Orientation for New Employees Essay

Do you believe your design of the detailed organization chart indicates centralized or decentralized lines of authority for decision making? Can you explain your approach in one to two sentences? I do believe that my design is detailed centralized organization. In order for human resources to work, there has to be some type of organization. If there was no organization, HR would not function properly. At the hospital, HR has departments for specific needs. There is a department for Health Benefits and there is a different Coordinator for specific last names. I think it keeps it somewhat organized. Review the chapter text about information flow and Figures 2–2 and 2–3. Do you have â€Å"information flow-sheets† at your organization? What is the purpose for them? Are they always this formalized? Should they be? (If you don’t have a information flow sheet currently make one up for your organization) In the family practice we have two offices, I really did not know about flow sheets. I asked the billing person in the office and she did show me one and it is similar to 2-3. She did explain to me what they  are about and how they function for the office, but I don’t understand it as much. I think because I am more in the clinical side of the office it makes it hard for me to understand how they are used. She did mention they will be changing since the practice was bought out by the hospital. She stated it will be sometime in the upcoming year.

Free Essays on Harriet Jacobs

In Harriet Jacobs story, â€Å"From Incidents of a Slave Girl†, Jacobs discusses the hardships of being a female during slave times. Things such as being separated from her family on different occasions were downfalls that all slaves had to deal with. Throughout her story, Jacobs stays strong and never gives up on the fact that someday there will be brighter days. Jacobs was seemingly very close with her mistress and their children. As Jacobs grew older, she experienced the utmost harassment from her master. He whispered impure statements and his demeanor grew worse and worse. Her mistress, because of her age and the masters’ intentions, grew very jealous of Jacobs. Jacobs looking for someone to confide in had no one to turn to. Her grandmother had always been then for her, but at times like these, Jacobs could not approach her. Jacobs’ grandmother was a very proper lady that instilled that purity upon her granddaughter. She would not be able to deal with such impure things such as the sexual harassment that Jacobs encountered.... Free Essays on Harriet Jacobs Free Essays on Harriet Jacobs In the stories expressed by Harriet Jacobs, through the mindset of Linda Brent, some harsh realities were revealed about slavery. I’ve always known slavery existed and that it was a very immoral act. But never before have I been introduced to actual events that occurred. Thought the book Linda expresses how she wasn’t the worst off. Not to say her life wasn’t difficult, but she acknowledged that she knows she was not treated as bad as others. Linda’s life was without knowing she was a slave until she was bout six years old. Her father was skilled craftsmen and so his was allowed to work for his profit as long as he gave half to his master. Linda’s mother died when Linda was young, so her maternal grandmother took car of her and her brother William. Her grandmother had been freed by an elderly white woman. Aunt Martha, as was known, was very loved by many including whites and blacks especially by Linda. As soon as she realized her fate in slavery her grandmother became her only female figure of who she really loved and trusted. As slavery became more and more a part of Linda’s life began to soon change as she learned that she was owned by a white master and his mistress and that she was to do exactly what they asked of her without exception or question. Black slaves were not seen as humans but merely as property who served as servants. They could not accumulate property or belongings or authority because they too were property often compared to â€Å"chattel†. No man or woman had any value except for the price tag placed on them when they entered the bidding block. However, the destiny was different for a man than for a woman in slavery. For a black man, slavery meant long hours everyday, having a family But not having any authority amongst it, dealing with the constant reminder that he as a slave could not protect his wife or children form any harm done by the master, and that if he ever disobeyed he... Free Essays on Harriet Jacobs In Harriet Jacobs story, â€Å"From Incidents of a Slave Girl†, Jacobs discusses the hardships of being a female during slave times. Things such as being separated from her family on different occasions were downfalls that all slaves had to deal with. Throughout her story, Jacobs stays strong and never gives up on the fact that someday there will be brighter days. Jacobs was seemingly very close with her mistress and their children. As Jacobs grew older, she experienced the utmost harassment from her master. He whispered impure statements and his demeanor grew worse and worse. Her mistress, because of her age and the masters’ intentions, grew very jealous of Jacobs. Jacobs looking for someone to confide in had no one to turn to. Her grandmother had always been then for her, but at times like these, Jacobs could not approach her. Jacobs’ grandmother was a very proper lady that instilled that purity upon her granddaughter. She would not be able to deal with such impure things such as the sexual harassment that Jacobs encountered....

How to Respond to a Request for a Writing Critique

How to Respond to a Request for a Writing Critique How to Respond to a Request for a Writing Critique How to Respond to a Request for a Writing Critique By Mark Nichol You’ve been asked to critique another person’s writing. Perhaps you’re in a writing group. Maybe a colleague has a novel, or a short story, or a collection of their poems, they want to share with you. Or it may be a friend, or a family member, who requests your help. Easy, right? Not at all. Your response will be based on a variety of factors. First, who, exactly, is this person making this perfectly reasonable but deceptively simple-sounding request? How well do you know them, and how comfortable are you with critiquing their writing and they with receiving the criticism? And when they asked you for your assistance, how, precisely, did they pose their request? When someone asks you, in a context outside a professional working relationship, to look over something they wrote, your first response should be, â€Å"What, precisely, would you like me to do?† Their answer will depend, of course, on both their familiarity with the critiquing process and their self-awareness. If they respond that they just want assurance that their work is readable, that they’re headed in the right direction, that the concept and the narrative are potentially appealing to a wide readership, you have it relatively easy. You’ll simply be reading the piece of writing and spending a matter of minutes sharing, in writing or in conversation, your general impressions. But you’re still confronted with the possibility that your honest answer to their question â€Å"Is it any good?† will be no. I’ll get back to that in a moment. If they ask for a more substantial review, one involving notes and/or revisions, because they know you have writing and/or editing experience and can give them guidance, make sure you mention two things: One, they must know the distinction between substantive and mechanical editing. Two, they need to understand what they’ve asked of you. Substantive editing involves reviewing a piece of writing holistically, examining its structure, pacing, and overall impact, and determining whether it is well organized or would be improved with shuffling of sentences, paragraphs, or sections. (Rare is the early draft of a piece of writing that is not improved with at least some reorganization.) A substantive editor will also make occasional notes about phrasing or word choice. Mechanical editing, by contrast, is attention to grammar, syntax, style, spelling, punctuation, and other minutiae though a limited holistic appraisal is part of the process. Once you’re confident that the difference is understood, let the supplicant know that it’s best to manage these distinct tasks in two stages, and that at this point, during the draft stage, only the substantive review will be productive. I suggested earlier that you bring up two issues. The other thing you must do is manage expectations about your commitment of time and energy. Many beginning writers haven’t acquired a perspective about how long editing takes. Make it clear that for you to do anything more than read for general impressions, in order to give the piece of writing the attention it deserves, you would expect to be able to get through only a few pages per hour. For that reason, you would like them to select a chapter from the novel or a section of the short story or a reasonably small fraction of the collected poems for you to review, and to be patient about a response. Remember that part above about me getting back to you about something? That something is honest appraisal. I’ll go into detail in another post about how to appraise, but here is a brief caution: In agreeing to critique someone’s writing, whether superficially or in depth, you are agreeing to respond truthfully about someone’s success in communicating heartfelt expression about something that means a lot to them. As obvious as that may seem to you, I suggest that your response include something like this: â€Å"Understand that no matter how good a writer you are, there will be areas for improvement, and I want to be honest with you about them so that you can become even better. I’d expect no less from you if you looked over something I’ve written. So, unless you’ve done multiple drafts and had someone do substantive editing and someone else do mechanical editing, be prepared for the fact I’m going to find things in your writing that need work. Also, it’s possible that what you’ve written may appeal to others but not to me, but if that’s the case, I’ll still try to advise you about what you can do to make it even more appealing to others.† This statement may seem unduly frank and intimidating, but I think it’s important that you say it. By stating something like this up front, you’re not implying that the writer is a fragile narcissist who will crumble at the slightest hint of criticism; you’re preparing them to get what they asked for: a candid, productive evaluation of something they’ve put a lot of time and effort into but must be prepared to work on even more before it is ready for publication, if that is their goal. And if you must forthrightly state your opinion that the writer should abandon the idea (but not their desire to share other ideas), or that the presentation is awkward or ineffective (but has potential for success if they’re willing to put a lot more work into it), you’ve done your duty, and it is the other person’s responsibility to accept your conclusions with good grace. But be sure to preface the medicine with a spoonful of sugar: Find something positive to begin your report. I’ll go into more detail about that and other appraisal techniques in a later post. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Writing Basics category, check our popular posts, or choose a related post below:7 Types of Narrative Conflict50 Idioms About Fruits and Vegetables10 Terms for the Common People

Company Security Essay Example | Topics and Well Written Essays - 2000 words

Company Security - Essay Example The needs of users of  the data provided via a network and subsequently develop a security policy and plan that addresses the security issues concerned (Langer, 2001). The ensuing distribution of data in client or server networks leads to increased susceptibility of the system to fraud, damage by malicious software, misuse, as well as physical damage. With business organizations and their stakeholders developing complex networks, security issues become a key factor of consideration. The security systems developed by such organizations must seek to protect all areas of concern across the network to prevent the occurrence of unethical practices in relation to the information flowing through the system. The value of security in a client/server network plays an inevitable role in protecting the data, as well as the ethical concerns of the parties involved thus, requiring the development of a comprehensive network security policy as reviewed in this context and with reference to ZXY Cor poration. In order to enhance secure access control over the network, the company can apply advanced authorization, as well as access control methodologies that would subsequently enhance network security. The interrelated methods of user authentication and authorization that are applicable will depend on the sensitivity of the section of the network and the information that may be accessible. Shared resources in the network are available for all the users except the resource owner. As such, the security system needs to protect such information from unauthorized access and use. In the network’s access control framework, unique security identifiers (SIDs) may embody the users in the system, and they are subsequently assigned permissions and rights that provide information to the operating system concerning what each of the users can do in the system. Each of the resources in the network has a designated owner who grants  permission  to users. In

Case studing (nursing science) Study Example | Topics and Well Written Essays - 750 words

Studing (nursing science) - Case Study Example His heart rate is increasing as well as his breathe per minutes. At his age, excitement is very much increased and is there for increasing also the cardiovascular activity. The cardiovascular system helps transport oxygen and nutrients to tissues, transport carbon dioxide and other metabolites to the lungs and kidneys, and distribute hormones throughout the body. The cardiovascular system also assists with thermoregulation. The runner's sympathetic nervous system is activated (central command), and catecholamines are released from the adrenal medulla. This is the reason in cardiac acceleration, increased myocardial contractility, increased cardiac output, peripheral vasoconstriction, and an increase in blood pressure. As the race started the following factors in the cardiovascular system are considered: the heart rate, peripheral resistance, skin blood flow, cardiac output, and blood flow distribution. Cardiovascular changes at the start of the game include the compression of the blood vessels in the contracting muscle leading to a reduction in the blood flow. Heart rate continues to increase during the race, until the rate reaches a plateau of about 180 beats/min at maximum effort. Peripheral resistance decreases because of relaxation of arterioles in active muscle and skin (as body temperature rises). Skin blood flow increases, which aids in heat loss. Blood flow to inactive muscle, kidney, and gastrointestinal tract is reduced. Because BP is a major determinant of afterload, the left ventricular wall stress, and thus the cardiac workload, is significantly higher. As the intensity of the race increases the BP is also increasing from 120 mmHg to approximately 200 mmHg. Maximum oxygen uptake leve l (VO2max) is reached during this state. Cardiac output increases during the race until 40% of VO2max (maximum oxygen uptake level) is reached. Cardiac output rises from approximately 80 mL/beat to approximately 120 mL/beat. HR increases with intensity until VO2max is reached. HR rises from approximately 70 beats per minute to approximately 200 beats per minute. Cardiac output increases with intensity until VO2max is reached. Cardiac output rises from approximately 5 L/min to approximately 25-30 L/min. (Suleman, 2006). The race is almost over the athletes are chasing to cross the finish line first. There is an increase in PaCO2 in the Kenyan athlete. PACO2 represents the amount of CO2 in solution. When there is an increase in blood PACO2, there is an increase in ventilation. During this stage more oxygen is needed and more CO2 and metabolic acid are produced. There is an increased cardiac output because the tissues need more oxygen supplied to them. This is also caused due to an increase of lung ventilation to support gas tensions in arterial blood, which experiences faster blood flow. When an individual is on the move, the venous blood shows signs of decreased O2 levels, increased CO2 levels, and an increase in H+ levels. During the race the blood flow to the leg muscles increases because of the local factors, which includes: the release of vasodilator metabolites (e.g. adenosine); the increase in muscle temperature; and the local decreased in pH (increased CO2 and lactic acid). The arterioles dilate and more capillaries open (capillary recruitment). Venous return is facilitated in running by the following: sympathetic-mediated contraction of capacitance vessels ; muscle compression of the leg veins with one-way

Collaboration and Consultation in Education Research Paper

Collaboration and Consultation in Education - Research Paper Example According to the research findings, it can, therefore, be said that collaborative learning is accomplished through the use of active engagement activities designed to exploit knowledge and to facilitate the sharing of the workload. In this method, learners can generate their individual parts of a larger assignment and then the parts are compiled as a group work. Collaboration is also a style employed by professionals in order to achieve a common and a shared goal. There are several terminologies that may be used interchangeably when discussing cooperation strategies. These terms include consultation, teamwork, collaborative work and collaborative consultation. However, the collaboration will be employed in this paper as the umbrella concept for the various collaborative strategies. Furthermore, there are different forms in which collaboration techniques are created. These are the student collaboration, teacher-student collaboration, teacher-parent collaboration, and student-parent co llaboration. All these forms of cooperation are primarily meant to help enhance the learning process of a student and to ensure they achieve the best in education. Collaboration is both advantageous in teaching and learning when it happens on various levels. Collective prioritizing of education by the students, teachers, members of a family, and the community as a whole is beneficial to teaching and learning process. The benefits will be more felt when all the stakeholders engage in activities that promote learning institutions, educators, and students. Additionally, the advantage of collaboration becomes more evident when teachers collaborate with other teachers to support innovative classroom practices. And aim at the high level of expectations for themselves and students as well. Further, the benefits of collaboration can be achieved more when students are granted the chance to work together for common academic goals in manners that improve learning.

Predicting Effects of Environmental Contaminants

Predicting Effects of Environmental Contaminants 1.1. Debunking some chemical myths†¦ In October 2008, the Royal Society of Chemistry announced they were offering  £1 million to the first member of the public that could bring a 100% chemical free material. This attempt to reclaim the word ‘chemical from the advertising and marketing industries that use it as a synonym for poison was a reaction to a decision of the Advertising Standards Authority to defend an advert perpetuating the myths that natural products were chemical free (Edwards 2008). Indeed, no material regardless of its origin is chemical free. A related common misconception is that chemicals made by nature are intrinsically good and, conversely, those manufactured by man are bad (Ottoboni 1991). There are many examples of toxic compounds produced by algae or other micro-organisms, venomous animals and plants, or even examples of environmental harm resulting from the presence of relatively benign natural compounds either in unexpected places or in unexpected quantities. It is therefore of prime impo rtance to define what is meant by ‘chemical when referring to chemical hazards in this chapter and the rest of this book. The correct term to describe a chemical compound an organism may be exposed to, whether of natural or synthetic origins, is xenobiotic, i.e. a substance foreign to an organism (the term has also been used for transplants). A xenobiotic can be defined as a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual. A grasp of some of the fundamental principles of the scientific disciplines that underlie the characterisation of effects associated with exposure to a xenobiotic is required in order to understand the potential consequences of the presence of pollutants in the environment and critically appraise the scientific evidence. This chapter will attempt to briefly summarise some important concepts of basic toxicology and environmental epidemiology relevant in this context. 1.2. Concepts of Fundamental Toxicology Toxicology is the science of poisons. A poison is commonly defined as ‘any substance that can cause an adverse effect as a result of a physicochemical interaction with living tissue'(Duffus 2006). The use of poisons is as old as the human race, as a method of hunting or warfare as well as murder, suicide or execution. The evolution of this scientific discipline cannot be separated from the evolution of pharmacology, or the science of cures. Theophrastus Phillippus Aureolus Bombastus von Hohenheim, more commonly known as Paracelsus (1493-1541), a physician contemporary of Copernicus, Martin Luther and da Vinci, is widely considered as the father of toxicology. He challenged the ancient concepts of medicine based on the balance of the four humours (blood, phlegm, yellow and black bile) associated with the four elements and believed illness occurred when an organ failed and poisons accumulated. This use of chemistry and chemical analogies was particularly offensive to his contempo rary medical establishment. He is famously credited the following quote that still underlies present-day toxicology. In other words, all substances are potential poisons since all can cause injury or death following excessive exposure. Conversely, this statement implies that all chemicals can be used safely if handled with appropriate precautions and exposure is kept below a defined limit, at which risk is considered tolerable (Duffus 2006). The concepts both of tolerable risk and adverse effect illustrate the value judgements embedded in an otherwise scientific discipline relying on observable, measurable empirical evidence. What is considered abnormal or undesirable is dictated by society rather than science. Any change from the normal state is not necessarily an adverse effect even if statistically significant. An effect may be considered harmful if it causes damage, irreversible change or increased susceptibility to other stresses, including infectious disease. The stage of development or state of health of the organism may also have an influence on the degree of harm. 1.2.1. Routes of exposure Toxicity will vary depending on the route of exposure. There are three routes via which exposure to environmental contaminants may occur; Ingestion Inhalation Skin adsorption Direct injection may be used in environmental toxicity testing. Toxic and pharmaceutical agents generally produce the most rapid response and greatest effect when given intravenously, directly into the bloodstream. A descending order of effectiveness for environmental exposure routes would be inhalation, ingestion and skin adsorption. Oral toxicity is most relevant for substances that might be ingested with food or drinks. Whilst it could be argued that this is generally under an individuals control, there are complex issues regarding information both about the occurrence of substances in food or water and the current state-of-knowledge about associated harmful effects. Gases, vapours and dusts or other airborne particles are inhaled involuntarily (with the infamous exception of smoking). The inhalation of solid particles depends upon their size and shape. In general, the smaller the particle, the further into the respiratory tract it can go. A large proportion of airborne particles breathed through the mouth or cleared by the cilia of the lungs can enter the gut. Dermal exposure generally requires direct and prolonged contact with the skin. The skin acts as a very effective barrier against many external toxicants, but because of its great surface area (1.5-2 m2), some of the many diverse substances it comes in contact with may still elicit topical or systemic effects (Williams and Roberts 2000). If dermal exposure is often most relevant in occupational settings, it may nonetheless be pertinent in relation to bathing waters (ingestion is an important route of exposure in this context). Voluntary dermal exposure related to the use of cosmetics raises the same questions regarding the adequate communication of current knowledge about potential effects as those related to food. 1.2.2. Duration of exposure The toxic response will also depend on the duration and frequency of exposure. The effect of a single dose of a chemical may be severe effects whilst the same dose total dose given at several intervals may have little if any effect. An example would be to compare the effects of drinking four beers in one evening to those of drinking four beers in four days. Exposure duration is generally divided into four broad categories; acute, sub-acute, sub-chronic and chronic. Acute exposure to a chemical usually refers to a single exposure event or repeated exposures over a duration of less than 24 hours. Sub-acute exposure to a chemical refers to repeated exposures for 1 month or less, sub-chronic exposure to continuous or repeated exposures for 1 to 3 months or approximately 10% of an experimental species life time and chronic exposure for more than 3 months, usually 6 months to 2 years in rodents (Eaton and Klaassen 2001). Chronic exposure studies are designed to assess the cumulative toxici ty of chemicals with potential lifetime exposure in humans. In real exposure situations, it is generally very difficult to ascertain with any certainty the frequency and duration of exposure but the same terms are used. For acute effects, the time component of the dose is not important as a high dose is responsible for these effects. However if acute exposure to agents that are rapidly absorbed is likely to induce immediate toxic effects, it does not rule out the possibility of delayed effects that are not necessarily similar to those associated with chronic exposure, e.g. latency between the onset of certain cancers and exposure to a carcinogenic substance. It may be worth here mentioning the fact that the effect of exposure to a toxic agent may be entirely dependent on the timing of exposure, in other words long-term effects as a result of exposure to a toxic agent during a critically sensitive stage of development may differ widely to those seen if an adult organism is exposed to the same substance. Acute effects are almost always the result of accidents. Otherwise, they may result from criminal poisoning or self-poisoning (suicide). Conversely, whilst chronic exposure to a toxic agent is general ly associated with long-term low-level chronic effects, this does not preclude the possibility of some immediate (acute) effects after each administration. These concepts are closely related to the mechanisms of metabolic degradation and excretion of ingested substances and are best illustrated by 1.1. Line A. chemical with very slow elimination. Line B. chemical with a rate of elimination equal to frequency of dosing. Line C. Rate of elimination faster than the dosing frequency. Blue-shaded area is representative of the concentration at the target site necessary to elicit a toxic response. 1.2.3. Mechanisms of toxicity The interaction of a foreign compound with a biological system is two-fold: there is the effect of the organism on the compound (toxicokinetics) and the effect of the compound on the organism (toxicodynamics). Toxicokinetics relate to the delivery of the compound to its site of action, including absorption (transfer from the site of administration into the general circulation), distribution (via the general circulation into and out of the tissues), and elimination (from general circulation by metabolism or excretion). The target tissue refers to the tissue where a toxicant exerts its effect, and is not necessarily where the concentration of a toxic substance is higher. Many halogenated compounds such as polychlorinated biphenyls (PCBs) or flame retardants such as polybrominated diphenyl ethers (PBDEs) are known to bioaccumulate in body fat stores. Whether such sequestration processes are actually protective to the individual organisms, i.e. by lowering the concentration of the toxicant at the site of action is not clear (OFlaherty 2000). In an ecological context however, such bioaccumulation may serve as an indirect route of exposure for organisms at higher trophic levels, thereby potentia lly contributing to biomagnification through the food chain. Absorption of any compound that has not been directed intravenously injected will entail transfer across membrane barriers before it reaches the systemic circulation, and the efficiency of absorption processes is highly dependent on the route of exposure. It is also important to note that distribution and elimination, although often considered separately, take place simultaneously. Elimination itself comprises of two kinds of processes, excretion and biotransformation, that are also taking place simultaneously. Elimination and distribution are not independent of each other as effective elimination of a compounds will prevent its distribution in peripheral tissues, whilst conversely, wide distribution of a compound will impede its excretion (OFlaherty 2000). Kinetic models attempt to predict the concentration of a toxicant at the target site from the administered dose. If often the ultimate toxicant, i.e. the chemical species that induces structural or functional alterations resulting in toxicity, is the compound administered (parent compound), it can also be a metabolite of the parent compound generated by biotransformation processes, i.e. toxication rather than detoxication (Timbrell 2000; Gregus and Klaassen 2001). The liver and kid neys are the most important excretory organs for non-volatile substances, whilst the lungs are active in the excretion of volatile compounds and gases. Other routes of excretion include the skin, hair, sweat, nails and milk. Milk may be a major route of excretion for lipophilic chemicals due to its high fat content (OFlaherty 2000). Toxicodynamics is the study of toxic response at the site of action, including the reactions with and binding to cell constituents, and the biochemical and physiological consequences of these actions. Such consequences may therefore be manifested and observed at the molecular or cellular levels, at the target organ or on the whole organism. Therefore, although toxic responses have a biochemical basis, the study of toxic response is generally subdivided either depending on the organ on which toxicity is observed, including hepatotoxicity (liver), nephrotoxicity (kidney), neurotoxicity (nervous system), pulmonotoxicity (lung) or depending on the type of toxic response, including teratogenicity (abnormalities of physiological development), immunotoxicity (immune system impairment), mutagenicity (damage of genetic material), carcinogenicity (cancer causation or promotion). The choice of the toxicity endpoint to observe in experimental toxicity testing is therefore of critical importance. In recent years, rapid advances of biochemical sciences and technology have resulted in the development of bioassay techniques that can contribute invaluable information regarding toxicity mechanisms at the cellular and molecular level. However, the extrapolation of such information to predict effects in an intact organism for the purpose of risk assessment is still in its infancy (Gundert -Remy et al. 2005). 1.2.4. Dose-response relationships 83A7DC81The theory of dose-response relationships is based on the assumptions that the activity of a substance is not an inherent quality but depends on the dose an organism is exposed to, i.e. all substances are inactive below a certain threshold and active over that threshold, and that dose-response relationships are monotonic, the response rises with the dose. Toxicity may be detected either as all-or-nothing phenomenon such as the death of the organism or as a graded response such as the hypertrophy of a specific organ. The dose-response relationship involves correlating the severity of the response with exposure (the dose). Dose-response relationships for all-or-nothing (quantal) responses are typically S-shaped and this reflects the fact that sensitivity of individuals in a population generally exhibits a normal or Gaussian distribution. Biological variation in susceptibility, with fewer individuals being either hypersusceptible or resistant at both end of the curve and the maj ority responding between these two extremes, gives rise to a bell-shaped normal frequency distribution. When plotted as a cumulative frequency distribution, a sigmoid dose-response curve is observed ( 1.2). Studying dose response, and developing dose response models, is central to determining safe and hazardous levels. The simplest measure of toxicity is lethality and determination of the median lethal dose, the LD50 is usually the first toxicological test performed with new substances. The LD50 is the dose at which a substance is expected to cause the death of half of the experimental animals and it is derived statistically from dose-response curves (Eaton and Klaassen 2001). LD50 values are the standard for comparison of acute toxicity between chemical compounds and between species. Some values are given in Table 1.1. It is important to note that the higher the LD50, the less toxic the compound. Similarly, the EC50, the median effective dose, is the quantity of the chemical that is estimated to have an effect in 50% of the organisms. However, median doses alone are not very informative, as they do not convey any information on the shape of the dose-response curve. This is best illustrated by 1.3. While toxicant A appears (always) more toxic than toxicant B on the basis of its lower LD50, toxicant B will start affecting organisms at lower doses (lower threshold) while the steeper slope for the dose-response curve for toxicant A means that once individuals become overexposed (exceed the threshold dose), the increase in response occurs over much smaller increments in dose. Low dose responses The classical paradigm for extrapolating dose-response relationships at low doses is based on the concept of threshold for non-carcinogens, whereas it assumes that there is no threshold for carcinogenic responses and a linear relationship is hypothesised (s 1.4 and 1.5). The NOAEL (No Observed Adverse Effect Level) is the exposure level at which there is no statistically or biologically significant increase in the frequency or severity of adverse effects between exposed population and its appropriate control. The NOEL for the most sensitive test species and the most sensitive indicator of toxicity is usually employed for regulatory purposes. The LOAEL (Lowest Observed Adverse Effect Level) is the lowest exposure level at which there is a statistically or biologically significant increase in the frequency or severity of adverse effects between exposed population and its appropriate control. The main criticism of NOAEL and LOAEL is that there are dependent on study design, i.e. the dose groups selected and the number of individuals in each group. Statistical methods of deriving the concentration that produces a specific effect ECx, or a benchmark dose (BMD), the statistical lower confidence limit on the dose that produces a defined response (the benchm ark response or BMR), are increasingly preferred. To understand the risk that environmental contaminants pose to human health requires the extrapolation of limited data from animal experimental studies to the low doses critically encountered in the environment. Such extrapolation of dose-response relationships at low doses is the source of much controversy. Recent advances in the statistical analysis of very large populations exposed to ambient concentrations of environmental pollutants have however not observed thresholds for cancer or non-cancer outcomes (White et al. 2009). The actions of chemical agents are triggered by complex molecular and cellular events that may lead to cancer and non-cancer outcomes in an organism. These processes may be linear or non-linear at an individual level. A thorough understanding of critical steps in a toxic process may help refine current assumptions about thresholds (Boobis et al. 2009). The dose-response curve however describes the response or variation in sensitivity of a population. Biologica l and statistical attributes such as population variability, additivity to pre-existing conditions or diseases induced at background exposure will tend to smooth and linearise the dose-response relationship, obscuring individual thresholds. Hormesis Dose-response relationships for substances that are essential for normal physiological function and survival are actually U-shaped. At very low doses, adverse effects are observed due to a deficiency. As the dose of such an essential nutrient is increased, the adverse effect is no longer detected and the organism can function normally in a state of homeostasis. Abnormally high doses however, can give rise to a toxic response. This response may be qualitatively different and the toxic endpoint measured at very low and very high doses is not necessarily the same. There is evidence that nonessential substances may also impart an effect at very low doses ( 1.6). Some authors have argued that hormesis ought to be the default assumption in the risk assessment of toxic substances (Calabrese and Baldwin 2003). Whether such low dose effects should be considered stimulatory or beneficial is controversial. Further, potential implications of the concept of hormesis for the risk management of the combinations of the wide variety of environmental contaminants present at low doses that individuals with variable sensitivity may be exposed to are at best unclear. 1.2.5. Chemical interactions In regulatory hazard assessment, chemical hazard are typically considered on a compound by compound basis, the possibility of chemical interactions being accounted for by the use of safety or uncertainty factors. Mixture effects still represent a challenge for the risk management of chemicals in the environment, as the presence of one chemical may alter the response to another chemical. The simplest interaction is additivity: the effect of two or more chemicals acting together is equivalent to the sum of the effects of each chemical in the mixture when acting independently. Synergism is more complex and describes a situation when the presence of both chemicals causes an effect that is greater than the sum of their effects when acting alone. In potentiation, a substance that does not produce specific toxicity on its own increases the toxicity of another substance when both are present. Antagonism is the principle upon which antidotes are based whereby a chemical can reduce the harm ca used by a toxicant (James et al. 2000; Duffus 2006). Mathematical illustrations and examples of known chemical interactions are given in Table 1.2. Table 1.2. Mathematical representations of chemical interactions (reproduced from James et al., 2000) Effect Hypothetical mathematical illustration Example Additive 2 + 3 = 5 Organophosphate pesticides Synergistic 2 + 3 = 20 Cigarette smoking + asbestos Potentiation 2 + 0 = 10 Alcohol + carbon tetrachloride Antagonism 6 + 6 = 8 or 5 + (-5) = 0 or 10 + 0 = 2 Toluene + benzene Caffeine + alcohol Dimercaprol + mercury There are four main ways in which chemicals may interact (James et al. 2000); 1. Functional: both chemicals have an effect on the same physiological function. 2. Chemical: a chemical reaction between the two compounds affects the toxicity of one or both compounds. 3. Dispositional: the absorption, metabolism, distribution or excretion of one substance is increased or decreased by the presence of the other. 4. Receptor-mediated: when two chemicals have differing affinity and activity for the same receptor, competition for the receptor will modify the overall effect. 1.2.6. Relevance of animal models A further complication in the extrapolation of the results of toxicological experimental studies to humans, or indeed other untested species, is related to the anatomical, physiological and biochemical differences between species. This paradoxically requires some previous knowledge of the mechanism of toxicity of a chemical and comparative physiology of different test species. When adverse effects are detected in screening tests, these should be interpreted with the relevance of the animal model chosen in mind. For the derivation of safe levels, safety or uncertainty factors are again usually applied to account for the uncertainty surrounding inter-species differences (James et al. 2000; Sullivan 2006). 1.2.7. A few words about doses When discussing dose-response, it is also important to understand which dose is being referred to and differentiate between concentrations measured in environmental media and the concentration that will illicit an adverse effect at the target organ or tissue. The exposure dose in a toxicological testing setting is generally known or can be readily derived or measured from concentrations in media and average consumption (of food or water for example) ( 1.7.). Whilst toxicokinetics help to develop an understanding of the relationship between the internal dose and a known exposure dose, relating concentrations in environmental media to the actual exposure dose, often via multiple pathways, is in the realm of exposure assessment. 1.2.8. Other hazard characterisation criteria Before continuing further, it is important to clarify the difference between hazard and risk. Hazard is defined as the potential to produce harm, it is therefore an inherent qualitative attribute of a given chemical substance. Risk on the other hand is a quantitative measure of the magnitude of the hazard and the probability of it being realised. Hazard assessment is therefore the first step of risk assessment, followed by exposure assessment and finally risk characterization. Toxicity is not the sole criterion evaluated for hazard characterisation purposes. Some chemicals have been found in the tissues of animals in the arctic for example, where these substances of concern have never been used or produced. This realization that some pollutants were able to travel far distances across national borders because of their persistence, and bioaccumulate through the food web, led to the consideration of such inherent properties of organic compounds alongside their toxicity for the purpose of hazard characterisation. Persistence is the result of resistance to environmental degradation mechanisms such as hydrolysis, photodegradation and biodegradation. Hydrolysis only occurs in the presence of water, photodegradation in the presence of UV light and biodegradation is primarily carried out by micro-organisms. Degradation is related to water solubility, itself inversely related to lipid solubility, therefore persistence tends to be correlated to lipid solubility (Francis 1994). The persistence of inorganic substances has proven more difficult to define as they cannot be degraded to carbon and water. Chemicals may accumulate in environmental compartments and constitute environmental sinks that could be re-mobilised and lead to effects. Further, whilst substances may accumulate in one species without adverse effects, it may be toxic to its predator(s). Bioconcentration refers to accumulation of a chemical from its surrounding environment rather than specifically through food uptake. Conversely, biomagnification refers to uptake from food without consideration for uptake through the body surface. Bioaccumulation integrates both paths, surrounding medium and food. Ecological magnification refers to an increase in concentration through the food web from lower to higher trophic levels. Again, accumulation of organic compounds generally involves transfer from a hydrophilic to a hydrophobic phase and correlates well with the n-octanol/water partition coefficient (Herrchen 2006). Persistence and bioaccumulation of a substance is evaluated by standardised OECD tests. Criteria for the identification of persistent, bioaccumulative, and toxic substances (PBT), and very persistent and very bioaccumulative substances (vPvB) as defined in Annex XIII of the European Directive on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (Union 2006) are given in table 1.3. To be classified as a PBT or vPvB substance, a given compound must fulfil all criteria. Table 1.3. REACH criteria for identifying PBT and vPvB chemicals Criterion PBT criteria vPvB criteria Persistence Either: Half-life > 60 days in marine water Half-life > 60 days in fresh or estuarine water Half-life > 180 days in marine sediment Half-life > 120 days in fresh or estuarine sediment Half-life > 120 days in soil Either: Half-life > 60 days in marine, fresh or estuarine water Half-life > 180 days in marine, fresh or estuarine sediment Half-life > 180 days in soil Bioaccumulation Bioconcentration factor (BCF) > 2000 Bioconcentration factor (BCF) > 2000 Toxicity Either: Chronic no-observed effect concentration (NOEC) substance is classified as carcinogenic (category 1 or 2), mutagenic (category 1 or 2), or toxic for reproduction (category 1, 2 or 3) there is other evidence of endocrine disrupting effects 1.3. Some notions of Environmental Epidemiology A complementary, observational approach to the study of scientific evidence of associations between environment and disease is epidemiology. Epidemiology can be defined as â€Å"the study of how often diseases occur and why, based on the measurement of disease outcome in a study sample in relation to a population at risk.† (Coggon et al. 2003). Environmental epidemiology refers to the study of patterns and disease and health related to exposures that are exogenous and involuntary. Such exposures generally occur in the air, water, diet, or soil and include physical, chemical and biologic agents. The extent to which environmental epidemiology is considered to include social, political, cultural, and engineering or architectural factors affecting human contact with such agents varies according to authors. In some contexts, the environment can refer to all non-genetic factors, although dietary habits are generally excluded, despite the facts that some deficiency diseases are envir onmentally determined and nutritional status may also modify the impact of an environmental exposure (Steenland and Savitz 1997; Hertz-Picciotto 1998). Most of environmental epidemiology is concerned with endemics, in other words acute or chronic disease occurring at relatively low frequency in the general population due partly to a common and often unsuspected exposure, rather than epidemics, or acute outbreaks of disease affecting a limited population shortly after the introduction of an unusual known or unknown agent. Measuring such low level exposure to the general public may be difficult when not impossible, particularly when seeking historical estimates of exposure to predict future disease. Estimating very small changes in the incidence of health effects of low-level common multiple exposure on common diseases with multifactorial etiologies is particularly difficult because often greater variability may be expected for other reasons, and environmental epidemiology has to rely on natural experiments that unlike controlled experiment are subject to confounding to other, often unknown, risk factors. However, it may still be of i mportance from a public health perspective as small effects in a large population can have large attributable risks if the disease is common (Steenland and Savitz 1997; Coggon et al. 2003). 1.3.1. Definitions What is a case? The definition of a case generally requires a dichotomy, i.e. for a given condition, people can be divided into two discrete classes the affected and the non-affected. It increasingly appears that diseases exist in a continuum of severity within a population rather than an all or nothing phenomenon. For practical reasons, a cut-off point to divide the diagnostic continuum into ‘cases and ‘non-cases is therefore required. This can be done on a statistical, clinical, prognostic or operational basis. On a statistical basis, the ‘norm is often defined as within two standard deviations of the age-specific mean, thereby arbitrarily fixing the frequency of abnormal values at around 5% in every population. Moreover, it should be noted that what is usual is not necessarily good. A clinical case may be defined by the level of a variable above which symptoms and complications have been found to become more frequent. On a prognostic basis, some clinical findings may carry an a dverse prognosis, yet be symptomless. When none of the other approaches is satisfactory, an operational threshold will need to be defined, e.g. based on a threshold for treatment (Coggon et al. 2003). Incidence, prevalence and mortality The incidence of a disease is the rate at which new cases occur in a population during a specified period or frequency of incidents. Incidence = The prevalence of a disease is the proportion of the population that are cases at a given point in time. This measure is appropriate only in relatively stable conditions and is unsuitable for acute disorders. Even in a chronic disease, the manifestations are often intermittent and a point prevalence will tend to underestimate the frequency of the condition. A better measure when possible is the period prevalence defined as the proportion of a population that are cases at any time within a stated pe