Hard x-ray photon-in-photon-out spectroscopy with lifetime resolution – of XAS, XES, RIXSS and HERFD

Spectroscopic techniques that aim to resolve the electronic configuration and local coordination of a central atom by detecting inner-shell radiative decays following photoexcitation using hard X-rays are presented. The experimental setup requires an X-ray spectrometer based on perfect crystal Bragg optics. The possibilities arising from non-resonant (X-Ray Emission Spectroscopy - XES) and resonant excitation (Resonant Inelastic X-Ray Scattering Spectroscopy – RIXSS, High-Energy-Resolution Fluorescence Detected (HERFD) XAS) are discussed when the instrumental energy broadenings of the primary (beamline) monochromator and the crystal spectrometer for x-ray emission detection are on the order of the core hole lifetimes of the intermediate and final electronic states. The small energy bandwidth in the emission detection yields line-sharpened absorption features. In transition metal compounds, electron-electron interactions as well as orbital splittings and fractional population can be revealed. Combination with EXAFS spectroscopy enables to extent the k-range beyond unwanted absorption edges in the sample that limit the EXAFS range in conventional absorption spectroscopy

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study

Objective. Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Methods. Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Results. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). Conclusion. One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low Qo

The decay of turbulence in rotating flows

We present a parametric space study of the decay of turbulence in rotating flows combining direct numerical simulations, large eddy simulations, and phenomenological theory. Several cases are considered: (1) the effect of varying the characteristic scale of the initial conditions when compared with the size of the box, to mimic "bounded" and "unbounded" flows; (2) the effect of helicity (correlation between the velocity and vorticity); (3) the effect of Rossby and Reynolds numbers; and (4) the effect of anisotropy in the initial conditions. Initial conditions include the Taylor-Green vortex, the Arn'old-Beltrami-Childress flow, and random flows with large-scale energy spectrum proportional to $k^4$. The decay laws obtained in the simulations for the energy, helicity, and enstrophy in each case can be explained with phenomenological arguments that separate the decay of two-dimensional from three-dimensional modes, and that take into account the role of helicity and rotation in slowing down the energy decay. The time evolution of the energy spectrum and development of anisotropies in the simulations are also discussed. Finally, the effect of rotation and helicity in the skewness and kurtosis of the flow is considered.Comment: Sections reordered to address comments by referee

Multiproxy analysis of permafrost preserved faeces provides an unprecedented insight into the diets and habitats of extinct and extant megafauna

The study of faecal samples to reconstruct the diets and habitats of extinct megafauna has traditionally relied on pollen and macrofossil analysis. DNA metabarcoding has emerged as a valuable tool to complement and refine these proxies. While published studies have compared the results of these three proxies for sediments, this comparison is currently lacking for permafrost preserved mammal faeces. Moreover, most metabarcoding studies have focused on a single plant-specific DNA marker region. In this study, we target both the commonly used chloroplast trnL P6 loop as well as nuclear ribosomal ITS (nrITS). The latter can increase taxonomic resolution of plant identifications but requires DNA to be relatively well preserved because of the target length (∼300–500 bp). We compare DNA results to pollen and macrofossil analyses from permafrost and ice-preserved faeces of Pleistocene and Holocene megafauna. Samples include woolly mammoth, horse, steppe bison as well as Holocene and extant caribou. Most plant identifications were found using DNA, likely because the studied faeces contained many vegetative remains that could not be identified using macrofossils or pollen. Several taxa were, however, identified to lower taxonomic levels uniquely with macrofossil and pollen analysis. The nrITS marker provides species level taxonomic resolution for commonly encountered plant families that are hard to distinguish using the other proxies (e.g. Asteraceae, Cyperaceae and Poaceae). Integrating the results from all proxies, we are able to accurately reconstruct known diets and habitats of the extant caribou. Applying this approach to the extinct mammals, we find that the Holocene horse and steppe bison were not strict grazers but mixed feeders living in a marshy wetland environment. The mammoths showed highly varying diets from different non-analogous habitats. This confirms the presence of a mosaic of habitats in the Pleistocene ‘mammoth steppe’ that mammoths could fully exploit due to their flexibility in food choice

Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling

Kleefstra syndrome (KS) is a neurodevelopmental disorder caused by mutations in the histone methyltransferase EHMT1. To study the impact of decreased EHMT1 function in human cells, we generated excitatory cortical neurons from induced pluripotent stem (iPS) cells derived from KS patients. Neuronal networks of patient-derived cells exhibit network bursting with a reduced rate, longer duration, and increased temporal irregularity compared to control networks. We show that these changes are mediated by upregulation of NMDA receptor (NMDAR) subunit 1 correlating with reduced deposition of the repressive H3K9me2 mark, the catalytic product of EHMT1, at the GRIN1 promoter. In mice EHMT1 deficiency leads to similar neuronal network impairments with increased NMDAR function. Finally, we rescue the KS patient-derived neuronal network phenotypes by pharmacological inhibition of NMDARs. Summarized, we demonstrate a direct link between EHMT1 deficiency and NMDAR hyperfunction in human neurons, providing a potential basis for more targeted therapeutic approaches for KS

Demographic characteristics and quality of life of patients with unexplained complaints: a descriptive study in general practice

OBJECTIVE: About 13% of GPs' consultations involve unexplained complaints (UCs). These complaints can progress to chronic conditions like medically unexplained symptoms, chronic functional symptoms or somatoform disorders. Little is known about the demographic characteristics and quality of life of patients with early stage UCs. Our study objective was to describe these characteristics. Additionally we compared them with other patient groups to serve as a frame of reference. METHODS: Descriptive study in general practices. Patients with early stage UCs who had not had elaborate diagnostic investigations were included. Demographic characteristics were compared to a Dutch general practice population. Quality of life scores were measured with the RAND-36 and compared to another Dutch general practice population and to depressed patients. RESULTS: Data of 466 patients were available for analysis. Mean age was 44 years and 74% were females, mostly higher educated. Of the patients, 63% presented with unexplained fatigue. On average, quality of life was poor (mean RAND-36 domain scores 37-73), also in comparison with other groups. CONCLUSION: General practice patients presenting with UCs have a remarkably poor quality of life. Future research should explore how early identification of patients at risk of developing chronicity can take place. Awareness of potential poor quality of life may influence GPs' medical decision makin