The Genetic Origin of the Indo-Europeans.

The Yamnaya archaeological complex appeared around 3300BCE across the steppes north of the Black and Caspian Seas, and by 3000BCE reached its maximal extent from Hungary in the west to Kazakhstan in the east. To localize the ancestral and geographical origins of the Yamnaya among the diverse Eneolithic people that preceded them, we studied ancient DNA data from 428 individuals of which 299 are reported for the first time, demonstrating three previously unknown Eneolithic genetic clines. First, a "Caucasus-Lower Volga" (CLV) Cline suffused with Caucasus hunter-gatherer (CHG) ancestry extended between a Caucasus Neolithic southern end in Neolithic Armenia, and a steppe northern end in Berezhnovka in the Lower Volga. Bidirectional gene flow across the CLV cline created admixed intermediate populations in both the north Caucasus, such as the Maikop people, and on the steppe, such as those at the site of Remontnoye north of the Manych depression. CLV people also helped form two major riverine clines by admixing with distinct groups of European hunter-gatherers. A "Volga Cline" was formed as Lower Volga people mixed with upriver populations that had more Eastern hunter-gatherer (EHG) ancestry, creating genetically hyper-variable populations as at Khvalynsk in the Middle Volga. A "Dnipro Cline" was formed as CLV people bearing both Caucasus Neolithic and Lower Volga ancestry moved west and acquired Ukraine Neolithic hunter-gatherer (UNHG) ancestry to establish the population of the Serednii Stih culture from which the direct ancestors of the Yamnaya themselves were formed around 4000BCE. This population grew rapidly after 3750-3350BCE, precipitating the expansion of people of the Yamnaya culture who totally displaced previous groups on the Volga and further east, while admixing with more sedentary groups in the west. CLV cline people with Lower Volga ancestry contributed four fifths of the ancestry of the Yamnaya, but also, entering Anatolia from the east, contributed at least a tenth of the ancestry of Bronze Age Central Anatolians, where the Hittite language, related to the Indo-European languages spread by the Yamnaya, was spoken. We thus propose that the final unity of the speakers of the "Proto-Indo-Anatolian" ancestral language of both Anatolian and Indo-European languages can be traced to CLV cline people sometime between 4400-4000 BCE.

Haplotype-based inference of recent effective population size in modern and ancient DNA samples.

Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficult in ancient DNA data and in underrepresented populations with limited reference data. In this work, we introduce an accurate method for inferring effective population size variation during the past ~2000 years in both modern and ancient DNA data, called HapNe. HapNe infers recent population size fluctuations using either IBD sharing (HapNe-IBD) or linkage disequilibrium (HapNe-LD), which does not require phasing and can be computed in low coverage data, including data sets with heterogeneous sampling times. HapNe shows improved accuracy in a range of simulated demographic scenarios compared to currently available methods for IBD-based and LD-based inference of recent effective population size, while requiring fewer computational resources. We apply HapNe to several modern populations from the 1,000 Genomes Project, the UK Biobank, the Allen Ancient DNA Resource, and recently published samples from Iron Age Britain, detecting multiple instances of recent effective population size variation across these groups.

Artificial Neural Network Approach to the Analytic Continuation Problem.

Inverse problems are encountered in many domains of physics, with analytic continuation of the imaginary Green's function into the real frequency domain being a particularly important example. However, the analytic continuation problem is ill defined and currently no analytic transformation for solving it is known. We present a general framework for building an artificial neural network (ANN) that solves this task with a supervised learning approach. Application of the ANN approach to quantum Monte Carlo calculations and simulated Green's function data demonstrates its high accuracy. By comparing with the commonly used maximum entropy approach, we show that our method can reach the same level of accuracy for low-noise input data, while performing significantly better when the noise strength increases. The computational cost of the proposed neural network approach is reduced by almost three orders of magnitude compared to the maximum entropy method.

Long-term kidney transplant survival in patients with continent urinary diversion.

OBJECTIVES: To report the long-term survival of transplanted kidneys in patients with a continent urinary diversion. METHODS: Between January 1987 and July 2015, 16 patients with a median age of 37 years (range 21-63 years) underwent kidney transplantation on a continent urinary diversion. A total of 14 patients presented irreversible dysfunction of the lower urinary tract, and two patients had required radical cystectomy because of bladder cancer. All continent urinary diversions were carried out before the transplantation. There were nine Kock pouches, five Mainz pouches, one Mainz neobladder and one Hautmann neobladder. A total of 11 patients had a previous non-continent urinary diversion. Of the transplants, 14 came from brain-dead donors and two from related living donors. RESULTS: The median post-transplantation follow up was 171 months (range 30-298 months). Two patients died, while six patients lost their transplant and resumed hemodialysis. Nine patients (56.2%) were alive with a functional transplant at the end of follow up. The most common allograft complication was acute pyelonephritis, but no graft was lost as a result of urinary diversion complications. The kidney transplant survival rate was 73.3% after 10 years, and 66.6% after 15 years. Among patients who still had a functional transplant at the time of the study, creatinine clearance was >30 mL/min for seven patients and <30 mL/min for two patients. CONCLUSIONS: The present study is the longest series to date of renal transplantation on continent urinary diversions. The long-term outcome shows that the presence of a continent urinary diversion does not reduce transplant survival.

Relationship between cranial mechanics and dysmorphic dentofacial characteristics: a cross-sectional study.

AIMS: The aim of the present study was to evaluate if cranial dysfunctions felt by osteopaths could correlate with sagittal dysmorphologies diagnosed by orthodontists, using cephalometric traces in the sagittal plane. Metholology: One hundred and six children between 6 and 12 years old (42 boys and 64 girls) were tested by an osteopath to determine if the cranial movement felt was considered to be eased in flexion or extension. To test reproducibility intra-operator, 27 randomly selected subjects were tested twice, at a one-month interval by the same osteopath before the start of their orthodontic treatment. These tests were then correlated with a cephalometric analysis of the sagittal plane to determine what type of dysmorphology existed, if any, as well as the angle of the spheno-occipital synchondrosis (SOS). RESULTS: Practitioners systematically found more cranial movement in extension for all the bones in patients in skeletal class II than in the others. Similarly, they systematically found more cranial movement in flexion in patients in skeletal class III than in the other skeletal classes. However, there was no significant difference found in SOS angulation between skeletal classes I, II, and III. DISCUSSION: This study tends to confirm the correlation, described previously by orthodontists, between the mobility of the bones of the cranial vault and dysmorphic dentofacial characteristics in the sagittal plane. Anomalies during development could lead to the typical cranial characteristics of flexion or extension. As such, these situations could be related to skeletal classes III and II respectively.

[Dento-facial orthopedics and osteopathy]. / Orthopédie dento-faciale et ostéopathie.

Osteopathy has grown rapidly. Given their common action on children and adolescents, the collaboration between dentofacial orthopedics and osteopathy is increasingly common. It therefore becomes necessary and urgent to investigate whether, based on data acquired from science, there is evidence of possible interrelations between the two disciplines. After reviewing the literature, very few scientific publications demonstrate the utility of osteopathy and its relationships with other disciplines. However, the relationship between occlusion and posture seem relatively proven, especially in the sagittal direction. On the other hand, although the mobility of the cranial bones is established, the primary respiratory motion is still subject to controversy, even among osteopaths. This, even as orthodontics has long been accused of countering the primary respiratory motion of cranial bones (PRM). Today osteopaths do not reject orthodontics anymore, because the return to a physiological bite situation is considered beneficial. According to expert opinion (without proof, however), some orthodontic devices (like headgears) which block the sutures are still to be avoided and require appropriate monitoring osteopathy. The controversy over the adverse effects of orthodontic treatment is becoming more nuanced by osteopaths, and modern orthodontics claiming a «global¼ approach of patient, collaboration may be possible in future year.

Characterisation of indomethacin and nifedipine using variable-temperature solid-state NMR.

We have characterised the stable polymorphic forms of two drug molecules, indomethacin (1) and nifedipine (2) by 13C CPMAS NMR and the resonances have been assigned. The signal for the C-Cl carbon of indomethacin has been studied as a function of applied magnetic field, and the observed bandshapes have been simulated. Variable-temperature 1H relaxation measurements of static samples have revealed a T1rho minimum for indomethacin at 17.8 degrees C. The associated activation energy is 38 kJ mol(-1). The relevant motion is probably an internal rotation and it is suggested that this involves the C-OCH3 group. Since the two drug compounds are potential candidates for formulation in the amorphous state, we have examined quench-cooled melts in detail by variable-temperature 13C and 1H NMR. There is a change in slope for T1H and T1rhoH at the glass transition temperature (Tg) for indomethacin, but this occurs a few degrees below Tg for nifedipine, which is perhaps relevant to the lower real-time stability of the amorphous form for the latter compound. Comparison of relaxation time data for the crystalline and amorphous forms of each compound reveals a greater difference for nifedipine than for indomethacin, which again probably relates to real-time stabilities. Recrystallisation of the two drugs has been followed by proton bandshape measurements at higher temperatures. It is shown that, under the conditions of the experiments, recrystallisation of nifedipine can be detected already at 70 degrees C, whereas this does not occur until 110 degrees C for indomethacin. The effect of crushing the amorphous samples has been studied by 13C NMR; nifedipine recrystallises but indomethacin does not. The results were supported by DSC, powder XRD, FTIR and solution-state NMR measurements.