Early contact between late farming and pastoralist societies in southeastern Europe.

Archaeogenetic studies have described two main genetic turnover events in prehistoric western Eurasia: one associated with the spread of farming and a sedentary lifestyle starting around 7000-6000 BC (refs. 1-3) and a second with the expansion of pastoralist groups from the Eurasian steppes starting around 3300 BC (refs. 4,5). The period between these events saw new economies emerging on the basis of key innovations, including metallurgy, wheel and wagon and horse domestication6-9. However, what happened between the demise of the Copper Age settlements around 4250 BC and the expansion of pastoralists remains poorly understood. To address this question, we analysed genome-wide data from 135 ancient individuals from the contact zone between southeastern Europe and the northwestern Black Sea region spanning this critical time period. While we observe genetic continuity between Neolithic and Copper Age groups from major sites in the same region, from around 4500 BC on, groups from the northwestern Black Sea region carried varying amounts of mixed ancestries derived from Copper Age groups and those from the forest/steppe zones, indicating genetic and cultural contact over a period of around 1,000 years earlier than anticipated. We propose that the transfer of critical innovations between farmers and transitional foragers/herders from different ecogeographic zones during this early contact was integral to the formation, rise and expansion of pastoralist groups around 3300 BC.

Estimating human mobility in Holocene Western Eurasia with large-scale ancient genomic data.

The recent increase in openly available ancient human DNA samples allows for large-scale meta-analysis applications. Trans-generational past human mobility is one of the key aspects that ancient genomics can contribute to since changes in genetic ancestry-unlike cultural changes seen in the archaeological record-necessarily reflect movements of people. Here, we present an algorithm for spatiotemporal mapping of genetic profiles, which allow for direct estimates of past human mobility from large ancient genomic datasets. The key idea of the method is to derive a spatial probability surface of genetic similarity for each individual in its respective past. This is achieved by first creating an interpolated ancestry field through space and time based on multivariate statistics and Gaussian process regression and then using this field to map the ancient individuals into space according to their genetic profile. We apply this algorithm to a dataset of 3138 aDNA samples with genome-wide data from Western Eurasia in the last 10,000 y. Finally, we condense this sample-wise record with a simple summary statistic into a diachronic measure of mobility for subregions in Western, Central, and Southern Europe. For regions and periods with sufficient data coverage, our similarity surfaces and mobility estimates show general concordance with previous results and provide a meta-perspective of genetic changes and human mobility.

Dark-field computed tomography reaches the human scale.

X-ray computed tomography (CT) is one of the most commonly used three-dimensional medical imaging modalities today. It has been refined over several decades, with the most recent innovations including dual-energy and spectral photon-counting technologies. Nevertheless, it has been discovered that wave-optical contrast mechanisms-beyond the presently used X-ray attenuation-offer the potential of complementary information, particularly on otherwise unresolved tissue microstructure. One such approach is dark-field imaging, which has recently been introduced and already demonstrated significantly improved radiological benefit in small-animal models, especially for lung diseases. Until now, however, dark-field CT could not yet be translated to the human scale and has been restricted to benchtop and small-animal systems, with scan durations of several minutes or more. This is mainly because the adaption and upscaling to the mechanical complexity, speed, and size of a human CT scanner so far remained an unsolved challenge. Here, we now report the successful integration of a Talbot-Lau interferometer into a clinical CT gantry and present dark-field CT results of a human-sized anthropomorphic body phantom, reconstructed from a single rotation scan performed in 1 s. Moreover, we present our key hardware and software solutions to the previously unsolved roadblocks, which so far have kept dark-field CT from being translated from the optical bench into a rapidly rotating CT gantry, with all its associated challenges like vibrations, continuous rotation, and large field of view. This development enables clinical dark-field CT studies with human patients in the near future.

PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans.

OBJECTIVE: Fat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and how this variant evolved in humans has not been studied to date. DESIGN: Here we analyse ancient DNA to track the history of this allele throughout human history. In total, 6444 published ancient (modern humans, Neanderthal, Denisovan) and 3943 published present day genomes were used for analysis after extracting genotype calls for PNPLA3 p.I148M. To quantify changes through time, logistic and, by grouping individuals according to geography and age, linear regression analyses were performed. RESULTS: We find that archaic human individuals (Neanderthal, Denisovan) exclusively carried a fixed PNPLA3 risk allele, whereas allele frequencies in modern human populations range from very low in Africa to >50% in Mesoamerica. Over the last 15 000 years, distributions of ancestral and derived alleles roughly match the present day distribution. Logistic regression analyses did not yield signals of natural selection during the last 10 000 years. CONCLUSION: Archaic human individuals exclusively carried a fixed PNPLA3 allele associated with fatty liver, whereas allele frequencies in modern human populations are variable even in the oldest samples. Our observation might underscore the advantage of fat storage in cold climate and particularly for Neanderthal under ice age conditions. The absent signals of natural selection during modern human history does not support the thrifty gene hypothesis in case of PNPLA3 p.I148M.

Robust Sample Information Retrieval in Dark-Field Computed Tomography with a Vibrating Talbot-Lau Interferometer.

X-ray computed tomography (CT) is a crucial tool for non-invasive medical diagnosis that uses differences in materials' attenuation coefficients to generate contrast and provide 3D information. Grating-based dark-field-contrast X-ray imaging is an innovative technique that utilizes small-angle scattering to generate additional co-registered images with additional microstructural information. While it is already possible to perform human chest dark-field radiography, it is assumed that its diagnostic value increases when performed in a tomographic setup. However, the susceptibility of Talbot-Lau interferometers to mechanical vibrations coupled with a need to minimize data acquisition times has hindered its application in clinical routines and the combination of X-ray dark-field imaging and large field-of-view (FOV) tomography in the past. In this work, we propose a processing pipeline to address this issue in a human-sized clinical dark-field CT prototype. We present the corrective measures that are applied in the employed processing and reconstruction algorithms to mitigate the effects of vibrations and deformations of the interferometer gratings. This is achieved by identifying spatially and temporally variable vibrations in air reference scans. By translating the found correlations to the sample scan, we can identify and mitigate relevant fluctuation modes for scans with arbitrary sample sizes. This approach effectively eliminates the requirement for sample-free detector area, while still distinctly separating fluctuation and sample information. As a result, samples of arbitrary dimensions can be reconstructed without being affected by vibration artifacts. To demonstrate the viability of the technique for human-scale objects, we present reconstructions of an anthropomorphic thorax phantom.

Modeling Vibrations of a Tiled Talbot-Lau Interferometer on a Clinical CT.

X-ray computed tomography (CT) is an invaluable imaging technique for non-invasive medical diagnosis. However, for soft tissue in the human body the difference in attenuation is inherently small. Grating-based X-ray phase-contrast is a relatively novel imaging method which detects additional interaction mechanisms between photons and matter, namely refraction and small-angle scattering, to generate additional images with different contrast. The experimental setup involves a Talbot-Lau interferometer whose susceptibility to mechanical vibrations hindered acquisition schemes suitable for clinical routine in the past. We present a processing pipeline to identify spatially and temporally variable fluctuations occurring in an interferometer installed on a continuously rotating clinical CT gantry. The correlations of the vibrations in the modular grating setup are exploited to identify a small number of relevant fluctuation modes, allowing for a sample reconstruction free of vibration artifacts.

Initial Characterization of Dark-Field CT on a Clinical Gantry.

X-ray computed tomography (CT) is an important non-destructive imaging technique, particularly in clinical diagnostics. Even with the latest innovations like dual-energy and photon-counting CT, the image contrast is solely generated from attenuation in the tissue. An extension - fully compatible with these novelties - is dark-field CT, which retrieves an additional, so-called dark-field contrast. Unlike the attenuation channel, the dark-field channel is sensitive to tissue microstructure and porosity below the resolution of the imaging system, which allows additional insights into the health of the lung tissue or the structure of calcifications. The potential clinical value has been demonstrated in several preclinical studies and recently also in radiography patient studies. Just recently the first dark-field CT for the human body was established at the Technical University of Munich and in this paper, we discuss the performance of this prototype. We evaluate the interferometer components and the imposed challenges that the integration into the CT gantry brings by comparing the results to simulations and measurements at a laboratory setup. The influence of the clinical X-ray source on the Talbot-Lau interferometer and the impact of vibrations, which are immanent on the clinical CT gantry, are analyzed in detail to reveal their characteristic frequencies and origin. A beam hardening correction is introduced as an important step to adapt to the poly-chromatic spectrum and make quantitative dark-field imaging possible. We close with an analysis of the image resolution and the applied patient dose, and conclude that the performance is sufficient to suggest initial patient studies using the presented dark-field CT system.

Advanced Phase-Retrieval for Stepping-Free X-Ray Dark-Field Computed Tomography.

Grating-based phase- and dark-field-contrast X-ray imaging is a novel technology that aims to extend conventional attenuation-based X-ray imaging by unlocking two additional contrast modalities. The so called phase-contrast and dark-field channels provide enhanced soft tissue contrast and additional microstructural information. Accessing this additional information comes at the expense of a more intricate measurement setup and necessitates sophisticated data processing. A big challenge for translating grating-based dark-field computed tomography to medical applications lies in minimizing the data acquisition time. While a continuously moving detector is ideal, it prohibits conventional phase stepping techniques that require multiple projections under the same angle with different grating positions. One solution to this problem is the so-called sliding window processing approach that is compatible with continuous data acquisition. However, conventional sliding window techniques lead to crosstalk-artifacts between the three image channels, if the projection of the sample moves too fast on the detector within a processing window. In this work we introduce a new interpretation of the phase retrieval problem for continuous acquisitions as a demodulation problem. In this interpretation, we identify the origin of the crosstalk-artifacts as partially overlapping modulation side bands. Furthermore, we present three algorithmic extensions that improve the conventional sliding-window-based phase retrieval and mitigate crosstalk-artifacts. The presented algorithms are tested in a simulation study and on experimental data from a human-scale dark-field CT prototype. In both cases they achieve a substantial reduction of the occurring crosstalk-artifacts.

Technical Design Considerations of a Human-Scale Talbot-Lau Interferometer for Dark-Field CT.

Computed tomography (CT) as an important clinical diagnostics method can profit from extension with dark-field imaging, as it is currently restricted to X-rays' attenuation contrast only. Dark-field imaging allows access to more tissue properties, such as micro-structural texture or porosity. The up-scaling process to clinical scale is complex because several design constraints must be considered. The two most important ones are that the finest grating is limited by current manufacturing technology to a [Formula: see text] period and that the interferometer should fit into the CT gantry with minimal modifications only. In this work we discuss why an inverse interferometer and a triangular G1 profile are advantageous and make a compact and sensitive interferometer implementation feasible. Our evaluation of the triangular grating profile reveals a deviation in the interference pattern compared to standard grating profiles, which must be considered in the subsequent data processing. An analysis of the grating orientation demonstrates that currently only a vertical layout can be combined with cylindrical bending of the gratings. We also provide an in-depth discussion, including a new simulation approach, of the impact of the extended X-ray source spot which can lead to large performance loss and present supporting experimental results. This analysis reveals a vastly increased sensitivity to geometry and grating period deviations, which must be considered early in the system design process.