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Background: Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.

Methods: For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 090. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.

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Findings: We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (432%, 95% CI 301-629, vs 354%, 117-1024, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (2124%, 1522-2890, vs 1204%, 867-1660, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 781%, 397-1477, vs 660%, 374-1138, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 640%, 506-805, vs 637%, 474-849, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 556%, 379-855, and the prevalence estimate was higher in HICs than that in LMICs (737%, 435-1366, vs 509%, 364-724). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 23662 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 7291% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (7408 million), whereas the Eastern Mediterranean Region had the least (1467 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.

Interpretation: Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.

Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.

Risk assessment occurs over different temporal and spatial scales and is selected for when individuals show an adaptive response to a threat. Here, we test if birds respond to the threat of brood parasitism using the acoustical cues of brood parasites in the absence of visual stimuli. We broadcast the playback of song of three brood parasites (Chalcites cuckoo species) and a sympatric non-parasite (striated thornbill, Acanthiza lineata) in the territories of superb fairy-wrens (Malurus cyaneus) during the peak breeding period and opportunistic breeding period. The three cuckoo species differ in brood parasite prevalence and the probability of detection by the host, which we used to rank the risk of parasitism (high risk, moderate risk, low risk).

Risk assessment and behavioural response towards a threat are important areas of individual competence that influence survival and fitness[1, 2]. Throughout a lifetime, individuals are faced with a variety of threats, including infectious disease, adverse weather conditions, limited food availability, predation and brood parasitism. Both predation risk and brood parasitism have the attribute that they create a sudden threat, such as being killed or injured, or lowered reproductive success after a single moment of parasitism. Thus, individuals may be selected for different patterns of risk assessment based on the magnitude of risk and the temporal time-frame during which the threat can be detected[3, 4].

In the context of predation threat, risk assessment usually includes two risk components: risk to self of defending against the predator, and risk to offspring of being consumed by the predator. Thus, the observed defence behaviour (investment and risk taking) towards a specific predator is a result of both risk components. When the predation threat for defending parents is very high, and when parental death would result in the deaths of dependent offspring, parental risk taking should focus on parental survival. But parents could show a Kamikaze response and sacrifice their lives if offspring have a chance of survival without parental care, especially when parents have little opportunity for future reproduction[17]. For these reasons, analysis of risk assessment and response to threat in predation contexts needs to be interpreted within a life-history framework that addresses trade-offs for parents and offspring between reproductive investment and survival, and current versus future reproductive opportunity[10, 18].

Brood parasites do not represent a survival risk to defending parents. Therefore, brood parasite-host systems provide ideal conditions to study risk taking and parental investment specifically in relation to brood survival while controlling for risk to parental survival[19].

To test acoustical discrimination and investment by adult wrens towards heterospecific cuckoo songs (produced presumably by cuckoos for mate attraction and territory defence[55]), we compare host wren response as the number of alarm calls (low cost behaviour), approach distance (high cost behaviour), and latency to respond to the broadcast of a song stimulus in the wren territory during the peak (September and October) and opportunistic (April and May) breeding periods. The song stimuli used in the experimental playback trials were previously recorded from a sympatric non-parasite and three cuckoo species. Given that the threat posed by a singing brood parasite to the defending host is low, several predictions can be formulated to quantify risk assessment in the absence of threats to parental survival: (1) If wrens recognise the level of threat (cuckoo species) for offspring survival based on vocalisations, they should respond differently to the vocalisation of a threat (sympatric cuckoo species) versus the vocalisation of a non-threat (allopatric cuckoo and sympatric non-parasite, in this case striated thornbill, Acanthiza lineata). This prediction is about macro-level risk perception for the threat posed by brood parasites versus non-brood parasites. (2) At the micro-level of risk perception, we would expect wrens to react differently to vocalisations of different cuckoo species (species-level threats) that pose different levels of risk of brood parasitism. (3) If wrens adjust their response intensity based on the energetic costs of the defence and the risk probability, then we expect that low cost defence (alarm calls) will be observed across the year to the cuckoo species that pose the highest threat, but high cost defence (approach) would only be observed during the peak breeding period.

During the peak breeding period, wrens consistently adjusted their response to the playback of cuckoo song. Wrens had more alarm calls, a closer approach, and a shorter latency to respond to the playback of cuckoo species that had higher risk of parasitism (Figure 1, Table 1). Post-hoc pairwise comparisons (pairwise comparisons based on HSD) showed that wrens had the highest response for calls, approach, and latency to the high and intermediate risk cuckoo species (both P < 0.03), but no significant difference for calls to the low and intermediate risk cuckoo (both P > 0.1). 006ab0faaa