Benchmarking kinship estimation tools for ancient genomes using pedigree simulations.

There is growing interest in uncovering genetic kinship patterns in past societies using low-coverage palaeogenomes. Here, we benchmark four tools for kinship estimation with such data: lcMLkin, NgsRelate, KIN, and READ, which differ in their input, IBD estimation methods, and statistical approaches. We used pedigree and ancient genome sequence simulations to evaluate these tools when only a limited number (1 to 50 K, with minor allele frequency ≥0.01) of shared SNPs are available. The performance of all four tools was comparable using ≥20 K SNPs. We found that first-degree related pairs can be accurately classified even with 1 K SNPs, with 85% F1 scores using READ and 96% using NgsRelate or lcMLkin. Distinguishing third-degree relatives from unrelated pairs or second-degree relatives was also possible with high accuracy (F1 > 90%) with 5 K SNPs using NgsRelate and lcMLkin, while READ and KIN showed lower success (69 and 79% respectively). Meanwhile, noise in population allele frequencies and inbreeding (first-cousin mating) led to deviations in kinship coefficients, with different sensitivities across tools. We conclude that using multiple tools in parallel might be an effective approach to achieve robust estimates on ultra-low-coverage genomes.

A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition.

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and diet. We present 13 ancient genomes (c. 8500 to 7500 cal BCE) from Pre-Pottery Neolithic Çayönü in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Çayönü was a genetically diverse population, carrying mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organized along biological family lines. We document bodily interventions such as head shaping and cauterization among the individuals examined, reflecting Çayönü's cultural ingenuity. Last, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesize that Upper Mesopotamia's cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication.

Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.

Human inbreeding has decreased in time through the Holocene.

The history of human inbreeding is controversial.1 In particular, how the development of sedentary and/or agricultural societies may have influenced overall inbreeding levels, relative to those of hunter-gatherer communities, is unclear.2-5 Here, we present an approach for reliable estimation of runs of homozygosity (ROHs) in genomes with ≥3× mean sequence coverage across >1 million SNPs and apply this to 411 ancient Eurasian genomes from the last 15,000 years.5-34 We show that the frequency of inbreeding, as measured by ROHs, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to small population size instead of consanguinity. Cases of high consanguinity were rare and only observed among members of farming societies in our sample. Despite the lack of evidence for common consanguinity in our ancient sample, consanguineous traditions are today prevalent in various modern-day Eurasian societies,1,35-37 suggesting that such practices may have become widespread within the last few millennia.

Developing Adaptive Serious Games for Children With Specific Learning Difficulties: A Two-phase Usability and Technology Acceptance Study.

BACKGROUND: Specific learning difficulties (SpLD) include several disorders such as dyslexia, dyscalculia, and dysgraphia, and the children with these SpLD receive special education. However, the studies and the educational material so far focus mainly on one specific disorder. OBJECTIVE: This study's primary goal is to develop comprehensive training material for different types of SpLD, with five serious games addressing different aspects of the SpLD. The second focus is measuring the impact of adaptive difficulty level adjustment in the children's and their educators' usability and technology acceptance perception. Receiving feedback from the children and their educators, and refining the games according to their suggestions have also been essential in this two-phase study. METHODS: A total of 10 SpLD educators and 23 children with different types of SpLD tested the prototypes of the five serious games (ie, Word game, Memory game, Category game, Space game, and Math game), gave detailed feedback, answered the System Usability Scale and Technology Acceptance Model (TAM) questionnaires, and applied think-aloud protocols during game play. RESULTS: The games' standard and adaptive versions were analyzed in terms of average playtime and the number of false answers. Detailed analyses of the interviews, with word clouds and player performances, were also provided. The TAM questionnaires' average and mean values and box plots of each data acquisition session for the children and the educators were also reported via System Usability Scale and TAM questionnaires. The TAM results of the educators had an average of 8.41 (SD 0.87) out of 10 in the first interview and an average of 8.71 (SD 0.64) out of 10 in the second interview. The children had an average of 9.07 (SD 0.56) out of 10 in the first interview. CONCLUSIONS: Both the educators and the children with SpLD enjoyed playing the games, gave positive feedback, and suggested new ways for improvement. The results showed that these games provide thorough training material for different types of SpLD with personalized and tailored difficulty systems. The final version of the proposed games will become a part of the special education centers' supplementary curriculum and training materials, making new enhancements and improvements possible in the future.

Variable kinship patterns in Neolithic Anatolia revealed by ancient genomes.

The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,1 mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,2 household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Asikli Höyük and Çatalhöyük. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Asikli Höyük and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Çatalhöyük and Barcin, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Çatalhöyük,3-5 and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.

A Canine Gait Analysis Protocol for Back Movement Assessment in German Shepherd Dogs.

Objective-To design and test a motion analysis protocol for the gait analysis of adult German Shepherd (GS) dogs with a focus in the analyses of their back movements. Animals-Eight clinically healthy adult large-sized GS dogs (age, 4 ± 1.3 years; weight, 38.8 ± 4.2 kg). Procedures-A six-camera stereo-photogrammetric system and two force platforms were used for data acquisition. Experimental acquisition sessions consisted of static and gait trials. During gait trials, each dog walked along a 6 m long walkway at self-selected speed and a total of six gait cycles were recorded. Results-Grand mean and standard deviation of ground reaction forces of fore and hind limbs are reported. Spatial-temporal parameters averaged over gait cycles and subjects, their mean, standard deviation and coefficient of variance are analyzed. Joint kinematics for the hip, stifle and tarsal joints and their average range of motion (ROM) values, and their 95% Confidence Interval (CI) values of kinematics curves are reported. Conclusions and Clinical Relevance-This study provides normative data of healthy GS dogs to form a preliminary basis in the analysis of the spatial-temporal parameters, kinematics and kinetics during quadrupedal stance posture and gait. Also, a new back movement protocol enabling a multi-segment back model is provided. Results show that the proposed gait analysis protocol may become a useful and objective tool for the evaluation of canine treatment with special focus on the back movement.

Exergames Encouraging Exploration of Hemineglected Space in Stroke Patients With Visuospatial Neglect: A Feasibility Study.

BACKGROUND: Use of exergames can complement conventional therapy and increase the amount and intensity of visuospatial neglect (VSN) training. A series of 9 exergames-games based on therapeutic principles-aimed at improving exploration of the neglected space for patients with VSN symptoms poststroke was developed and tested for its feasibility. OBJECTIVES: The goal was to determine the feasibility of the exergames with minimal supervision in terms of (1) implementation of the intervention, including adherence, attrition and safety, and (2) limited efficacy testing, aiming to document possible effects on VSN symptoms in a case series of patients early poststroke. METHODS: A total of 7 patients attended the 3-week exergames training program on a daily basis. Adherence of the patients was documented in a training diary. For attrition, the number of participants lost during the intervention was registered. Any adverse events related to the exergames intervention were noted to document safety. Changes in cognitive and spatial exploration skills were measured with the Zürich Maxi Mental Status Inventory and the Neglect Test. Additionally, we developed an Eye Tracker Neglect Test (ETNT) using an infrared camera to detect and measure neglect symptoms pre- and postintervention. RESULTS: The median was 14 out of 15 (93%) attended sessions, indicating that the adherence to the exergames training sessions was high. There were no adverse events and no drop-outs during the exergame intervention. The individual cognitive and spatial exploration skills slightly improved postintervention (P=.06 to P=.98) and continued improving at follow-up (P=.04 to P=.92) in 5 out of 7 (71%) patients. Calibration of the ETNT was rather error prone. The ETNT showed a trend for a slight median group improvement from 15 to 16 total located targets (+6%). CONCLUSIONS: The high adherence rate and absence of adverse events showed that these exergames were feasible and safe for the participants. The results of the amount of exergames use is promising for future applications and warrants further investigations-for example, in the home setting of patients to augment training frequency and intensity. The preliminary results indicate the potential of these exergames to cause improvements in cognitive and spatial exploration skills over the course of training for stroke patients with VSN symptoms. Thus, these exergames are proposed as a motivating training tool to complement usual care. The ETNT showed to be a promising assessment for quantifying spatial exploration skills. However, further adaptations are needed, especially regarding calibration issues, before its use can be justified in a larger study sample.

User Perspectives on Exergames Designed to Explore the Hemineglected Space for Stroke Patients With Visuospatial Neglect: Usability Study.

BACKGROUND: Visuospatial neglect due to stroke is characterized by the inability to perceive stimuli emerging in the area opposite to the side of brain damage. Besides adopting conventional rehabilitation methods to treat neglect symptoms, the use of virtual reality (VR) is becoming increasingly popular. We designed a series of 9 exergames aimed to improve exploration of the neglected side of space. When new VR interventions are designed, it is important to assess the usability aspects of such management strategies within the target population. To date, most studies used questionnaires to assess user satisfaction with the intervention or product being tested. However, only a combination of both quantitative and qualitative data allows a full picture of user perspective. OBJECTIVE: The purpose of this study was to quantitatively and qualitatively assess patient and therapist perspectives of a VR intervention based on the series of 9 exergames designed to explore hemineglected space. Specifically, we wanted to evaluate (1) perceived-user friendliness of the exergames, (2) attitude towards using the exergames, and (3) intention to use the exergames in the future. METHODS: A total of 19 participants (7 patients, 12 therapists) evaluated the exergames they had used 5 times a week during 3 weeks. The Technology Acceptance Model (TAM) questionnaire was filled out after the intervention. Based on those responses, we conducted focus group interviews (with therapists) and individual interviews (with patients). To analyze the TAM questionnaires, we used descriptive statistics. We adopted content and comparative analysis to analyze the interviews and drew illustration maps to analyze the focus group interviews. RESULTS: The therapists took a more critical stance with a mean TAM questionnaire total score of 48.6 (SD 4.5) compared to the patients who had a mean total score of 56.1 (SD 12.3). The perceived user-friendliness score was 5.6 (SD 1.4) for patients and 4.9 (SD 1.4) for therapists. The attitude towards using the exergames was rated 4.8 (SD 1.9) by patients and 3.6 (SD 1.4) by therapists, respectively. The intention to use the exergames in the future was rated 3.9 (SD 2.1) by patients and 3.7 (SD 1.8) by therapists. We gained information on how to improve the exergames in the interviews. CONCLUSIONS: Patients and therapists perceived the exergames as user-friendly; however, using the games further with the actual test version was not perceived as conceivable. The therapists were generally more critical towards future use than the patients. Therefore, involving both users to achieve acceptable and user-friendly versions of game-based rehabilitation for the future is deemed crucial and warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT02353962; https://clinicaltrials.gov/ct2/show/NCT02353962 (Archived by WebCite at http://www.webcitation.org/6soxIJlAZ).

A markerless estimation of the ankle-foot complex 2D kinematics during stance.

A markerless technique is proposed and applied to estimate the two-dimensional joint kinematics of the shank and foot complex during the stance phase. Image sequences were acquired with a single camera from three healthy subjects while walking barefoot and with socks. Automatic segmentation of the shank and foot was performed to isolate the moving body from the background. A multi-rigid body model for the shank and foot complex, with the relevant segment anatomical axes, was defined and an image cross-correlation technique was applied to detect the anatomical axes locations throughout the movement. The proposed markerless technique was validated by acquiring the same trials also with a stereophotogrammetric marker-based system and a simple marker set. Differences in the joint kinematics estimates obtained with the two techniques fall in most cases within the intra-subject variability showing that, in selected applications, the markerless technique may replace more expensive and more experimental time demanding marker-based techniques.