Books on the topic 'High-risk activism'

The monograph examines the statement that the combination of innovation activity and corporate social responsibility should create a synergistic effect of sustainable development of the enterprise. It is shown that increasing loyalty on the part of a large number of stakeholder groups (especially employees, consumers, suppliers, etc.) and reducing the level of risk perception on the part of financial stakeholders, consumers, etc. through the emergence of a "halo" or "halo" of responsible business are extremely important for high-risk innovation activities, increase the effectiveness of project management. At the same time, a positive perception on the part of stakeholders should affect the competitiveness of the company as a whole and its economic efficiency. For students and teachers, as well as all those interested in the economy of enterprises.

Little attention has been devoted to the impact of corporate governance practices on firms’ innovative performance. This chapter reviews the literature to show that there is theoretical ambiguity. There is the argument that corporate governance and new forms of finance realign managers’ interests, with greater efficiency for all types of investments. However, some argue that innovative R&D has distinctive characteristics, like high risk and long-term horizon, that may modify the efficiency effect. The issue has generated many studies where the long tradition of positive relationships between governance and efficiency is now contrasted by some recent empirical evidence suggesting a negative relationship. The chapter argues that shareholder primacy or owner activism in corporate governance and new forms of finance represent a potential mismatch with innovation.

The incidence of morbidity and mortality related to CVD is rather low in a paediatric population. Studies investigating the relationship between physical activity, physical fitness, and cardiovascular health in children and adolescents are therefore mostly limited to CVD risk factors as outcome measures. For this reason, this chapter will focus on the association of physical activity and physical fitness with CVD risk factors in children and adolescents. These risk factors can be divided into the so-called traditional CVD risk factors; that is, lipoproteins [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG)], blood pressure, body fatness, and diabetes, and ‘new’ CVD risk factors; that is, other lipoproteins [lipoprotein(a) (Lp(a)), apolipoprotein (apo)B, and apoA-1], coagulation and inflammation markers [fibrinogen, C-reactive protein (CRP)], homocysteine, and heart rate variability.

This book argues that the rampant hate-filled attacks against women online are best understood as patterned resistance to women’s political voice and visibility. This abuse and harassment coalesces into an often-unrecognized form of gender inequality that constrains women’s use of digital public spaces, much as the pervasive threat of sexual intimidation and violence constrain women’s freedom and comfort in physical public spaces. What’s more, the abuse exacerbates inequality among women, those from racial, ethnic, religious, and/or other minority groups, are disproportionately targeted. Drawing on in-depth interviews with women who have been on the receiving end of digital hate, Credible Threat shows that the onslaught of epithets and stereotypes, rape threats, and unsolicited commentary about their physical appearance and sexual desirability come at great professional, personal, and psychological costs for the women targeted—and also with underexplored societal level costs that demand attention. When effective, identity-based attacks undermine women’s contributions to public discourse, create a climate of self-censorship, and at times, push women out of digital publics altogether. Given the uneven distribution of toxicity, those women whose voices are already most underrepresented (e.g., women in male-dominated fields, those from historically undervalued groups) are particularly at risk. In the end, identity-based attacks online erode civil liberties, diminish public discourse, limit the knowledge we have to inform policy and electoral decision making, and teach all women that activism and public service are unappealing, high-risk endeavors to be avoided.

It is now recognized that cardiovascular disease (CVD) is partly a paediatric problem, i.e. the onset begins in childhood, although clinical symptoms may not become apparent until later in life. Therefore, from a primary prevention point of view, the extent to which physical activity or physical fitness in childhood may deter this process is of utmost importance. Although physical activity and CRF at a young age have not been directly linked to the incidence of CVD, evidence thus far supports cardiovascular health benefits of early higher physical activity and CRF levels on cardiometabolic risk factors like obesity, blood pressure, insulin resistance, and their maintenance throughout the course of life. By affecting these intermediary pathways, lifelong (high-intensity) physical activity may also deter the age-related decreases in CRF and related signs of premature arterial ageing.

Antifibrinolytics can prevent excessive bleeding during surgery and are also used to reduce established bleeding. By blocking the effects of plasmin, they prevent premature clot breakdown and enhance clot stability. The CRASH-2 trial showed that use of tranexamic acid in those with or at high risk of traumatic haemorrhage reduced mortality by 9%. Importantly for a drug that affects haemostasis, there appears to be no increased risk of either arterial or venous thromboembolism. Aprotinin while an excellent agent in reducing bleeding disproves previous assumption that reducing bleeding improves outcome, for the BART study demonstrated an increased mortality compared with tranexamic acid and EACA. It is still used occasionally in very high risk cardiac surgery patients. DDAVP (desmopressin) stimulates platelet function and is of use in patients with uraemia, although needs to be given with an antifibrinolytics, because it does also stimulate fibrinolytic activity. Off-license use of rVIIa is waning, clinical trials have as yet failed to show major benefit. Moreover, there is a high rate of arterial thrombosis after using rVIIA.

♦ Stress fractures are fractures occurring as the result of repetitive, submaximal loads, in the absence of a specific precipitating traumatic event.♦ These fractures can be subdivided into two groups on the basis of aetiology. Whereas ‘fatigue fractures’ result from the excessive repetitive (i.e. abnormal) loading of normal bone, ‘insufficiency fractures’ are fractures resulting from normal forces acting on abnormal bone.♦ Early diagnosis allows the initiation of effective treatment that can prevent prolonged pain and disability, as well as avoiding the progression to displacement or a non-union.♦ While management decisions are generally focused on activity modification, protection of weight bearing, and immobilization, there is a subset of fractures at high risk for progression to complete fracture, non-union, or delayed union. These high-risk stress fractures, including tension-side femoral neck fractures and anterior tibial cortex fractures, require aggressive treatment to prevent the sequelae of poor healing.

The need for a new approach to cardiovascular disease prevention, both secondary and primary, that is different from traditional health service provision through hospital cardiac rehabilitation services and general practice is evident. The targets set in the cardiovascular prevention guidelines for modifiable cardiovascular risk factors-smoking, diet and physical activity, weight and its distribution, blood pressure, lipids, and diabetes-are not being adequately achieved for either coronary or other vascular patients or for those at high multifactorial risk of developing CVD. There is also evidence of an increasing disparity in levels of risk between different community groups, largely attributable to social determinants of health. Community-based prevention centres provide a novel approach to reducing cardiovascular risk, in which there is shared working between professionals and the public and a shared understanding of the barriers that individuals experience in their attempts to engage in effective measures for both secondary and primary prevention.

Lifestyle factors contribute appreciably to endometrial cancer risk, with obesity accounting for over one-third of incident cases in high-income societies. Unlike cervical cancer, which is a model of viral carcinogenesis, endometrial cancer is considered a model of hormonal carcinogenesis, as use of unopposed estrogens postmenopausally and obesity are the best-established risk factors. Endometrial cancer is also the only known malignancy for which cigarette smoking has been shown to confer protection. Risk reduction conferred by current smoking, past oral contraceptive use, childbearing, and physical activity is believed to be mediated by hormones. This may also apply to the increase in risk associated with obesity, which increases peripheral production of estrogens, and with diabetes mellitus. Hence, it should be possible to prevent a substantial fraction of endometrial cancers through lifestyle modification. Pathological classification of endometrial cancer is currently evolving and studies are revealing different molecular subtypes within the same histological groups.

The etiology of kidney cancer remains largely unknown. Cigarette smoking, obesity, and hypertension are well-established risk factors for kidney cancer. Although the current evidence is relatively mixed, other emerging risk factors include use of nonsteroidal anti-inflammatory drugs (NSAIDs), occupational exposure to trichloroethylene, and high parity in women. In contrast, physical activity and alcohol consumption have been consistently inversely associated with risk of kidney cancer. There is no convincing evidence of a causal link with any other specific food items or nutrients. Most kidney cancers are sporadic, and current studies of common genetic variants report mixed results, but genetic variations may also contribute to the etiology of kidney cancer. Further research is warranted to identify new environmental causes, to better understand the genetic and molecular processes, and to account for different molecular subtypes with specific genetic or tumor characteristics.

This chapter presents an overview of the risk assessment process with an in-depth description of the related terminology. Critical study features that should be included to maximize utility of data for risk assessment for any experimental study are presented as an aid for academic scientists interested in designing studies with utility in the risk assessment process. The second half of this chapter summarizes the current state of regulatory policy regarding EDCs in the United States and abroad. Topics addressed include the Toxic Substances Control Act (TSCA) and a detailed accounting of the changes enacted by the recent 2016 revisions to TSCA. These policies are compared to the Registration Evaluation Authorization and Restriction of Chemicals (REACH) laws that govern chemical safety assessment in the European Union. The Endocrine Disruptor Screening Program (EDSP) and current efforts toward developing high-throughput methods for screening chemicals for endocrine-disrupting activity are also summarized.

Can immunocompromised children be safely and effectively vaccinated? This chapter discusses the recommendations from the European League Against Rheumatism (EULAR) for the immunization of immunocompromised patients. Patients with rheumatic or autoinflammatory diseases treated with high-dose glucocorticoids, high-dose disease-modifying anti-rheumatic drugs (DMARDs), or biologicals are considered immunocompromised. Safe and effective vaccination is crucial in these patients, given their increased risk of infection. Safe vaccination implies that vaccination has no effect on disease activity and has only mild adverse effects. Effective vaccination denotes that patients are protected against infections after immunization. Particularly in severely immunosuppressed patients, concerns arise on the safety of (live-attenuated) vaccines and on the detrimental effect of immunosuppressive treatment on the immunogenicity of vaccines. Overall, vaccinations do not increase disease activity and do not cause severe adverse events. Although non-live vaccines are safe, it is recommended to withhold live-attenuated vaccines in patients on high-dose immunosuppressive drugs and biologicals. However, booster vaccinations can be considered when essential. Generally, immunogenicity of vaccines is good with some exceptions: responses are reduced in patients on high-dose glucocorticoids and rituximab; methotrexate reduces responses to (pneumococcal) polysaccharide vaccines; and anti-tumour necrosis factor alpha (TNFα‎) may lower vaccine-induced antibody concentrations. Offering vaccination before immunosuppressive drugs and/or measuring antibodies after immunization is recommended.

Can immunocompromised children be safely and effectively vaccinated? This chapter discusses the recommendations from the European League Against Rheumatism (EULAR) for the immunization of immunocompromised patients. Patients with rheumatic or autoinflammatory diseases treated with high-dose glucocorticoids, high-dose disease-modifying antirheumatic drugs (DMARDs), or biologicals are considered immunocompromised. Safe and effective vaccination is crucial in these patients, given their increased risk of infection. Safe vaccination implies that vaccination has no effect on disease activity and has only mild adverse effects. Effective vaccination denotes that patients are protected against infections after immunization. Particularly in severely immunosuppressed patients, concerns arise on the safety of (live-attenuated) vaccines and on the detrimental effect of immunosuppressive treatment on the immunogenicity of vaccines. Overall, vaccinations do not increase disease activity and do not cause severe adverse events. It is recommended to withhold live-attenuated vaccines in patients on high-dose immunosuppressive drugs and biologicals, but booster vaccinations can be considered when essential. Generally, immunogenicity of vaccines is good with some exceptions: responses are reduced in patients on high-dose glucocorticoids and rituximab; methotrexate reduces responses to (pneumococcal) polysaccharide vaccines; and tumour necrosis factor alpha (TNFα‎) may lower vaccine-induced antibody concentrations and may cause accelerated waning of immunity. Offering vaccination before immunosuppressive drugs and/or measuring antibodies after immunization is recommended.

Primary prevention has enormous potential to reduce the human, social, and economic costs of cancer worldwide. The following sections discuss the development and application of preventive interventions in six broad areas of public health: tobacco control, the prevention of obesity and physical inactivity, prevention of infection-related cancers, protection against excessive exposure to ultraviolet light, preventive drug therapies (chemoprevention), and the regulation of carcinogenic exposures. All of these areas affect multiple types of cancer and massive numbers of people. Different interventions are at varying stages of development. For example, effective, evidence-based approaches have been developed over several decades to reduce tobacco use, prevent chronic infection with hepatitis B virus, protect children from excessive sun exposure, regulate exposures in high-income countries, and reduce breast cancer incidence and recurrence in high-risk women. More recent efforts are seeking to identify upstream measures to prevent excessive weight gain, reduce caloric intake, and increase physical activity.

Harm reduction is defined as a set of policies, programs, and practices aimed at reducing the negative health, social, and economic consequences associated with various behaviors. Although classically applied to the treatment of substance use disorders, its scope has broadened over time to include high-risk sexual activity, nonadherence to treatment, and other behaviors that may lead to negative consequences. In addition to providing relevant historical context for scenarios encountered, this chapter uses a case to demonstrate how a provider might take a nonjudgmental and humanistic approach to identifying maladaptive behaviors and apply evidence-based, realistic interventions to reduce associated harms. Specific topics discussed include opioid use disorder, tobacco use disorder, female sex work, and nonadherence to psychotropic medications.

Clinical governance appeared as a concept in the UK in the late 1990s following scandals in which patients were harmed as a consequence of health care failures. Further international research estimates that one in ten inpatients suffer harm as a result of their health care, leading to death in some cases. Clinical governance is a framework centred around domains of patient safety, clinical effectiveness, and patient experience, underpinned by effective teamwork, leadership, and communication. Its aim is to ensure consistent, reliable, high-quality care delivered by competent individuals in a safe environment. Understanding why things go wrong in health care is key to finding solutions to ensure patient safety. Health care is an increasingly high-risk activity at organizational, departmental, and individual levels, and hazard identification and management are important. Recent recognition of human factors as contributing to many adverse events has facilitated the exploration of how health care professionals function within the context of a high-pressure, unpredictable environment. Lessons from non-health care industries have changed focus from blaming individuals for errors to understanding systems and how they can promote or mitigate failure. The development of non-technical skills, such as teamwork, is vital, and a number of approaches to improving this element of human behaviour are described.

Distinguishing between the needs of adults and those of adolescents, this chapter concentrates on practical operational approaches to both addiction and pain in the ephebiatric population. The susceptibility of this group to substance use disorders, and the profound impact on the developing brain and body of substances of misuse, is complicated further by their high level of physical activity and vulnerability to trauma. Data are provided from the Monitoring the Future project to profile the substance use risk of this population; a summary table is included giving the prevalence of various substances of misuse among youths. Unique requirements in their treatment are addressed, with emphasis placed on a network therapy, enlistment of family cooperation, and neighborhood resources. Noting that this is a population for whom physicians may be reluctant to initially consider medication, safety profiles are examined.

The research about the relation of mining and health has traditionally been carried out ex post, that is, with evaluation of the effects of mining on the health profiles of miners or exposed people, time after to the start of this economic activity. This limits the evaluation of the impact of mining on health, given the lack of knowledge about health indicators prior to the start of mining, or due to the absence of a baseline to analyze series of time. In addition, specific indicators such as vector-borne diseases (for example, malaria morbidity or mortality in endemic areas with mining activity), respiratory problems, effects of contamination with materials used in mining, among other topics, are generally investigated in illegal mining contexts. In Colombia there are few publications about the health profiles in legal mining areas, prior to the mining phase, as a determining aspect to establish a baseline that allows quantitative evaluation of the impacts of this economic activity on the health of the exposed people. This research analyzes the health profile of the residents of a geographic area with the presence of underground gold mining in Buriticá-Antioquia, according to sociodemographic conditions during 2019. The central outcomes of this profile were risk factors related to health services and lifestyle, felt morbidity, overweight and obesity, high blood pressure, STIs, breast disorders, lung conditions, all with their potential socio-economic risks.

The Tree Faller’s Manual is an essential handbook for forest operators and others who need to fell trees manually using a hand-held chainsaw. This manual builds on the information provided by the Chainsaw Operator’s Manual. Tree felling is a high risk activity. Many fatalities and serious injuries have occurred as a result of being struck by falling trees, dislodged tree limbs or other dangers in the area. Most of these accidents are caused by using unsafe felling techniques and not following safe work procedures. This manual will guide the faller to safer work techniques. The manual is based on the national competency standards for the forest and forest products industry where tree-felling is covered using three categories: basic, intermediate and advanced. Basic tree felling applies to trees that are relatively small, with a single stem and no defects. Intermediate tree felling covers trees with single or multiple stems, limited defects, and lean and weight distribution that can be adapted to felling direction. Advanced tree felling applies to larger and more complex trees and includes trees deemed to be more hazardous. Workplace safety, risk assessment and site preparation are included along with the theory, techniques and tools for each of the tree-felling categories.

Women and men with neurological disease more often suffer from depression in relation to pregnancy and delivery than other parents. Perinatal depression may harm the parent-child relationship as well as the health of the child. Postnatal psychosis, suicide, and infanticide are rare but severe consequences of the disorder. Symptoms of perinatal depression may overlap with symptoms of neurological disease. Both disorders may aggravate each other. Side effects from neurological treatment could mimic symptoms of depression, and antidepressive drugs could worsen neurological symptoms and interact with other treatment. Neurological patients should be evaluated for risk factors for perinatal depression before delivery. These include previous psychiatric disease, sexual or psychical abuse, sleep problems, high neurological disease activity, and low social support. Pregnant women with previous psychotic episodes or bipolar disease should be referred for psychiatric evaluation before delivery. All patients should be screened for depressive symptoms during follow-up using a 3-step method.

This chapter examines specific challenges faced by MSMEs. These challenges arise from factors such as size, lack of available collateral, undiversified nature, and lack of suitable external governance mechanisms, all of which contribute to a high MSME failure rate. As such, it is crucial for insolvency regimes to be responsive to MSMEs’ particular requirements. The chapter then discusses the need for cost-effective insolvency regimes tailored to these requirements, and the problems inherent in the development of such regimes. Cost-effective insolvency proceedings can encourage non-viable distressed firms to exit the market and efficiently recycle their assets to new uses, provide viable distressed firms with the chance to reorganize their operations and liability in order to continue in business, provide higher returns to MSME creditors and thereby incentivize lending in this sector, and encourage greater entrepreneurial activity and new firm creation. Ultimately, an effective MSME insolvency regime can alleviate the downside risk of a venture, in turn increasing the number and variety of people pursuing entrepreneurial activities.

Biomarker testing in the evaluation of a patient with acute chest pain is best established for cardiac troponins that allow the diagnosis of myocardial infarction, risk estimation of short- and long-term risk of death and myocardial infarction, and guidance of pharmacological therapy, as well as the need and timing of invasive strategy. Newer, more sensitive troponin assays have become commercially available and have the capability to detect myocardial infarction earlier and more sensitively than standard assays, but they are hampered by a lack of clinical specificity, i.e. the ability to discriminate myocardial ischaemia from myocardial necrosis not related to ischaemia such as myocarditis, pulmonary embolism, or decompensated heart failure. Strategies to improve clinical specificity (including strict adherence to the universal myocardial infarction definition and the need for serial troponin measurements to detect an acute rise and/or fall of cardiac troponin) will improve the interpretation of the increasing number of positive results. Other biomarkers of inflammation, activated coagulation/fibrinolysis, and increased ventricular stress mirror different aspects of the underlying disease activity and may help to improve our understanding of the pathophysiological mechanisms of acute coronary syndromes. Among the flood of new biomarkers, there are several novel promising biomarkers, such as copeptin that allows an earlier rule-out of myocardial infarction in combination with cardiac troponin, whereas MR-proANP and MR-proADM appear to allow a refinement of cardiovascular risk. GDF-15 might help to identify candidates for an early invasive vs conservative strategy. A multi-marker approach to biomarkers becomes more and more attractive, as increasing evidence suggests that a combination of several biomarkers may help to predict individual risk and treatment benefits, particularly among troponin-negative subjects. Future goals include the acceleration of rule-in and rule-out of patients with suspected acute coronary syndrome, in order to shorten lengths of stay in the emergency department, and to optimize patient management and the use of health care resources. New algorithms using high-sensitivity cardiac troponin assays at low cut-offs alone, or in combination with additional biomarkers, allow to establish accelerated rule-out algorithms within 1 or 2 hours.

Biomarker testing in the evaluation of a patient with acute chest pain is best established for cardiac troponins that allow the diagnosis of myocardial infarction, risk estimation of short- and long-term risk of death and myocardial infarction, and guidance of pharmacological therapy, as well as the need and timing of invasive strategy. Newer, more sensitive troponin assays have become commercially available and have the capability to detect myocardial infarction earlier and more sensitively than standard assays, but they are hampered by a lack of clinical specificity, i.e. the ability to discriminate myocardial ischaemia from myocardial necrosis not related to ischaemia such as myocarditis, pulmonary embolism, or decompensated heart failure. Strategies to improve clinical specificity (including strict adherence to the universal myocardial infarction definition and the need for serial troponin measurements to detect an acute rise and/or fall of cardiac troponin) will improve the interpretation of the increasing number of positive results. Other biomarkers of inflammation, activated coagulation/fibrinolysis, and increased ventricular stress mirror different aspects of the underlying disease activity and may help to improve our understanding of the pathophysiological mechanisms of acute coronary syndromes. Among the flood of new biomarkers, there are several novel promising biomarkers, such as copeptin that allows an earlier rule-out of myocardial infarction in combination with cardiac troponin, whereas MR-proANP and MR-proADM appear to allow a refinement of cardiovascular risk. GDF-15 might help to identify candidates for an early invasive vs conservative strategy. A multi-marker approach to biomarkers becomes more and more attractive, as increasing evidence suggests that a combination of several biomarkers may help to predict individual risk and treatment benefits, particularly among normal-troponin subjects. Future goals include the acceleration of rule-in and rule-out of patients with suspected acute coronary syndrome, in order to shorten lengths of stay in the emergency department, and to optimize patient management and the use of health care resources. New algorithms using high-sensitivity cardiac troponin assays at low cut-offs alone, or in combination with additional biomarkers, allow to establish accelerated rule-out algorithms within 1 or 2 hours.

Biomarker testing in the evaluation of a patient with acute chest pain is best established for cardiac troponins that allow the diagnosis of myocardial infarction, risk estimation of short- and long-term risk of death and myocardial infarction, and guidance of pharmacological therapy, as well as the need and timing of invasive strategy. Newer, more sensitive troponin assays have become commercially available and have the capability to detect myocardial infarction earlier and more sensitively than standard assays, but they are hampered by a lack of clinical specificity, i.e. the ability to discriminate myocardial ischaemia from myocardial necrosis not related to ischaemia such as myocarditis, pulmonary embolism, or decompensated heart failure. Strategies to improve clinical specificity (including strict adherence to the universal myocardial infarction definition and the need for serial troponin measurements to detect an acute rise and/or fall of cardiac troponin) will improve the interpretation of the increasing number of positive results. Other biomarkers of inflammation, activated coagulation/fibrinolysis, and increased ventricular stress mirror different aspects of the underlying disease activity and may help to improve our understanding of the pathophysiological mechanisms of acute coronary syndromes. Among the flood of new biomarkers, there are several novel promising biomarkers, such as copeptin that allows an earlier rule-out of myocardial infarction in combination with cardiac troponin, whereas MR-proANP and MR-proADM appear to allow a refinement of cardiovascular risk. GDF-15 might help to identify candidates for an early invasive vs conservative strategy. A multi-marker approach to biomarkers becomes more and more attractive, as increasing evidence suggests that a combination of several biomarkers may help to predict individual risk and treatment benefits, particularly among normal-troponin subjects. Future goals include the acceleration of rule-in and rule-out of patients with suspected acute coronary syndrome, in order to shorten lengths of stay in the emergency department, and to optimize patient management and the use of health care resources. New algorithms using high-sensitivity cardiac troponin assays at low cut-offs alone, or in combination with additional biomarkers, allow to establish accelerated rule-out algorithms within 1 or 2 hours.

Image-based measurements of myocardial blood flow afford the assessment of coronary circulatory function. They reflect functional consequences of coronary stenoses, diffuse epicardial vessel disease and microvascular dysfunction and structural changes and thus provide a measure of the total ischemic burden. Measured flows contain therefore clinically important predictive information. Fundamental to flow measurements are the tissue tracer kinetics, their description through tracer kinetic models, high spatial and temporal resolution imaging devices and accurate extraction of radiotracer tissue concentrations from dynamically acquired images for estimating true flows from the tissue time activity curves. A large body of literature on measurements of myocardial blood flow exists for defining in humans normal values for flow at baseline and during hyperemic stress as well as for the myocardial flow reserve. The role of PET for flow measurements has been well established; initial results with modern SPECT devices are encouraging. Responses of myocardial blood flow to specific challenges like pharmacologic vasodilation and to sympathetic stimulation can uncover functional consequences of focal epicardial coronary stenoses, of conduit vessel disturbances and disease and impairments of microvascular function. Apart from risk stratification, flow measurements may allow detection of early preclinical disease, influence treatment strategies and identify therapy responses.

In the UK, the four commonest cancers—lung cancer, breast cancer, colon cancer, and prostate cancer—result in around 62 000 deaths every year. Although deaths from cancer have fallen in the UK over the last 20 years, the UK still suffers from higher cancer death rates than many other countries in Western Europe. In 1999, the UK government produced a White Paper called Saving Lives: Our Healthier Nation that outlined a national target to reduce the death rate from cancer by at least 20% in people under 75 by 2010. The subsequent NHS Cancer Plan of 2000 designed a framework by which to achieve this target through effective prevention, screening, and treatment programmes as well as restructuring and developing new diagnostic and treatment facilities. But do we know enough about the biology of the development of cancer for government health policies alone to force dramatic changes in survival? The science behind the causes of cancer tells us that its origin lies in acquired or inherited genetic abnormalities. Inherited gene mutation syndromes and exposure to environmental mutagens cause cancer, largely through abnormalities in DNA repair mechanisms, leading to uncontrolled cell proliferation. Although screening those thought to be at highest risk, and regulating exposure to environmental carcinogens such as tobacco or ionizing radiation, have reduced, and will continue to reduce, cancer deaths, there are many other environmental factors that have been shown to increase the population risk of cancer. These will be outlined in this chapter. However, the available evidence is largely from retrospective and cross-sectional population-based studies and therefore limits the ability to apply this knowledge to the risk of the individual patient who may been seen in clinic. Although we may be able to put him or her into a high-, intermediate-, or low-risk category, the question ‘will I get cancer, doc?’ is one that we cannot answer with certainty. The NHS Cancer Plan of 2000, designed to reduce cancer deaths in this country and to bring UK treatment results in line with those other countries in Europe, focuses on preventing malignancy as part of its comprehensive cancer management strategy. It highlights that the rich are less likely to develop cancer, and will survive longer if they are diagnosed than those who live in poverty. This may reflect available treatment options, but is more likely to be related to the lifestyle of those with regular work, as they may be more health aware. The Cancer Plan, however, suggests that relieving poverty may be more labour intensive and less rewarding than encouraging positive risk-reducing behaviour in all members of the population. Eating well can reduce the risk of developing many cancers, particularly of the stomach and bowel. The Cancer Plan outlines the ‘Five-a-Day’ programme which was rolled out in 2002 and encouraged people to eat at least five portions of fruit and vegetables per day. Obese people are also at higher risk of cancers, in particular endometrial cancer. A good diet and regular exercise not only reduce obesity but are also independent risk-reducing factors. Alcohol misuse is thought to be a major risk factor in around 3% of all cancers, with the highest risk for cancers of the mouth and throat. As part of the Cancer Plan, the Department of Health promotes physical activity and general health programmes, as well as alcohol and smoking programmes, particularly in deprived areas. Focusing on these healthy lifestyle points can potentially reduce an individual lifetime risk of all cancers. However, our knowledge of the biology of four cancers in particular has led to the development of specific life-saving interventions. Outlined in this chapter are details regarding ongoing prevention strategies for carcinomas of the lung, the breast, the bowel, and the cervix.

The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function. Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator. Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.

The goals of treatment in renal vasculitis are to stop vasculitic activity and recover renal function. Subsequent strategies are required to prevent vasculitis returning and to address longer-term co-morbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk.Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as azathioprine, to prevent relapse. Plasma exchange improves renal recovery in severe presentations. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Methotrexate is effective in non-renal vasculitis but difficult to use in patients with renal impairment. Mycophenolate mofetil seems to be effective but there is less long-term evidence.Drug toxicity contributes to co-morbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn.Disease relapse occurs in about 50% of patients. Early detection is less likely to lead to an adverse affect on outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.Renal impairment at diagnosis is a strong predictor of patient survival and renal outcome. Other predictors include patient age, antineutrophil cytoplasmic antibody subtype, disease extent and response to therapy. Chronic kidney disease can stabilize for many years but the risks of end-stage renal disease are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful with similar outcomes to other causes of end-stage renal disease.

Any public debate about air pollution starts with the premise that air pollution cannot be good for you, so we should have less of it. However, it is much more difficult to determine how much is dangerous, and even more difficult to decide how much we are willing to pay for improvements in measured air pollution. Recent UK estimates suggest that fine particulate pollution causes about 6500 deaths per year, although it is not clear how many years of life are lost as a result. Some deaths may just be brought forward by a few days or weeks, while others may be truly premature. Globally, household pollution from cooking fuels may cause up to two million premature deaths per year in the developing world. The hazards of black smoke air pollution have been known since antiquity. The first descriptions of deaths caused by air pollution are those recorded after the eruption of Vesuvius in ad 79. In modern times, the infamous smogs of the early twentieth century in Belgium and London were clearly shown to trigger deaths in people with chronic bronchitis and heart disease. In mechanistic terms, black smoke and sulphur dioxide generated from industrial processes and domestic coal burning cause airway inflammation, exacerbation of chronic bronchitis, and consequent heart failure. Epidemiological analysis has confirmed that the deaths included both those who were likely to have died soon anyway and those who might well have survived for months or years if the pollution event had not occurred. Clean air legislation has dramatically reduced the levels of these traditional pollutants in the West, although these pollutants are still important in China, and smoke from solid cooking fuel continues to take a heavy toll amongst women in less developed parts of the world. New forms of air pollution have emerged, principally due to the increase in motor vehicle traffic since the 1950s. The combination of fine particulates and ground-level ozone causes ‘summer smogs’ which intensify over cities during summer periods of high barometric pressure. In Los Angeles and Mexico City, ozone concentrations commonly reach levels which are associated with adverse respiratory effects in normal and asthmatic subjects. Ozone directly affects the airways, causing reduced inspiratory capacity. This effect is more marked in patients with asthma and is clinically important, since epidemiological studies have found linear associations between ozone concentrations and admission rates for asthma and related respiratory diseases. Ozone induces an acute neutrophilic inflammatory response in both human and animal airways, together with release of chemokines (e.g. interleukin 8 and growth-related oncogene-alpha). Nitrogen oxides have less direct effect on human airways, but they increase the response to allergen challenge in patients with atopic asthma. Nitrogen oxide exposure also increases the risk of becoming ill after exposure to influenza. Alveolar macrophages are less able to inactivate influenza viruses and this leads to an increased probability of infection after experimental exposure to influenza. In the last two decades, major concerns have been raised about the effects of fine particulates. An association between fine particulate levels and cardiovascular and respiratory mortality and morbidity was first reported in 1993 and has since been confirmed in several other countries. Globally, about 90% of airborne particles are formed naturally, from sea spray, dust storms, volcanoes, and burning grass and forests. Human activity accounts for about 10% of aerosols (in terms of mass). This comes from transport, power stations, and various industrial processes. Diesel exhaust is the principal source of fine particulate pollution in Europe, while sea spray is the principal source in California, and agricultural activity is a major contributor in inland areas of the US. Dust storms are important sources in the Sahara, the Middle East, and parts of China. The mechanism of adverse health effects remains unclear but, unlike the case for ozone and nitrogen oxides, there is no safe threshold for the health effects of particulates. Since the 1990s, tax measures aimed at reducing greenhouse gas emissions have led to a rapid rise in the proportion of new cars with diesel engines. In the UK, this rose from 4% in 1990 to one-third of new cars in 2004 while, in France, over half of new vehicles have diesel engines. Diesel exhaust particles may increase the risk of sensitization to airborne allergens and cause airways inflammation both in vitro and in vivo. Extensive epidemiological work has confirmed that there is an association between increased exposure to environmental fine particulates and death from cardiovascular causes. Various mechanisms have been proposed: cardiac rhythm disturbance seems the most likely at present. It has also been proposed that high numbers of ultrafine particles may cause alveolar inflammation which then exacerbates preexisting cardiac and pulmonary disease. In support of this hypothesis, the metal content of ultrafine particles induces oxidative stress when alveolar macrophages are exposed to particles in vitro. While this is a plausible mechanism, in epidemiological studies it is difficult to separate the effects of ultrafine particles from those of other traffic-related pollutants.