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The Dark Energy Camera is a new imager with a 2°. 2 diameter field of view mounted at the prime focus of the Victor M. Blanco 4m telescope on Cerro Tololo near La Serena, Chile. The camera was designed and constructed by the Dark Energy Survey Collaborationand meets or exceeds the stringent requirements designed for the widefield and supernova surveys for which the collaboration uses it. The camera consists of a five-element optical corrector, seven filters, a shutter with a 60 cm aperture, and a charge-coupled device (CCD) focal plane of 250 μm thick fully depleted CCDs cooled inside a vacuum Dewar. The 570 megapixel focal plane comprises 62 2k × 4k CCDs for imaging and 12 2k × 2k CCDs for guiding and focus. The CCDs have 15 μm × 15 μm pixels with a plate scale of 0 263 pixel −1. A hexapod system provides state-of-the-art focus and alignment capability. The camera is read out in 20 s with 6-9 electronreadout noise. This paper provides a technical description of the cameraʼs engineering, construction, installation, and current status.

Knee osteoarthritis (OA) is believed to be highly prevalent today because of recent increases in life expectancy and body mass index (BMI), but this assumption has not been tested using long-term historical or evolutionary data. We analyzed long-term trends in knee OA prevalence in the United States using cadaver-derived skeletons of people aged ≥50 y whose BMI at death was documented and who lived during the early industrial era (1800s to early 1900s; n = 1,581) and the modern postindustrial era (late 1900s to early 2000s; n = 819). Knee OA among individuals estimated to be ≥50 y old was also assessed in archeologically derived skeletons of prehistoric hunter-gatherers and early farmers (6000-300 B.P.; n = 176). OA was diagnosed based on the presence of eburnation (polish from bone-on-bone contact). Overall, knee OA prevalence was found to be 16% among the postindustrial sample but only 6% and 8% among the early industrial and prehistoric samples, respectively. After controlling for age, BMI, and other variables, knee OA prevalence was 2.1-fold higher (95% confidence interval, 1.5-3.1) in the postindustrial sample than in the early industrial sample. Our results indicate that increases in longevity and BMI are insufficient to explain the approximate doubling of knee OA prevalence that has occurred in the United States since the mid-20th century. Knee OA is thus more preventable than is commonly assumed, but prevention will require research on additional independent risk factors that either arose or have become amplified in the postindustrial era.arthritis | aging | obesity | mismatch disease | evolutionary medicine

The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1–2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses.

In theory, competition between asexual lineages can lead to second-order selection for greater evolutionary potential. To test this hypothesis, we revived a frozen population of Escherichia coli from a long-term evolution experiment and compared the fitness and ultimate fates of four genetically distinct clones. Surprisingly, two clones with beneficial mutations that would eventually take over the population had significantly lower competitive fitness than two clones with mutations that later went extinct. By replaying evolution many times from these clones, we showed that the eventual winners likely prevailed because they had greater potential for further adaptation. Genetic interactions that reduce the benefit of certain regulatory mutations in the eventual losers appear to explain, at least in part, why they were outcompeted.

The repeatability of evolutionary change is difficult to quantify because only a single outcome can usually be observed for any precise set of circumstances. In this study, however, we have quantified the frequency of parallel and divergent genetic changes in 12 initially identical populations of Escherichia coli that evolved in identical environments for 20,000 cell generations. Unlike previous analyses in which candidate genes were identified based on parallel phenotypic changes, here we sequenced four loci (pykF, nadR, pbpA-rodA, and hokB͞sokB) in which mutations of unknown effect had been discovered in one population, and then we compared the substitution pattern in these ''blind'' candidate genes with the pattern found in 36 randomly chosen genes. Two candidate genes, pykF and nadR, had substitutions in all 11 other populations, and the other 2 in several populations. There were very few cases, however, in which the exact same mutations were substituted, in contrast to the findings from conceptually related work performed with evolving virus populations. No random genes had any substitutions except in four populations that evolved defects in DNA repair. Tests of four different statistical aspects of the pattern of molecular evolution all indicate that adaptation by natural selection drove the parallel changes in these candidate genes.bacterial evolution ͉ mutation ͉ natural selection ͉ parallel evolution P arallel evolution and convergent evolution occur when two or more lineages independently evolve similar or identical features. Parallel evolution and convergent evolution are usually distinguished on the basis that parallelism involves changes in homologous features among closely related organisms, whereas convergence can involve changes in different antecedent features among more distantly related organisms (1-3). Both parallel evolution and convergent evolution provide strong evidence that the derived similarities resulted from adaptation by natural selection, provided the state-space of possible changes is so large that it is improbable that the observed similarities arose by a purely random process. There are many compelling examples of parallel evolution in nature, including recent studies of lizard morphology (4) and fish behavior (5), showing that certain phenotypes evolved repeatedly when separate populations independently colonized similar environments. Also, some pathogens exhibit striking parallel genomic changes, including multiple HIV lineages that substituted similar mutations conferring antiviral drug resistance (6) and several strains of Escherichia coli that independently acquired similar virulence factors by horizontal transfer (7).Yet, despite these and other compelling examples of parallel evolution (8 -10), it has proven difficult to quantify evolutionary repeatability. In principle, even the most basic quantification of parallel evolution would include the number of potential instances of parallel outcomes, which could be compared with the actual number seen. In practice, however, th...

When resistance to anticancer or antimicrobial drugs evolves in a patient, highly effective chemotherapy can fail, threatening patient health and lifespan. Standard practice is to treat aggressively, effectively eliminating drug-sensitive target cells as quickly as possible. This prevents sensitive cells from acquiring resistance de novo but also eliminates populations that can competitively suppress resistant populations. Here we analyse that evolutionary trade-off and consider recent suggestions that treatment regimens aimed at containing rather than eliminating tumours or infections might more effectively delay the emergence of resistance. Our general mathematical analysis shows that there are situations in which regimens aimed at containment will outperform standard practice even if there is no fitness cost of resistance, and, in those cases, the time to treatment failure can be more than doubled. But, there are also situations in which containment will make a bad prognosis worse. Our analysis identifies thresholds that define these situations and thus can guide treatment decisions. The analysis also suggests a variety of interventions that could be used in conjunction with cytotoxic drugs to inhibit the emergence of resistance. Fundamental principles determine, across a wide range of disease settings, the circumstances under which standard practice best delays resistance emergence—and when it can be bettered.

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