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The initial roll-out of the English Bowel (Colorectal) Cancer Screening programme, during 2006 and 2009, found uptake to be low (54%) and socially graded. The current analysis used data from 2010 to 2015 to test whether uptake is increasing and becoming less socially graded over time.


This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.


Background: E-cigarette use is rising with the majority of vapers purchasing their e-cigarettes in vape shops. We investigated the smoking/vaping trajectories and quit-smoking success rates of smokers deciding to start vaping for the first time and buying their e-cigarette in brick-and-mortar vape shops in Flanders. Methods: Participants filled out questionnaires assessing smoking/vaping behaviour at three moments (intake, after three and six months) and smoking status was biochemically verified using eCO measurements. Results: Participants (n = 71) were regular smokers (MeCO-intake = 22 ppm), half of whom reported a motivation to quit smoking in the near future. Participants bought 3rd/4th generation e-cigarettes and e-liquid with a nicotine concentration averaging 7 mg/mL. A smoking reduction of 53% (17 cigarettes per day (CPD) at intake to 8 CPD after six months) was observed, whereas eCO decreased to 15 ppm. Eighteen percent of participants had quit smoking completely (eCO = 2 ppm), another 25% had at least halved CPD, whereas 57% had failed to reduce CPD by at least 50% (including 13% lost to follow-up). Quitters consumed more e-liquid than reducers and those who continued to smoke. Conclusions: Around one in five smoking customers buying their first e-cigarette in a brick-and-mortar vape shop had quit smoking completely after six months.


Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burdensome to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here, we introduce TimeSignature, an algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using distinct microarrays and further validate it against a new set of samples profiled by RNA-sequencing. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2 h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique among expression-based predictors and addresses a major challenge in the development of generalizable, clinically useful tests.


Abstract and depictive representations produced by drawing-known from Europe, Africa and Southeast Asia after 40,000 years ago-are a prime indicator of modern cognition and behaviour1. Here we report a cross-hatched pattern drawn with an ochre crayon on a ground silcrete flake recovered from approximately 73,000-year-old Middle Stone Age levels at Blombos Cave, South Africa. Our microscopic and chemical analyses of the pattern confirm that red ochre pigment was intentionally applied to the flake with an ochre crayon. The object comes from a level associated with stone tools of the Still Bay techno-complex that has previously yielded shell beads, cross-hatched engravings on ochre pieces and a variety of innovative technologies2-5. This notable discovery pre-dates the earliest previously known abstract and figurative drawings by at least 30,000 years. This drawing demonstrates the ability of early Homo sapiens in southern Africa to produce graphic designs on various media using different techniques.


Dorsal and ventral hippocampus regions exert cognition and emotion-related functions, respectively. Since both regions display rhythmic activity, specific neural oscillatory pacemakers may underlie their functional dichotomy. Type 1 theta oscillations are independent of cholinergic transmission and are observed in the dorsal hippocampus during movement and exploration. In contrast, type 2 theta depends on acetylcholine and appears when animals are exposed to emotionally laden contexts such as a predator presence. Despite its involvement in emotions, type 2 theta has not been associated with the ventral hippocampus. Here, we show that optogenetic activation of oriens-lacunosum moleculare (OLM) interneurons in the ventral hippocampus drives type 2 theta. Moreover, we found that type 2 theta generation is associated with increased risk-taking behavior in response to predator odor. These results demonstrate that two theta oscillations subtypes originate in the two hippocampal regions that predominantly underlie either cognitive or emotion-related functions.


Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results. Notably, the uninfected population of macrophages exhibits the most rapid and extensive changes in gene expression, related to type I IFN signaling. In contrast, infected macrophages exhibit a delayed and attenuated transcriptional response distinguished by preferential expression of IFNB1 at late time points. Biochemical and genomic studies of infected macrophages indicate that ZIKV infection causes both a targeted defect in the type I IFN response due to degradation of STAT2 and reduces RNA polymerase II protein levels and DNA occupancy, particularly at genes required for macrophage identity. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected macrophages thereby reveals the coincident evolution of dominant proviral or antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure.


A defining feature of human cognition is the ability to quickly and accurately alternate between complex behaviors. One striking example of such an ability is bilinguals' capacity to rapidly switch between languages. This switching process minimally comprises disengagement from the previous language and engagement in a new language. Previous studies have associated language switching with increased prefrontal activity. However, it is unknown how the subcomputations of language switching individually contribute to these activities, because few natural situations enable full separation of disengagement and engagement processes during switching. We recorded magnetoencephalography (MEG) from American Sign Language-English bilinguals who often sign and speak simultaneously, which allows to dissociate engagement and disengagement. MEG data showed that turning a language “off” (switching from simultaneous to single language production) led to increased activity in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC), while turning a language “on” (switching from one language to two simultaneously) did not. The distinct representational nature of these on and off processes was also supported by multivariate decoding analyses. Additionally, Granger causality analyses revealed that (i) compared with “turning on” a language, “turning off” required stronger connectivity between left and right dlPFC, and (ii) dlPFC activity predicted ACC activity, consistent with models in which the dlPFC is a top-down modulator of the ACC. These results suggest that the burden of language switching lies in disengagement from the previous language as opposed to engaging a new language and that, in the absence of motor constraints, producing two languages simultaneously is not necessarily more cognitively costly than producing one.


Between 1985 and 2014, the number of US doctoral graduates in Anthropology increased from about 350 to 530 graduates per year. This rise in doctorates entering the work force along with an overall decrease in the numbers of tenure-track academic positions has resulted in highly competitive academic job market. We estimate that approximately79% of US anthropology doctorates do not obtain tenure-track positions at BA/BS, MA/MS, and PhD institutions in the US. Here, we examine where US anthropology faculty obtained their degrees and where they ultimately end up teaching as tenure-track faculty. Using data derived from the 2014-2015 AnthroGuide and anthropology departmental web pages, we identify and rank PhD programs in terms of numbers of graduates who have obtained tenure-track academic jobs; examine long-term and ongoing trends in the programs producing doctorates for the discipline as a whole, as well as for the subfields of archaeology, bioanthropology, and sociocultural anthropology; and discuss gender inequity in academic anthropology within the US.


Checkpoint blockade immunotherapy targeting the PD-1/PD-L1 inhibitory axis has produced remarkable results in the treatment of several types of cancer. Whereas cytotoxic T cells are known to provide important antitumor effects during checkpoint blockade, certain cancers with low MHC expression are responsive to therapy, suggesting that other immune cell types may also play a role. Here, we employed several mouse models of cancer to investigate the effect of PD-1/PD-L1 blockade on NK cells, a population of cytotoxic innate lymphocytes that also mediate antitumor immunity. We discovered that PD-1 and PD-L1 blockade elicited a strong NK cell response that was indispensable for the full therapeutic effect of immunotherapy. PD-1 was expressed on NK cells within transplantable, spontaneous, and genetically induced mouse tumor models, and PD-L1 expression in cancer cells resulted in reduced NK cell responses and generation of more aggressive tumors in vivo. PD-1 expression was more abundant on NK cells with an activated and more responsive phenotype and did not mark NK cells with an exhausted phenotype. These results demonstrate the importance of the PD-1/PD-L1 axis in inhibiting NK cell responses in vivo and reveal that NK cells, in addition to T cells, mediate the effect of PD-1/PD-L1 blockade immunotherapy.