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We apply a continuation method to recently optimized stellarator equilibria with excellent quasi-axisymmetry to generate new equilibria with a wide range of rotational transform profiles. Using these equilibria, we investigate how the rotational transform affects fast-particle confinement, the maximum coil–plasma distance, the maximum growth rate in linear gyrokinetic ion-temperature gradient simulations and the ion heat flux in corresponding nonlinear simulations. We find values of two-term quasi-symmetry error comparable to or lower than those of the similar Landreman–Paul (Phys. Rev. Lett., vol. 128, 2022, 035001) configuration for values of the mean rotational transform $\bar {\iota }$ between $0.12$ and $0.75$. The fast-particle confinement improves with $\bar {\iota }$ until $\bar {\iota } = 0.73$, at which point the degradation in quasi-symmetry outweighs the benefits of further increasing $\bar {\iota }$. The required coil–plasma distance only varies by about ${\pm }10\,\%$ for the configurations under consideration, and is between $2.8$ and $3.3\ \mathrm {m}$ when the configuration is scaled up to reactor size (minor radius $a=1.7\ \mathrm {m}$ and volume-averaged magnetic field strength of $5.86\ \mathrm {T}$). The maximum growth rate from linear gyrokinetic simulations increases with $\bar {\iota }$, but also shifts towards higher $k_y$ values. The maximum linear growth rate is sensitive to the choice of flux tube at rational $\bar {\iota }$, but this can be compensated for by taking the maximum over several flux tubes. The corresponding ion heat fluxes from nonlinear simulations display a non-monotonic relation to $\bar {\iota }$. Sufficiently large positive shear is destabilizing. This is reflected in both linear growth rates and nonlinear heat fluxes.
Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.
Objectives
We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.
Aims
We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.
Methods
The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.
Results
Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.
Conclusions
The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.
Elucidating the detailed process of ligand binding to a receptor is pharmaceutically important for identifying druggable binding sites. With the ability to provide atomistic detail, computational methods are well poised to study these processes. Here, accelerated molecular dynamics (aMD) is proposed to simulate processes of ligand binding to a G-protein-coupled receptor (GPCR), in this case the M3 muscarinic receptor, which is a target for treating many human diseases, including cancer, diabetes and obesity. Long-timescale aMD simulations were performed to observe the binding of three chemically diverse ligand molecules: antagonist tiotropium (TTP), partial agonist arecoline (ARc) and full agonist acetylcholine (ACh). In comparison with earlier microsecond-timescale conventional MD simulations, aMD greatly accelerated the binding of ACh to the receptor orthosteric ligand-binding site and the binding of TTP to an extracellular vestibule. Further aMD simulations also captured binding of ARc to the receptor orthosteric site. Additionally, all three ligands were observed to bind in the extracellular vestibule during their binding pathways, suggesting that it is a metastable binding site. This study demonstrates the applicability of aMD to protein–ligand binding, especially the drug recognition of GPCRs.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Method
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Results
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
Conclusion
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
Emotion perception may be impaired after stroke. No study on emotion perception after stroke has taken the influence of post-stroke depressive symptoms into account, although depressive symptoms themselves may hamper emotion perception.
Objective:
To compare the perception of emotional facial expressions in stroke patients with and without depressive symptoms.
Methods:
Twenty-two stroke patients participated whose depressive symptoms were classified using the Montgomery-Åsberg Depression Rating Scale (cutoff = 10) and who were compared with healthy controls. Emotion recognition was measured using morphed images of facial expressions.
Results:
Patients with depressive symptoms performed worse than controls on all emotions; patients without depressive symptoms performed at control level. Patients with depressive symptoms were less sensitive to the emotions anger, happiness and sadness compared with patients without depressive symptoms.
Conclusions:
Post-stroke depressive symptoms impair emotion perception. This extends findings in bipolar disorder indicating that emotion perception deficits are strongly related to the level of depression.
The technique of accelerator mass spectrometry (AMS) offers a complementary tool for studying long-lived radionuclides in nuclear astrophysics: (1) as a tool for investigating nucleosynthesis in the laboratory; and (2) via a direct search of live long-lived radionuclides in terrestrial archives as signatures of recent nearby supernova-events. A key ingredient to our understanding of nucleosynthesis is accurate cross-section data. AMS was applied for measurements of the neutron-induced cross sections 13C(n,γ) and 14N(n,p), both leading to the long-lived radionuclide 14C. Solid samples were irradiated at Karlsruhe Institute of Technology with neutrons closely resembling a Maxwell–Boltzmann distribution for kT = 25 keV, and with neutrons of energies between 123 and 178 keV. After neutron activation the amount of 14C nuclides in the samples was measured by AMS at the VERA (Vienna Environmental Research Accelerator) facility. Both reactions, 13C(n,γ)14C and 14N(n,p)14C, act as neutron poisons in s-process nucleosynthesis. However, previous experimental data are discordant. The new data for both reactions tend to be slightly lower than previous measurements for the 25 keV Maxwell–Boltzmann energy distribution. For the higher neutron energies no previous data did exist for 13C(n,γ), but model calculations indicated a strong resonance structure between 100 and 300 keV which is confirmed by our results. Very limited information is available for 14N(n,p) at these energies. Our new data at 123 and 178 keV suggest lower cross sections than expected from previous experiments and data evaluations.
In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet–disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe.
Objective:
Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods:
Plasma levels of six carotenoids – α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin – were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids.
Results:
Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35μmoll−1 for men in Malmö, Sweden vs. 2.79μmoll−1 for men in Ragusa/Naples, Italy; 1.61μmoll−1 for women in The Netherlands vs. 3.52μmoll−1 in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (α-carotene: 0.06μmoll−1 for men in Murcia, Spain vs. 0.25μmoll−1 for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R2=27.3%), followed by BMI (partial R2=5.2%), gender (partial R2=2.7%) and smoking status (partial R2=2.8%). Females had higher total carotenoid levels than males across Europe.
Conclusions:
Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.
Diagnosing ischaemic stroke and determining its cause is difficult in children. Both are important for selection of treatment and prediction of outcome. This study explored the diagnostic changes that lead to a delay in the correct diagnosis of paediatric stroke. Case histories of 45 children with ischaemic stroke (31 males, 14 females; median age 6y; age range 2mo–16y) were retrospectively reviewed. The initial clinical diagnosis, based on the interpretation of presenting symptoms, was compared with the final aetiological stroke diagnosis after completion and review of diagnostic work-up. The type of diagnostic change, consequent time delay until correct diagnosis, reasons for change of diagnosis, and alterations to management were evaluated. Twenty-four diagnostic changes were identified; 19 in ‘primary stroke diagnosis’ (symptoms initially not attributed to stroke), and five in ‘aetiological diagnosis’ (incorrect initial determination of type or cause of stroke). The median interval between initial and final diagnosis was 7 days (3h–2y). The change in diagnosis led to therapeutic alterations in 17 patients. Risk factors for childhood stroke differ from those in adults. Stroke is frequently not recognized as the cause of the child's symptoms, and the correct determination of stroke aetiology takes time. We recommend that children with stroke be evaluated in a centre with expertize, using standardized diagnostic protocols and careful follow-up.
In this paper we find conditions which guarantee that a given flow $\Phi$ on a compact metric space X admits a Lyapunov 1-form $\omega$ lying in a prescribed Čech cohomology class $\xi\in\check H^1(X;\mathbb{R})$. These conditions are formulated in terms of the restriction of $\xi$ to the chain recurrent set of $\Phi$. The result of the paper may be viewed as a generalization of a well-known theorem by Conley about the existence of Lyapunov functions.
Little is known about long-term physical sequelae, cognitive functioning, and quality of life of children who have had a haemorrhagic stroke. Fifty-six patients (29 females, 27 males) under 16 years of age at time of the bleeding were studied. Mean age at time of bleeding was 7.7 years (range 1 month to 15.9 years). The primary site and cause of the bleeding at baseline were determined. Occurrences of death, re-bleedings, and seizures during follow-up were recorded. Patients who survived were invited for a follow-up examination including physical check-up, general screening of cognition, and an inventory of subjective health perception. Thirteen children died directly as a result of the haemorrhage; nine experienced a recurrent bleeding, which was fatal in three; six children developed epileptic seizures. At follow-up 36 of 56 patients were still alive. Mean follow-up time was 10.3 years (range 1.3 to 19.9 years) and mean age was 18.6 years (range 1.8 to 34.1 years). There was no patient lost to follow-up. Five patients declined to visit the hospital. In 15 out of 31 patients who could be examined, no physical impairment was observed, 11 had a hemiparesis of varying severity, and three had symptoms of cerebellar ataxia. One child had persisting tetraparesis and one persisting paraparesis. Signs of cognitive deficits were found in 15 patients. Of the children who survive haemorrhagic stroke, the physical and functional prognosis is relatively good, as almost all children were independent at follow-up. However, only a quarter of the surviving children had no physical or cognitive deficit after a mean follow-up period of 10 years. The majority had low self-esteem as well as emotional, behavioural, and health problems.
Reference intervals for human placental lactogen (hPL) and dU-estrogens (dU-E) in uncomplicated twin pregnancies are found to be higher than singleton pregnancies and considerably wider. Significantly more monozygotic than dizygotic pregnancies, and significantly more monoplacental than diplacental pregnancies showed hPL values below the median on the normal range curve. The same was not found for dU-E. Significantly more growth-retarded fetuses were found in monoplacental than diplacental pregnancies. The benefit of measuring the two parameters in order to identify the intrauterine growth retarded fetuses were evaluated in terms of sensitivity and specificity. Both parameters were found less suitable for the purpose.
A total of 146 twin pregnancies were studied to evaluate the importance of bed rest. A significantly reduced frequency of preterm delivery was found after bed rest in hospital as compared to bed rest at home or no bed rest at all. An increase in gestational age and in birth weight was seen after bed rest. No effect was found on the intrauterine increase of fetal weight per time. Early routine ultrasound is recommended, so that effective bed rest may be instituted in due time.
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