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Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease. National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City.

Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

First impressions of social traits, such as trustworthiness or dominance, are reliably perceived in faces, and despite their questionable validity they can have considerable real-world consequences. We sought to uncover the information driving such judgments, using an attribute-based approach. Attributes (physical facial features) were objectively measured from feature positions and colors in a database of highly variable “ambient” face photographs, and then used as input for a neural network to model factor dimensions (approachability, youthful-attractiveness, and dominance) thought to underlie social attributions. A linear model based on this approach was able to account for 58% of the variance in raters’ impressions of previously unseen faces, and factor-attribute correlations could be used to rank attributes by their importance to each factor. Reversing this process, neural networks were then used to predict facial attributes and corresponding image properties from specific combinations of factor scores. In this way, the factors driving social trait impressions could be visualized as a series of computer-generated cartoon face-like images, depicting how attributes change along each dimension. This study shows that despite enormous variation in ambient images of faces, a substantial proportion of the variance in first impressions can be accounted for through linear changes in objectively defined features.

Tumors evade the immune system though a myriad of mechanisms. Using checkpoint inhibitors to help reprime T cells to recognize tumor has had great success in malignancies including melanoma, lung, and renal cell carcinoma. Many tumors including prostate cancer are resistant to such treatment. However, Sipuleucel-T, a dendritic cell (DC) based immunotherapy, improved overall survival (OS) in prostate cancer. Despite this initial success, further DC vaccines have failed to progress and there has been limited uptake of Sipuleucel-T in the clinic. We know in prostate cancer (PCa) that both the adaptive and the innate arms of the immune system contribute to the immunosuppressive environment. This is at least in part due to dysfunction of DC that play a crucial role in the initiation of an immune response. We also know that there is a paucity of DC in PCa, and that those there are immature, creating a tolerogenic environment. These attributes make PCa a good candidate for a DC based immunotherapy. Ultimately, the knowledge gained by much research into antigen processing and presentation needs to translate from bench to bedside. In this review we will analyze why newer vaccine strategies using monocyte derived DC (MoDC) have failed to deliver clinical benefit, particularly in PCa, and highlight the emerging antigen loading and presentation technologies such as nanoparticles, antibody-antigen conjugates and virus co-delivery systems that can be used to improve efficacy. Lastly, we will assess combination strategies that can help overcome the immunosuppressive microenvironment of PCa.

In accordance with ancient Egyptian beliefs, the preservation of the body after death was an important prerequisite for the continued existence of the deceased in the afterlife. This involved application of various physical interventions and magical rituals to the corpse. Computed tomography (CT), as the gold-standard technology in the field of paleoradiology, enables deeper insights into details of artificial body preservation. Therefore, CT was applied to investigate age at death, sex, mummification techniques, and the state of soft tissue preservation in 21 child mummies. The specimens are housed in European museums and were found in various archaeological sites. This sample included 12 males, 7 females, and two specimens of unknown sex, all between the ages of one and 14 years. Time periods were determined by radiocarbon dating, and time-related indicators of funerary equipment and decoration. Most of the mummies date from the Late Period to the Roman Period (664 BC–395 AD). Differences were identified concerning techniques of wrapping and embalming and removal of brain and internal organs, depending on age at death, social status and the archaeological site of the individuals. The variety and multifaceted nature of mummification and soft tissue preservation was analyzed in an integrated approach including a large number of specimens. The study highlights the significance of subadult remains as valuable bioarcheological archives to investigate burial customs and religious concepts in past societies.

Background Facial trustworthiness impressions influence important social decisions, including economic choices, hiring decisions and criminal justice outcomes. Most research has focused on the face attributes associated with various impressions, implicitly regarding these impressions as stable over time. However, our perception is dynamically shaped by past visual experience through two opposite serial effects: negative aftereffects (bias away from the past) and serial dependence (bias towards the past). Here, we investigated how past visual experience biases first impressions of trustworthiness by using a trustworthiness rating task. Specifically, we tested how basic stimulus properties such as exposure duration to a previous face, feature similarity, and spatial proximity to previous faces determine the direction and strength of the biases. Results We found that (1) exposure duration determined the direction of the bias with negative aftereffects following prolonged adaptor exposure and (positive) serial dependence after brief adaptor exposure. Furthermore, (2) increased identity similarity between previous and current faces enhanced attractive biases, whereas different identities led to repulsion. Finally, (3) relative spatial distance between adaptor and test faces modulated the strength of serial dependence but not negative aftereffects. Conclusions Our paradigm enabled us to provide evidence for, and to dissociate, attractive and repulsive serial biases in trustworthiness impressions. Our findings demonstrate the specific conditions under which these impressions can be dynamically shaped by past experience. Importantly, the influence of basic stimulus properties of time, space, and feature similarity on serial effects indicates that these biases cannot be entirely explained by high-level factors such as decision or memory.

Radiant frost is a significant production constraint to wheat (Triticum aestivum) and barley (Hordeum vulgare), particularly in regions where spring-habit cereals are grown through winter, maturing in spring. However, damage to winter-habit cereals in reproductive stages is also reported. Crops are particularly susceptible to frost once awns or spikes emerge from the protection of the flag leaf sheath. Post-head-emergence frost (PHEF) is a problem distinct from other cold-mediated production constraints. To date, useful increased PHEF resistance in cereals has not been identified. Given the renewed interest in reproductive frost damage in cereals, it is timely to review the problem. Here we update the extent and impacts of PHEF and document current management options to combat this challenge. We clarify terminology useful for discussing PHEF in relation to chilling and other freezing stresses. We discuss problems characterizing radiant frost, the environmental conditions leading to PHEF damage, and the effects of frost at different growth stages. PHEF resistant cultivars would be highly desirable, to both reduce the incidence of direct frost damage and to allow the timing of crop maturity to be managed to maximize yield potential. A framework of potential adaptation mechanisms is outlined. Clarification of these critical issues will sharpen research focus, improving opportunities to identify genetic sources for improved PHEF resistance.

In the quest to increase the critical temperature T c of cuprate superconductors, it is essential to identify the factors that limit the strength of superconductivity. The upper critical field H c2 is a fundamental measure of that strength, yet there is no agreement on its magnitude and doping dependence in cuprate superconductors. Here we show that the thermal conductivity can be used to directly detect H c2 in the cuprates YBa 2 Cu 3 O y , YBa 2 Cu 4 O 8 and Tl 2 Ba 2 CuO 6+ δ , allowing us to map out H c2 across the doping phase diagram. It exhibits two peaks, each located at a critical point where the Fermi surface of YBa 2 Cu 3 O y is known to undergo a transformation. Below the higher critical point, the condensation energy, obtained directly from H c2 , suffers a sudden 20-fold collapse. This reveals that phase competition—associated with Fermi-surface reconstruction and charge-density-wave order—is a key limiting factor in the superconductivity of cuprates. The point at which a magnetic field kills superconductivity in the cuprates has been difficult to measure. Grissonnanche et al . use thermal conductivity measurements to reliably determine this field and find that it drops suddenly below some critical doping, suggesting the onset of a new competing phase.

Binding to cellular receptors initiates viral replication and dictates sites in the host infected by the virus. As illustrated by mammalian orthoreovirus (reovirus), viruses can bind several types of receptors using distinct capsid components to facilitate the viral entry steps of attachment, internalization, and disassembly. The outer of the two concentric capsids of reovirus virions is formed by four viral proteins, three of which bind receptors. These capsid-receptor interactions mediate stepwise entry of reovirus, dictate viral tropism in infected animals, and expand the viral host range. Engagement of independent receptors by different capsid proteins is a property of many pathogenic viruses and illustrates common themes of receptor use in viral entry and disease.

There is a growing interest in the antiquity of cancer and ongoing discussion of the apparent scarcity of malignant tumors in ancient human remains, especially those of soft tissues. We systematically assessed bone and soft tissue tumors on 45 whole-body computed tomography (CT) scans of ancient Egyptian mummies. In one of 45 cases (2%), malignant skeletal disease (probably skeletal metastases) was detected. In five of 45 cases (11%), probably malignant soft tissue masses were identified. The soft tissue masses showed distinct margins, various internal structures, and higher densities compared to preserved adjacent soft tissues. In the two cases with intra-abdominal soft tissue masses, no preserved original organs were detectable. In conclusion, malignant tumors, even those of soft tissues are detectable on CT images of ancient Egyptian mummies. The recognizability, CT characteristics, and frequency of soft tissue tumors represent new knowledge and offer a novel approach for the field of paleo-oncology.