† mechanism. Interestingly, Clf A is expressed during stationary phase and binds to the ÃŽ ³ chain of Fg. ClfB is expressed at the exponential growth phase and binds to the C-terminus of Fg AÃŽ ± chain. This portion of Fg has been reported to be involved in the coagulation process and wound healing . Fn and Fg interactions have been blamed particularly in S. aureus wound infection and infective endocarditis in humans. Fg binding alone could initiate experimental endocarditis in mice and has been correlated with valve colonization. However, cell invasion and persistence of the infection only occurred when the Fn-binding ability was enabled (via FnBPs). Both interactions were statistically correlated to disease severity. Binding to Fg and Fn simultaneously significantly accelerated the rate of internalization into cultured endothelial cells. In this regard FnBPA that is capable of binding both proteins may play an important role in establishing endocarditis . Platelets accumulation on the heart valve is another critical factor for the development of infective endocarditis. S. aureus-induced platelet aggregation is a complicated and multifactorial process and was suggested to be dependent on Fg or fibrin. FnBPA, ClfA, ClfB and SdrE (serine-aspartate repeat protein) were shown to be able to cause platelet aggregation independently of other S. aureus surface proteins. ClfA displayed the strongest aggregation effect among the last three. SdrE required the presence of plasma to cause aggregation, although the mediator was not identified. ClfA was proposed to interact with platelet indirectly through an Fg bridge or directly with platelet surface protein p118. Other studies have argued that ClfA-specific IgG also participated in platelet activation by cross-linking ClfA to platelet FcÃŽ ³RIIa receptor . 1.3 S. aureus toxinsdirect damage of host cells S. aureus produces a range of cytotoxins, including the ÃŽ ² barrel pore forming toxin (e.g. ÃŽ ± hemolysin); the two component pore forming leukocidins and the exfoliative toxin. Besides the effects of reducing viable phagocytes and weakening host immune system, S. aureus cytotoxins are currently believed to contribute to bacterial dissemination. Lysis of host cells might also provide nutrients for proliferating bacteria, especially iron from hemolysis . These toxins have different prevalence in different diseases. Exfoliative toxin (ET) operates at the epidermal layer of the skin and causes staphylococcal scalded-skin syndrome. ET-A acts as serine protease and specifically cleaves Desmoglian-1 (Dsg-1). Dsg-1 is a cell-cell adhesion molecule expressed on epidermal keratinocytes. Cleavage of Dsg-1 disrupts the superficial layer of epidermis and helps bacterial invasion. ÃŽ ±-hemolysin (Hla) is strongly implicated in S. aureus lung infections. Active and passive immunization of Hla strongly protected mice against S. aureus pneumonia. Hla is released as a water soluble monomer and oligomerises on the host cell membrane to insert the hydrophobic stem domains. Seven Hla monomers are required to form a pore which eventually leads to cell lysis. At sub-lethal concentrations of Hla, host cells produce pro-inflammatory cytokines like IL-8; IL-6; vasoregulators (PGI2, PGE2 and thromboxane), which could have detrimental systemic effect. The exp ression of twenty S. aureus virulence factors were disrupted individually or in combination and the virulence of the resultant deletion mutants were compared in a mice pneumonia model. Deletion of argA, which encodes a component of the arg gene regulation system, resulted in almost complete loss of virulence. Only the Hla deletion mutant produced comparable effects, indicating the importance of Hla in causing lung tissue damage. Human neutrophils can resist Hla lysis but these cells are targeted by Leukocidins. Leukocidins are thought to act in the similar way as Hla. Among the leukocidins, Panton-valentine leukocidin (PVL) is found in all CA-MRSA (community acquired-MRSA) isolates and strongly associated with CA-MRSA infection. However in mouse models of abscess, sepsis, and pneumonia, the severity of diseases caused by PVL- deletion strains were not significantly different from that caused by the wt strains. More surprisingly, PVL-expressing S. aureus strains did not lyse human ne utrophils better than that without PVL. However, it is not clear how these experimental conditions resemble the amount and time of PVL production during infection in human. Another significant problem is that PVL might be human specific and might not work in mice. Nevertheless, a new class of leukocidal molecules, the ÃŽ ± type phenol-soluble modulin (PSMÃŽ ±), was produced at a considerably high level by CA-MRSA. They were shown to contribute to the increased neutrophil lysis, skin lesion formation and mortality rate of experimental animals caused by CA-MRSA infection . 1.4 Interaction of S. aureus with host immune system 1.4.1 Brief overview of host defense against S. aureus Host defense against S. aureus mainly relies on the innate immune system, in particular, neutrophil mediated killing. The integrity of skin and mucosal layer is the first line of defense against invading bacteria. They also encounter antimicrobial substances released by epithelial cells and phagocytes (e.g. defensins; cathelicidins and lysosome). Defensins and cathelicidin are positively charged antimicrobial peptides that could permeate the bacterial membrane. Lysozyme is produced by many cell types and secreted into various tissues. It cleaves bacterial cell wall peptidoglycan at ÃŽ ² 1-4 glycosidic linkage between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Innate pattern recognition receptors (e.g. Toll-like receptor 2) and immunoglobulin also detect the presence of S. aureus. The latter is recognized by C1q and initiates the complement classical pathway (CP) or directly activates phagocytosis through Fc receptor expressed on neutrophils or monocytes. The human comp lement system is discussed in more detail below. One outcome of complement activation is the production of anaphylatoxin C3a and C5a. Together with formyl methionine peptides produced by bacteria, these chemoattractants are sensed by their receptors expressed on leukocytes and attract leukocytes to the sites of infection. Leukocyte recruitment is accomplished through highly coordinated interactions between adhesins on leukocytes and endothelial cells. Leukocytes change from rolling in the blood stream to firm adhesion to the endothelium and then transmigrate through the endothelial layer. Subsequent migration of leukocytes to infection sites is mediated by integrin interacting with ECM proteins. Once they reach the infection site, the phagocytes recognize antibodies or complement fragments deposited on the bacterial surface through their respective receptors. Phagocytosis then occurs. The phagosome is fused to the lysosome to form the phagolysosome for enzyme-mediated and oxygen fre e radical mediated destruction . 1.4.2 The human complement system The human complement system is a sequentially activated proteolytic cascade that involves more than 30 fluid phase and surface bound proteins. It is one of the key elements of the innate immune system that connects bacterial recognition, leukocyte chemotaxis; phagocytosis as well as adaptive immunity . Three main activation pathways are utilized to recognize foreign and danger signals. The classical pathway (CP) senses antigen bound antibody by C1q. Bacterial carbohydrate ligand is recognized by mannose binding lectin (MBL) or ficolins and initiates the lectin pathway (LP). Upon ligand recognition, both pathways use their specific proteases to cleave C4 and then C2. The resultant C4b2a (the C3 convertase) converts C3 to C3a and C3b. The Alternative pathway (AP) starts by direct binding of C3b to the bacterial surface generated by spontaneous lysis of C3 to C3b called â€Å"tick-over†. Factor B that associates with surface-bound C3b is subsequently cleaved to Bb and forms the alternative pathway C3 convertase C3bBb. The amplification loop of C3 activation is started. C3 cleavage is the central event and merging point in the three pathways. Accumulation of surface bound C3b changes the substrate specificity of C3 convertase to C5. C5 cleavage produces C5a and C5b. The latter m ediates the formation of the membrane attack complex C5b-9 (MAC), which inserts into the target cell membrane and ultimately causes lysis of target cells. C3a and C5a are powerful anaphylotoxin that trigger neutrophil homing. The overall picture of this complex system is depicted in Fig. 1.1 MASP: mannose-binding lectin–associated serine proteases. Figure adapted from Walport et al 2001 (Ref.). Three main outcomes of complement activation are: 1, chemotaxis of leukocytes via C5a and C3a; 2, C3b mediated phagocytosis via complement receptors on phagocytes; and 3, lysis of bacteria by MAC. It is also suggested by recent studies that the C3b presented on bacterial surface are critical factors for B cell activation and the production of specific antibodies. Although the MAC complex cannot function on gram positive bacteria like S. aureus, leukocytes mediated killing is critical for fighting against S. aureus infection . 1.4.3 S. aureus Immune evasion molecules 1.4.3.1 Resistance to antimicrobial substances S. aureus circumvents antimicrobial substances by three main strategies: 1, changing surface charges; 2, modifying the substrates of antimicrobial substances and 3, inactivating antimicrobial substances. S. aureus employs two enzymes to change the highly negatively charged teichoic acid in its cell wall (WTA). DltABCD (Dlt operon) adds D-alanine to WTA and the multiple peptide resistance factor F (Mprf) participates in the modification of membrane phosphatidylglycerol with L-lysine. Both modifications increase bacterial surface charges and thus reduce the attraction to the cationic defensins. dlt or MprF defective strains were killed more efficiently by neutrophil oxygen-independent killing. The former was much less able to cause arthritis and mortality in mice sepsis and arthritis models . S. aureus avoids lysozyme cell wall cleavage by modifying its cell wall peptidoglycan. O-acetyltransferase (OatA) was proposed to mediate this response. OatA catalyses the acetylation of muramic acid, which results in the addition of an acetyl group on S. aureus peptidoglycan. An oatA- strain was sensitive to lysozyme, while complementary expression of the enzyme restored its resistance . Two enzymes have been reported to directly inactivate antimicrobial peptides. Aureolysin (a metalloproteinase) could cleave and therefore inactivate cathelicidin LL-37. Staphylokinase (SAK), a secreted plasminogen binding protein, was reported to form a complex with ÃŽ ± defensin and almost completely blocked its antimicrobial activity. This activity was independent of plasminogen binding. S. aureus strains that produce SAK had a higher survival rate in vitro and higher virulence in a mouse arthritis model . 1.4.3.2 Prevent phagocytosis and opsonision 1.4.3.2.1 General anti-opsonin molecules S. aureus clinical isolates produce a capsular polysaccharide outer cell wall. Serotypes 5 and 8 of the capsular polysaccharide are associated with increased virulence. The capsule is anti-opsonic via blocking of surface deposition of opsonins and their receptor/ligand interaction. Immunoglobulins are targeted by protein A (SpA) and its homologues Sbi (S. aureus IgG-binding protein), SSL7 (Staphylococcal superantigen-like protein 7) and SAK. SpAis a 42 kDa surface anchored molecule. It has four to five IgG binding units that could interact with IgG Fc portion. This interaction presents IgG to leukocytes Fc receptor in the wrong orientation and therefore prevents recognition. In the present of IgG, strains expressing high level of SpA were shown to be more resistant to leukocyte phagocytosis than SpA-poor strains, especially when the sole source of opsonin was purified IgG. Opposite results occurred with IgG-deficient serum, indicating SpA confers protection against neutrophil through IgG interaction. Sbi contains two IgG binding sites at the N-terminal domain. The significance of the Sbi/IgG interaction remains to be fully established. SAK forms a complex with plasminogen and converts plasminogen to plasmin. Plasmin cleaves IgG and C3b deposited on S. aureus resulting in reduced recognition by phagocytes and likely impaired initiation of C1q mediated CP activation . 1.4.3.3 Complement inhibition S. aureus is now recognized as ‘a master of complement evasion. Unlike other bacteria which use host factors to ‘disguise the bacteria or inhibit complement activation, S. aureus produces a group of proteins to attack the key elements of the complement cascades. The list of anti-complement virulence factors is growing. So far, five complement inhibitors have been demonstrated and well characterized: SCIN; Efb; Ehp; SSL7 and Sbi. Interestingly, SCIN, Efb, Ehp and Sbi all use a triple ÃŽ ± helix bundle as their functional domain while their modes of action are markedly different (Fig. 1.2). SSL7 belongs to the SSL protein family. Its function will be discussed in context with other members of the family in a later section. 1.4.3.3.1 SCIN SCIN (staphylococcal complement inhibitor) is a human-specific 9.8 kDa secreted protein with a trip ÃŽ ± helix structure (Fig. 1.2) and is produced by 90% of S. aureus strains. SCIN was shown to inhibit all three complement activation pathways. In the presence of SCIN, the deposition of C3b and MAC were prevented, so was the C2b and Ba release. However the amount of surface bound C3 convertases (both forms) were increased, suggesting SCIN had a stabilizing effect on this complex. SCIN bound to surface-immobilized C3b directly and the binding site was predicted to involve the C3b MG7 and MG8 domain and the area nearby. This was confirmed by the co-crystallized SCIN-C3bBb complex. In vitro binding studies suggested the complex was likely to form in a 1:1 or 2:2 ratio. Indeed in the crystal structure, the complex appeared as a SCIN2C3b2Bb2 heterodimer that was bridged by the two SCIN molecules cross-linking the two C3b fragments. However this cross-linkage was not critical in SCIN compl ement inhibition as monomeric interaction also resulted in stable and inhibited C3 convertase. Native C3 could still associate with the SCIN-C3 convertase complex, but the production of C3b was largely inhibited, suggesting the convertase was likely trapped in a dysfunctional yet stable state by SCIN. Moreover, SCIN exerted a partial competition for factor B binding to C3b and a complete competition for factor H/C3b binding. The significance of the inhibition on factor H was not clear although reducing iC3b (inactive product of the cleavage of C3b) mediated downstream signaling could be beneficial for the bacterium. Physiologically, C3 convertase decays shortly after assembly. This disassociation is required for further cleavage of C2 and factor B. Thus SCIN functions by preventing C3 convertase decay; hindering conformational activation of C3 convertase and possibly by blocking C3b/iC3b mediated signaling . 1.4.3.3.2 Efb Efb (extracellular fibrinogen-binding protein) and the recently discovered Ehp (Efb-homologous protein aka Ecb) have been shown to inhibit C3b deposition in AP and C5 convertase activity in all three pathways. The efb gene is present in 85% of S. aureus isolates sequenced to date. Its inhibitory effects on complement mediated lysis and neutrophil activation in response to C5a have been demonstrated. The Efb complement binding domain (Efb-c) is also a triple ÃŽ ± helix huddle, although the arrangement is different from SCIN (Fig.1.2). It binds both C3 and C3b via the C3d fragment. However, which of the C3 forms is the primary target of Efb is debated. Structural-biochemical analysis suggested the binding affinity of Efb-C to native C3 was higher than that to C3b. The binding was proposed to induce conformational changes in C3 and prevent proper cleavage of the molecule. This view was challenged by Jongerius et al based on the observation that C3 cleavage was not influenced by Efb-C in CP/LP. Instead, they suggested Efb-C attacked complement intermediates that contain C3b. Therefore, in CP/LP, C3 convertase (C4b2a) was not affected by Efb but C5 convertase (C4b2aC3b) was inhibited, as evidenced by the decreased C5a production. Ehp was found to contain two C3d binding sites and showed higher levels of inhibition compared to Efb, though the mechanism of action was proposed to be similar. Nevertheless, the C3d fragment carries another important task: mediating interaction with complement receptor 2 (CR2) on B cells and facilitating B cell activation. Both Efb-C and Ehp were shown to completely inhibit C3d:CR2 interaction and its stimulatory effect on a B lymphoma cell line. The predicted binding site of CR2 on C3d was in close proximity to the residues that have been shown to be involved in Efb-C:C3d and Ehp:C3d binding. The exact competition mechanism remains to be confirmed . 1.4.3.3.3 Sbi Sbi is another secreted S. aureus protein that targets C3 activation. Sbi binds C3b but has a stronger affinity to C3dg. The binding was shown to be improved when the C3a domain was also present. These observations suggested the C3dg and C3a portion of C3 were important for Sbi/C3 interaction. By comparing binding profiles of different domains of Sbi, the C3 binding site was proposed to be located in its fourth domain (Sib IV). Interestingly, Sbi IV alone inhibited AP activation in a dose-dependent manner. However when the third domain was also present, incubation of human serum with this recombinant protein induced activation of complement, as shown by the degradation of native C3. A distinctive C3 derivative was present in Sbi-III-IV treated serum, whose molecular weight and migration behavior on two dimensional SDS-PAGE correspond to a transacylation product of C3b and Sbi. The cleavage of C3 activates an internal thioester moiety in the C3b fragment, which allows C3b to form cova lent bonds with hydroxyl groups in close proximity (e.g. bacterial surface). Thus it was proposed the Sbi III-IV provided a fluid-phase transacylation target for C3 cleavage and cause non-effective activation of the alternative pathway. Since mutational study confirmed the Sbi-IV was responsible for the complement inhibitiory effect, Sbi-III was proposed to be important in consumptive complement activation. Once again, Sbi IV adopts the triple helix structure, arranged in a similar fashion as Efb-c and Ehp (Fig. 1.2). Just like Efb and Ehp, the binding of C3dg to CR2 was inhibited by Sbi-III-IV, implying that Sbi may also influence adaptive immunity . 1.4.3.4 Preventing phagocyte extravasation and chemotaxis 1.4.3.4.1 CHIPS; FLIPr and FLIPr-like CHIPS (the chemotaxis inhibitory protein of S. aureus) was identified for its ability to prevent neutrophil chemotaxis to formylated peptide and C5a. CHIPS encodes a 121-amino acids (aa) secreted protein and presents in 62% of S. aureus clinical isolates. Postma et al demonstrated that CHIPS selectively and directly bound to C5a receptor (C5aR) and formylated peptide receptor (FPR) expressed on cell surface and competed with their respective ligands for binding. Receptor activation, as measured by the Ca2+ influx and murine neutrophil migration to the injury site, was inhibited. The two receptors were shown to interact with different areas on CHIPS. The N-terminal 6 residues of CHIPS, F1 and F3 in particular, were identified as the FPR binding sites. While the C5aR-binding domain was mapped to residues 31-121, which forms a packed structure similar to the ÃŽ ² grasp domain. Arginine 44 and lysine 95 were shown to be critical for its antagonizing activity. C5aR binds CHIPS through its N-terminus residues 10-18. These residues were suggested to be either involved directly in C5a binding or were required to stabilize the interaction. Therefore, CHIPS may function by direct competing with C5a or by disrupting the formation of the stable ligand/receptor complex . Two more S. aureus proteins were found to inhibit neutrophil chemotaxis. The secreted FPR-like 1 inhibitory protein (FLIPr) and its homologue FLIPr-like bound FPR and FPR-like 1 receptor (FPRL1). The N-terminal 6 residues of both proteins were important in both interactions but the phenylalanine was not critical for FRP binding. The inhibition of FPRL-1 by both proteins occurred in the nanomolar range. FLIPr-like was shown to be a potent inhibitor for FPR with activity comparable to CHIPS. However, animal infection models with chips or flipr isogenic deletion strains has not been reported. The contribution of CHIPS in bacterial infection is yet to be determined . 1.4.3.4.2 Map Map (MHC class II analog protein a.k.a. Eap) is a multifunctional 60-70 kDa secreted protein expressed by 97% of S. aureus isolates. It is an anti-inflammatory molecule that reduces leukocyte availability and function. Map can interact with a wide range of host ligands, including Fg, Fn and ICAM-1 (intercellular adhesion molecule-1). Map largely blocked ICAM-1 mediated firm adhesion and transmigration of neutrophil. In a peritonitis mice model, intraperitoneal injection of Map or pre-treatment of mice with Map showed 50-75% inhibition of neutrophil recruitment. Neutrophil infiltration in mice infected with a map- strain was 2-3 folds higher than that seen with a map+ strain, demonstrating Map inhibits ICAM-1 mediated neutrophil migration in vivo. Interaction of Map with ICAM-1 may modify signal transduction in leukocytes. NF-ÃŽ ºB activation and tissue factor release in THP-1 cells were diminished by Map treatment. A substantial amount of IL-6 and TNF-ÃŽ ± and a smaller amount of IL- 4 were released from Map treated human CD14+ PBMC in vitro. Anti-ICAM-1 antibody blocked the action, suggesting the induction was also mediated by ICAM-1. It is not clear if cellular processes other than cytokine production are also influenced, although Maps effect on PBMCs appears to be dose dependent . In addition to the cytokine changes, T cell function was impaired by Map. Mice treated with Map showed significantly reduced T cell mediated delayed-type hypersensitivity (DTH) and T cell proliferation. Adoptive transfer of T cells from Map-treated mice to untreated recipients prevented the recipients from developing DTH when challenged with allergen. The Map

Essay examples --

Sympathy is a feeling of understanding which cannot be easily denied. Feeling sympathy towards someone or something comes naturally to humans. It is not required that one must undergo the same challenges to understand a person’s struggle. The extent of one’s sympathy depends upon the extremity of one’s plights. Regardless of who or what, everyone has felt sympathy or has been given sympathy. Euripides, a famous Grecian playwright wrote Greek tragedies known for eliciting sympathy from the audience. An example of this is Euripides’ play Medea. Medea is one of Euripides’ most well known characters Euripides created Medea to be a sympathetic character. Medea was originally published in Greek; therefore many aspects of the play may have been lost in translation as it is difficult to translate both the literal and implied meaning of the original play. Although many may dispute that Medea is a sympathetic character it is evident through, various sacrific ial acts of love, Medea’s unstable mental state and role as a foreign woman in the ancient Greece society help Euripides portray Medea as a sympathetic character as conveyed by his social commentary. Sacrifices are often made in one’s everyday life. However, it is the repercussions of these sacrifices that elicit sympathy from one’s peers. Medea with, â€Å"...her heart unhinged in her love for Jason...persuaded the daughters of Pelias to kill their father† (Euripides 8-10). Euripides uses a mythological allusion by briefly referring to the legendary journey of Jason and the Argonauts. Euripides portrays Medea as a character who selflessly victimizes herself. Through this sacrificial act of love Medea, victimizes herself by acquiring enemies on Jason’s behalf. Furthermore, Medea betrays her... ...cal to further develop a clear understanding of her motives. Although Medea’s actions were arbitrary and illogical, the reasoning behind her actions was completely selfless and motivated by love. Additionally, Medea’s irrational state of mind contributes to her illogical selfless actions. Euripides demonstrates how Medea allows herself to be a victim to her anger which overpowers her rational thinking. Furthermore, Euripides’ social commentary on the role of women and foreigners in the ancient Greece society display how Medea is poorly judged due to both these factors and her disinterest in conforming to societal norms. Therefore, it is apparent that Euripides created Medea as a sympathetic character. Although many aspects of the original play may have been lost in translation, it is proven that Medea is in fact a sympathetic character as shown through her plights.

Human Resources Essay

Human resources involves a wide variety of activities related to the arrangement and implementation of organisational policies, the requirement of opportunities for monitoring, evaluation and change and the application of resources to the fulfilment of organisational ends. Aspects of ‘people management’ include: * The recruitment, retention and dismissal of staff. * The training, development and promotion of staff. * Liaison with employee organisations and trade unions. These are areas with which the human resources staff is involved. The overall purpose of the human resources function can for that reason be identified as: * To attract and retain good high-quality staff. * To ensure that the organisation operates within the law in relation to employment and health and safety. The Philip Markham organisation believes they will not be successful if they do not have the commitment of all staff and intend to look after all their employee’s needs through the functions of the human resources department. Finance The overall contribution of the finance function can be grouped in to three main areas: > Preparing accounts. > Preparing wages and salaries. > Obtaining capital and resources. Philip Markham employs ten members of staff in the finance department. The department makes sure internal customers receive the money they are owed and customers pay their bills. To keep control of finances the organisation allocates different department budgets and expects them to keep to there planned levels income and expenditure. Finance also has the task of preparing all the accounts each year so that they comply with legal responsibilities to the Inland Revenue. They also complete VAT returns to HM Customs and Excise. Pete Martin the management accountant at Philip Markham is responsible for checking that production levels and sales are on target. He advises all internal customers who are the directors, about the current financial health of the organisation on a weekly basis. An additional responsibility for the finance function is advising the organisation about more money for the purpose of expansion to buy raw materials or expensive equipment so it can remain competitive obtaining extra finance, called CAPITAL at the best rates possible. Production The contribution production makes to the overall business is to make a product and provide a service. The core function of the production department is to obtain the resources required by the organisation and transform those into a product. The production function is also concerned with organising the resources to produce the goods and service in the most appropriate way. Philip Markham carry out three different operations in their production department, these are as follows: > Purchasing > Manufacturing > Despatch The layout of the production area has been designed to maximise the flow of materials when producing the shirts from cutting to finishing. The cutting area is near to the stores so that materials can be transported the minimum distance. Quality control is extremely important to Philip Markham and each team cutters, machinists and finishers is responsible for ensuring that quality is right at every stage of the process. The shirts and ties pass to the packing department, which is part of despatch. All items are boxed and labelled and goods linked to the correct paperwork and the dispatchers that each box includes the correct delivery note and advice note for the haulier. Also part of the production function is purchasing staff and the designers. Purchasing is responsible for obtaining the best quality fabrics at the best prices and making sure all raw materials are delivered on time. Sales and Marketing The contribution sales and marketing makes to the overall business is to identify what the customer needs and providing it. The activities of sales and marketing include: > Market research – to find out what customer’s need and customer opinions on proposed and existing products or services. > Promotion – to inform the customers that their particular organisation can fulfil these needs. > Sales – to provide the goods or service the customer thinks he or she needs. The contribution of sales and marketing is vital in that it directly influences the number of sales that are made and as a result the profitability of the company. Each functional area operates to support the business aims and objectives and a range of activities goes on in each one. How the functional areas interact with one another is important. For an organisation to be efficient and effective there must be links between the people who work in different functional areas, especially when their activities overlap. Philip Markham is aiming to set up an e-commerce site to sell classic menswear and their objective is to be the leading British supplier of this type of clothing on the Internet within the next two years and double sales home and abroad within the same period. In order to achieve such a particular set of aims and objectives the organisation will need the support of a representative from finance, production and sales and marketing. The finance representative can present all the facts and figures that need to be considered when exploring this venture. The overall budget set-aside for web-page development and marketing is à ¯Ã‚ ¿Ã‚ ½80,000 in the first year. Tina the financial manager believes this is generous given the financial position of the company. She believes it will be vital to control costs of setting up this new venture and to focus on those products that will bring in the most profit for the company. Her key consideration is that the site should be secure (identified by a padlock symbol), as payments will be made over the Internet. She has also advised that because VAT regulations differ, a separate order form would need to be completed by purchasers from abroad. The site would have to have a communications link with finance as all payments must be logged, collected and recorded by finance before orders are fulfilled by dispatch. Finance would have to notify dispatch when payments had been received. Only then can goods can be sent. The production representatives Tariq Choudrey (Production Director) and Marsha Webb (Manufacturing Manager) have concerns about the Internet site. Marsha believes there is a limit as to how much production rates can increase to meet additional orders without sacrificing quality. Details which need to be addressed are as follows: > The cutting tables – new tables have been requested for two years. They are essential if orders increase at a cost of à ¯Ã‚ ¿Ã‚ ½15,000 each. > The eleven sewers produce on average five shirts a day each. The maximum which can be produced without additional staff is seven unless quality is sacrificed. > The three finishers spend a lot of time on special orders. More staff will be needed in this area unless the website only allows for ‘standard orders’. > The despatch manager advises unless more mechanisation is introduced more staff will be needed if orders have to be completed quickly. > It would be easier to sell knitwear and overcoats on the website most of which are supplied by other companies. However the suppliers of knitwear and overcoats would need at least two months notice if the volume of orders were going to increase substantially. The manufacturing manager supports the overall ideas but stresses it is absolutely no use trying to sell goods which cannot be produced in a reasonable time period as this would do more harm than good to the company’s reputation. Production need to be involved in the communication process at all times unless they are fully aware of what is happening at all times there wont be any goods to sell. The sales and marketing function are excited by this new venture. Jade Marsh (sales and marketing director) would like to see the task of setting the website given to a professional web development firm who are likely to charge à ¯Ã‚ ¿Ã‚ ½40,000 to à ¯Ã‚ ¿Ã‚ ½50,000 for a site with multi-media images. This will be vital to show the type of fabric that can be selected, the colour and the designs especially for the ties. The site must be user-friendly quick to access and use and that it can cope with a large number of ‘hits’ without crashing. She believes the key date for it to be finalised is September, so that the company can benefit from Christmas orders. In order for the site to be marketed it will cost money, it must be registered with good search engines. She would like to have special offers to tempt visitors to return again. All stationary must be reprinted to include the website address. During the first year the site needs advertising as widely as possible. The sales and marketing director believes that the e-commerce should be located in marketing (as it is a method of selling goods). Ideally she would like two more staff, one to join the mail-order team and be responsible for Internet orders and another to join customer services in case there are any problems with goods sold over the Internet. She believes this would minimise communication problems as all sales will be controlled in one area. She estimates that the company could sell 200,000 shirts and 150,000 ties if a good job of setting up and marketing the website was accomplished. The human resources function is concerned about three main aspects. > Where the website operations will be controlled. > How the website will be developed. Kim Fields the administration and IT service manager believes she should have control of website operations as she is IT manager especially as computer staff are responsible to her. She believes maintenance of the site will be crucial, it is important to set it up fairly quickly and then it can expand. Kim considers the most sensible route for website development would be to hire their own multi-media web developer to set up the page and sub-contract specialist parts to an outside firm if needed. In addition a programme/copywriter would be needed. The software and other associated costs would be about à ¯Ã‚ ¿Ã‚ ½10,000. Having these staff would mean that the website could be continually updated in house. Keith is concerned about the effect on staff, he is anxious that the mail-order clerks should be trained to be able to print off and process orders arriving through the website as well as carrying out their current job. He thinks they will need extra help at busy periods such as Christmas. If the website is to be successful than eventually another member of staff may be required. He believes it to be more sensible to move this group of staff to the HR/Admin department so there would be better communications with the computer staff. Keith considers any communication problems during planning the stages can be solved by regular meetings between the IT and sales staff. Finance will also need to be included. Philip Markham has always aimed to produce menswear of excellent quality at affordable prices. The fabric used for shirts is of highest quality and designers aim to produce new designs each year. The functional areas which relates to these aims is the production department, finance department, human resources and sales and marketing. The first action to take would be in human resources the company needs to recruit the best people for the job including cutters, machinists, and finishers and look after them whilst they work. The finance function make sure that a budget is maintained when buying materials, paying wages and embarking in market research when embarking on achieving these particular aims. The finance function can give up-to-date information on the level of expenditure at any time. The production function uphold quality control at Philip Markham ands each team cutters, machinists and finishers is responsible for ensuring that quality is right at every stage of the process. Production is responsible for obtaining the best quality fabrics at the best prices and making sure all raw materials are delivered on time Human resources relates to these aims because their function is to recruit and train staff to meet all customer needs in relation to providing a service. The function incorporates company policy to treat employees fairly and equally in all aspects relating to their employment. A content workforce will achieve a friendly atmosphere and staff are keen to help consumers as well as each other.

The Deadly Effects of Pain and Hopelessness

The Deadly Effects of Pain and Hopelessness Hashtag: #WorldSuicidePreventionDay The Deadly Effects of Pain and Hopelessness Pain according to a clinical study has been associated with the desire for hastened death but people experiencing severe depression and hopelessness are more likely to develop suicidal ideation.   Suicidal ideation according to the study performed by a Pain and Psychiatry Services group among cancer patients was not directly caused by intense pain but the degree of depression and mood disturbances. This is because although majority or 87% of the 185 cancer patients who had experienced significant pain and expressed their desire to end their lives, none of them intend to act.   Since patient’s perception of poor relief, a state often associated with aspects of hopelessness and subsequent desire for hastened death, pain is an indirect but powerful contributor to suicidal ideation. Pain according to the literature affects a person’s quality of life, sense of control, and weakens the ability of family members to provide support; pain, not motives is the most cause of suicide thoughts and behavior on campus.   Along with risk factors such as difficulties in the relationship, substance abuse, impulsive and aggressive behavior, family history, and others, 1 in 10 college students seriously considers suicide due to significant depression. The most common and most painful is the death of a loved one and associated grief as such can trigger an assortment of negative reactions such as anxiety, remorse, rage, and other. However, assessment of the student’s suicidal intention suggests that in terms of determining how far a student will go (including death), knowledge and understanding of student’s perception regarding the pain are more important than his or her situation. This is because, in a suicidal person experiencing extreme psychological pain or â€Å"psychache† a term coined by Edwin Shneidman in 2005, anything that is perceived as a viable solution to escape his or her emotional desperation and unbearable emotions can lead to escalation. Want to know more? Go here: Relieving Students School-Related Stress The Killing of Three Muslin-American College Students Violence against Female University Students Womens Right to Education The Misdemeanors of Well-Educated People in Public Office Warning Signs, Triggers, Risk and Protective Factors Some of the warning signs that a person experiencing intense pain  and extreme emotional desperation will take his own life   include withdrawal, giving away his or her prized possessions, talking about death, refusing help, verbal threats, and others. The conditions that will likely trigger pursuit of suicidal ideation, on the other hand, include embarrassment, bullying, sudden transitions or change of circumstances, substance abuse, conflict, bullying, and others. Risk factors are gender, race, cognitive or emotional, others. Study of suicidal behavior in high school and college students suggests that predictors of suicidal ideation are similar to both genders and races. Males reported greater loneliness and substance abuse than females. Depression and suicidal ideation are common among females, but they fear death and injury more than males who, according to the study have greater fear of social disapproval. Carrying a weapon at school is predictive of suicidal attempts among males of all ethnicities while perceived parent and family connectedness is a protective factor for black, Hispanic, and white boys and girls.   Finally, in terms of coping and help seeking attitude, boys often used maladaptive coping strategies such keeping the problem to themselves, hiding their feelings,   and using drugs and alcohol.

Adopting a Start-up Mentality for your Books Reedsy

Adopting a Start-up Mentality for your Books Reedsy Adopt A Startup Mentality For Your Books - By Dr. Sean Wise â€Å"I think I’m the only person who has made the authors into Lego people†At the Reedsy blog, we like to bring together the publishing world and the tech world. We think authors can learn a lot from entrepreneurs (and vice-versa), and today’s interview is dedicated to just that.Dr. Sean Wise is a Canadian entrepreneur, investor, mentor and successful author. He just released his latest book, Startup Opportunities, that he co-wrote with Brad Feld. How do two of the most successful startup investors out there go about marketing their book? Sean shares their secrets on how they engage with readers (careful, it involves Lego figures).He also gives his perspective on the changes the publishing industry is undergoing and on a few startups contributing to its disruption.If you want to see him drive through Toronto in a cab, get out, and walk home - all while chatting with us - just play the video, it’s awesome. Else, the transcript is just below! Dr. Sean Wise, it’s great to have you here. You’re a teacher at Ryerson university on entrepreneurship, are a mentor, advisor and investor, and have been involved with startups pretty much all your life, right? Could you give us a bit of background on that?Absolutely! I was born very, very young, and I grew from there. At 13 I had an experience that confirmed to me that I would never make a good employee and I started my first business. I’m now 43 and I have started 5 of my own businesses, but for the most of my working career I’ve been a venture capitalist. So I’ve been an entrepreneur, a ‘funder’, a founder, a mentor, and all of that has been to accomplish one goal: to help entrepreneurs succeed. Help people fail faster, learn quicker, etc. All of my books to date have been around that topic.That’s fantastic. And talking about your books, you wrote your first book and self-published it in 2007, back when digital publishing almo st wasn’t a thing. Why did you choose the self-publishing route?Well, I think you’d call it self-publishing. I had written a column for the Globe and Mail, which is a national newspaper in Canada, and at the end of a two-year run as a columnist on entrepreneurship, they asked if I’d like to wrap all the articles together, put a cover on it, and publish it. So they published it with me. It was â€Å"self-publishing† because we owned 100% of it, but it was edited and pushed out by a newspaper chain, so it was a very unique experience.My second book was bought by a large publisher called Penguin: it was How To Be A Business Super Hero and it combined my love for comic books with my need to help people understand that business isn’t only about money.For my third book, which came out three years ago, I went back to self-publishing. I published it with a magazine called Profit Magazine, and it’s another book about entrepreneurship called Hot or No t. In Canada (like in England) we have a version of that great TV show called Dragon’s Den (it’s now in 27 countries) and I spent 5 seasons working there to help entrepreneurs get the funding they needed to succeed.Now, full circle for my latest book: FG Press is half self-publishing, half traditional publishing. It’s really a startup publishing brand that is trying to figure out what publishing isn’t doing well at all, and what can be done better.Yes, FG Press is one of these actors that shows how exciting the publishing industry is in its current state. What is it that has changed, exactly, and how do you see it moving forwards?Well, I’m not smart enough to talk about what everyone else is talking about, but I know what I am excited about, so I’ll focus on that. For many many years, the publishing industry has been pretty much like the music industry or the film industry: you had these experts; and these experts, whether they were editors or acquisitions people, were in charge of deciding what the world needed. Without an editor’s blessing, you couldn’t have a book: there was no one to publish or distribute it.But like with most things, the internet has had a dramatic effect on the distribution portion of books. Now that books are digital, we know they’re just like Napster was for music: you can send them over email, you can move them digitally, you can read them on your phone, etc. So it’s made distribution a lot easier. Combine that with Amazon’s self-publishing tools, with Goodread’s ability to engage your authors, with Wattpad that can replace your editor with fans, and you really have eliminated the ability of one superstar sitting there and saying â€Å"your book isn’t good enough†.Now, that’s a double-edged sword. Now that there is no longer some expert that you need to tell, there also is no filter, so the biggest problem with publishing today is that anyone can publish. So how do you get past that?Exactly, and I think that’s a question for all forms of content in general, now that we have user-generated content, right?Absolutely. So it’s not a matter of whether my book is good or not, it’s a matter of whether I can get into people’s funnel: â€Å"can I get them to think about my book, can I resonate with them?† as opposed to â€Å"can I get on the shelves at Barnes and Noble?†.And that’s why it’s so important to build a readership before you publish your book. Which is exactly what you’re doing right now with Brad Feld. You’ve co-authored a book with him, Startup Opportunities, and you’re pretty much everywhere around the world talking about that book!Yes, I’m surprised - but happily so - , it looks like we’re going to have a 20-city book tour. We started last week with 5 cities in Canada, and we’re going to move from there ac ross the US, and who knows, if we’re blessed, we’ll even come to Europe!We’re doing that to build a readership and to engage with our users. It’s very similar if you’re aware of The Lean Startup. That book says that before you sink millions and millions of dollars into building a product, check if anyone cares.So before Brad and I got too deep in this book we started talking to readers, startups, just to ask them questions and to really understand what the need was. So we really based this book, Startup Opportunities, on the idea that people should not start stupid startups, that the problem isn’t just â€Å"how to start a company?†.Before we even launched, we had sold 1500 copies. And I can only hope that that continues and that we’re able to find something that resonates with our readers.What kind of out-of-the box marketing have you done for this book that could inspire other non-fiction authors out there?I think I’m the only person who has made the authors into Lego people. So Brad and I have Lego people that will travel with us, and if people want to tweet a picture of us and them, they’ve got to tweet the little Lego people and whoever tweets that and gets the most retweets, will get their own Lego figures, custom-made for them.I’ve never seen anyone make action figures out of authors and I thought that was kind of fun. So that was pretty unusual. The book tour is pretty standard, the Twitter is pretty standard. We did an infographics and a slideshare, too, which are now also pretty standard.Where do you find your inspiration for all this? I think the greatest thing about the transparency the internet allows, is that everyone can learn from everyone. So I wouldn’t want you to think that all these ideas are mine. I’ve stolen them from other successful authors. In fact, as a professor of entrepreneurship I teach that to my students: â€Å"steal with integrity and pr ide everywhere†. I try to give full attribution: I follow Seth Godin and Guy Kawasaki, they’re sort of my â€Å"author idols†, and I try to see what they’re doing and learn.But as far as I know, I am the only person who has a Lego version of Brad Feld and a Lego version of me.And that’s really really cool. It’s actually the mindset that certain authors in publishing are missing: what could I do that would be cool for my readers, or cool in general?I think, people look at Brad Feld and he’s got 5 or 6 bestsellers, he’s a multi-millionaire, a successful venture capitalist; but they don’t realise that his goal is still the same as every other author: to connect with the readers. All of these new tools are just ways to connect, and I think they’re fabulous because they cut out the middle person.I agree. Talking about â€Å"new tools† if you had to find two startups in the publishing industry that you find partic ularly interesting and are going to follow closely, which would they be? I’m a big fan of Goodreads. I know they’re owned by Amazon right now and that makes them not a startup, but I just think connecting your readers with your authors is so important.If I couldn’t choose Goodreads, I might choose Wattpad. They’ve got about 25 million readers and allows authors to put manuscripts up and get feedback. I’m much more interested in what other founders think about my book than what my father thinks about my book. I want to hear directly from them. Amazing authors who have millions of readers are using Wattpad to engage with them and get their books even tighter. So Wattpad would be one.I’m also another big fan of changing business models. So I found Netflix to be nice because it disrupted Blockbuster. And I think what Scribd is doing with comic books, audiobooks and digital books, this â€Å"all you can eat for $9.99†, is going to impact t he business in a disruptive way. I used to buy my comic books every week at the comic book store. And then I evolved into the digital comic book store, called Comixology. Then, I moved from Comixology, when they got bought by Amazon, to directly purchasing from Amazon.Now Scribd comes along, and it has over 100,000 comic books from Marvel, from Image, and all the things that I love, and instead of paying $30 a month in comic book sales, I pay $9,99. So it caters to another demographic. When I was young, for my birthday, I would always ask for some money for the comic book store. But now I don’t need that, I would ask for a subscription to Scribd, for $9.99.These are part of this bigger ecosystem that’s developing and what I think is most interesting is that it’s developing exactly the same. iTunes is the same as Kindle. Netflix is the same as Next Issue for magazines or Oyster for books or Scribd for comic books.So for me, if I look at the next 5 years, which is what I like to invest on - not companies that are amazing today, but companies that will be amazing in 2020 - I ask myself: what is the next revolution going to be? How do we emulate what’s going on in the music business in the book business? How can I increase my tour sales and keep my book sales up? How do I accept to give an album away for free?Brad and I actually discussed whether we should do a â€Å"pay what you can† model. Radiohead did that for music and they made more money than they would have if they had sold at $9.99. Again, I think these things are still in flux, and we live in an unbelievable time, because every industry is changing, and publishing is just slow because it has very big anchor tenants.Thank you so much for these insights, and for your time, Sean. I look forward to reading Startup Opportunities!Follow Dr. Sean Wise and Reedsy on Twitter:  @SeanWise  and @ReedsyHQWhat kind of out-of-the-box marketing have you  done for your book? How do you build your readership? Which publishing startups do you think are going to succeed? Leave us your thoughts, or any question for Sean, in the comments below!

Journals Article Example | Topics and Well Written Essays - 250 words

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The Cultural Perspective of the American Civil War Essay

The Cultural Perspective of the American Civil War - Essay Example With each passing year, the need for slaves in the South led to an increasingly different culture from the North. The North underwent a period of technological advancements that stimulated export and subsequent revenue, allowing it to forge ahead of the South as the Northern culture incorporated office jobs, busy lifestyles, and factories (Weidenmier 879). The North saw an expansion of mass communication, education, literacy, and urbanization, while also being more progressive. This was in stark contrast to the South that was more traditional and rural oriented. The North had a more materialistic and coarse way of life, which led to its population being disdainful of the manner in which the Southern people lived, and viewing it as a sign that they were superior. While the North modernized, the South relied more on its traditional values, leading to the exacerbation of the ever-increasing differences between the two regions (Weidenmier 879). Due to the use of slaves in the South, its white population had no need to do manual labor, which left them with a lot of free time. They would entertain guests and take part in society enhancing activities. The minimal contact between the North and South states during this period led to an establishment of stereotypes about the way that those in the South lived (Bestor 34). In economic terms, those in the South preferred the simple and slow life, while the Northerners were more profit oriented. Due to these, both regions felt superior to the other. For this reason, it is no longer feasible to assume that only the South was responsible for the Civil War because the polar opposite nature of the two cultures pushed each other further apart until violence was the only way to solve the issues between... The North underwent a period of technological advancements that stimulated export and subsequent revenue, allowing it to forge ahead of the South as the Northern culture incorporated office jobs, busy lifestyles, and factories. The North saw an expansion of mass communication, education, literacy, and urbanization, while also being more progressive. This was in stark contrast to the South that was more traditional and rural oriented. The North had a more materialistic and coarse way of life, which led to its population being disdainful of the manner in which the Southern people lived and viewing it as a sign that they were superior. While the North modernized, the South relied more on its traditional values.Due to the use of slaves in the South, its white population had no need to do manual labor, which left them with a lot of free time. They would entertain guests and take part in society enhancing activities. The minimal contact between the North and South states during this period led to an establishment of stereotypes about the way that those in the South lived. In economic terms, those in the South preferred the simple and slow life, while the Northerners were more profit oriented. Due to these, both regions felt superior to the other. For this reason, it is no longer feasible to assume that only the South was responsible for the Civil War because the polar opposite nature of the two cultures pushed each other further apart until violence was the only way to solve the issues between them.