Academic literature on the topic 'Fifth Century B.C'

AbstractGregory D. Alles has suggested that economic theory can be a valuable supplement to cognitive theories of religion. The cult of Athena at Athens supplies evidence to support this suggestion. Athena may have origins in the cognitive structures of the human mind as an extraordinary agent. However, she developed economic functions in fifth-century B. C. E. Athens. The sanctuary of Athena served as a bank that funded Athenian civic endeavours. Athena's sanctuary was able to do this because she was a disembodied agent with functions similar to those of a modern United States corporation, which is also a disembodied agent.

This study examines the manifestations of French humanism in sixteenth-century intellectual culture, through an analysis, for the first time, of the entirety of the works of Pierre Boaistuau. An eminent French humanist writer, on whose life little information exists, Boaistuau emerges far more prolific than any previous study has hitherto recognised. Thus, on a first level, his case offers the opportunity for an exploration of the developments of French print culture at the time. In addition, careful examination of the contents of his widely circulated works sheds new light on the ways humanist themes and values were incorporated into contemporary literary production, and were used for different purposes which surpassed the mere celebration of ancient learning. Boaistuau employed seven genres in order to compile seven books of different natures, all of them however grafted onto a humanist framework. Associated with narrative fiction, Renaissance philosophy, political theory, the study of history, and natural philosophy, his works demonstrate how the classical past and the humanist values of virtue, erudition, and self-discipline were used in a variety of ways in mid sixteenth-century France: for promotion of a moralising message, praise of the French monarchy, bolstering the Catholic faith, and enhancing the understanding of the natural world.

British musical style changed dramatically after 1880 primarily due to factors which may be subsumed under the general heading of nationalism. This change from an essentially Germanic style has been termed the British musical renaissance by many writers on the subject. Within this new musical language, several distinctive substyles arose. One of these, British pastoral style, has been alluded to by Frank Howes and others, but these allusions do not contribute to an understanding of the works purportedly belonging to that style. It is the purpose of this study to define British pastoral style and examine its relation to the British musical renaissance. The method employed for defining style will be that of Jan LaRue's as described in his Guidelines for Style Analysis. What is British pastoral style? Judging from the literature, British pastoral style is a type of British music written between 1900 and 1950 which evokes pastoral images, especially those associated with the British landscape. A stylistic analysis of selected works will define British pastoral style through enumeration and discussion of the style's musical constituents. A more refined definition of British pastoral style is achieved by an in-depth analysis of E. J. Moeran's Fantasy Quartet, which represents a large portion of British pastoral music, that is, works featuring the oboe. Finally, an examination of British pastoral style's relation to the British musical renaissance will reveal reasons for this particular manifestation of British musical style.

Thesis (DPhil (History))--University of Stellenbosch, 2010.
ENGLSIH ABSTRACT: This study is a political biography of D.F. Malan (1874–1959), the first of the apartheid-era Prime Ministers, and covers the years 1874 to 1954, when Malan retired from politics. It endeavours to provide a warts-and-all account of D.F. Malan which challenges prevalent myths and stereotypes surrounding his public persona and his political orientation. While the overwhelming focus is on Malan’s political career, special attention is paid to his personal life in order to paint a multi-faceted picture of his character. The biography is written in the form of a seamless narrative and employs a literary style of writing. It is based on archival research which utilised Malan’s private collection, as well as the private collections of his Nationalist contemporaries. Malan takes the centre stage at all times, as the biography focuses on his perceptions and experiences. Malan’s views regarding Afrikaner nationalism, which was his foremost political priority, are described, and are related to his views of British imperialism as well as other ideologies such as communism and totalitarianism. This study demonstrates that there is a notable link between Malan’s perceptions of race relations and his concerns about the poor white problem. It reveals that Malan’s racial policy was, to some extent, fluid, as were his views on South Africa’s constitutional position. Debates about South Africa’s links to Britain and the nature of the envisioned republic preoccupied Afrikaner nationalists throughout the first half of the twentieth century – and served as an outlet for regional and generational tensions within the movement. Malan’s clashes with nationalists such as Tielman Roos, J.B.M. Hertzog and J.G. Strijdom are highlighted as an indication of the internecine power struggles within the National Party (NP). By emphasising these complexities, this study seeks to contribute to a nuanced understanding of the South African past.
AFRIKAANSE OPSOMMING: Hierdie studie is politieke biografie van D.F. Malan (1874–1959), die eerste van die apartheid-era Eerste Ministers, en dek die jare 1874 tot 1954, toe Malan uit die politiek getree het. Dit poog om onversuikerde beeld van Malan te skets wat heersende mites en stereotipes aangaande sy openbare beeld en sy benadering tot die politiek uitdaag. Die fokus is hoofsaaklik op Malan se politieke loopbaan, maar besondere aandag word aan sy private lewe geskenk om sodoende veelsydige portret van sy karakter te skilder. Die biografie is in die vorm van naatlose narratief geskryf en maak van literêre skryfstyl gebruik. Dit is gebaseer op argivale navorsing, waartydens daar van D.F. Malan se privaat versameling gebruik gemaak is, sowel as die privaat versamelings van sy tydgenote. Malan is ten alle tye die sentrale figuur en die biografie fokus op sy persepsies en ervarings. Malan se denke oor Afrikaner nasionalisme, wat sy vernaamste prioriteit was, word beskryf en in verband gebring met sy opinie van Britse imperialisme, sowel as ander ideologieë soos kommunisme en totalitarisme. Die studie wys op die verband tussen Malan se denke oor rasseverhoudinge en sy besorgdheid oor die armblanke vraagstuk. Dit dui daarop dat Malan se rassebeleid tot sekere mate vloeibaar was. Dit was ook die geval met sy benadering tot Suid-Afrika se konstitusionele posisie. Afrikaner nasionaliste het tydens die eerste helfte van die twintigste eeu baie aandag geskenk aan debatte oor Suid-Afrika se verhouding tot Brittanje en die aard van die voorgenome republiek. Dit was tot mate weerligafleier vir reeds bestaande spanning tussen die onderskeie streke en generasies. Malan se botsings met nasionaliste soos Tielman Roos, J.B.M. Hertzog en J.G. Strijdom word belig as aanduiding van die diepgewortelde magstryd binne die Nasionale Party (NP). Deur op hierdie kompleksiteite klem te lê, poog die studie om bydrae te lewer tot meer genuanseerde begrip van die Suid-Afrikaanse verlede.

Before 1891, it was commonly accepted that the most important source for the rule of the Four Hundred in Athens in 411 BCE was Thucydides' description. The situation changed thanks to the publication of the Aristotelian treatise On the Athenian Constitution, whose version of events differed markedly from Thucydides' one. There followed many attempts at determining which of the two versions was most reliable, or at combining the two versions. These controversies are the focal point of this thesis, but its ambitions are not limited to them: its ambition is also to reconstruct the chronology of the rule of the Four Hundred as precisely as is possible in context of the Peloponnesian war; and to formulate the limitations that are imposed on us by the character of sources at our disposal. Continuity of the coup with earlier developments and its impact on subsequent events are dealt with more briefly.

AbstractIn his 1966 John Danz lectures, Francis H. C. Crick decried vitalism in the life sciences. Why did he do this three decades after most historians and philosophers of science regarded vitalism as dead? This essay argues that, by advocating the reduction of biology to physics and chemistry Crick was: (a) attempting to imbue the life sciences with greater prestige, (b) paving the way for bioengineering and the reduction of consciousness to molecules, and (c) trying to root out religious sentiment in the life sciences. In service of these goals, Crick deployed vitalism as a straw man enemy. His wave of so-called vitalists in the middle of the twentieth century in fact raised legitimate questions regarding the relationship of organisms to their DNA molecules that Crick was ill-equipped to answer. Moreover, most were not vitalists at all but advocates for what I term bioexceptionalism—an argument for the methodological utility of keeping biological pursuits within their own domains, distinct from physics and chemistry, regardless of the ontological status of living things. Nevertheless, Crick’s status as a “cross-worlds influencer” entrenched a philosophically-enervated reductionism in the life sciences for decades.

AbstractThis chapter analyses the links between transatlantic migration and the social policies that gave Uruguay the fame of being Latin America’s first welfare state in the early twentieth century. Three lines of impact will be examined: (a) how Uruguayan politicians framed health and labour legislation as a means to attract migrant workers and used the reforms in their recruitment of European migrants; (b) how migrants shaped the labour movement, which successfully demanded and negotiated social policies, and organised welfare in mutual societies; and (c) how second- and third-generation migrants formed part of social policy reform circles.

Abstract The definitions of genera and subgenera used in the classification of the Dacini have been in a continual state of change for over a century. The early definitions were based on often homoplasious morphological characters, some examples for the Oriental and Australian regions being Tryon (1927), Perkins (1937), Hardy (1951), May (1951) and Drew (1972). More recently revised subgeneric definitions for most species groups were published by Drew and Hancock (2016) and Hancock and Drew (2006, 2015, 2016, 2017a,b,c,d,e, 2018a,b,c, 2019), based on detailed analyses of dacine biogeography, host plant biology and morphology. This chapter discusses the evolutionary origins of the Dacini, the host plant and its influence on speciation in the Dacini.

This chapter provides a partial explanation for the apparent success of the many democratic revolutions in mid 5th century Sicily. It makes three primary points. First, the presence of mercenaries and displaced peoples constituted an existential threat to each of the new Sicilian democracies. For example, mercenaries – all of whom previously worked for the then recently deposed tyrants – might support an aspiring tyrant simply for pay. Second, no city could solve the problems posed by mercenaries and displaced peoples by itself. If City A, for example, does not welcome home its former residents currently living in City B, City B might not be able to welcome home its former residents currently living in City C, and so on. For the third point it draws upon the work of Michael Chwe and Barry Weingast and argues that the promulgation of a koinon dogma (Diod. Sic. 11.76.5) helped the citizens of the relevant poleis solve their “inter‐polis coordination problem” and thus helped consolidate the several democratic revolutions in Greek Sicily.

A brief reprise of the geological aspects, organization, physical constraints, and appearance of each city will remind us of their common and unique features. Then we can compare them by groups linked by research questions. Agrigento is built on two ridges of 120 and 320–390 m, setting generous limits not yet filled by the modern city. A plain extends from the lower ridge south to the sea. Vistas were provided along contours and across elevations. Grouping the public buildings on stony ridges, with temples above and below and government structures along the west side, made economic and aesthetic sense. Landslides provide important clues to the nature of the hill the city is built on, and they correlate with occupation of various parts of the site. Additionally, the water system shows unexpected correlation with the families of discontinuities in the stone rather than the surface grid of the streets (Ercoli and Crouch 1998; Crouch 1989). Morgantina stretches along a ridge about 600 m in elevation. The agora most clearly reveals the interface of urban design and geology. Sanctuaries and fountains were the focus during the fifth century B. C. E. In the third century, modest but elegant new architecture (theater, great steps, flanking stoas, fountains, sanctuary) combined with pragmatic engineering as framework and connector between points of observation. Morgantina had one aqueduct, from the springs that later supplied Aidone. The site has numerous springs although some are now dry or give less than 1 l/s. Yet, during the third century B. C. E. when the population was at its maximum, the aquifer was also at maximum, and higher springs were fed from it more amply than at present. Improper management of water resources likely hastened the demise of the town after the Roman conquest. At the turn of the era, the shift from small rural towns to great landed estates as centers of population affected Morgantina strongly. Deforestation of the hills and mountains for fuel and building materials could have resulted in desiccation, with climate change a related factor. Occupation by the Hispanii (Spanish veterans) who replaced the Hellenized Sicilians after 211 B. C. E. coincided with a negative water balance.

This chapter focuses on some problems associated with Stephanus' ultimate sources, and considers how much his text contributes to the subject of ethnic terminology. Stephanus is not the earliest writer on or compiler of a catalogue of places and ethnics, but his work alone survives, though only in an epitomised form, and is thus the essential part of the evidence. The goal is to interrogate the text in the hope that it will throw more light on the various aspects of ethnic formations in general use. The chapter examines the text of the Epitome with especial reference to the main sources of earlier date, with particular consideration to (a) Alexander Polyhistor, of Miletus, a contemporary of Sulla, to whom he owed his Roman citizenship, with the nomen Cornelius, whose enormous output — some thirty separate titles in all — included numerous works concerned with ethnic forms; (b) Herennius Philon of Byblos, the Phoenician‐Greek ‘translator’ or author of the Phoenician history which passed under the name of Sanchuniathon, and author of a work on ‘Famous Cities and their Famous Sons’, which included much information on ethnic forms; and (c) Alexandrian Oros, of the fourth/fifth century ad, who formed perhaps the final link between Stephanus and his predecessors, and also between Stephanus and contemporary or later writers.

Haemophilia B, an X-linked recessive disease with an incidence of 1/30,000 newborn males, is due to defects in the gene for coagulation factor IX, which is on the long am of the X chromosome at band Xq27.1. This gene consists of approximately 34 Kb and contains 8 exons which specify a mRtfc of 2803 residues coding for a protein of 415 aa preceded by a prepro signal peptide of 46 aa. Coripanson of the functional domains of the factor IX protein with the exon structure of the gene supports the exon/protein domain hypothesis of gene evolution. The factor IX gene seems to be formed by a number of functionally and evolutionally independent modules. The signal peptide and the gla (γcarboxy-glutamic) region encoded in the first three exons are homologous to those of factor X, protein C and prothrombin. Thevfourth and fifth exons which code for the connecting peptide are homologous to one another and to the epidermal growth factor, a module that has been used in the construction of a great variety of proteins including different members of the coagulation and fibrinolytic pathways. The sixth exon encodes the activation peptide region, while the catalytic region of factor IX is coded by the seventh and eighth exon. This is at variance with other serine protease genes that have different exons for the segments containing the cardinal ami no-acids of the active centre (histidine, aspartic acid and serine).Natural selection acts against detrimental mutations of the factor IX gene and at each generation a proportion of haemophilia B genes is eliminated, as a significant number of patients does not reproduce. There appears to be no selective advantage to the heterozygote and therefore haemophilia B is maintained in the population by new mutations. Consequently, a significant proportion of patients should be born to non-carrier mothers, and unrelated patients should carry different gene defects, as recently verified by detailed analysis of individual haemophilia B genes.The defects of factor IX described so far comprise both point mutations and gene deletions. The latter affect either part or the whole of the gene and are often associated with the development of antibodies against therapeutically adninistered factor IX (the inhibitor complication). Since gene deletions may result in the complete absenceof factor IX synthesis or in the production of an extremely abnormal product, it has been suggested that mutationspreventing the synthesis of a factor IX gene product capable of inducing immune tolerance to normal factor IX is important in predisposing to the inhibitor complication.Among the point mutations described so far, those affecting the signal peptide are of particular interest. Substitutions of the arginine at positions -4 and -1 cause failure of propeptide cleavage. Thus they indicate that the propeptide consists of 18 aa an(lthat lts excision is necessary for factor IX function. It appears also that the propeptide contains a signal for γcarboxylation which has been conserved during the evolution of different γcarboxylated proteins.In spite of coagulant treatment, haemophilia B is a serious disease and one for which genetic counselling is required. Paramount for this is the detection of carriers and the diagnosis ofaffected male fetuses. DNA probes derived from the cloned factor IX gene have been used for this purpose. Carrier and first or second trimester prenatal diagnoses have been done using factors IX gene markers to follow the transmission of haemophilia B genes. Six sequence variations causing restriction fragment length polymorphisms (RFLP) in the factor IX gene have been detected and used as markers for such indirect diagnoses The efficiency of the above markers is reduced by linkage disequilibrium but, nevertheless, they offer definite carrier and nremtal diagnoses in 75-80% of the relatives of familial cases of haemophilia B.The indirect detection of gene defects is of modest help in the counselling of individuals from the families of isolated patients, but new methods for the direct detection of gene mutations promise better results in such families and also the attainment of % diagnostic success in relatives of familial cases.Finally the successful expression of recombinant factor IX genes in tissue culture and transgenic mammals raises hopes of therapeutic advances.

The existential question: do we have a preferential in comparison with other forms leads the author to the conclusion that it is necessary to create a new planetary scale superorganism, for which he is offered the method of ecometrics of the future. It will have to reflect the degree of efficiency usage of key resources: a) human indicators of labor productivity, the level of unemployment, the creative and routine activities ratio, the development level of culture and the percentage of the healthy population, the «level of happiness»; b) monetary situation - the ratio of productive capital to speculative capital, capital productivity, planned economy versus chaotic economy of competitive overproduction; c) energy situation - the degree of utilization and level of environmental clean energy, its renewability; d) material questions- the depth of processing of wastes and ores, the cyclical development of resources, the degree of technological redistribution of products; e) informational resources - education of the population and the economy innovations, planning efficiency, the capacity of communication channels (including the mass media) and their reliability, the speed and quality of feedback between the state and the population.

This article is focused on analysis of the hypothesis of the local song folklore origins of the famous poetic phenomenon chuci (elegies/songs of Chu) that represents the literary heritage of the southern (Yangtze Basin) region of the Ancient China (the Zhou epoch, 11th–3rd centuries B. C.) and is associated with the emergence of the Chinese poetry. Although today the thesis about the folklore origins of chuci, or rather of the poetic pieces presented by the Chuci (Verses/Elegies of Chu, Songs of the South) collection, is generally accepted, the author argues that, first, during the 1st–7th centuries A. D. the chuci poetry was stable considered within the Chinese book knowledge to be created by exclusively the literary genius of Qu Yuan (4th–3rd centuries B. C.), the great poet of the Chu Kingdom (11th–3rd centuries B. C.). Secondly, the views on chuci as an autochthonous (“southern”) poetic tradition dating back to the local folk art emerged in the 12th–13th centuries and finally established itself in the Chinese literature studies of the first third of the 20th century, all these under the influence of the ideological processes, caused by synchronic historical and political events. Thirdly, although the existence of developed song-poetic folklore in Chu Kingdom seems quite permissible, it for some reason remained out of fixation by that day written sources, including transmitted texts and archaeological materials (epigraphic inscription and excavated manuscripts). Therefore, almost nothing is known as a matter of fact of the hypothetic Chu song folklore what makes it impossible to recognize its true influence on origins and further on evolution of the chuci tradition.

"In the 21st century agronomy students need to take the responsibility of their career planning. Upon graduation, they are called to combine knowledge, skills, and values, in order to support as change agents, farmers’ decision making aiming at sustainable agriculture and rural development. To reinforce such a role it is deemed necessary to cultivate student agency, namely, a sense of responsible and active participation in society. Students need to be able to set achievable goals, collaborate successfully in order to solve problems, and act in-line with a professional ethos supporting the wellness of the community and the sustainability of earth. Hence, the need of competence-based education in our century is usually taken as granted. Higher education should adopt educational methods and tools that would support students’ competence development. Experiential learning, represented by Kolb’s Experiential Learning Cycle (KELC), is an essential part of such an approach and includes four stages: concrete experience, reflective observation, abstract conceptualization, and active experimentation. In this paper, we explore the effectiveness of experiential learning aiming at the acquisition and/or development of competencies on the part of Agricultural University of Athens (AUA) students. To attain such an objective, we carried out a pilot with 69 AUA students, in spring of 2021. Students were divided into three groups (A, B, and C). Each group, attended a 3-hour meeting, using different approaches (A=traditional lecturing, B=experiential learning based on KELC and C=investigative case-based learning). Furthermore, students were offered a participatory class regarding rural advisors’ profile and planet sustainability. Due to the COVID-19 pandemic, online tools were adopted. Students participated in pre- and post-survey based on a questionnaire. Focus groups and observation methods were also utilized to further explore and validate quantitative data. In this paper we report the design and the quantitative and qualitative findings, particularly focused on the experiential learning approach."

Thus far in reporting the findings of our project “Fifty Years After: Black Employment in the United States Under the Equal Employment Opportunity Commission,” our analysis of what has happened to African American employment over the past half century has documented the importance of manufacturing employment to the upward socioeconomic mobility of Blacks in the 1960s and 1970s and the devastating impact of rationalization—the permanent elimination of blue-collar employment—on their socioeconomic mobility in the 1980s and beyond. The upward mobility of Blacks in the earlier decades was based on the Old Economy business model (OEBM) with its characteristic “career-with-one-company” (CWOC) employment relations. At its launching in 1965, the policy approach of the Equal Employment Opportunity Commission assumed the existence of CWOC, providing corporate employees, Blacks included, with a potential path for upward socioeconomic mobility over the course of their working lives by gaining access to productive opportunities and higher pay through stable employment within companies. It was through these internal employment structures that Blacks could potentially overcome barriers to the long legacy of job and pay discrimination. In the 1960s and 1970s, the generally growing availability of unionized semiskilled jobs gave working people, including Blacks, the large measure of employment stability as well as rising wages and benefits characteristic of the lower levels of the middle class. The next stage in this process of upward socioeconomic mobility should have been—and in a nation as prosperous as the United States could have been—the entry of the offspring of the new Black blue-collar middle class into white-collar occupations requiring higher educations. Despite progress in the attainment of college degrees, however, Blacks have had very limited access to the best employment opportunities as professional, technical, and administrative personnel at U.S. technology companies. Since the 1980s, the barriers to African American upward socioeconomic mobility have occurred within the context of the marketization (the end of CWOC) and globalization (accessibility to transnational labor supplies) of high-tech employment relations in the United States. These new employment relations, which stress interfirm labor mobility instead of intrafirm employment structures in the building of careers, are characteristic of the rise of the New Economy business model (NEBM), as scrutinized in William Lazonick’s 2009 book, Sustainable Prosperity in the New Economy? Business Organization and High-Tech Employment in the United States (Upjohn Institute). In this paper, we analyze the exclusion of Blacks from STEM (science, technology, engineering, math) occupations, using EEO-1 employment data made public, voluntarily and exceptionally, for various years between 2014 and 2020 by major tech companies, including Alphabet (Google), Amazon, Apple, Cisco, Facebook (now Meta), Hewlett Packard Enterprise, HP Inc., Intel, Microsoft, PayPal, Salesforce, and Uber. These data document the vast over-representation of Asian Americans and vast under-representation of African Americans at these tech companies in recent years. The data also shine a light on the racial, ethnic, and gender composition of large masses of lower-paid labor in the United States at leading U.S. tech companies, including tens of thousands of sales workers at Apple and hundreds of thousands of laborers & helpers at Amazon. In the cases of Hewlett-Packard, IBM, and Intel, we have access to EEO-1 data from earlier decades that permit in-depth accounts of the employment transitions that characterized the demise of OEBM and the rise of NEBM. Given our findings from the EEO-1 data analysis, our paper then seeks to explain the enormous presence of Asian Americans and the glaring absence of African Americans in well-paid employment under NEBM. A cogent answer to this question requires an understanding of the institutional conditions that have determined the availability of qualified Asians and Blacks to fill these employment opportunities as well as the access of qualified people by race, ethnicity, and gender to the employment opportunities that are available. Our analysis of the racial/ethnic determinants of STEM employment focuses on a) stark differences among racial and ethnic groups in educational attainment and performance relevant to accessing STEM occupations, b) the decline in the implementation of affirmative-action legislation from the early 1980s, c) changes in U.S. immigration policy that favored the entry of well-educated Asians, especially with the passage of the Immigration Act of 1990, and d) consequent social barriers that qualified Blacks have faced relative to Asians and whites in accessing tech employment as a result of a combination of statistical discrimination against African Americans and their exclusion from effective social networks.

Background Lung cancer is the number one cause of cancer death worldwide.(1) It is the fifth most commonly diagnosed cancer in Australia (12,741 cases diagnosed in 2018) and the leading cause of cancer death.(2) The number of years of potential life lost to lung cancer in Australia is estimated to be 58,450, similar to that of colorectal and breast cancer combined.(3) While tobacco control strategies are most effective for disease prevention in the general population, early detection via low dose computed tomography (LDCT) screening in high-risk populations is a viable option for detecting asymptomatic disease in current (13%) and former (24%) Australian smokers.(4) The purpose of this Evidence Check review is to identify and analyse existing and emerging evidence for LDCT lung cancer screening in high-risk individuals to guide future program and policy planning. Evidence Check questions This review aimed to address the following questions: 1. What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? 2. What is the evidence of potential harms from lung cancer screening for higher-risk individuals? 3. What are the main components of recent major lung cancer screening programs or trials? 4. What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Summary of methods The authors searched the peer-reviewed literature across three databases (MEDLINE, PsycINFO and Embase) for existing systematic reviews and original studies published between 1 January 2009 and 8 August 2019. Fifteen systematic reviews (of which 8 were contemporary) and 64 original publications met the inclusion criteria set across the four questions. Key findings Question 1: What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? There is sufficient evidence from systematic reviews and meta-analyses of combined (pooled) data from screening trials (of high-risk individuals) to indicate that LDCT examination is clinically effective in reducing lung cancer mortality. In 2011, the landmark National Lung Cancer Screening Trial (NLST, a large-scale randomised controlled trial [RCT] conducted in the US) reported a 20% (95% CI 6.8% – 26.7%; P=0.004) relative reduction in mortality among long-term heavy smokers over three rounds of annual screening. High-risk eligibility criteria was defined as people aged 55–74 years with a smoking history of ≥30 pack-years (years in which a smoker has consumed 20-plus cigarettes each day) and, for former smokers, ≥30 pack-years and have quit within the past 15 years.(5) All-cause mortality was reduced by 6.7% (95% CI, 1.2% – 13.6%; P=0.02). Initial data from the second landmark RCT, the NEderlands-Leuvens Longkanker Screenings ONderzoek (known as the NELSON trial), have found an even greater reduction of 26% (95% CI, 9% – 41%) in lung cancer mortality, with full trial results yet to be published.(6, 7) Pooled analyses, including several smaller-scale European LDCT screening trials insufficiently powered in their own right, collectively demonstrate a statistically significant reduction in lung cancer mortality (RR 0.82, 95% CI 0.73–0.91).(8) Despite the reduction in all-cause mortality found in the NLST, pooled analyses of seven trials found no statistically significant difference in all-cause mortality (RR 0.95, 95% CI 0.90–1.00).(8) However, cancer-specific mortality is currently the most relevant outcome in cancer screening trials. These seven trials demonstrated a significantly greater proportion of early stage cancers in LDCT groups compared with controls (RR 2.08, 95% CI 1.43–3.03). Thus, when considering results across mortality outcomes and early stage cancers diagnosed, LDCT screening is considered to be clinically effective. Question 2: What is the evidence of potential harms from lung cancer screening for higher-risk individuals? The harms of LDCT lung cancer screening include false positive tests and the consequences of unnecessary invasive follow-up procedures for conditions that are eventually diagnosed as benign. While LDCT screening leads to an increased frequency of invasive procedures, it does not result in greater mortality soon after an invasive procedure (in trial settings when compared with the control arm).(8) Overdiagnosis, exposure to radiation, psychological distress and an impact on quality of life are other known harms. Systematic review evidence indicates the benefits of LDCT screening are likely to outweigh the harms. The potential harms are likely to be reduced as refinements are made to LDCT screening protocols through: i) the application of risk predication models (e.g. the PLCOm2012), which enable a more accurate selection of the high-risk population through the use of specific criteria (beyond age and smoking history); ii) the use of nodule management algorithms (e.g. Lung-RADS, PanCan), which assist in the diagnostic evaluation of screen-detected nodules and cancers (e.g. more precise volumetric assessment of nodules); and, iii) more judicious selection of patients for invasive procedures. Recent evidence suggests a positive LDCT result may transiently increase psychological distress but does not have long-term adverse effects on psychological distress or health-related quality of life (HRQoL). With regards to smoking cessation, there is no evidence to suggest screening participation invokes a false sense of assurance in smokers, nor a reduction in motivation to quit. The NELSON and Danish trials found no difference in smoking cessation rates between LDCT screening and control groups. Higher net cessation rates, compared with general population, suggest those who participate in screening trials may already be motivated to quit. Question 3: What are the main components of recent major lung cancer screening programs or trials? There are no systematic reviews that capture the main components of recent major lung cancer screening trials and programs. We extracted evidence from original studies and clinical guidance documents and organised this into key groups to form a concise set of components for potential implementation of a national lung cancer screening program in Australia: 1. Identifying the high-risk population: recruitment, eligibility, selection and referral 2. Educating the public, people at high risk and healthcare providers; this includes creating awareness of lung cancer, the benefits and harms of LDCT screening, and shared decision-making 3. Components necessary for health services to deliver a screening program: a. Planning phase: e.g. human resources to coordinate the program, electronic data systems that integrate medical records information and link to an established national registry b. Implementation phase: e.g. human and technological resources required to conduct LDCT examinations, interpretation of reports and communication of results to participants c. Monitoring and evaluation phase: e.g. monitoring outcomes across patients, radiological reporting, compliance with established standards and a quality assurance program 4. Data reporting and research, e.g. audit and feedback to multidisciplinary teams, reporting outcomes to enhance international research into LDCT screening 5. Incorporation of smoking cessation interventions, e.g. specific programs designed for LDCT screening or referral to existing community or hospital-based services that deliver cessation interventions. Most original studies are single-institution evaluations that contain descriptive data about the processes required to establish and implement a high-risk population-based screening program. Across all studies there is a consistent message as to the challenges and complexities of establishing LDCT screening programs to attract people at high risk who will receive the greatest benefits from participation. With regards to smoking cessation, evidence from one systematic review indicates the optimal strategy for incorporating smoking cessation interventions into a LDCT screening program is unclear. There is widespread agreement that LDCT screening attendance presents a ‘teachable moment’ for cessation advice, especially among those people who receive a positive scan result. Smoking cessation is an area of significant research investment; for instance, eight US-based clinical trials are now underway that aim to address how best to design and deliver cessation programs within large-scale LDCT screening programs.(9) Question 4: What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Assessing the value or cost-effectiveness of LDCT screening involves a complex interplay of factors including data on effectiveness and costs, and institutional context. A key input is data about the effectiveness of potential and current screening programs with respect to case detection, and the likely outcomes of treating those cases sooner (in the presence of LDCT screening) as opposed to later (in the absence of LDCT screening). Evidence about the cost-effectiveness of LDCT screening programs has been summarised in two systematic reviews. We identified a further 13 studies—five modelling studies, one discrete choice experiment and seven articles—that used a variety of methods to assess cost-effectiveness. Three modelling studies indicated LDCT screening was cost-effective in the settings of the US and Europe. Two studies—one from Australia and one from New Zealand—reported LDCT screening would not be cost-effective using NLST-like protocols. We anticipate that, following the full publication of the NELSON trial, cost-effectiveness studies will likely be updated with new data that reduce uncertainty about factors that influence modelling outcomes, including the findings of indeterminate nodules. Gaps in the evidence There is a large and accessible body of evidence as to the effectiveness (Q1) and harms (Q2) of LDCT screening for lung cancer. Nevertheless, there are significant gaps in the evidence about the program components that are required to implement an effective LDCT screening program (Q3). Questions about LDCT screening acceptability and feasibility were not explicitly included in the scope. However, as the evidence is based primarily on US programs and UK pilot studies, the relevance to the local setting requires careful consideration. The Queensland Lung Cancer Screening Study provides feasibility data about clinical aspects of LDCT screening but little about program design. The International Lung Screening Trial is still in the recruitment phase and findings are not yet available for inclusion in this Evidence Check. The Australian Population Based Screening Framework was developed to “inform decision-makers on the key issues to be considered when assessing potential screening programs in Australia”.(10) As the Framework is specific to population-based, rather than high-risk, screening programs, there is a lack of clarity about transferability of criteria. However, the Framework criteria do stipulate that a screening program must be acceptable to “important subgroups such as target participants who are from culturally and linguistically diverse backgrounds, Aboriginal and Torres Strait Islander people, people from disadvantaged groups and people with a disability”.(10) An extensive search of the literature highlighted that there is very little information about the acceptability of LDCT screening to these population groups in Australia. Yet they are part of the high-risk population.(10) There are also considerable gaps in the evidence about the cost-effectiveness of LDCT screening in different settings, including Australia. The evidence base in this area is rapidly evolving and is likely to include new data from the NELSON trial and incorporate data about the costs of targeted- and immuno-therapies as these treatments become more widely available in Australia.