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\"This book by Richard G. Stevens is a comprehensive introduction to the nature of political philosophy. It offers definitions of philosophy and politics, showing the tension between the two and the origin of political philosophy as a means of resolution of that tension. Plato and Aristotle are examined in order to see the search for the best political order. Inquiry is then made into political philosophy's new tension brought about by the growth of revealed religion in the Middle Ages. It then examines the changes introduced by modernity and gives an overview of postmodern political thought. The book covers the most influential philosophers and directs readers to the classics of political philosophy, guiding them in studying them. It is an approachable introduction to a complex subject, not just a history of it. It is a point of entry into the subject for students and for others as well\"-- Provided by publisher.

Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.

Over the past 3 billion years, an endogenous circadian rhythmicity has developed in almost all life forms in which daily oscillations in physiology occur. This allows for anticipation of sunrise and sunset. This physiological rhythmicity is kept at precisely 24 h by the daily cycle of sunlight and dark. However, since the introduction of electric lighting, there has been inadequate light during the day inside buildings for a robust resetting of the human endogenous circadian rhythmicity, and too much light at night for a true dark to be detected; this results in circadian disruption and alters sleep/wake cycle, core body temperature, hormone regulation and release, and patterns of gene expression throughout the body. The question is the extent to which circadian disruption compromises human health, and can account for a portion of the modern pandemics of breast and prostate cancers, obesity, diabetes and depression. As societies modernize (i.e. electrify) these conditions increase in prevalence. There are a number of promising leads on putative mechanisms, and epidemiological findings supporting an aetiologic role for electric lighting in disease causation. These include melatonin suppression, circadian gene expression, and connection of circadian rhythmicity to metabolism in part affected by haem iron intake and distribution.

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours.

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.

Disruptions in iron homeostasis are linked to a broad spectrum of chronic conditions including cardiovascular, malignant, metabolic, and neurodegenerative disease. Evidence supporting this contention derives from a variety of analytical approaches, ranging from molecular to population-based studies. This review focuses on key epidemiological studies that assess the relationship between body iron status and chronic diseases, with particular emphasis on atherosclerosis ,metabolic syndrome and diabetes. Multiple surrogates have been used to measure body iron status, including serum ferritin, transferrin saturation, serum iron, and dietary iron intake. The lack of a uniform and standardized means of assessing body iron status has limited the precision of epidemiological associations. Intervention studies using depletion of iron to alter risk have been conducted. Genetic and molecular techniques have helped to explicate the biochemistry of iron metabolism at the molecular level. Plausible explanations for how iron contributes to the pathogenesis of these chronic diseases are beginning to be elucidated. Most evidence supports the hypothesis that excess iron contributes to chronic disease by fostering excess production of free radicals. Overall, epidemiological studies, reinforced by basic science experiments, provide a strong line of evidence supporting the association between iron and elevated risk of cardiovascular disease and diabetes. In this narrative review we attempt to condense the information from existing literature on this topic.

Breast cancer risk is high in industrialized societies, and increases as developing countries become more Westernized. The reasons are poorly understood. One possibility is circadian disruption from aspects of modern life, in particular the increasing use of electric power to light the night, and provide a sun-free environment during the day inside buildings. Circadian disruption could lead to alterations in melatonin production and in changing the molecular time of the circadian clock in the suprachiasmatic nuclei (SCN). There is evidence in humans that the endogenous melatonin rhythm is stronger for persons in a bright-day environment than in a dim-day environment; and the light intensity necessary to suppress melatonin at night continues to decline as new experiments are done. Melatonin suppression can increase breast tumorigenesis in experimental animals, and altering the endogenous clock mechanism may have downstream effects on cell cycle regulatory genes pertinent to breast tissue development and susceptibility. Therefore, maintenance of a solar dayaligned circadian rhythm in endogenous melatonin and in clock gene expression by exposure to a bright day and a dark night, may be a worthy goal. However, exogenous administration of melatonin in an attempt to achieve this goal may have an untoward effect given that pharmacologic dosing with melatonin has been shown to phase shift humans depending on the time of day it's given. Exogenous melatonin may therefore contribute to circadian disruption rather than alleviate it.

In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (group 2A), primarily based on experimental and epidemiologic evidence for breast cancer. In order to examine options for evidence-based preventive actions, 16 researchers in basic, epidemiological and applied sciences convened at a workshop in Copenhagen 26-27 October 2011. This paper summarizes the evidence from epidemiological and experimental studies and presents possible recommendations for prevention of the effects of night work on breast cancer. Among those studies that quantified duration of shift work, there were statistically significant elevations in risk only after about 20 years working night shift. It is unclear from these studies whether or not there is a modest but real elevated risk for shorter durations. Hence, restriction of the total number of years working night shift could be one future preventive recommendation for shift workers. The diurnal secretion of melatonin by the pineal gland with peak in secretory activity during the night is a good biochemical marker of the circadian rhythm. Disruption of the diurnal melatonin secretion pattern can be diminished by restricting the number of consecutive night shifts. Reddish light and reduced light intensity during work at night could potentially help diminish the inhibitory activity of light with strong intensity on the melatonin secretion, but further mechanistic insight is needed before definite recommendations can be made. Earlier or more intensive mammography screening among female night shift worker is not recommended because the harm-benefit ratio in this age group may not be beneficial. Preventive effects of melatonin supplementation on breast cancer risk have not been clearly documented, but may be a promising avenue if a lack of side effects can be shown even after long-term ingestion.women with previous or current breast cancer should be advised not to work night shifts because of strong experimental evidence demonstrating accelerated tumor growth by suppression of melatonin secretion. Work during the night is widespread worldwide. To provide additional evidence-based recommendations on prevention of diseases related to night shift work, large studies on the impact of various shift schedules and type of light on circadian rhythms need to be conducted in real work environments.

Objectives: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. Data sources: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. Data extraction: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. Data synthesis: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. Conclusions: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.