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Purpose: To evaluate the long-term effects of an Arts on Prescription (AoP) programme on sense of coherence (SOC) in Sweden. Design: A controlled intervention study with a quasi-experimental prospective design, including questionnaires at baseline, with follow-ups at 6 and 12 months. Participants were on sick leave due to common mental disorders (CMD) and/or non-specific musculoskeletal pain, recruited from primary care in six regions. The intervention group also included participants from open psychiatric care. The study sample comprised 586 participants (335 in the intervention group and 251 in the control group). Results: Both groups showed a significantly stronger SOC at follow-up, with a medium effect size for the intervention group and a small effect size for the control group. No statistically significant difference in SOC change over time was observed between the groups. Participants from open psychiatric care in the intervention group showed a significant improvement in SOC compared to those from primary care. Concerns about finances had a significant main effect on SOC for the entire study population. Originality: Unlike most AoP studies, this controlled study with a relatively large sample provides insights into the long-term effects of AoP on SOC, with results reported using p-values and effect sizes.

Abstract Additive nanotechnology enable curvilinear and three-dimensional (3D) magnetic architectures with tunable topology and functionalities surpassing their planar counterparts. Here, we experimentally reveal that 3D soft magnetic wireframe structures resemble compact manifolds and accommodate magnetic textures of high order vorticity determined by the Euler characteristic, χ. We demonstrate that self-standing magnetic tetrapods (homeomorphic to a sphere; χ = + 2) support six surface topological solitons, namely four vortices and two antivortices, with a total vorticity of + 2 equal to its Euler characteristic. Alternatively, wireframe structures with one loop (homeomorphic to a torus; χ = 0) possess equal number of vortices and antivortices, which is relevant for spin-wave splitters and 3D magnonics. Subsequent introduction of n holes into the wireframe geometry (homeomorphic to an n-torus; χ

Abstract Using ab initio density functional theory with static mean-field correlations, we calculate the Heisenberg and Dzyaloshinskii-Moriya interactions (DMI) for an atomistic spin Hamiltonian for the lacunar spinel, GaV4S8. The parameters describing these interactions are used in atomistic spin dynamics and micromagnetic simulations. The magnetic properties of the lacunar spinel GaV4S8, a material well-known from experiment to host magnetic skyrmions of Néel character, are simulated with these ab initio calculated parameters. The Dzyaloshinskii-Moriya contribution to the micromagnetic energy is a sum of two Lifshitz invariants, supporting the formation of Néel skyrmions and its symmetry agrees with what is usually expected for C 3ν -symmetric systems. There are several conclusions one may draw from this work. One concerns the quantum nature of the magnetism, where we show that the precise magnetic state of the V4 cluster is crucial for understanding quantitatively the magnetic phase diagram. In particular, we demonstrate that a distributed-moment state of each V4 cluster explains well a variety of properties of GaV4S8, such as the band gap, observed Curie temperature and especially the stability of Néel skyrmions in the experimentally relevant temperature and magnetic-field range. In addition, we find that electronic correlations change visibly the calculated value of the DMI.

Abstract Finding the ground state of complex many-body systems, such as magnetic materials containing topological textures, like skyrmions, is a fundamental and long-standing problem. We present here a genetic-tunneling-driven variance-controlled optimization method, that efficiently identifies the ground state of two-dimensional skyrmionic systems. The approach combines a local energy-minimizer backend and a metaheuristic global search frontend. The method is shown to perform significantly better than simulated annealing. Specifically, we demonstrate that for the Pd/Fe/Ir(111) system, our method correctly and efficiently identifies the experimentally observed spin spiral geometry, skyrmion lattice and ferromagnetic ground states as a function of the external magnetic field. To our knowledge, no other optimization method has until now succeeded in doing this. We envision that our findings will pave the way for evolutionary computing in mapping out phase diagrams for spin systems in general.

We aimed to use the digital platform maintained by the local health service providers in Southeast Sweden for integrated monitoring of disparities in vaccination and morbidity during the COVID-19 pandemic. The monitoring was performed in the adult population of two counties (n = 657,926) between 1 February 2020 and 15 February 2022. The disparities monitored were relocated (internationally displaced), substance users, and suffering from a psychotic disorder. The outcomes monitored were COVID-19 vaccination, SARS-CoV-2 test results, and hospitalization with COVID-19. Relocated residents displayed an increased likelihood of remaining unvaccinated and a decreased likelihood of testing as well as increased risks of primary SARS-CoV-2 infection and hospitalization compared with the general population. Suffering from a major psychiatric disease was associated with an increased risk of remaining unvaccinated and an increased risk of hospitalization but a decreased risk of SARS-CoV-2 infection. From the digital monitoring, we concluded that the relocated minority received insufficient protection during the pandemic, suggesting the necessity for comprehensive promotion of overall social integration. Persons with major psychiatric diseases underused vaccination, while they benefitted from proactively provided testing, implying a need for active encouragement of vaccination. Further research is warranted on legal and ethical frameworks for digital monitoring in vaccination programs.

The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be captured by electron repopulation respectively correlation-induced modifications of the electronic structure, requiring to take the local Coulomb interaction into account.

We previously reported that indoor odorous chloroanisoles (CAs) are still being emitted due to microbial methylation of hazardous chlorophenols (CPs) present in legacy wood preservatives. Meanwhile, Swedish researchers reported that this malodor, described since the early 1970s, is caused by hazardous mold. Here, we examined to what extent CP-treated wood contains mold and if mold correlates with perceived odor. We found no studies in PubMed or Web of Science addressing this question. Further, we investigated two schools built in the 1960s with odor originating from crawlspaces. No visible mold was evident in the crawlspaces or on the surfaces of treated wood samples. Using a microscope, varying amounts of mold growth were detected on the samples, all containing both CP(s) and CA(s). Some samples smelled, and the odor correlated with the amount of mold growth. We conclude that superficial microscopic mold on treated wood suffices produced the odor. Further, we argue that CPs rather than mold could explain the health effects reported in epidemiological studies that use mold odor as an indicator of hazardous exposure.

We present a metaheuristic conditional neural-network-based method aimed at identifying physically interesting metastable states in a potential energy surface of high rugosity. To demonstrate how this method works, we identify and analyze spin textures with topological charge Q ranging from 1 to −13 (where antiskyrmions have Q

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) entails several risk factors for incisional hernia (IH). A few reports available showing incidences between 7% and 17%. At our institution fascia closure has been performed in a 4:1 suture to wound length manner, with a continuous 2-0 polydiaxanone suture (PDS-group) or with a 2-0 polypropylene suture preceded by a reinforced tension line (RTL) suture (RTL-group). Our hypothesis was that these patients might benefit from reinforcing the suture line with a lower IH incidence in this group. The aim was to evaluate the 1-year IH-incidence of the two different closures.Methods: Patients eligible for inclusion were treated with CRS/HIPEC between 2004 and 2019. IH was diagnosed by scrutinizing CT-scans 1 year ±3 months after surgery. Additional data was retrieved from clinical records and a prospective CRS/HIPEC-database.Results: Of 193 patients, 129 were included, 82 in the PDS- and 47 in the RTL-group. RTL-patients were 5 years younger, had less blood loss and more frequent postoperative neutropenia. No difference regarding sex, BMI, recent midline incisions, excision of midline scars, peritoneal cancer index score, complications (≥Clavien-Dindo 3b), or chemotherapy. Ten IH (7.8%) were found, 9 (11%) in the PDS- and 1 (2.1%) in the RTL-group (p = 0.071).Conclusion: An IH incidence of 7.8% in patients undergoing CRS/HIPEC is not higher than after laparotomies in general. The IH incidence in the PDS-group was 11% compared to 2% in the RTL-group. Even though significance was not reached, the difference is clinically relevant, suggesting an advantage with RTL suture.

We report on local nowcasting (short-term forecasting) of coronavirus disease (COVID-19) hospitalizations based on syndromic (symptom) data recorded in regular healthcare routines in Östergötland County (population ≈465,000), Sweden, early in the pandemic, when broad laboratory testing was unavailable. Daily nowcasts were supplied to the local healthcare management based on analyses of the time lag between telenursing calls with the chief complaints (cough by adult or fever by adult) and COVID-19 hospitalization. The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.80; mean absolute percentage error

Neuromorphic computing mimics the brain's architecture to create energy-efficient devices. Reconfigurable synapses are crucial for neuromorphic computing, which can be achieved through memory-resistive (memristive) switching. Graphene-based memristors have shown nonvolatile multibit resistive switching with desirable endurance. Through first-principles calculations, we study the structural and electronic properties of graphene in contact with an ultra-thin alumina overlayer and demonstrate how one can use charge doping to exert direct control over its interfacial covalency, reversibly switching between states of conductivity and resistivity in the graphene layer. We further show that this proposed mechanism can be stabilized through the p-type doping of graphene, e.g., by naturally occurring defects, the passivation of dangling bonds or defect engineering.

Abstract ReX2 (X = S, Se) remains a copious source of controversies and unanswered questions due to its widely contrasting experimental and theoretical results. With the help of comparative first‐principles electronic structure and phonon calculations, the correct structures for both systems are established, which minimize the apparent divergence of different experimental results. It is demonstrated that ReS2 and ReSe2 are neither iso‐structural nor iso‐electronic. The contributions of the in‐plane and out‐of‐plane orbitals at the band‐edges of the bulk and monolayers are coordinated with their anisotropic optical response. Under moderately high pressure, both of these systems are observed to undergo a semiconductor to metal transition. With the help of a combined full‐potential density functional theory and multiplet ligand field theory (DFT+MLFT) approach, the X‐ray spectral properties of these two systems are analyzed in the light of their intricate differences of optimized structures and electronic correlations.

Abstract Bioprinting is increasingly used to create complex tissue constructs for an array of research applications, and there are also increasing efforts to print tissues for transplantation. Bioprinting may also prove valuable in the context of drug screening for personalized medicine for treatment of diseases such as cancer. However, the rapidly expanding bioprinting research field is currently limited by access to bioprinters. To increase the availability of bioprinting technologies we present here an open source extrusion bioprinter based on the E3D motion system and tool changer to enable high-resolution multimaterial bioprinting. As proof of concept, the bioprinter is used to create collagen constructs using freeform reversible embedding of suspended hydrogels (FRESH) methodology, as well as multimaterial constructs composed of distinct sections of laminin and collagen. Data is presented demonstrating that the bioprinted constructs support growth of cells either seeded onto printed constructs or included in the bioink prior to bioprinting. This open source bioprinter is easily adapted for different bioprinting applications, and additional tools can be incorporated to increase the capabilities of the system.

Abstract Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by brain accumulation of aggregated amyloid-beta (Aβ) and alpha-synuclein (αSYN), respectively. In order to develop effective therapies, it is crucial to understand how the Aβ/αSYN aggregates can be cleared. Compelling data indicate that neuroinflammatory cells, including astrocytes and microglia, play a central role in the pathogenesis of AD and PD. However, how the interplay between the two cell types affects their clearing capacity and consequently the disease progression remains unclear. Methods The aim of the present study was to investigate in which way glial crosstalk influences αSYN and Aβ pathology, focusing on accumulation and degradation. For this purpose, human-induced pluripotent cell (hiPSC)-derived astrocytes and microglia were exposed to sonicated fibrils of αSYN or Aβ and analyzed over time. The capacity of the two cell types to clear extracellular and intracellular protein aggregates when either cultured separately or in co-culture was studied using immunocytochemistry and ELISA. Moreover, the capacity of cells to interact with and process protein aggregates was tracked using time-lapse microscopy and a customized “close-culture” chamber, in which the apical surfaces of astrocyte and microglia monocultures were separated by a

Abstract Tetragonal ( $${\hbox{L1}}_{0}$$ L1 0 ) FeNi is a promising material for high-performance rare-earth-free permanent magnets. Pure tetragonal FeNi is very difficult to synthesize due to its low chemical order–disorder transition temperature ( $$\approx {593}$$ ≈ 593 K), and thus one must consider alternative non-equilibrium processing routes and alloy design strategies that make the formation of tetragonal FeNi feasible. In this paper, we investigate by density functional theory as implemented in the exact muffin-tin orbitals method whether alloying FeNi with a suitable element can have a positive impact on the phase formation and ordering properties while largely maintaining its attractive intrinsic magnetic properties. We find that small amount of non-magnetic (Al and Ti) or magnetic (Cr and Co) elements increase the order–disorder transition temperature. Adding Mo to the Co-doped system further enhances the ordering temperature while the Curie temperature is decreased only by a few degrees. Our results show that alloying is a viable route to stabilizing the ordered tetragonal phase of FeNi.

High-temperature body-centered cubic (BCC) γ-U is effectively stablized by γ-(U,Zr) alloys that also make it feasible to use it as a nuclear fuel. However, relatively little research has focused on γ-(U,Zr) alloys due to their instability at room temperature. The effect of Zr composition on its mechanical properties is not clear yet. Herein, we perform molecular dynamics simulations to investigate the mechanical and dynamical stabilities of γ-(U,Zr) alloys under high temperatures, and we calculate the corresponding lattice constants, various elastic moduli, Vickers hardness, Debye temperature, and dynamical structure factor. The results showed that γ-U, β-Zr, and γ-(U,Zr) are all mechanically and dynamically stable at 1200 K, which is in good agreement with the previously reported high-temperature phase diagram of U-Zr alloys. We found that the alloying treatment on γ-U with Zr can effectively improve its mechanical strength and melting points, such as Vickers hardness and Debye temperature, making it more suitable for nuclear reactors. Furthermore, the Zr concentrations in γ-(U,Zr) alloys have an excellent effect on these properties. In addition, the dynamical structure factor reveals that γ-U shows different structural features after alloying with Zr. The present simulation data and insights could be significant for understanding the structures and properties of UZr alloy under high temperatures.

Biofilms are arguably the most important mode of growth of bacteria, but how antibiotic resistance emerges and is selected in biofilms remains poorly understood. Several models to study evolution of antibiotic resistance have been developed, however, their usability varies depending on the nature of the biological question. Here, we developed and validated a microfluidic chip (Brimor) for studying the dynamics of enrichment of antibiotic-resistant bacteria in biofilms using real-time monitoring with confocal microscopy. In situ extracellular cellulose staining and physical disruption of the biomass confirmed Escherichia coli growth as biofilms in the chip. We showed that seven generations of growth occur in 16 h when biofilms were established in the growth chambers of Brimor, and that bacterial death and growth rates could be estimated under these conditions using a plasmid with a conditional replication origin. Additionally, competition experiments between antibiotic-susceptible and -resistant bacteria at sub-inhibitory concentrations demonstrated that the antibiotic ciprofloxacin selected for antibiotic resistance in bacterial biofilms at concentrations 17-fold below the minimal inhibitory concentration of susceptible planktonic bacteria. Overall, the microfluidic chip is easy to use and a relevant model for studying the dynamics of selection of antibiotic resistance in bacterial biofilms and we anticipate that the Brimor chip will facilitate basic research in this area.

The timing of influenza case incidence during epidemics can differ between regions within nations and states. We conducted a prospective 10-year evaluation (January 2008–February 2019) of a local influenza nowcasting (short-term forecasting) method in 3 urban counties in Sweden with independent public health administrations by using routine health information system data. Detection-of-epidemic-start (detection), peak timing, and peak intensity were nowcasted. Detection displayed satisfactory performance in 2 of the 3 counties for all nonpandemic influenza seasons and in 6 of 9 seasons for the third county. Peak-timing prediction showed satisfactory performance from the influenza season 2011–12 onward. Peak-intensity prediction also was satisfactory for influenza seasons in 2 of the counties but poor in 1 county. Local influenza nowcasting was satisfactory for seasonal influenza in 2 of 3 counties. The less satisfactory performance in 1 of the study counties might be attributable to population mixing with a neighboring metropolitan area.

We report the existence of entangled steady-states in bipartite quantum magnonic systems at elevated temperatures. We consider dissipative dynamics of two magnon modes in a bipartite antiferromagnet, subjected to interaction with a phonon mode and an external rotating magnetic field. To quantify the bipartite magnon–magnon entanglement, we use entanglement negativity and compute its dependence on temperature and magnetic field. We provide evidence that the coupling between magnon and phonon modes is necessary for the entanglement, and that, for any given phonon frequency and magnon–phonon coupling rate, there are always ranges of the magnetic field amplitudes and frequencies for which magnon–magnon entanglement persists at room temperature.

The competition between plastic deformation mechanisms in FeCrCoNiAlx high-entropy alloys is explored as a function of temperature by first-principle theory. Investigating the generalized stacking fault energy, we identify a strong interplay between the magnetic and chemical effects. At cryogenic conditions (ferromagnetic state), full-slip is accompanied by martensitic transformation, whereas increasing temperature towards room-temperature (paramagnetic state) changes the deformation mechanism to full-slip plus twinning. Alloying with Al reduces the susceptibility for stacking fault formation in the ferromagnetic state and promotes twinning in the paramagnetic state. The present advance in magneto-plasticity reveals new opportunities for tailoring the mechanical response in high-entropy alloys.

The growing availability of big data in healthcare and public health opens possibilities for infectious disease control in local settings. We prospectively evaluated a method for integrated local detection and prediction (nowcasting) of influenza epidemics over 5 years, using the total population in Östergötland County, Sweden. We used routine health information system data on influenza-diagnosis cases and syndromic telenursing data for July 2009–June 2014 to evaluate epidemic detection, peak-timing prediction, and peak-intensity prediction. Detection performance was satisfactory throughout the period, except for the 2011–12 influenza A(H3N2) season, which followed a season with influenza B and pandemic influenza A(H1N1)pdm09 virus activity. Peak-timing prediction performance was satisfactory for the 4 influenza seasons but not the pandemic. Peak-intensity levels were correctly categorized for the pandemic and 2 of 4 influenza seasons. We recommend using versions of this method modified with regard to local use context for further evaluations using standard methods.

The underlying mechanism behind the metal-to-insulator transition in VO_{2} is still a topic of intense debate. The two leading theoretical interpretations associate the transition with either electron-lattice or electron-electron correlations. Novel experimental results are required to converge towards one of the two scenarios. Here we report on a temperature-dependent angle-resolved photoelectron study of VO_{2} thin films across the metal-to-insulator transition. The obtained experimental results are compared to density functional theory calculations. We find an overall energy shift and compression of the electronic band structure across the transition while the overall band topology is conserved. The results demonstrate the importance of electron-electron correlations in establishing the insulating state.

Synthetic bone models are used to train surgeons as well as to test new medical devices. However, currently available models do not accurately mimic the complex structure of trabecular bone, which can provide erroneous results. This study aimed to investigate the suitability of stereolithography (SLA) to produce synthetic trabecular bone. Samples were printed based on synchrotron micro-computed tomography (micro-CT) images of human bone, with scaling factors from 1 to 4.3. Structure replicability was assessed with micro-CT, and mechanical properties were evaluated by compression and screw pull-out tests. The overall geometry was well-replicated at scale 1.8, with a volume difference to the original model of

The manipulation of topologically protected field configurations such as skyrmions, merons, and antimerons, already predicted and experimentally observed in noncentrosymmetric magnets, could definitely have potential applications in logic gate operations as carriers of information. Here, we present and elaborate a proof of concept on how to construct a three-input noncanonical majority gate on a kagome ferromagnet lacking inversion symmetry. By taking advantage of the existence of edge modes in a kagome magnet, it is possible to create topological excitations such as merons and antimerons at the edge of the material. Using atomistic spin dynamics simulations, we determine the precise physical conditions for the creation and annihilation of merons and antimerons and, in a second stage, we describe the majority gate functionality.

Abstract Background Sclerosing mesenteritis (SM) is sometimes used as an umbrella-term for idiopathic inflammatory conditions in the mesentery. Mesenteric panniculitis (MP) is a radiological finding and its relation to clinical SM is not fully understood. The aims of this study were to determine whether any correlation could be found between the radiological findings and the clinical disease course. Methods Patients observed due to idiopathic inflammation of the mesentery were identified. If SM could be verified histologically or MP radiologically, the patients were included in this descriptive retro perspective study. Results Typical radiological changes were observed in 27 patients. A majority (23/27) of these patients had mild to moderate symptoms. This group with typical radiology was labelled MP. Four patients were included due to histologically verified disease but had uncharacteristic radiology involving multiple compartments of the abdomen. All four had marked systemic inflammation, fever and fluctuating radiologic findings. Three had severe disease with multiple hospitalisations and complications but responded promptly to corticosteroids. This group was denoted SM. Conclusions We have identified two subgroups of patients; firstly, MP with stable and characteristic radiologic changes and secondly SM with atypical radiology and a more aggressive clinical course. We propose that the term SM should be reserved for this latter condition.

Abstract An essential property of magnetic devices is the relaxation rate in magnetic switching which strongly depends on the energy dissipation. This is described by the Landau-Lifshitz-Gilbert equation and the well known damping parameter, which has been shown to be reproduced from quantum mechanical calculations. Recently the importance of inertia phenomena have been discussed for magnetisation dynamics. This magnetic counterpart to the well-known inertia of Newtonian mechanics, represents a research field that so far has received only limited attention. We present and elaborate here on a theoretical model for calculating the magnetic moment of inertia based on the torque-torque correlation model. Particularly, the method has been applied to bulk itinerant magnets and we show that numerical values are comparable with recent experimental measurements. The theoretical analysis shows that even though the moment of inertia and damping are produced by the spin-orbit coupling, and the expression for them have common features, they are caused by very different electronic structure mechanisms. We propose ways to utilise this in order to tune the inertia experimentally, and to find materials with significant inertia dynamics.

Intravital imaging is an invaluable tool for studying the expanding range of immune cell functions. Only in vivo can the complex and dynamic behavior of leukocytes and their interactions with their natural microenvironment be observed and quantified. While the capabilities of high-speed, high-resolution confocal and multiphoton microscopes are well-documented and steadily improving, other crucial hardware required for intravital imaging is often developed in-house and less commonly published in detail. In this report, we describe a low-cost, multipurpose, and tissue-stabilizing in vivo imaging platform that enables sensing and regulation of local tissue temperature. The effect of tissue temperature on local blood flow and leukocyte migration is demonstrated in muscle and skin. Two different models of vacuum windows are described in this report, however, the design of the vacuum window can easily be adapted to fit different organs and tissues.

We present the first experimental determination of the intra-atomic exchange energy between the inner 4f and the outer 6s5d shells in rare-earth elements. Inelastic electron tunneling spectroscopy on individual rare-earth atoms adsorbed on metal-supported graphene reveals an element-dependent excitation, with energy between 30 and 170 meV, linearly increasing with the spin angular momentum of the 4f shell. This observation is possible owing to the strong spin polarization of the outer shells, characteristic of rare-earth adatoms on graphene. This polarization gives rise to a giant magnetoresistance of up to 75% observed for Dy on graphene/Ir(111) single-atom magnets. Density functional theory calculations of the 6s5d shell spin polarizations and of their intra-atomic exchange constants with the 4f shell yield exchange energies in agreement with the experimental values. These results prove that the description of the spin dynamics in RE considering only the 4f-5d interaction is oversimplified. A more realistic treatment requires us to consider a multishell intra-atomic exchange in which both 6s and 5d shells are taken into account, with the 4f-6s contribution possibly prevailing over the 4f-5d one. Our findings are important for the general understanding of magnetism in rare earths, whether they are in bulk compounds or as surface adsorbed atoms and clusters. The results presented here also push for a revision of the description of the spin dynamics in rare-earth-based systems.

The magneto-optical response of Fe and Ni during ultrafast demagnetization is studied experimentally and theoretically. We have performed pump-probe experiments in the transverse magneto-optical Kerr effect (T-MOKE) geometry using photon energies that cover the M absorption edges of Fe and Ni between 40 and 72 eV. The magnetic asymmetry was obtained by forming the difference of reflected intensities obtained for two opposite orientations of the sample magnetization. Density functional theory (DFT) was used to calculate the magneto-optical response of different magnetic configurations, representing different types of excitations: long wavelength magnons, short wavelength magnons, and Stoner excitations. In the case of Fe, we find that the calculated asymmetry is strongly dependent on the specific type of magnetic excitation. Our modeling also reveals that during remagnetization Fe is, to a reasonable approximation, described by magnons, even though small nonlinear contributions could indicate some degree of Stoner excitations as well. In contrast, we find that the calculated asymmetry in Ni is rather insensitive to the type of magnetic excitations. However, there is a weak nonlinearity in the relation between asymmetry and the off-diagonal component of the dielectric tensor, which does not originate from the modifications of the electronic structure. Our experimental and theoretical results thus emphasize the need to consider a coupling between asymmetry and magnetization that may be more complex than a simple linear relationship. This insight is crucial for the microscopic interpretation of ultrafast magnetization experiments.

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization.This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course.This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction.Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration.In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

STUDY OBJECTIVE:To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. BACKGROUND:Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. METHODS:Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". RESULTS:There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation. CONCLUSION:Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.

Introduction: Patients who suffer from chewing and swallowing disorders, i.e. dysphagia, may have difficulties ingesting normal food and liquids. In these patients a texture modified diet may enable that the patient maintain adequate nutrition. However, there is no generally accepted definition of ‘texture’ that includes measurements describing different food textures. Objective: Objectively define and quantify categories of texture-modified food by conducting rheological measurements and sensory analyses. A further objective was to facilitate the communication and recommendations of appropriate food textures for patients with dysphagia. Design: About 15 food samples varying in texture qualities were characterized by descriptive sensory and rheological measurements. Results: Soups were perceived as homogenous; thickened soups were perceived as being easier to swallow, more melting and creamy compared with soups without thickener. Viscosity differed between the two types of soups. Texture descriptors for pâtés were characterized by high chewing resistance, firmness, and having larger particles compared with timbales and jellied products. Jellied products were perceived as wobbly, creamy, and easier to swallow. Concerning the rheological measurements, all solid products were more elastic than viscous (G′>G″), belonging to different G′ intervals: jellied products (low G′) and timbales together with pâtés (higher G′). Conclusion: By combining sensory and rheological measurements, a system of objective, quantitative, and well-defined food textures was developed that characterizes the different texture categories.

Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

Motoneurons receive a barrage of inputs from descending and reflex pathways. Much of our understanding about how these inputs are transformed into motor output in humans has come from recordings of single motor units during voluntary contractions. This approach, however, is limited because the input is ill-defined. Herein, we quantify the discharge of soleus motor units in response to well-defined trains of afferent input delivered at physiologically-relevant frequencies. Constant frequency stimulation of the tibial nerve (10-100 Hz for 30 s), below threshold for eliciting M-waves or H-reflexes with a single pulse, recruited motor units in 7/9 subjects. All 25 motor units recruited during stimulation were also recruited during weak (

Although three-dimensional testicular cell cultures have been demonstrated to mimic the organization of the testis in vivo and support spermatogenesis the optimal culture conditions and requirements remain unknown. Therefore, utilizing an established three-dimensional cell culture system that promotes differentiation of premeiotic murine male germ cells as far as elongated spermatids, the present study was designed to test the influence of different culture media on germ cell differentiation, Leydig cell functionality and overall cell survival. Single-cell suspensions prepared from 7-day-old rat testes and containing all the different types of testicular cells were cultured for as long as 31 days, with or without stimulation by gonadotropins. Leydig cell functionality was assessed on the basis of testosterone production and the expression of steroidogenic genes.Gonadotropins promoted overall cell survival regardless of the culture medium employed. Of the various media examined, the most pronounced expression of Star and Tspo, genes related to steroidogenesis, as well as the greatest production of testosterone was attained with DMEM + glutamine. Although direct promotion of germ cell maturation by the cell culture medium could not be observed, morphological evaluation in combination with immunohistochemical staining revealed unfavorable organization of tubules formed de novo in the three-dimensional culture, allowing differentiation to the stage of pachytene spermatocytes. Further differentiation could not be observed, probably due to migration of germ cells out of the cell colonies and the consequent lack of support from Sertoli cells.In conclusion, the observations reported here show that in three-dimensional cultures, containing all types of rat testicular cells, the nature of the medium per se exerts a direct influence on the functionality of the rat Leydig cells, but not on germ cell differentiation, due to the lack of proper organization of the Sertoli cells.

Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45-85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.

An understanding of the occurrence and comparative timing of influenza infections in different age groups is important for developing community response and disease control measures. This study uses data from a Scandinavian county (population 427.000) to investigate whether age was a determinant for being diagnosed with influenza 2005-2010 and to examine if age was associated with case timing during outbreaks. Aggregated demographic data were collected from Statistics Sweden, while influenza case data were collected from a county-wide electronic health record system. A logistic regression analysis was used to explore whether case risk was associated with age and outbreak. An analysis of variance was used to explore whether day for diagnosis was also associated to age and outbreak. The clinical case data were validated against case data from microbiological laboratories during one control year. The proportion of cases from the age groups 10-19 (p

Patterns of protein interactions provide important insights in basic biology, and their analysis plays an increasing role in drug development and diagnostics of disease. We have established a scalable technique to compare two biological samples for the levels of all pairwise interactions among a set of targeted protein molecules. The technique is a combination of the proximity ligation assay with readout via dual tag microarrays. In the proximity ligation assay protein identities are encoded as DNA sequences by attaching DNA oligonucleotides to antibodies directed against the proteins of interest. Upon binding by pairs of antibodies to proteins present in the same molecular complexes, ligation reactions give rise to reporter DNA molecules that contain the combined sequence information from the two DNA strands. The ligation reactions also serve to incorporate a sample barcode in the reporter molecules to allow for direct comparison between pairs of samples. The samples are evaluated using a dual tag microarray where information is decoded, revealing which pairs of tags that have become joined. As a proof-of-concept we demonstrate that this approach can be used to detect a set of five proteins and their pairwise interactions both in cellular lysates and in fixed tissue culture cells. This paper provides a general strategy to analyze the extent of any pairwise interactions in large sets of molecules by decoding reporter DNA strands that identify the interacting molecules.

Di-2-ethylhexyl (DEHP) phthalate, one of the phthalates most widely distributed in the environment, causes reproductive toxicity that is attributable to the action of its primary metabolite, mono (2-ethylhexyl) phthalate (MEHP). Here, we have investigated the effects of MEHP on steroidogenesis by primary cultures of rat Leydig cell progenitors and immature granulosa cells. This phthalate stimulated basal steroidogenesis and StAR expression in both types of steroidogenic cells. However, when MEHP was incubated with (Bu)2cAMP, steroid production was increased in granulosa cells and suppressed in Leydig cell progenitors, a process associated with up-regulation of StAR expression. Our data suggest that MEHP exerts gender-specific adverse effects on the hormonal function of the developing gonads. This may be involved in the development of pathological conditions including disorders of prenatal sex development that may attenuate future reproductive health.

Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 µl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use.