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Abstract The main focus of this research is to discuss the perspective of the teamwork and its impaction organizational performance and success. Also highlight the Meanings of Team and its work sprit towards batter organizational performance and specific to its impact on the success of organization that provided the basis for this research study. In this research study a thoroughly focus was on organization and teamwork. The aim of this research is to deliver a participative view of teamwork in the organization, and also discourses the major issues and emphases on the recent work that opens the basis to move research onward. There is much worth in taking a more focus on the essential areas of teamwork. The team signifies the spirit and working capacity of the employees as team to bring organization to the success. The various explanations, definitions, processes, dimensions, team size and benefits etc. regarding the above topic teamwork and organizational success is highlighted. Keywords: Teamwork, Success, Organization, Performance, Work Groups, Employees Introduction It is indeed human beings have learned in their beginning of life to work together as (Team) that have made such a remarkable developments as unique specie. Human beings have experience throughout their social history, lived, loved, grow younger to older and worked together in groups said West M.A. (2012).The mutual social knowledge of living and functioning together creates connection among people, society and families. When work is done cooperatively as a team it can achieve extremely extra work than individually. Team can be defined as in the human society to live, to work and to play and to cooperate with others for particular task. According to John W. Newstrom et al (1993) “team is the process of assessing performance of workers, passing information and exploring methods to increase performance”. If observe closely, one can discover the instances of The Government: Research Journal of Political Science Supplementary Edition Vol. III 88 The Government social (teams) they are functioning either effectively or ineffectively everywhere; organizations, schools, work place, home etc. “Coordinating the events of people is like sand house, making by using a sole particles of sand” expressed Belbin, R. M.(2010). Moreover it is one of the general myths that the skill of team member is more important than their vigor, attention and determination for the tasks. Another widespread myth is that the team members are not alone accountable for the achievements or failures of their tasks the truth is that the members are the small parts in the teams and their individual abilities effect on the various results in team. The working relationships exist among team that might sight these relationships at different levels of involvement or relationships among the members as they move towards the degree of communication, integration and commitment increases. Terry L.G. et al (1980) expressed that “The skills are essential if members have to work together efficiently in complex situations, only development of skills and relationships, involvement on the task regarding the particular task might be selected for reaching at target that is considered as a definition of a team”. Team often perform higher when they work together with sprit that enable them to achieve a collective goal at the workplace, it is not only benefits to the organization also affects the workers confidence and success. Cooperating on various tasks reduces workloads for all team members and enables them to share duties or ideas. Work as a team is the part of everyone's life, as one is a member of a family team, staff team, school team, and community teams etc., so as to understand how to work effectively as a team member. Especially there is a need when task is threatened with increasingly many problems for example; the energy problem has effects on organization, family life, and social development and the multi-dimensional nature of many problems require a scientific skill based problem solving approach. Terry L.G, et al (1980) expressed that “The skills, competencies and efforts of team by setting priorities the team can have better impact on the problems solving such efforts can reduce work load, work duplication, and produce a result better than separate efforts”. There are some processes of teamwork by adopting those the objectives can be achieved easily. Le Pine, et al, (2008) identified10 teamwork processes that fall in three categories following are those. TEAMWORK PROCESSES TRANSITION PROCESSES •Mission analysis •Goal specification •Strategy formulation ACTION PROCESSES •Monitoring progress toward goals •Systems monitoring •Team monitoring and backup behavior •Coordination INTERPERSONAL PROCESSES •Conflict management •Motivation and confidence building •Affect management Team Work 89 Teamwork process reduces the work stress on every member which permits members to complete given important task of organization; teamwork offers members an opening to pledge with each other. Also it develops relations between the members who start a teamwork they usually sense appreciated on productive accomplishment of task. It may be cited one of the best instances of surgical team; where surgeon is assisted by his team; nurses, anesthetist and experts etc., everyone knows that their success depends upon the teamwork. In addition they are devoted to the aim that is human life it is easy to succeed with best teamwork. The important role of manager is the team building, trust building, confidence building, in the team to achieve the task. In the Situation where all team members contribute the task, it develops the positive relationship in the team that improves the trust of team members.“Functions effectively members of team must be flexible, committed, trusting each other and help to each other’s in the progress and the achievement of goals” Expressed Plamínek (2008). The accountability of every member in the team must be increased so that they do not let each other down therefore they do their best for the achievements of their teams. In contrast, working alone on a task the pressure is generally high in team in those cases of small confidence impacts fewer on members. Team consists on members who always vary from each other’s in skills, knowledge and abilities but working together that is an opportunity for them to gain skills and knowledge from each other’s that they had never before. Working alone on a task is a challenge and using the ideas of each other brings them to come up with a mutual resolution and the achievement of the task. Nowadays theoretical development and research has rested largely a new trend that is emerging within the organizations as an essential process of teamwork. Teamwork has brought a new move in the research and development to the inputs and outputs that bound, constrain and impact on the team processes within organizations said Ilgen, D.R. (1999). The world is changes fast, any one set of instructions can’t be sufficient, changes needs flexible members, teams and organizations so as to be effective on task. This paper suggests that in teams members must use the exclusive human abilities. Cannon B.et al (1995) has précised dimensions of teams into three categories: Team dimensions 1-Cognitions: include associations, task team-mate characteristics, team mission, objectives, norms, and resources, team role interaction patterns, skills, roles, and team orientation. 2-Skills: consist on adaptability, shared situational awareness and mutual concept to conflict resolution. 90 The Government 3-Attitudes: symbolize motivation, collective potency, shared vision, team cohesion, mutual trust, collective orientation and importance of. Teamsize Researchers have given different approvals about the best size of team as Katzenbachetet al (1993) suggested that the teams should comprise on a dozen or so members which are enough to achieve a task. Although seven is the best size of the team in the organizational practices said Scharf, A. (1989). Several views of researchers are expressed in the literatures and it is difficult to decide which better is because their opinions are based on their own observations. The team size matters in the proper output and performance however from an empirical research it is also difficult to decide the suitable team size and what to accept. This study suggests that team size has a practical link with efficacy such as few or many member shave impact on the performance but size matters. Proper size of team improves the performance maximum stated Campion M. A et al (1996).These different results are expected due to the fact that appropriate team size is required for task, environment and situation where team works. However, larger teams can also experience coordination problems that delay performance. Sheppard, J. A. (1993) expressed that the question of best team’s size is a complex one; more research is required on this topic to explain the impact of team size on given definite task. Literature Review Across many different organizations and industries teamwork is focused to increase the performance of employees’ their unity and also create work culture. Organizations those regularly develop new ideas or products using a project-based approach and assemble teams in order to focus responsibilities to achieve the object. Researchers have given dissimilar meanings of “teams”. Dyer W.G. (2007) said that “teams are groups of people who trust in cooperation, if members are expert the success of goal is more possible”. It is essential due to the problemsolving cooperation added from many minds of team members working on a resolution of problems. Team members contribute their thoughts together to make exclusive plans for dealing with problems and this unity enhance the result due to interaction, trust and teamwork. Teamwork means a "work done by several companions with each doing a part but all subordinating personal prominence to the efficiency of the whole" Merriam, (2012). In addition combined employees are expected less hostile to each other and accepting more of each other’s decisions. Unity of employees can increase the flow of work in organization. When employee’s working together as a team, they learn from each other that awareness is based on their personal experiences and from coworkers; Team Work 91 employees from different departments may acquire knowledge from each other. The main object for organizations is to hold the team effort to achieve output and quality; team is a key to achieve quality productivity. According to Maddux et al (2003) “some of the organizations have major benefits from the use of teamwork which are showed in the following chart: Benefits of Teamwork 1 Improving quality of work life for employees 2 Reducing absenteeism and increasing turnover 3 Increasing innovation and change 4 Improving organizational adaptability and flexibility A real team is mostly one where members are allowed to take decisions that how to complete task. That authority enables them to control the work process, decreases the outside control and increases the sense of duty for work. Team always feels superiority on workplace and they rely on each other’s being there. Plamínek (2008) said that “affiliation with teamwork gives member a sense of belonging, interaction and recognition of success”. These actions support to remove the sense of loneliness of team member in organization. Effective teams can also improve efficacy through communication and trust between the team members, quality of work and decrease in absenteeism contribute to positive impact on team. Involving employees in teamwork helps the organization remain open to new ideas.“The world of organizations is shifting individualism is out and collectivism is in, power is out, empowerment is in.” stated G. M. Parker (1998). This study discovers the experiences and difficulties of teamwork that employees and organizations are facing nowadays due to big transformation and enlarged globalization. In recent years a remarkable amendment has been emerged in the belief of team working organizations. The modern study has explored that the scope of teamwork have been appeared in system rooted in belief, and employees accept changes that denoting a modern organizational system. The organizations which are responsive to the changes appear to achieve greater satisfaction. Although it may be suggested that, the managers should assess the values and beliefs of their employees to play more dedicated role in the development of organization by making sprit to face the modern challenges. Organizational cultural is much significant and it has the excessive impact on the performance of organization and employees’ but it is quiet arguable topic that the culture of teamwork can be developed according to the requirement. It is difficult to specify the relationships and to assess the reliable set of values to use as they believed symbol across the entire organizations. This review study focus that 92 The Government there is a great influence of organizational culture on the assumptions, values, and beliefs on the individuals’ considerations, actions and performances and so is vice versa, through learning, and training process. However the researchers believe that the organizational setup aids to unite employees of diverse cultures and dissimilar social backgrounds, traditions and have their own beliefs to work. Creating a positive teamwork culture it has several diverse aspects are goal setting, conflict resolution, empowerment, ability to accomplish tasks, measuring output and consideration for other teamwork cultures stated Pack L, et al April 27, (2012). Team work in the organization delivers employees the wisdom of unity; understand to each other’s, and reducing conflict. In addition teamwork in organization inspires employee for impartiality by affirming that no one is ignored in the organization and all treated equally. It is known that a team in organization is bound and sincere to work with dedication to bring the success. If the employees are committed and recognize the teamwork values and its benefits, as a part of the organization they can contribute a lot to the achievement of organization. One can finds the informal instances of team at these level, family, society, community, tribe and work groups etc., and formally team appears at the level of departments, functional groups, and other organizational units. The employees feel a greater sense of achievement for being a part of an organization, if they attain team work, having freedom to work not forced. The system gives best performance to achieve recognition and credit from their managers and it will increase their effort that helps them to contribute the organizational performance. Each team batter knows about their role and how to achieve tasks. The true spirit of teamwork gives benefit to organization in maintaining its standard by which it becomes identified. The team defines its specialty, and the way it is doing task that is perceived by the organization as well as its managers and it is secured by appreciation. Employees identify what they believe; that exist in their belief system and those understandings call them to change their views to develop and raise attention towards batter performance. The literature contains sufficient definitions of teamwork and the word team is used to denote a set of generally developed as to learn collective values, attitudes and cooperation to work. The study praises that the teamwork is mostly related with the team success for instance, Wagner (1995) described that “in the team individual is less valued and group is more valued, with”. It is found in the study that individualismcollectivism both regulates the relationships between team size, standing, and cooperation that have better effects on the cooperation of individualists rather than the cooperation of collectivists. Team Work 93 Conclusion The main concentration of this research paper is to examine more in-depth the fundamental of teamwork and its effectiveness to achieve the organizational goals. Teamwork provides vast amounts of knowledge and information, cultural differences each of these building a culture of teamwork and the skill to make the valuable solutions of the problems. To work efficiently, team members need a good understanding of how to do their job, to achieve goal and for that a basic way to ensure understanding is training, then they have to be motivated to do a job. Team is a vital activity of organization, when organization desires to perform sound it has to be confident that team functions effectively. Consequently it is compulsory to know how team performs, what manners within a team happen, and how they make decisions. If there is knowhow of teamwork events, it can be effective for the tasks that they have to accomplish. Organizations build up their own culture through tradition, history and structure these values can be accepted by team workers of an organization. The values and assumptions are the vital tools of organizations and are used as guidance for team. These have to do mostly with the basic dignity and worth of all members of team and the ability, necessity for them to solve the problems and work for the positive change. Through this review study is concluded that there is a good impact of teamwork on the organizations doings and success. Subsequently in recently developed literature there is a great focus amongst the social scientists and scholars’ in their discussion on the above topic teamwork. The above study is also an evidence of little effort to assess the significance of teamwork in organizations success. teams in organiz1.1945-1949: The immediate years after the Second World War ● At the end of 1945, Mao Zedong had come to see the USA as the greatest threat to his aspirations. a. He understood that East Asians were looking to the USA as the true liberator from Japanese imperialism. b. The USA’s support for the Kuomintang(KMT) and the restoration of U.S. authority in formerly Japanese Manchuria clashed with the CCP’s plans to use the region for its own needs in the impending civil war between the CCP and the GMD. ■ To compound matters, while the KMT was recognised internationally as the official government in China, Mao and the CCP saw the party as a puppet of U.S. imperialism. ● While Mao saw the USA as the greater threat to the CCP’s plans, Soviet actions also frustrated him. a. The USSR provided minimal and incoherent support for the Chinese Communists in Yan’an and Manchuria. b. Stalin also attempted to extract territorial and economic concessions from the Guomindang government in the Friendship and Alliance Treaty China signed in August 1945 under American and Soviet pressure in exchange for Soviet entry into the Second World War against Japan. ● The emerging superpower conflict over Europe and over American intervention in the impending civil war in China led to Mao’s ideological perception of the 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 8 USA as an aggressive imperialist power that was hostile towards other countries, especially the USSR and China. ● In 1946, Mao promoted the theory of the intermediate zone, which envisioned a global united front against American imperialism. a. Mao saw the emerging superpower conflict as an American-Soviet contest for the intermediate zones, the capitalist, colonial and semi- colonial countries of West Europe, Africa, and Asia. b. Mao believed that the USSR was the defender of world peace. c. The intermediate zone, which included China, would not be part of the socialist camp. d. Despite the tremendous potential that U.S. aid held for China’s reconstruction, Mao’s ideological worldview and the impending civil war against the Guomindang prevented him from seeking normalised relations with the USA. In 1949, Mao decided to lean towards the side of the USSR despite two decades of unreliable support from them. e. Mao saw the anti-bourgeois campaigns in East Europe as evidence that China should isolate capitalist-bourgeois forces within it.2 f. Stalin had expelled Yugoslavia from the socialist camp as its leader, Tito was seen to have directly challenged Stalin’s authority. ■ Mao thus saw it as imperative to stress close unity to the USSR lest he was seen as a second Josip Broz Tito. At the same time, Mao sought a loose partnership with the USSR because Mao believed that China should preserve a high measure of self- reliance and zili gengsheng (自力更生) (regeneration through one’s own efforts). ● When the People’s Republic of China was formed on 1 October, 1949, relations between China’s and the USSR’s communists had improved substantially. a. However, the Chinese Communist Party (CCP) was also aware that the USSR never treated Chinese interests as a priority. What the CCP failed to fully understand was that Stalin ruled East Europe much like it was his empire and how this would have implications for China. b. In Mao’s first visit to the USSR in December 1949, Stalin was non- committal regarding the interests raised by the Chinese, and treated Mao as an underling as he feared that closer relations with the PRC would cause the USSR to lose privileges gained from the KMT. _________________________ 2 What Mao did not realise at that point was that the anti-bourgeois campaigns in East European countries were part of Stalin’s intentional design to consolidate the power of communists in them. 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 9 A note on Sino-American relations 2. Early 1950: The USA’s hands-off policy towards Taiwan begins to change ● By early 1950, the Truman administration had written off Taiwan and believed it was only a matter of time before the island fell to the PLA. ● Two events in early 1950 changed the USA’s position on East Asia. ○ The formation of the USSR-PRC alliance in February 1950 ○ The North Korean invasion of South Korea in June 1950 3. 1950: The Sino-Soviet Friendship, Alliance and Mutual Assistance Treaty ● Signed on 14 February, 1950. 3.1Implications for Sino-Soviet relations ● Stalin saw it as a means to get concessions that he had failed to get from the Kuomintang (KMT) government in 1945. ● For Mao and the newly founded People’s Republic of China (PRC), the alliance would provide security against U.S. imperialism and allow the PRC to get economic aid for reconstruction from the USSR. ● The Chinese realised soon after the 1950 treaty had been signed that the Soviet Union was intent on exploiting the agreement in its own favour. 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 10 ● The Sino-Soviet alliance was officially directed against Japanese militarism and its allies, especially the USA. ● The Sino-Soviet alliance comprised three elements: party, military and economic relations. ○ Party: The Chinese Communist Party (CCP) was included in the customs of communist party internationalism, such as regular exchange of party delegations to congresses of the fraternal parties in Stalin’s socialist camp. ■ This move was meant to bring the PRC’s ideological beliefs about communism into greater alignment with the USSR’s. ○ Military: The alliance was supposed to provide the newly formed and weak PRC with a strategic deterrent and military aid against the USA on three fronts: Guomindang-held Taiwan, divided Korea, and Vietnam where France attempted to reestablish its colonial control. ■ Convinced that the USA would aggressively seek ways to undermine the CCP-led PRC through Taiwan, Korea and Vietnam, Mao sought an active defence. ● While in Moscow, Mao unsuccessfully asked Stalin to provide military assistance for the liberation of Taiwan. ● At the beginning of 1950, the PRC delivered large-scale military aid to Hanoi. The PRC was the first country to grant the communist-led Democratic Republic of Vietnam diplomatic recognition on 18 January 1950; Mao persuaded Stalin to do so on 30 January 1950. ● The PRC committed itself to North Korea, where Mao saw the commitment to North Korea both as a defence against U.S. imperialism and as support for a fellow communist country. ○ Economic: During Mao’s first stay in Moscow, Stalin had personally promised the delivery of fifty projects for primary industrialisation. ■ The agreement also led to a series of supplementary ones, such as a US$ 300 million loan that the PRC would repay with a mixture of strategic materials, rubber, agricultural products, goods for daily use and hard currency. ■ Significantly, Stalin used Soviet military and economic aid to extract concessions similar to those he failed to get from the Guomindang government in 1945. ■ The USSR and PRC would disagree on the pace and extent of the PRC’s planned development. ● In the last five weeks of Stalin’s life in early 1953, he attempted to pressure the PRC to reduce the planned 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 11 development speed to a mere annual growth of 13-14 percent, and to plan individual projects in detail beforehand. These moves would potentially result in the PRC’s economy growing at a slower rate than initially projected. ● However, after Stalin’s death on 5 March 1953, the PRC’s Zhou Enlai decided to use his visit of condolence to the USSR to press forward negotiations. ○ When talks resumed in 1 April 1953, Beijing pressed for 150 Soviet industrial projects, but Moscow reduced them to 91 on the basis of insufficient data provided by the Chinese. ■ The economic disarray after China’s civil war and the economic pressures that came with the Korean War influenced recovery and reconstruction in the early years of the PRC. ● Despite the PRC being unable to tap into Soviet economic assistance immediately, mutual trade between China and the USSR nevertheless increased 6.5 times from 1950 to 1956. ● Together with the 50 projects promised by Stalin in 1950, the final version of the First FYP for the PRC included 141 Soviet and 68 East European projects in a total of 649 planned. Three thousand Soviet advisers sent to China in subsequent years were directly linked to the First FYP. ● By 1955, over 60 percent of China’s goods exchange was with the USSR. ● Soviet economic assistance to China added up to the largest foreign development venture in the socialist camp ever. ○ The total number of planned projects amounted to between 300 and 360 projects. ○ However, the number of total finished projects ranged between 134 and 150. ● Transfers of knowledge and expertise were important to China’s economic development. ○ A study on Soviet experts counts 1,445 political advisers and 9,313 technical specialists sent to China until their sudden withdrawal in mid-1960. ■ For political reasons, the gradual withdrawal of advisers began after late 1956. “On this night, we share a roof protecting us from fleets of inequity. Our unification promises a better tomorrow. Those larger than myself, sitting on their marble thrones, sipping blood from cups composed of human skin and singing songs of so-called virtue, grow weaker each moment. Their caravans are revolting. There is hope yet. There is progress! Though tonight may mark a countdown, it is still a celebration. Look at all we have done, not just for Trials but for Palatium Infra as a whole. In four years, when I’m no longer Sovereignty, the Spoiled Purity and his people will continue to strive. So drink! Smoke! Crush up those exotic plants and snort them! We will not falter, weaken, or wane. Our influence is expanding, and somebody new opens their eyes every day. Even the Silbys of Aculeus have reached alarming potentials despite their embittered minds. So long as you relish in tonight, dance, and pray to your “dead” Gods, our revolution shall rise beyond the bounds of class, and when I’m only a commoner, we shall rise again beyond our brainwashed adversaries! Cheers, my people. Cheers!” Followers raised their cups. Some clinked theirs together. Others stood still and screamed breathlessly in agreement. I smiled with courtesy, then stepped off my platform. My voice still rang across the cellar. Speeches before were grander. Those displays were supposed to be emptying, and yet this one left me bloated, swollen tight. I watched as they popped the corks of their bottles and chanted in the name of Purity. Maybe the quality of my words wasn’t what mattered to them anyway, so long as I screamed loud enough. There’s no merit in attacking your people, a voice corrected me. “That’s right,” I said aloud. “Knox, my-my Sovereign!” squealed a nearby devotee, jittering as he stuffed his face with catered pastries. He was one I’d never seen before or had failed to remember. “Look what I’ve found! It’s wine, and not the shoddy Infran kind, either. Earth-made with good fruit! I don’t know how anyone managed to get their hands on this. Maybe some space travel mischief.” He giggled and held up a small glass bottle. “How neat.” “I want you to have it, Sir.” I nodded my head. “Yes, of course. Thank you.” Backing off into the midst of rowdy disciples, I clutched the bottle. What a waste of grapes. It could have been jam instead. Earthly food had a superior taste, ripe with delicate intricacies and nostalgia, but Palatium Infra had mastered the art of alcohol. Why waste your time with a drunkenness so sad and sickening? The booze of trash. Not many more followers approached me. The barren peroration must have upset them. My hands itched to submerge into my suit pockets, and my legs stood suddenly numb, wobbling. Four more years until I’m nothing. But tonight, you are nothing. “Shut up,” I told myself. Tightly packed together in the corner of the dwelling sat the Sibyls. A mound of writhing fabric and tones of skin made up their unified silhouette. I snapped the strap of the nearest gown, balancing on my hands and knees, waving the bottle before them. In their almost rodent nature, narrow noses prodded my way. Their dresses wrinkled and fell to their ankles. Knees dropped, and eyes widened. Many grumbled at me like hungry she-beasts. Those newer ones with faded curtains for hair, sunken eyes, and dirtied nails looked, hid their face, then sobbed. I imagined them in a pack together, fighting wildly against the Spoiled Purity in their rat decorum–biting down with square teeth laced with rabies. “I’ve got you all something,” I said. “Go back off to your pedestal and yap some more. We don’t want it.” A woman rose from the pile and spat. “You don’t even know what it is yet. It's Earth hooch, or more likely a near-flawless replica. I figured you girls would also like a chance to enjoy yourselves tonight.” “Your playmates have been harassing us since the moment you hung the banners and opened the cellar door.” The youngest, with a striking cyan mop upon her head, uncoiled from the mass. What was she now? 20, 21? We celebrated a birthday recently, I thought as she spun around me. “I remember something about a promise. Multiple promises, actually. Are you trying to bribe us into just shutting up and taking it? Because if another sticky, 40-year-old, Earth-born virgin gropes my shoulder, I’m going to have an aneurysm!” the girl continued. “Why not an Infran follower? Do you like it when they touch you?” I returned her accusing tone. “I’m sorry, sweet prophets, that you feel I’ve neglected my duties. I’ll keep a better eye out. Remember, you can always just holler if somebody is bothering you. And Anwen, friend, if I’ve ever tried to bribe you with anything, it was certainly the hair dye. I mean, look at you! Such handsomeness!” I exclaimed. The other Siblys began to encircle her, uttering compliments or even announcements of their envy. Anwen disappeared in a wink with flushed cheeks back into the mound. “I’ll just leave this here.” Smiling, I set down the bottle. ** “141, 143. . .” I counted each step as I trekked the staircase. There was no doubt I lost track somewhere. The ledges kept spawning under my feet, infinitely multiplying until I wasn’t moving at all–swallowing me up in a whirlpool of stone. My tie still hung around my neck, and my blazer remained tied around my hips as a skirt. Streaks of red dribbled off from the cavity in my chest. It was a gorgeous marking, sensual to my fingertips as I traced its edges. Purity, oh, Purity. Purity and his wings of burnt skin. Purity and his many faces. Purity the spoiled. Purity the mutilated. The Silbys did not bother waiting for me. On bare feet, they stormed up the stairs to their room. A trail of red, though in paint unlike mine, streamed after them. None looked remotely near me as they squeaked and gossiped intangibly. I saved them, those Infran broads, enlightened them. As much as they liked to deny it, spit at me, and bask in the thought of their victimhood, in this home, they stood empowered. You’ve done well, my thoughts affirmed, though in the manner of an insincere commentator rather than a hype man. Teeth grace in tile violin goes laundry paper when. It dissolved into an intruding drivel. I rubbed my head and sniveled. “Do you need help, Knox?” called a Silby. Fattened by my coddling, her shadow fell upon me from the doorway steps ahead. I attempted counting again. There must’ve been at least another hundred between me and her. “I’m hallucinating some,” I said, breathing deeply to suppress a burp as I struggled to recall her name. Two syllables. Typically Latin, though sometimes English. Drops of slobber leaked from my mouth. “I’m hallucinating some, Tybal. Do you like your name, Tybal? I would have named you something better. Ty-Tyballinia. No, we’d have to eliminate the ‘ball’ aspect. It sounds too crude.” “One foot in front of the other,” she said. So I walked. Mess greeted me at the doorway. Dirtied culinary obscured the dark wooden countertops, and the sink lay running. I approached the kitchen table, sat, and set my face down upon its cool wooden surface. Assaulting my nose was the smell of neglected flowers, like soil mixed with the kind of sweet cough medicine that would have left me gagging as a child. Open windows whispered songs of the twilight hour through the vessels of busy trolleys and shooting guns. My mouth strained to vomit, but there was nothing in my stomach to regurgitate except the petals of Stulto’s bloom, which came out effortlessly in little sputters. Teetering, I stood up and brushed disgorged plant parts off the tabletop. “Love,” I said as I slogged up yet another staircase. “Are you awake?” She said she’d wait. Somebody’s gotten her. No, she always misses movie night. That sleepyhead, I assured myself. There was a stirring amidst the manor’s cloak of dusk. Portraits of myself, my wife, and my daughter turned to face me as the hallway lights flickered, escaping their quartz frames to penetrate my ears with nonsense. The taxidermied heads of Infran creatures bared their teeth. I stopped to stare at my favorite, an adabactor with daunting spiked tusks poking out from its forehead. Its nose remained black and sharp, and its eyes wide with malice. “Where is my Spes, Adaba-boy? Is she sleepy?” There’s someone in the house. The sounds of the stirring rose along with my blood pressure. Footsteps orbited around me, drawing near and far and then near again, little dancers in the dark. The carpet immersed me in its mass of purples and blues, leaving my skin stained indigo and my vision abstracted. I toiled to reach the master bedroom across the aisle as it stretched out to me with bright lights and celestial howling, like a dove struggling in a pool of oil. Never again with Stulto’s bloom. Never again on what was already a bad night. My hand brushed the doorknob, and the high abruptly faded into only a persistent hum-buzz twirling around my brain. The portraits returned to their typical depression–Spes posing with her ax, Ari’s school photo, and myself in the cap I wore when addressing the military with the Verbis emblem embroidered in its center. All lifeless shots. Who were they for when they captured not the subject’s essence but only some fragment of their identity? They used to feel personal, not advertisements of some supposed characters. Servants, babysitters, and likewise civilian guests, I reminded myself, mustn’t forget whose home they’re in. Yet my body moved independently, taking Ari’s from its hook and laying it backward against the wall to hide her distant grin and tamed posture. It was time for new pictures. Sweet ones, real ones; time was ticking. I approached my own when the stirring began again. Groans and squeals erupted from the vents as if someone had set a pen of pigs loose in my crawlspace. No, not the crawlspace, my bedroom door. I turned the ruby knob. Underneath a blanket wrestled my two squealing piglets, their skins melting together beneath the layer of duvet. Fishnet leggings and manicured nails outstretched and scraped at the sheet beneath them. One raised its head, a salmon-colored man with sweat running down his forehead. Through the crack in the door, we met eyes, his Infran Dr. Sesuss nose flaring its narrow nostrils. No mark of the Spoiled Purity existed carved onto his naked body. My chest felt tight. I stepped back. I was suffocating. Spes emerged from the linens, her hair flowing down her back and her dark skin glistening in front of the bedroom window. She giggled and held the man, the blanket falling and revealing inches of her body I had not seen in months. “Darling,” whispered the rosy-faced man, “look.” He was unfathomably ugly and grotesquely young, with beady, lifeless pupils that dilated when he faced me. The excess flesh on his face sagged while he bit down on his thin lips. My wife faced me, gasped, and strained to cover herself. Suddenly, I was a stranger. A small child who had walked into his parents having sex. I unfurled the door completely. “Get out of my house,” I said. The man stayed in place. “Get out of my house,” I repeated. “Knox,” Spes began. Tears ran down her round cheeks. “Shut up!” I turned to the man, picking up a marble trophy from on top of my dresser. “Get out of my house! I’ll kill you!” “Knox!” Spes sobbed. “God damn it! I hate you! You barely look at me. Every day, there’s less passion. God, God, God, I don’t want to fuck a dead man!” she screamed, “You get out! Get! Get!” My hands wrapped tighter around the statue. That pig of a man was attached to her at the side, his face equipped with a scowl that challenged mine. He thought I was weak; frail like a decaying dementia-ridden senior. I imagined his skull bashed in, his scowl gone, and the feist and confidence in his face beaten into numbness. A new portrait was in order of such brutality, him as a splintered slab of wood, rashed and beaten, a carcass licking my boot. The churning in my brain had come back. Every wall shook. Clock faces came to life and rang in alarm. Indescribable noises caressed my eardrum before breaking into sorrowful weeps. Was it my own? I stared at Spes in motionless frenzy, clenched my teeth, and screamed like a siren. Passionless. What a lie! An excuse, more like. One that erased all my ventures, reducing me to a nobody. But I was not a nobody. I thought of my sect, my campaigns, my endurance through the political brutality of my empty hive-mind world–even my collection of literature, maps, and artifacts. I thought of daring nights alone with Spes when we were young, ravaging each other, two sardonic eggheads suddenly overcome with desire. The veins in my neck throbbed as I gasped for air. It was all I had. I threw the figurine at the man’s head. Eye shut, I heard the thud. A million singing voices of victory flooded out of the cracks in the floorboard. Proving myself a man to the woman I loved in a display of fervent violence was passion. I strained my ears for his cries, though I did not look yet. There had to be a pause, a moment of relief, where I stood tall as a skyscraper and seemingly fought to stay contained in front of my wife and her wounded, quivering paramour. Frantic footsteps rushed off the bed and past my side. I turned and grappled against myself to seize my wife’s shoulder. “Spes!” My eyelids lifted. Escaping was the man with that same numb expression in which I had imagined him. “You’re insane,” he said. I swiveled back towards the bed. With her curly locks flowing over her breasts and her limbs bent at her sides, Spes sat limp pressed against the headboard, her forehead bludgeoned and the statue resting on her stomach. Lips pursed and sweet, my Renaissance beauty reclined there in the guise of a squashed bug. But she was not dead. The desk ornament I flung was only the size of my shoe. Spes, that dramatist, may have been slightly hurt but was far from dead. She only wanted me to think she was to observe me at my most distraught, like a leech feeding on misery. “Get up.” Staggering toward the bed, I said. “You wanted passion? I showed you passion. ‘Shoved it right into your head. Of course, we both know who that gesture was meant for. . .” I fumbled to find my wit. Cold skin met my hands as I stroked her face, unable to resist checking her pulse, even though she was not dead. “I love you, Spes,” I said. Rain pelted against a nearby window. “Spes, please. Please.” No vibration answered my plea. I lifted my hand, sitting next to her now. Tears did not come. There was not any blood on the trophy, but when I picked it up, it felt to be now only a cruel instrument. It depicted a younger me in white marble, with my glasses and collared shirt being the only things painted. Both were in pink. It was a favorable color. I scrambled from the bed to vomit pure digestive bile on the rug. My stomach heaved. I ran my nails along every piece of myself I saw, a dog chasing my tail. As I slammed myself against walls and convulsed, my own heart grew ever louder in my chest. “Dad? I heard–” Ari’s slippered feet hammered across the floor. “Mom? Mom?” I kept my eyes on the storm. Silence fell. “She-She isn’t—your—.” Gasps interrupted every syllable she spoke. “You’re a murderer. Bad. Like they said,” she breathed, “ You beat her!” The words became mush, alphabet soup. Ari ran back down the hall. “My-My mom is dead. . . .Yes. . . Manor of the Trials Sovereignty. . .Ari Sorkin. . . I’m afraid he’s going to hurt me,” she said, presumably over the phone. It was all too fast. I crawled onto the windowsill, opened the glass, and let myself plummet into the alley below. Gusts of wind howled. The lack of motion or sensation informed me I had passed and again lived. Another Palatium Infra, another strange planet in which the celestial endowed rotting men with the opportunity to inhabit. Was this it? Was it all just an impossible limbo of galactic traveling? My surroundings were overwhelmingly gray, an abyss of clouds. Perhaps I had now met the real coming world, and my family and old friends lived here, ready to rush to my sides, lift me up, and jump for joy. Spes would be there. She would be enraged, but at least she’d be there. You are a bad man. You are a bad man. My eyelashes fluttered. There was a tugging sensation in my leg. The fog was wavering along with my ascendance. “No,” I yearned, trying to grip the clouds and stick them in place. “Stay with me.” But the peace was fleeting. I felt the cement under me and the moist garments clinging to my figure. My leg burned. Carefully, I craned my neck, only to observe the promenade as my surroundings. The most underwhelming of filth and danger, individually Infran. Forever my coming world. What a fool I was, having forgotten my blessing. Those idiot Gods could not tell the difference between assassination and self-infliction; a faulty insurance plan. The urge to cry at last set over me, and so I sat and wailed hot salvia into my palm, shielding my mouth to muffle the noise. Thunder echoed my hushed howling. Raindrops turned to pebbles. Under the ambiance of the stormy night, I could have sworn I heard troops stomping, guns cocking, and the chanting of my name. They had all been waiting for this. Billboards came to life, and I could only sit and spectate as the scenery flashed red. I inhaled fear and sobriety through runny nostrils. “Trials Sovereign Vsevolod “Knox” Sorkin is currently at large for the suspected homicide of Spes Sorkin, breaking the first term of the Sovereignty Charter. We now instruct you to report any sightings of the Earth-born, caucasian, roughly 195 centimeters tall, brown-haired, and brown-eyed man to your local Guard post. One can identify the suspected convict specifically by an occult tattoo of Purity’s Coronet on his lower back. No attempted execution or elongated punishment will take place until our Guards conduct an autopsy proving his guilt, per Life’s 1238 commandment. We cannot be sure when or if the Gods will revoke his blessing. Remember, when Gods frown upon strife, opt for a peaceful life. We permit all grieving festivities until Cagidus 4th. Good year!” towering buildings sang out in broadcast, repeating that same convoluted message quicker the instant it ended. Sometimes, the announcer spoke in Latin for the Infran children, other times in Chinese, Hindi, or Spanish to cater to those of irrelevant tongues. You aren’t a bad man. You are a stupid boy. Puddles sloshed. Somebody was approaching. I didn’t dare waste any remaining energy avoiding the Guards and their prodding blades. How did that phrase go? You dug your grave. Now lie in it. And so I embraced the cement. “Knox?” said the Guard. No, her tone was too sincere, and no authority would proceed in such a manner. There wasn’t confirmation on whether or not I was armed, and it wasn’t as if she could shoot me first. She was a partygoer, having just left from the cellar’s backdoor. I shooed her away with my hand. She hovered, and I discerned her shadow hesitating over my body. A man could not rot in peace. “Come on, get up! They’re after you!” Hands reached around my torso, struggling to handle my weight as they urged me onto my feet. That leg, the burning one, my right, trembled and bent unnaturally upon impact with the ground. The partygoer slung my arm over her shoulder, balancing me. My eyes caught a glimpse of a cyan mop. “Anwen?” I rasped, “hu-who let you out?” Keys jangled in her hands–my keys. “I escaped,” she said casually, coercing me to walk beside her. “Quicken your pace. I just heard somebody on your front porch. ‘You see that compost bin down the alley? We’re gonna burrow right down into the depth of that. If they open it and uncover us, I’ll be on top, and I can hide you and act like I’m just a homeless amica trying to take a nap.” With a tightening grip, she led me like livestock to the stinking crate. “I don’t understand, Anwen,” I said. “They’re going to torture and kill you, stupid. You know they’ve been wanting to, and you just handed the opportunity to them!” “I understand that.” It was becoming increasingly challenging to hide the fragility emerging in my voice. “You said you were escaping. Why stop and help your captor?” “What else could I do? Leave you there?” Attempts to shove my wounded body inside its mass of discarded fruits and vegetables began. She yanked down upon my head and submerged me in the fertilizer sea. The evidence grows indisputable, I thought as I stared at the abruptly humane Infran girl, diving in after me, that I belong here. “Damn me to hell! I’ve killed her! My love is dead!” an uncontrollable cry leaped from my mouth. “Shut up! Soon you’ll be, too, if you don’t quiet down.” The actual noise of the Guards darted past us: disorientated marching, guns clanking against each other, cluttered belts rattling, the Latin squawking. One paused to open the bin’s lid, though only rummaged through the surface layer of peat before carrying on. “What are they talking about? I struggle with my Latin,” I whispered. “The search, mainly.” Aggression remained firey in Anwen’s clenched jaw. Though she sat on top of me, there was a monumental distance between our rain-soaked forms. I curled up into a ball, ducked my head between my knees, and dreamt of Spes, ignoring the stench of spoiled food rising from every crevice of my dwelling. The next coming world was due to adopt me again as I forced sleep. I prayed for a canyon of fluffy haze, where I waltzed with pale memories but found nothing but the petrifying stillness of my mind. Killed and ran. Violent as a Guard just to prove a point and watch it backfire. Why would any heaven want to welcome me? I clung to the picture of Spes in my head like it was the last ember of an extinguished flame. “Did you mean to kill her?” Anwen interrogated. “Someone like you would immutably believe yes.” “And who is someone like me? You can’t even treat me like a person for a moment, can you?” grating drama decorated her words. “You know my opinions. I have not seen much of your or your breed’s faces besides that of cruelty and ignorance.” I retorted. “I just saved you! Does that make me cruel and ignorant?” “It makes you an idiot, which is another word for somebody ignorant.” “And why am I an idiot?” She asked. “Because you helping me does no good. Thank you anyhow. Now, do yourself a favor and scram.” As she bent her leg in anticipation, preparing to strike me on the forehead, I sensed an invisible withdrawal widening the gap between us. “You never answered my question,” Anwen took me by the end of my tattered tie suddenly and started her game of shepherd and sheep over again, pulling me back up to the crate’s exit. It appeared as a shining light at the end of a maze of rubbish and mold. “No. Of course not. Spes was my everything,” I sniffled. “I knew it. You couldn’t even bring yourself to hit us, let alone murder your wife. The girls and I always figured you were sensitive.” My heart rate quickened. Today was one of humbling and misery–one to pray a hail spike would fall from the sky as sharp as a needle, pierce into my eyelid, and lobotomize me. I wished I could have merely died or hit my head hard enough not to have to deal with it all. No, I wished I was Anwen with her snarky, careless glow and lack of depth in her eyes. As we emerged from the compost bin together, I fantasized about strangling her until her face turned purple, her weakening spirit no longer categorizing me as “sensitive”, but the thought could only remind me of wielding that trophy and the microscopic traces of my wife’s tender skin tainting it, which turned my guts inside out. “That’s why I think you could use a little help,” Anwen said, “It seems like you can’t walk, either. Your leg is all twisted up.” She undid one of her trim pigtails and handed me the band. “Take off your tie and put up your hair. ‘Will make you less recognizable. Then swallow your pride and stick with me.”The student will understand the basic differences between physical weathering and erosion and be able to identify physical properties of common Earth-forming minerals. Performs complex skills: Describe how the three categories of rock are formed: igneous (formed from molten rock); sedimentary (pieces of other rocks and fossilized organisms); and metamorphic (formed from heat and pressure). Compare and contrast common minerals by their physical properties. (hardness, color, luster, cleavage, and streak color) Compare and contrast renewable and nonrenewable resources found on Earth. Compare and contrast the agents and the processes of physical weathering and erosion. (4.32C know that ethanol can be manufactured by: • reacting ethene with steam in the presence of a phosphoric acid catalyst at a temperature of about 300 ºC and a pressure of about 60–70 atm • the fermentation of glucose, in the absence of air, at an optimum temperature of about 30 ºC and using the enzymes in yeast 4.33C understand the reasons for fermentation, in the absence of air, and at an optimum temperatureChapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic Drug Alpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic Drugs Alpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitors aka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers (ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTN Treatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)What is a crime A crime is generally defined as an act or omission that is prohibited by criminal law Two critical ingredients of a crime are: 1) the commission of an act (Actus reus) 2) the mental intent to commit the act (Mens rea) A crime occurs when a person Commits an act or fails to commit an act when under a legal responsibility to do so Has the intent or mens rea to commit the act Does not have a legal defence or justification for committing the act and Violates a provision in criminal law The Social construction of crime Important to distinguish between behaviours that may be considered deviant by society and crimes Deviance is behaviour that is contrary to the norms and values of the larger society Crime is behaviour that breaks the law Deviance includes: Criminal behaviour and Wide range of other behaviours not against the law: May be frowned upon by the larger society What is viewed as deviant changes over time Crime includes: Social construction of crime Legal status of behaviours is not determined by behaviour itself but result of social response to the behaviour/persons/groups engaged in it Criminologists often conduct historical analyses to understand how social, economic and political environments may influence legislation Moral entrepreneurs Often play a key role in criminalizing certain activities Individuals, groups or organizations, seek action against certain groups of people/behaviours and bring pressure on legislators to enact criminal statutes The Origins and Application of the Criminal Law Differing perspectives on where criminal laws come from/ applied via the criminal justice system are reflected in two models 1) Value consensus model 2) Conflict Model Value consensus model Behaviours are defined as criminal/punishment imposed, reflect opinions/limits of tolerance Application of law, society reaffirms acceptable behaviours/social cohesion Conflict Model Crime and punishment reflect the power some groups have to influence, formulation/application of criminal law rich/privileged have an advantage in influencing law reform/criminal justice system The Canadian Legal System Is a common law system, with exception of Quebec which has a civil law system (Based on the French Code Napoleon) Common law is law based on custom, tradition, practice and generally unwritten Precedent is a judicial decision may be use as a standard in subsequent similar cases Canadian Courts Canadian courts organised in a hierarchy Supreme court of Canada is the highest court Stare decisis- principle whereby higher courts set precedents that lower courts must follow “To stand by what was decided” Like cases should be treated alike All courts below SSC bound to apply that same ruling in subsequent cases Criminal Law Body of law deals with conduct considered so harmful to society as a whole that it is prohibited by statute and prosecuted and punished by the government Functions of the Criminal Law In Canadian society, Criminal law provides the following functions Acts as a mechanism of social control Defines the parameters of acceptable behaviour Reduces the risk of personal retaliation Assists in general and specific deterrence Prosecutes criminalized behaviour Protects groups interests Principles of Canadian Law The Rule of Law The requirement that governments as well as individuals be subjected to Traced back to the English Magna Carta The essence of the rule of law is that No one person is above the law All persons are bound by the law All are entitled to protection by the law The law should be observed and enforced equally There is a standard to which criminal justice officials must adhere and will be held accountable Criminal Law Vs. Civil (Tort) Law Summary Crime is a social construction and is a reflection of changing time and mores Criminal law is not static and what behaviour legislatively defined as criminal can change overnight There are instances in which controversy arises when the criminal law is applied to issues of ethics, morality and religion The criminal law was identified as one type of public law and the functions of the criminal law were set out The rule of law and the charter of rights and freedoms are two key parts of the foundation of the criminal justice system There are several principles that also provide the foundation for Canadian law The role, principles origins and application of the criminal law were examined and a number of case studies were presented to illustrate the dynamic nature of the criminal law in a diverse society PASSIVE TRANSPORT Cell membranes help organisms maintain homeostasis by controlling what substances may enter or leave cells. Some substances can cross the cell membrane without any input of energy by the cell in a process known as passive transport. DIFFUSION The simplest type of passive transport is diffusion. Diffusion is the movement of molecules from an area of higher concentration to an area of lower concentration. This difference in the concentration of molecules across a distance is called a concentration gradient. Consider what happens when you add a sugar cube to a beaker of water. As shown in Figure 5-1, the sugar cube sinks to the bottom of the beaker. This sinking makes the concentration of sugar mole- cules greater at the bottom of the beaker than at the top. As the cube dissolves, the sugar molecules begin to diffuse slowly through the water, moving towards the lower concentration at the top. Diffusion is driven entirely by the molecules’ kinetic energy. Molecules are in constant motion because they have kinetic energy. Molecules move randomly, traveling in a straight line until they hit an object, such as another molecule. When they hit some- thing, they bounce off and move in a new direction, traveling in another straight line. If no object blocks their movement, they con- tinue on their path. Thus, molecules tend to move from areas where they are more concentrated to areas where they are less concentrated, or “down” their concentration gradient. In the absence of other influences, diffusion will eventually cause the molecules to be in equilibrium—the concentration of molecules will be the same throughout the space the molecules occupy. Returning to the example in Figure 5-1, if the beaker of water is left undisturbed, at some point the concentration of sugar molecules will be the same throughout the beaker. The sugar concentration will then be at equilibrium. SECTION 1 OBJECTIVES ● Explain how an equilibrium is established as a result of diffusion. ● Distinguish between diffusion and osmosis. ● Explain how substances cross the cell membrane through facilitated diffusion. ● Explain how ion channels assist the diffusion of ions across the cell membrane. VOCABULARY passive transport diffusion concentration gradient equilibrium osmosis hypotonic hypertonic isotonic contractile vacuole turgor pressure plasmolysis cytolysis facilitated diffusion carrier protein ion channel Sugar Water 1 2 3 FIGURE 5-1 Sugar molecules, initially in a high concentration at the bottom of a beaker, , will move about randomly through diffusion, , and eventually reach equilibrium, . At equilibrium the sugar concentration will be the same throughout the beaker. Diffusion occurs naturally because of the kinetic energy the molecules possess. 3 2 1 Copyright © by Holt, Rinehart and Winston. All rights reserved. 98 CHAPTER 5 It is important to understand that even at equilibrium the ran- dom movement of molecules continues. But because there is an equal concentration of molecules everywhere, molecules are just as likely to move in one direction as in any other. The random movements of many molecules in many directions balance one another, and equilibrium is maintained. Diffusion Across Membranes Cell membranes allow some molecules to pass through, but not others. If a molecule can pass through a cell membrane, it will diffuse from an area of higher concentration on one side of the membrane to an area of lower concentration on the other side. Diffusion across a membrane is also called simple diffusion, and only allows certain molecules to pass through the membrane. The simple diffusion of a molecule across a cell membrane depends on the size and type of molecule and on the chemical nature of the membrane. A membrane can be made, in part, of a phospho- lipid bilayer, and certain proteins can form pores in the membrane. Molecules that can dissolve in lipids may pass directly through the membrane by diffusion. For example, because of their nonpolar nature, both carbon dioxide and oxygen dissolve in lipids. Molecules that are very small but not soluble in lipids may diffuse across the membrane by moving through the pores in the membrane.