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Les hommes : s’ouvrir à leurs réalités et répon- Public Health order 20 mg cialis sublingual visa low testosterone erectile dysfunction treatment, 2005 purchase 20mg cialis sublingual with mastercard erectile dysfunction age graph, 96(Suppl 2): S78-S96 discount cialis sublingual american express impotence genetic. Intervention, 2002, 116: 37-51 23 Men’s health in Denmark Svend Aage Madsen PhD The current state of male health in Denmark Although Denmark is a welfare society and a country When you look at healthy life years at 50 years of age with high standards in health and gender equality, life for the same 25 European countries however, Denmark expectancy for Danish men is among the lowest in the is in frst place with 23. Danish men are When it comes to men’s use of health care system it has number sixteen of twenty. Danish men hospital patients seem to want the the attitudes to all kind of health and especially men’s disease and health services to take up only a small part health has been very laissez-faire and against any kind of their daily life and identity yet they occupy most of the of restrictions in Denmark. This point to a need for developing a have lower all-cancer survival than countries with better understanding of gender differences in patients’ similar national expenditure on health. The development of more ‘male- survival rate for prostate cancer among Danish men is sensitive’ health services should be a central issue in the only 47% compared with 75% in Europe as a whole. Presentation of the 2005 Men’s Health Prize; a well established activ- ity of the Danish Men’s Health Week. The prize was given by Else Smidt (right), head of prevention at the National Board of Health to Kristian Ditlev Jensen (left) for his famous autobiography about sexually abused boys. Health services have (the Prostate Cancer Patient Organisation); the Danish been slow to recognise particular issues affecting men Cancer Society; the Danish Family Planning Association; in relation to health. These issues include men’s in- the Confederation of Danish Industry; and Men’s Health creased risk of developing poor health because of risk- Society Denmark. The reason for this is more lack of in- terest and conservatism among health professionals than resistance from politicians. This is very much due to a refusal to accept gender as an important issue in health politics among medical staff. This is especially related to the laws and regu- that men will have more contact with and get more ac- lations and health services for men as fathers. Further- matter there has been a positive development, and it more the men’s taking active part in childcare seems to seems that men’s participation in at the birth, parental prevent divorces and it has been established that divorce leave (many places there are two to three months pa- is a threat to several aspects of a man’s health. Finally it rental leave with full salary for men), and caring for their seems that being engaged in parenthood also increases small children has a positive impact on men’s health a man’s taking care of his health and wellbeing. The future for male health in Denmark What we would like to see happen is the development An important way to achieve the goals of better cir- of a much bigger awareness on men’s health in public, cumstances for men’s health is the educational pro- political, and health opinion. There is a need to make changes in men’s health behaviours and in to include all kind of gender aspects, and not the least health services for men. In this area there are no positive develop- This might have an important impact on the lifestyle of ments for the time being but it is hoped that the Men’s Danish men, which is in imperative need of improve- Health Week 2009 in Denmark, which has ‘Men and ment in several areas, especially in the areas of smok- Cancer’ as focus will have a positive infuence on that. About the author Men’s Health Society, Denmark is a multidisciplinary organisation dedicated to the feld of men’s health in all its aspects. The society was founded in 2003 in connection with the frst Men’s Health Week in Denmark, and Men’s Health Week continues to be an important and highly prioritised activity. Through the Men’s Health Weeks the Danish Men’s Health Society collaborates with all kinds of national and local health organisations and authorities in the health areas. These co-operations contribute to the dissemination of knowledge on men’s health issues in different health spheres and around the country. Men’s Health Society, Denmark is engaged in the Nordic Network on Men’s Health and in organising the Nordic Men’s Health Conferences. Men’s Health Society, Denmark is also a member of the European Men’s Health Forum. He is the President of Men’s Health Society, Denmark and a member of the Board of Directors of the European Men’s Health Forum. Feminist objectives in the later veloped countries, men in England & Wales live shorter decades of the century focused most strongly on mat- lives than women (77. Overall, women’s activism has dence of the ten most common cancers that affect both succeeded in bringing about the acceptance by most sexes is almost twice as high in men). Men are also more people and most institutions, that discrimination on likely to develop most forms of serious illness earlier in the grounds of gender is unacceptable. This has been the lifespan (for example men aged 50 – 54 are fve times a signifcant political achievement and is arguably the more likely to die of coronary heart disease). It can be diffcult to see that gender ine- than women in personal health issues, and less likely qualities also sometimes affect men and boys. Health to engage with community processes built around mu- is the most signifcant case in point. This basic truth is way to address the health needs of men is to position the of course at the centre of the present wave of inter- issue where it properly belongs - within the debate about national interest in the links between masculinity and gender equalities. This approach – as in England & Wales has largely been led by men and we shall see later – has been crucial to the signifcant women with a professional or academic interest in the progress in the past two or three years in particular. These people have tended to be driven by profes- An essay explaining why the differences in health status sional concern. In other words, the campaign for bet- between men and women (whether to the disadvantage ter male health has differed fundamentally from the of either sex) should properly be regarded as a health in- activism on women’s health, which was essentially a equality forms the introduction to a report published by “grass roots” or “consumer” movement. It came ence of a reasonably-sized base among health work- in April 2006, when the Equality Act 2006 became law. This support was welcomed by ing was the greater willingness of funding bodies government departments keen to demonstrate that, to support research projects in the field. This latter although the primary political impetus was to build included government funding of an important two on the progress since the 1970s in achieving greater year project aimed at increasing uptake of chlamy- equality for women, there were benefts for both sexes dia screening by young men, the findings from which in the new law. This is of met on a number of occasions with health ministers central importance, since, in the feld of health specif- in the Labour administration who were interested in cally, outcomes are inarguably poorer for men. Rather it has given a solid base in law for the ar- health campaigners if it had not come at a time when there guments that the wisest advocates of better male health had already been several years of hard work and aware- were already making. If there had not been such a frame- the rate of progress and a sense that the improvements work in place then the Equality Act might have been noth- that are now steadily accruing are more likely to be lasting. Having said this, it should be added that the Equality Act Instead, and as a direct consequence of policy-makers thinking in a more concentrated way about gender inequalites, England & Wales have seen specifc account taken of male health at the highest possible level. Furthermore the Depart- tackle poorer outcomes in men; the National Chlamy- ment of Health’s own guidance to the Equality Act6 includes dia Screening Programme has published a detailed a strong emphasis on men’s health needs and behaviours. This would certainly require a long term commit- ancy are not keeping pace with the rest of the ment to the support and education of future generations population. Overall therefore, the ment “working together” with total of eleven non-gov- present situation in for male health England & Wales ernmental organisations “to improve knowledge and seems a positive one and, with good management skill”. The Department of Health promises that Stra- and a little bit of luck, promises to remain so for the tegic Partners will be “at the heart of shaping policy. He has written policy papers on several specifc aspects of men’s health and led a number of research projects. He is currently leading a three year government- funded project looking for ways to close the gap between men and women in the uptake of bowel cancer screening. He is also conducting a review (also government-funded) examining the most important issues in men’s mental health. David has represented the “men’s health interest” on a number of national and re- gional committees.

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Paul O buy cialis sublingual 20 mg without a prescription erectile dysfunction pump, Lepper M buy 20 mg cialis sublingual with visa impotence in women, Phelan W cialis sublingual 20 mg for sale top erectile dysfunction doctor, Dupertuis G, MacMillan A, McKean H (1963) A longitudinal study of coronary heart disease. People’s Republic of China—United States Cardiovascular and Cardiopulmonary Epidemiology Research Group (1992) An epidemiological study of cardio- vascular and cardiopulmonary disease risk factors in four populations in the People’s Republic of China. Progress Collaborative Group (2001) Randomised trial of a perindopril- based blood-pressure-lowering regimen among 6105 individuals with previ- ous stroke or transient ischaemic attack. SarrafZadegan N, AminiNik S (1997) Blood pressure pattern in urban and rural areas in Isfahan, Iran. Shelley E, Daly L, Kilcoyne D, Graham I, Mulcahy R (1991) Risk factors for coronary heart disease: a population survey in county Kilkenny, Ireland, in 1985. Strachan D, Rose G (1991) Strategies of prevention revisited: Effects of im- precise measurement of risk factors on the evaluation of “high-risk” and “population-based” approaches to prevention of cardiovascular disease. Suh I (2001) Cardiovascular mortality in Korea: a country experiencing epi- demiologic transition. Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P, Puska P (2000) Car- diovascular risk factor changes in Finland, 1972–1997. Vartiainen E, Puska P, Pekkanen J, Tuomilehto J, Jousilahti P (1994) Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. Wietlisbach V, Paccaud F, Rickenbach M, Gutzwiller F (1997) Trends in car- diovascular risk factors (1984–1993) in a Swiss region: results of three pop- ulation surveys. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. Cryan Editors M icrobial ndocrinology: T he icrobiota-G ut-B rain A xis in ealth and isease Editors Mark Lyte John F. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. The use of general descriptive names, registered names, trademarks, service marks, etc. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www. Mark Lyte: “To my loving wife and my two remarkable sons who are my pillars of strength” Prof. The first volume published by Springer in 2010, “Microbial Endocrinology: Interkingdom Signaling in Infec- tious Disease and Health”, contained little in regard to brain and behavior, but instead focused almost exclusively on aspects of infectious disease. Health conse- quences as such were mainly concerned with the role that stress could play in altering the interface between host and microbiota. The present volume is therefore a testament to the great strides during the intervening years which have illuminated the myriad ways in which microbiota interfaces with the host. It is anticipated that future volumes in this series will reflect the ever increasing acceleration of research into the microbiota–gut–brain axis. Preface If one was to ask whether a book dealing with the ability of the microbiota to influence the brain, and ultimately cognition and behavior, would have been possible just a few short years ago, the answer would most likely be no. However, this would not be an accurate reflection of the work that has been ongoing for many decades, but yet remained on the outer fringes of the disciplines that constitute the study of the mechanisms by which the microbiota and the brain communicate with each other. A comprehensive series of articles by Bested and colleagues [1] catalog the numerous studies going back over a century which amply demonstrate that the investigation of the role of the microbiota in brain function, and by extension mental health, has a long and varied (some may say checkered) scientific history. During this time it remained, for large measure, outside mainstream scientific inquiry following an initial burst of enthusiasm both in the scientific and public arenas at the turn of the twentieth century. That such scientific skepticism remained, and in many cases became entrenched, in the very scientific disciplines that form the basis of the microbiota–gut–brain axis is owed to a number of factors. One of these is surely the increasing specialization that occurred within each discipline over the years and the inherent lack of interdisciplinary thought that accompanied such specialization. With the advent of the concerted research into the microbiota and the microbiome, as best evidenced by the tremendous strides that the Human Microbiome Project has made over the last decade in cataloging the incredible diversity in the microbiota in health and disease, the realization that the microbiota has a role to play in the development and function of the nervous system and hence behavior and cognition, has once again entered into mainstream scientific and medical thought. In many conservative Learned Societies the concept that the gut and indeed the gut microbiota can have such an influence on brain & behavior is still looked upon with incredulity. In considering the microbiota as an interactive player in the host that can both respond to signals from the host and influence the host through the provision of the very same host signaling molecules (i. As such, the book is organized along three thematic lines which will provide the reader not only a fuller understanding of the capabilities of the microbiota to interface with the brain and form the microbiota–gut–brain axis, but will also provide detailed examination of the consequences of the microbiota-driven gut- to-brain communication for both health and disease. The first four chapters cover the “Basic Concepts Underlying the Microbiota–Gut–Brain Axis”; the next eight chapters examine the “Mechanistic Factors Influencing the Microbiota–Gut–Brain Axis” and the concluding seven chapters address the “Microbiota–Gut–Brain Axis in Health and Disease”. We have assembled a group of contributors who are recognized to be at the front of their respective fields to review the state of the art of this growing field. As the chapters in this book amply demonstrate, the field of microbiota–gut–brain axis is still in its infancy although its origins are now over a century old. With the advent of modern techniques ranging from deep pyrosequencing of the microbiota to brain imaging, the tools are in place to address those questions which were raised many decades ago. Given our evolving understanding of the complexity of the microbiota which when one couples that to the complexity of the brain and nervous system, this book represents only one more chapter in what promises to be a long and challeng- ing story. Contents Part I Basic Concepts Underlying the Microbiota-Gut-Brain Axis 1 Microbial Endocrinology and the Microbiota-Gut-Brain Axis. Dinan, and Catherine Stanton 11 Multidirectional Chemical Signalling Between Mammalian Hosts, Resident Microbiota, and Invasive Pathogens: Neuroendocrine Hormone-Induced Changes in Bacterial Gene Expression. Anjam Khan 12 Influence of Stressor-Induced Nervous System Activation on the Intestinal Microbiota and the Importance for Immunomodulation. Gareau 17 The Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential. Borre, PhD Neurogastroenterology Lab, Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland Brid P. Cryan, PhD Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland Timothy G. As such, microbial endocrinology represents the intersection of the fields of microbiology and neurobiology. The acquisition of neurochemical-based cell-to-cell signaling mechanisms in eukaryotic organisms is believed to have been acquired due to late horizontal gene transfer from prokaryotic microorganisms. When considered in the context of the microbiota’s ability to influence host behavior, microbial endocrino- logy with its theoretical basis rooted in shared neuroendocrine signaling mecha- nisms provides for testable experiments with which to understand the role of the microbiota in host behavior and as importantly the ability of the host to influence the microbiota through neuroendocrine-based mechanisms. Earlier that year I had submitted an application for the Pioneer Award entitled “The Microbial Organ in the Gut” where I proposed that bacteria in the gut were not only able to communicate with the brain and influence behavior, but also that the brain could likewise communicate with the gut bacteria to achieve regulation of microbial populations that would benefit the host. The mechanism by which this bi-directional communication was governed was proposed to be that of microbial endocrinology—the ability of bacteria to respond to as well as produce the same neurohormones found in the host.

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Since 400 μg daily is probably the upper limit of safety discount 20 mg cialis sublingual visa erectile dysfunction pump hcpc, daily doses of 100 to 200 μg may be more realistic objectives for inhibiting genetic damage and cancino- genesis in humans order cialis sublingual 20mg on-line impotence kidney. Yeast-based selenium is approximately 40% selenomethionine purchase cialis sublingual 20 mg free shipping erectile dysfunction treatment scams, 20% other amino acid conjugates (e. Selenite and selenate are more bioavailable than selenomethionine; however, selenomethionine appears more effective at increasing selenium status. In one animal study, co-administration of vitamin C nullified the chemopreventive effect of inorganic selenium (selenite), but not that of selenomethionine. Animal studies have confirmed that the dose and form of selenium compounds are critical factors in determining cellular responses, inorganic selenium at doses up to 10 μmol, and organic selenium compounds Chapter 91 / Selenium (Se) 643 at doses equal to or greater than 10 μmol eliciting distinctly different cellular responses. Nonetheless, such findings are sup- ported by epidemiologic studies, which have shown that low selenium sta- tus is associated with an increased total cancer incidence, particularly of gastrointestinal, prostate, and lung cancers. While the protective effect of selenium against cancer is fairly well docu- mented, there is less clinical evidence to support the anti-inflammatory effect of selenium in arthritis. A recent clinical trial failed to demonstrate that selenium treatment (200 μg/day) achieved any clinical benefit in rheuma- toid arthritis. It is possible that selenium deficiency and vitamin E deficiency can activate latent viruses such as herpes. It appears that a normally avirulent viral genome may become pathogenic in a nutritionally deprived host. An experimental animal study has also found that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and a reduction in bone mineral density. Hepatorenal damage, nausea, a metallic taste, nervous irritability, depression, weakness, unusual fatigue, and nausea and vomiting have also been reported. Clinically, findings consistent with selenium deficiency include fingernail and skin changes, cardiomyopathy, and skeletal muscle fatigue, tenderness, and weakness. Lu J, Jiang C: Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects, Nutr Cancer 40(1):64-73, 2001. Brighthope I: Nutritional medicine tables, J Aust Coll Nutr Env Med 17:20-5, 1998. El-Bayoumy K: The protective role of selenium on genetic damage and on cancer, Mutat Res 475(1-2):123-39, 2001. Peretz A, Siderova V, Neve J: Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial, Scand J Rheumatol 30(4):208-12, 2001. Moreno-Reyes R, Egrise D, Neve J, et al: Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia, J Bone Miner Res 16(8):1556-63, 2001. Sodium, the major cation in extracellular fluid, is critical for regulation of body fluids. It influences acid-base balance, nerve function, water balance, and blood pressure. The intake of sodium tends to be much higher than the recommended allowance, and a major source is from salt added to processed food. This active transport system main- tains an electrical potential with the inside of the cell being more negative than the outside. The excitability of nerve and muscle cells results from their ability to change this resting potential in response to electrochemical stimuli. Passive movement of sodium in distal renal tubular cells also influences fluid bal- ance. The epithelial sodium channel expressed in aldosterone-responsive epithe- lial cells of the kidney and colon plays a critical role in the control of sodium balance, blood volume, and blood pressure. Aldosterone conserves sodium by increasing activity of the sodium pump in the kidney. It is found in fruits and vegetables, but more concen- trated sources of sodium are table salt, sea salt, processed food, kelp, and cel- ery. This is far in excess of any physiologic need, and it is likely the harmful effects of sodium are expressed above a threshold of approximately 2. Two determinants of blood pressure are circulating blood volume and vascular tone, both of which are influenced by sodium. Sodium restriction is routinely recommended for borderline and definitive cases of hypertension. However, the hypothesis that suggests higher levels of salt in the diet leads to higher levels of blood pressure and increases the risk of cardiovascular disease remains unproven. Four of the popula- tions did have low levels of salt and blood pressure, but across the other 48 populations, blood pressures went down as salt levels went up. Recent rig- orous reviews of salt restriction trials in normal subjects show extremely small effects ranging from 1 to 2 mm Hg for systolic blood pressure and 0. Population studies have not been able to show an association between salt intake and unfavorable health outcome. Experimental evidence suggests that the effect of a large reduction in salt intake on blood pressure is modest. Furthermore, based on population and randomized studies, the effect of an extreme salt reduction of 100 mmol on blood pressure in hypertensive persons only accounts for about one third of the effect of antihypertensive medication. Despite sodium restriction being a popular clinical recommendation, the health conse- quences of sodium reduction have yet to be determined. Salt reduction may have unfavorable effects on heart rate and serum lev- els of renin, aldosterone, catecholamines, and lipids. In short-term clinical studies, very low sodium intakes (<50 mmol/day) have been associated with greater values for total and low-density lipoprotein cholesterol, fasting and postglucose insulin, uric acid, and plasminogen activator inhibitor-1. Routinely, advocating salt restriction in the management of hypertension is being questioned. Calculation of specific individual “salt-sensitive risk profiles” based on knowledge of hypertension genes and environmental risk factors influenc- ing the pressor response to salt is desirable. Genetically defined forms of a salt sensitivity and salt resistance in human monogenic diseases and in ani- mal models have been reviewed,8 as has the pathophysiology of essential hypertension. Swales J: Population advice on salt restriction: the social issues, Am J Hypertens 13(1 Pt 1):2-7, 2000. Graudal N, Galloe A: Should dietary salt restriction be a basic component of antihypertensive therapy? Zoccali C, Mallamaci F: The salt epidemic: old and new concerns, Nutr Metab Cardiovasc Dis 10(3):168-71, 2000. Kurokawa K: Salt, kidney and hypertension: why and what to learn from genetic analyses? Brighthope I: Nutritional medicine tables, J Aust Coll Nutr Env Med 17:20-5, 1998. Soybeans, and particularly the isoflavones contained in soy, have generated interest as chemopreventive agents.

This results in abnormal growth of a tumor microenvironment with cells forming blood tumor mass order generic cialis sublingual erectile dysfunction tumblr, first within an organ order cialis sublingual canada erectile dysfunction medicine reviews, then infiltrating vessels or stroma order cialis sublingual 20 mg online erectile dysfunction injections treatment, and cells of the immune adjacent tissues. Each of the hallmarks is influenced by also colonize distant organs via blood or multiple pathways, which have been rendered lymphatic vessels, so called metastases, causing dysfunctional by alterations in the genes of morbidity and death. Several discoveries leading to today’s knowledge Immunotherapy for tumors until 1995 about cancer represent breakthroughs that have been awarded with The Nobel Prize in Throughout history there are many accounts on Physiology or Medicine. Those discoveries tumors disappearing after infectious episodes, awarded have included infection as an etiological whereas the investigation of experimental factor (e g Rous 1966, for tumor-inducing viruses; infections as therapy for cancer patients dates th zur Hauzen 2008, for Human Papilloma virus as back to the late 19 century. The basic concept a cause of cervical cancer); and the relation behind such treatments has been the possibility between cellular and viral genes in pathogenesis that the infections stimulated the immune system, (e g Baltimore, Dulbecco and Themin 1975, for leading to an immune rejection of the tumor. In addition, novel reported on the treatment of malignant tumors by therapies have also been awarded the Nobel repeated “inoculation of erysipelas”, i. However, the first attempts in this field Elion and Hitchins 1988, for novel principles were by German clinicians 150 years ago leading to cytostatic drugs affecting the (Busch, 1868, Fehleisen, 1882). While infectious metabolism of nucleic acids, and Thomas 1990, therapy was practiced in numerous tumor for discoveries concerning bone marrow patients, the clinical outcome varied, causing transplantation, used to treat certain blood disbelief within the medical community. These therapies were introduced in the the concept is manifested in the form of latter half of the previous century to complement alternating intradermal and intracavitary the traditional methods of surgery and administration of Bacillus Calmette-Guerin to radiotherapy. Additional Nobel Prizes, including patients with bladder tumors (Morales et al 1976; in Chemistry, have awarded groundbreaking Alexandroff et all 1999). In the beginning of the last century Leo of cancer is rising in most countries of the world, Loeb mentioned the possible role of immunity for partly due to an increasing life span and the growth of experimentally transplanted tumors improved diagnosis; one out of three will develop (Loeb, 1902). It was apparent that a basic the disease and one of 6 will die of cancer understanding of the immune system was (Global Cancer Observatory, 2018). The scientific alleles within at the histocompatibility-2 (H-2) knowledge has led to programs for prevention locus in the mouse were key determinants for and early diagnosis. However, even dramatically tumor transplantation (Snell & Higgins, 1951) and improved prevention programs will not solve the George D. Snell became a Nobel laureate in problem, since it is estimated that at least 50% of 1980 for his work in this field. He T cell activation and the concept of discussed in depth the potential effects of natural costimulation and acquired immunity for cancer (Ehrlich, 1909). Sixty years later Sir Frank Macfarlane Burnet, T cells have been at the center stage in who shared the 1960 Nobel Prize "for discovery immunology, but up until the 1980s their antigen- of acquired immunological tolerance", proposed recognizing receptor remained elusive, whereas that the immune system serves as a surveillance the antigen-specific receptor on B cells was system for cancer (Burnet, 1970). Thus, during their differentiation B cells were known to rearrange A sign of the belief in immunotherapy for tumors their immunoglobulin genes (Nobel Prize to is that a very large part of the funding in the field Susumu Tonegawa in 1987), express the of immunology has been directed towards cancer resulting immunoglobulin protein on their surface research. This led to a number of fundamental and secrete large amounts of it into body fluids. Numerous reports on experimental animal studies Major developments for the understanding of demonstrated profound, beneficial effects of the cellular adaptive immune responses took place in immune system on tumor growth. The that allogeneic bone marrow transplants, apart deciphering of the underlying mechanisms was from serving as a replacement of hematopoietic an incremental process that took place during the tissue, also cause a graft-versus-leukemia effect 1980s and 1990s involving many laboratories all (Weiden et al. Lieping Chen, Peter colleagues as a decoy to block costimulation, Linsley and coworkers (Linsley et al. The first experiment was set up in his resides intracellularly in resting T cells, but laboratory at the University of California, Berkeley translocates rapidly to the membrane after in the end of 1994 with an immediate blinded activation (Lindsten et al. Both the This work represents the birth of a new concept above studies were possible through the for immunotherapy. With these studies, (granulocyte-macrophage colony stimulating Jedd Wolchok and Stephen Hodi together with factor). In a short period, Allison had thus proved scientists at Bristol-Myers Squibb Company that several different tumor types responded to advanced the clinical program for the study of the the same treatment strategy. The same year complete regression was reported in another trial in some treated melanoma patients, while severe autoimmune side effects were also observed (Phan et al. A special feature was the observation that treatment initially could even increase the tumor volume, “pseudoprogression”, owing to the infiltration of immune cells, rather than reducing it immediately, as usually seen with chemo- or radiotherapy. At the time there was Nobel Prize also originated in basic, curiosity- very limited interest from the pharmaceutical driven research, not primarily oriented towards industry for a treatment based on the removal of cancer. The open reading observation that the molecule was expressed, not frame predicted a protein with a transmembrane only by macrophages, dendritic cells and region, distantly related to the immunoglobulin additional immune cells, but also by certain gene superfamily. Honjo launched an ambitious program to published in 2002, one from Chen’s laboratory fully understand its function, in which the (Dong et al 2002) and another from the Kyoto generation of mice deficient for this molecule was groups of Minato and Honjo, in collaboration (Iwai central. Late in life, the mice developed in vivo, and that this could be reversed by a lupus like disease Nishimura et al. The paper by Iwai et al was took almost 10 years from the first discovery the first to discuss possible synergistic effects in before a distinct picture emerged. They identified it together with the groups of Gordon Freeman and Clive Wood (Freeman et al, 2000) and it was Figure 2. The paper from Honjo’s group most of which were durable and some resulting in presented several key conclusions that correctly complete tumor regression (Topalian et al. The first marketing advanced by the company Ono Pharmaceuticals, and manufacturing approval was granted 2014 in which at an early stage joined forces with Bristol- Japan. The first phase I nivolumab, for the treatment of unresectable or study, initiated in 2006, showed that the drug was metastatic melanoma. Please note the pseudoprogression at 2 months due to infiltrating immune cells and the reduced tumor size after 4 months. Cancer therapy using checkpoint inhibition and the curves that follow tumor-free survival today show a plateau. This not only on mono-treatment with each antibody, is a spectacular development when considering but also on combination treatment. Regardless of which therapy that is require aggressive immunomodulatory treatment employed, immune-related adverse events occur with e. The development is likely to continue, with There are several interesting observations on combination treatments – using different agents how processes upstream of the initial T cell to release the negative regulation of immune activation can correlate with the response of the responses, but also by combining them with patient. These processes include mutational load strategies to activate or improve immune in the tumor, and, as a consequence, its responses (e g vaccination, adoptive cell therapy) expression of antigens, previous infections or or simply combining them with existing modalities vaccination, and the microenvironment and the (surgery, chemotherapy, radiotherapy, hormone microbiome in niches such as the colon or the treatment and drugs targeting specific pathways) skin (Snyder et al. The actual mechanisms whereby the antibodies interfere with negative regulation are also Mechanisms in the clinical response and how complex. Furthermore, a major part of the effect several downstream mechanisms, mediated also occurs intratumorally to counteract exhaustion of by other cells of the immune system. There is intensive research going on, and the identification of key mechanisms and A crucial aspect in the future development is to biomarkers is likely to improve clinical efficacy improve understanding of these mechanisms, as and safety as well as patient selection. The three pillars of cancer treatment, all directed against the cancer cell, and the fourth, immune checkpoint inhibitor, based on unleashing an immune response against the tumor, added by Allison and Honjo. Concluding remarks the perhaps unprecedented research activities in the immune checkpoint field, it is likely that there This year’s Nobel Prize in Physiology or Medicine will be major developments regarding this awards the discovery of a novel principle for therapy at all levels.

Diefendorf D discount cialis sublingual 20mg online doctor who treats erectile dysfunction, Healey J discount 20 mg cialis sublingual amex erectile dysfunction caused by ptsd, Kalyn W purchase 20mg cialis sublingual overnight delivery erectile dysfunction treatment costs, editors: The healing power of vitamins, minerals and herbs, Surry Hills, Australia, 2000, Readers Digest. Donath F, Quispe S, Diefenbach K, et al: Critical evaluation of the effect of valerian extract on sleep structure and sleep quality, Pharmacopsychiatry 33:47- 53, 2000. Kuhlmann J, Berger W, Podzuweit H, et al: The influence of valerian treatment on “reaction time, alertness and concentration” in volunteers, Pharmacopsychiatry 32:235-41, 1999. Mills S, Bone K: Principles and practice of phytotherapy, Edinburgh, 2000, Churchill Livingstone. Wheatley D: Kava and valerian in the treatment of stress-induced insomnia, Phytother Res 15:549-51, 2001. Because the benefit of estrogen replacement is dubious at best,2 a preventive approach is strongly advocated for both women and men. In addition to clues provided by a family history and increasing age, major risk factors are smoking, hypertension, and hypercho- lesterolemia. Low vitamin E, high fibrinogen, and high plasma total homo- cysteine levels, and the even more sensitive plasma S-adenosylhomocysteine level, have emerged as important predictors of coronary artery disease. Angina, experienced as constricting substernal tightness that lasts a few sec- onds to 15 minutes, is an early warning sign of cardiac ischemia in men. The pain, relieved by sublingual nitroglycerine or rest, may radiate to the angle of the jaw, neck, back, left shoulder, or inner aspect of either arm. Compared with per- sons with stable angina, those with unstable and spasm angina are at greater risk for infarction. In persons with unstable angina, the pain lasts longer, occurs more frequently, and may occur at rest. In persons with spasm angina, pain is unpredictable and arrhythmia is more likely. Cardiac ischemia in women is often precipitated by coronary artery spasm, and heart attacks in one in three women are believed to go unre- ported. In women, chest tightness, nausea, and dizziness are common 345 346 Part Two / Disease Management indicators of myocardial ischemia. Cardiac ischemia should be ruled out in women who complain of breathlessness, perspiration, a sensation of flutter- ing in the heart, and chest tightness. Intervention is focused on factors predisposing to plaque formation and on prevention of vascular occlusion through clot formation or spasm. The acti- vated endothelium upregulates cell adhesion and cytokine release, creating an environment conducive to atherosclerosis. Major endothelium vasoconstrictors are thromboxane A2, prostaglandin H2, and endothelin 1. Smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus each adversely affect endothelial function. Although limiting sodium chloride affects blood pressure in older persons and patients with diabetes and hypertension, recent meta-analyses suggest that an adequate intake of minerals, certainly potassium and probably calcium, rather than restriction of sodium, should be the focus of dietary recommen- dations. Genistein, a phy- toestrogen found in soybeans, influences endothelium-dependent vasodilation with potency similar to that of estradiol. Genistein, like estra- diol, causes L-arginine/nitric oxide–dependent vasodilation. Docosahexaenoic acid decreases vascular adhesion, and eicosapentaenoic acid increases nitric oxide production. Despite inconsistent clinical results, around 4 g of ω-3 fatty acids daily does appear to improve endothelium function, especially in patients with diabetes. Evidence from a clinical trial suggests that dietary supplementation with ω-3 polyunsatu- rated fatty acids (900 mg daily) over 3. In a placebo-controlled, randomized trial in which a combined daily antioxidant supplement of vitamin E (600 mg), vitamin C (250 mg), and carotene (20 mg) was taken for an average of 5 years, no benefits were detected with respect to either vascular or nonvascular mortality and major vascular events. However, taking an antioxidant vitamin cocktail over 5 years, although not deemed beneficial, was regarded as “doing no harm. Furthermore, epidemi- ologic and experimental data suggest that a molar vitamin C/vitamin E plasma ratio of less than 0. Homocysteine is an intermediate produced in the conversion of methionine Chapter 33 / Ischemic Heart Disease 349 (an essential sulfur-containing amino acid) to cysteine. Cysteine is required for production of glutathione, a compound involved in oxidation-reduction reactions. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. In five to 10 times its normal concentration, homocysteine is likely to directly damage endothelium, promote prolifera- tion of vascular smooth muscle cells, exhibit procoagulant activity, and increase collagen synthesis. Results of animal studies and of a trial in which a single oral dose of glutamine (80 mg/kg) was administered to patients with chronic stable angina suggest that gluta- mine may be cardioprotective in patients with coronary heart disease. Clinical trials suggest that an effective dose is 180 mg of 5:1 hawthorn extract daily. Turmeric, unlike ginger, is thought to inhibit thromboxane without reducing prostacyclin activity. Garlic, taken as a fresh clove or 80 mg of garlic powder daily, reduces coagulation. Turmeric is most effective against hydroxyl radicals and, although weaker than vitamin C, appears more potent than vitamin E. This effect is detected 2 hours after consumption of 450 mL of tea and was also observed in subjects who drank 900 mL of tea daily for 4 weeks. Red wine and purple grape juice contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. Grapeseed extract (100 mg) daily and one glass (10 g) of red wine daily provide a similar cardiovascular benefit. Both in vitro incubation and oral supplementation with purple grape juice decrease platelet aggregation, increase platelet-derived nitric oxide release, and decrease superoxide pro- duction. The suppres- sion of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol con- sumption, in cardiovascular disease. Whatever the mechanism, a recent study of more than 25,000 male smokers, 50 to 69 years of age, with no pre- vious myocardial infarction, indicated that the intake of flavonols and flavones was inversely associated with nonfatal myocardial infarction. Chapter 33 / Ischemic Heart Disease 351 ● A daily intake of at least 130 mg of vitamin C and 67 mg of vitamin E may be required for cardiovascular health. Pirro M, Maurie’ge P, Tchernof A, et al: Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Que’bec Cardiovascular Study, Atherosclerosis 160:377-84, 2002. Carr M, Frei B: The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide, Free Radic Biol 28:1806-14, 2000. Hermansen K: Diet, blood pressure and hypertension, Br J Nutr 83(suppl 1): S113-S119, 2000. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico, Lancet 354:447-55, 1999. Marchioli R, Schweiger C, Levantesi G, et al: Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data, Lipids 36(suppl):S53-S63, 2001. A critical constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer, Biofactors 7:113-74, 1998. Cattaneo M: Hyperhomocysteinaemia and atherothrombosis, Ann Med 32(suppl 1):46-52, 2000.

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Under no circumstances is it permissible to sell or distribute on a commercial basis discount 20 mg cialis sublingual with mastercard blood pressure drugs erectile dysfunction, or to claim authorship of effective cialis sublingual 20mg erectile dysfunction diabetes pathophysiology, copies of material reproduced from this publication generic cialis sublingual 20mg fast delivery erectile dysfunction unani medicine. Except as expressly provided above, no part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. This material is intended for educational use only by practicing health care workers or students and faculty in a health care field. Communicable Disease Control Preface This lecture note was written because there is currently no uniformity in the syllabus and, for this course additionally, available textbooks and reference materials for health students are scarce at this level and the depth of coverage in the area of communicable diseases and control in the higher learning health institutions in Ethiopia. Although, this lecture note is prepared and intended for use primarily for nursing students, other health science students and health professionals can use it. After using this material, students are expected to be able to: describe the epidemiology and scope of communicable diseases in Ethiopia and factors involved in the transmission of communicable diseases; identify the preventive and control measures of each of the communicable diseases; play an active role in the prevention and control of communicable diseases; organize and implement effective health education on communicable diseases, and; participate in teaching junior staff and significant others in health courses on managing patients with communicable diseases. The last chapter has a brief description of nursing principles in the management of communicable diseases. Moreover, each disease has been discussed in terms of its definition, infectious agent, epidemiology, clinical manifestation, diagnostic criteria, treatment, nursing care (for some diseases) and prevention and control methods. I am also indebted to my students, to whom I owe much of what I have learned about teaching the communicable disease control course, and whose interest and participation have sustained my motivation during the arduous writing of this material. Tadesse Anteneh for his advice, encouragement, and support in the preparation of this lecture note. My deep appreciation also goes to Ato Keneni Gutema, Ato Arega Awoke and S/r Addisalem Yilma, for their constructive comments and suggestions on an earlier draft and for taking time out from their busy schedules to read it. I would like to acknowledge Ato Abraham Alano and Ato Yared Kifle, who reviewed the final draft and gave me invaluable comments and suggestions. Last but not least my thanks also go to W/t Yiftusra Abebe and W/t Tigist Ayele who have assisted me in accomplishing all of the secretarial work of this text. Diseases can be classified according to two major dimensions, namely the time course and cause. According to the time course, they are further classified as acute (characterized by a rapid onset and a short duration), and chronic disease (characterized by prolonged duration). However, most of the common diseases in Africa are environmental diseases (infectious) due to infection by living 1 Communicable Disease Control organisms. These are called communicable diseases, because they spread from person to person, or sometimes from animals to people. They occur at all ages but are most serious in childhood and they are to a great extent preventable. In developed countries where they have been prevented, other health conditions such as accidents and degenerative diseases become the most common. Therefore, communicable diseases remain very important in developing countries because: Many of them are very common Some of them are serious and cause death and disability Some of them cause widespread out breaks of disease or epidemics Most of them are preventable by fairly simple means. This is due to severeal factors including: Immunization 2 Communicable Disease Control Anti-microbial chemotherapy Improved nutrition Better sanitation and housing In less developed countries, however, especially in the tropics, infectious diseases continue to be one of the commonest causes of death, particularly in children. These are: Infectious diseases (communicable diseases) 80% of these can be prevented by simple sanitary measures. Accordingly: The top leading causes of outpatient visits were: - All types of malaria (10. Some of the components in the definition of epidemiology are: "Populations” Epidemiology focuses on the effects of disease on populations "Disease and health related conditions” Epidemiology indicates that everything around us and everything we do affects our health. The causes of diseases are classified epidemiologically as: Primary causes - Factors that are necessary for a disease to occur, and in whose absence the disease will not occur (e. Contributing, predisposing, or aggravating factors - Risk factors whose presence is associated with an increased probability that disease will occur/develop later(e. Poverty is the most powerful environmental determinant in the disease occurrence, Habit of cigarette 5 Communicable Disease Control smoking leads to lung cancer. Epidemics - the occurrence of any health related condition in a given population in excess of the usual frequency in that population. Endemic - a disease that is usually present in a population or in an area at a more or less stable level. Sporadic - a disease that does not occur in that population, except at occasional and irregular intervals. Infection - the entry and development or multiplication of an infectious agent in the body of man or animal 7. Infestation – presence of living infectious agent on the exterior surface of the body 9. Infectious agent- an agent capable of causing infection 6 Communicable Disease Control Review Questions 1. How do you compare the impact of communicable disease in Ethiopia with that of the developed world? What are some of communicable diseases that create major health problems in Ethiopia? Define the following terms: - Epidemiology - Epidemics - Endemic - Pandemic - Sporadic - Infection and infectious agent 4. Infectious agent: An organism that is capable of producing infection or infectious disease. On the basis of their size, etiological agents are generally classified into: Metazoa (multicellular organisms). Reservoir of infection: Any person, animal, arthropod, plant, soil or substance (or combination of these) in which an infectious agent normally lives and multiplies, on which it depends primarily for survival and where it reproduces itself in such a manner that it can be transmitted to a susceptible host. Man: There are a number of important pathogens that are specifically adapted to man, such as: measles, smallpox, typhoid, meningococcal meningitis, gonorrhea and syphilis. The term “zoonosis” is applied to disease transmission from animals to man under natural conditions. For example: Bovine tuberculosis - cow to man Brucellosis - Cows, pigs and goats to man Anthrax - Cattle, sheep, goats, horses to man Rabies - Dogs, foxes and other wild animals to man Man is not an essential part (usual reservoir) of the life cycle of the agent. Non-living things as reservoir: Many of the agents are basically saprophytes living in soil and fully adapted to live freely in nature. Biologically, they are usually equipped to withstand marked environmental changes in temperature and humidity. Clostridium botulinum etiologic agent of Botulism Clostridium tetani etiologic agent of Thetanus Clostridium welchi etiologic agent of gas gangrene c. Portal of exit (mode of escape from the reservoir): This is the site through which the agent escapes from the reservoir. Mode of transmission (mechanism of transmission of infection): Refers to the mechanisms by which an infectious agent is transferred from one person to another or from a reservoir to a new host. Direct transmission: Consists of essentially immediate transfer of infectious agents from an infected host or reservoir to an appropriate portal of entry.

Formal advice and support is normally appropriate when the student demonstrates: A continuing pattern of minor defcits which when viewed in isolation may seem insignifcant but when seen cumulatively indicate an issue which has not been resolved by informal advice and support An isolated (but not gross) lapse from previously high standards buy cialis sublingual 20 mg with visa erectile dysfunction treatment california. Formal advice and support including remediation therefore may generic cialis sublingual 20 mg without prescription erectile dysfunction doctor prescription, depending on the nature of the defcit buy cheap cialis sublingual on line erectile dysfunction kidney stones, be based on the outcome of initial informal advice and support, which was found to be insuffcient to produce the necessary improvement, or may be the frst recourse. All those involved in teaching and administrative support should be aware that there is a framework and clear channels for referral of a student for formal advice and support including remediation. Medical schools are best placed to decide on the requisite level of seniority, experience and competency that an effective evaluation group would comprise. Consideration should be given however as to whether it is appropriate for an individual who has been involved in providing informal advice and support to a particular student to participate in formal advice and support for the same student: it may be that these roles are best played by different individuals. While a number of individuals are likely to be involved in the process, an individual should be identifed as the focal point for liaison with the student regarding their identifed defcit. They should, after appropriate consultation, including with the student, draw up an action plan intended to address and resolve the student’s professionalism defcit(s). The action plan should be a joint commitment between the student and the identifed focal point of the Stage One group and should be: Relevant to the student and the issue(s) Transparent in terms of timescale and expected outcome(s) Realistic Measurable in terms of evaluation of the students’ progress and the scope for attainment of the plan. An action plan could include commitments regarding: Attending remedial teaching Attending a support service Additional mentoring or supervision Adhering to specifed behaviour(s) Discontinuing a specifed behaviour. If there is a positive outcome, there should be a sign off to this effect by the student and the school. The student may be advised to use informal support and advice to maintain that improvement. It is anticipated that in many cases attempted remediation via an action plan will be tried as a frst option, and that it is only if that attempt is unsuccessful that the student will be referred to Stage Two. However, it must be emphasised that there is no onus on the medical school to take this course of action. If the nature of the professional defcit is such as to make it appropriate, then the student should be directly referred to Stage Two, without frst going through Stage One. This would be the normal course of action in the case of a potential gross breach of professionalism. Defnitions in these Guidelines of what constitutes a potential gross breach cannot be too prescriptive. However, defcits which fall into categories 1 (criminality), 2 (attitudes and behaviour towards patients), 3 (abuse, aggression, threat of violence, use of violence) or 7 (alcohol or substance misuse) of the Annex to these Guidelines indicates that the course of action that should normally be taken by the medical school would be direct referral to Stage Two. Defcits in other categories may depending on the nature of the defcit indicate direct referral. In particular, the medical school should always consider the possibility of a gross breach, and direct referral to Stage Two, where the defcit includes but is not limited to: Potential signifcant compromising of patient safety, dignity or well-being Potential signifcantly compromising of the safety, dignity or well-being of fellow students, medical school / university staff, or staff on clinical training sites Potential or actual criminal activity (including online). In the case of potential signifcant compromising of the safety, dignity or well-being of others, or of potential or actual criminal activity, the referral to Stage Two would normally be accompanied by suspension from the programme pending the outcome of Stage Two; or by curtailment of the student’s activities so as to remove the opportunity for further potential breaches, e. The process for formation of the pool and the panel should be clear and comply with good practice in equality and diversity. There should be clear Therms of Reference detailing the composition, remit and responsibilities of the pool and the panel. The panel’s reporting arrangements within the medical school and the university should be clear, including the various levels of approval that are required post-panel, and the appeals process. The relationship between this process and other codes, policies and processes within the school or university should be clear. There should be generic timelines which are intended to apply to all stages of all cases. If for good reasons the school cannot meet the anticipated milestones, this should be clearly communicated to the student. The school should be prepared to adjust timelines if the student presents reasonable grounds for that adjustment. The majority of the members of each panel should be from the student’s own medical school, but each panel should have at least one external member. Members of staff who have been closely involved in providing informal or formal advice and support to a particular student should not be members of the panel hearing that student’s case. As well as medical school staff, schools should also consider whether the following should be included in the pool: Externs from outside the State Nominees from patient representative groups Nominees from healthcare organisations Students Those with legal qualifcations/experience Those with counselling qualifcations/experience. If a pool of assessors is jointly established by the schools, consideration should be given to joint training of assessors. It would also tend to promote consistency of approach among panel members and thereby consistency in the decision-making process, both within medical schools and among medical schools. Training should include developing comprehensive knowledge and understanding of the relevant internal polices and processes and their application and (in due course) comprehensive knowledge and understanding of these Medical Council Guidelines. Proceedings should be fair and transparent and, among other things, the process should: Provide the student in advance with the information upon which the Panel will adjudicate Advise the student in advance of their right to representation and/or support Ensure that the conduct of meetings is in line with best practice Ensure that the student (if they chose to attend) has an opportunity to make their case Make their decision on the grounds of balance of probability Prescribe an appropriate course of action Provide a report to both parties that clearly specifcs the decision and the reason for it Maintain all relevant records are kept of all panel deliberations, confdentially and in line with university policies and relevant data protection legislation. The range of options open to the panel should be specifed, and normally include: No defcit (no action required, informal advice and support may be indicated) Some defcit, such as to warrant a course of action not amounting to exclusion from the programme, which may include: ◊ An admonition/reprimand and/or ◊ A requirement to undertake an additional course of study/period of study, or to repeat a period of study, or undertake some other prescribed action and/or ◊ Restitution and/or ◊ Suspension for a specifed period. The fnding of some defcit should be reserved for cases where the Panel believes that there is at least the potential for the student to be remediated, and where the student is willing to take the action required. In a fnding of some defcit, the action taken should: Be appropriate for the specifc case and the issues that prompted the Panel meeting Include a timescale and an expected outcome that can be measured and used to benchmark progress Be proportionate, realistic and achievable. In all cases, the outcome should be communicated to the student in a timely manner. The process for formation of the pool and the panel should be clear and comply with good practice in equality and diversity. Those who have been closely involved in informal or formal advice and support for a particular student, and those who served on the panel that considered that student’s case, should not sit on the Appeals Panel. There should be clear Therms of Reference detailing the remit, responsibilities and composition of the Appeals pool and the panel. The Therms of Reference should include: The grounds on which an appeal may be made, including extenuating circumstances that may be taken into account The student’s representation at the appeal panel Admission or otherwise of fresh evidence The powers of the appeal panel The reporting arrangements of the appeal panel The potential outcomes, e. As always, patient safety and well-being and the interests of the public should be uppermost in the decision-making process. All panel-related information, including the outcome, should be dealt with in a confdential manner, in line with university policies and in accordance with relevant data protection legislation. It refects a decision that is taken based on all the evidence available, the student is not ft to proceed to the next year of the programme or to graduate as a doctor. If the panel fnds that exclusion is the only way of protecting patients, peers, staff or the public, then it is the appropriate action to take. Schools will have to strike the balance between allowing a student the time and opportunity to beneft from the framework that is in place for formal advice and support including remediation, and prolonging the student’s career beyond the point at which improvement is feasible, which benefts neither the student, the school, patients nor the public. It is not possible to provide a defnitive list of professionalism defcits that provide grounds for expulsion. However, the severity of a single transgression, or a pattern of repeated and apparently intractable transgressions of a less serious but still signifcant nature, should be taken into account. Some potential grounds for exclusion are that the student has: Behaved in a way that is fundamentally incompatible with being a doctor Shown a reckless disregard for patient safety Done serious harm to others, patients or otherwise, either deliberately or through incompetence, particularly when there is a continuing risk to patients Abused their position of trust 37 Medical Council A Foundation For The Future Violated a patient’s rights or exploited a vulnerable person Committed offences of a sexual nature, including involvement in child pornography Committed offences involving violence Been dishonest, including covering up their actions, especially when the dishonesty has been persistent Put their own interests before those of patients Persistently shown a disregard or lack of insight into the seriousness of their actions or the consequences. Possessing insight (having or showing an accurate and deep understanding; being perceptive) is not a panacea. A student may have an awareness of the underlying cause(s) of their unprofessionalism, and an awareness of the impact of that on others, without being willing or able to address it.