Increased climate seasonality during the late glacial in the Gebel Akhdar, Libya

Oxygen isotope analysis (δ18O) of caprine and bovine tooth enamel carbonates from the Haua Fteah cave (Gebel Akhdar massif, northeast Libya) reveals significant differences in palaeoseasonality during the last c. 70 ka. Data indicate different phases of human occupation of the region occurred under notably different climatic conditions. During the last glacial period, prior to the Last Glacial Maximum, a gradual increase in climate aridity occurred. This was followed in the late glacial (c. 16.6–14.7 ka) by considerably more arid conditions and much greater climate seasonality, which was likely produced by changing winter precipitation amounts and a strengthening of arid summer air masses. The high seasonality in the late glacial coincides with a period when human activity at the Haua Fteah greatly intensified. Significant changes in subsistence strategies and the seasonal exploitation of food resources also occurred at this time. The results presented here suggest that changes in the seasonal climate may have affected the seasonal supply of floral and faunal resources available to local human populations at the time, which resulted in changing subsistence practices

Pleistocene and Holocene palaeoclimates in the Gebel Akhdar (Libya) estimated using herbivore tooth enamel oxygen isotope compositions

The palaeoclimate of the Gebel Akhdar massif, in Cyrenaica, northeast Libya, is investigated using the stable oxygen isotope ratio (δ18O) of herbivore tooth enamel from the archaeological faunal assemblages of the Haua Fteah and Hagfet ed Dabba caves. Samples accumulated through human activity at the sites, thus climatic interpretations are in direct chronological association with periods of human presence in the local landscape. Wild Ammotragus lervia (Barbary sheep) and Bos sp. (auroch), and domestic Ovis sp. and Capra sp. from the Levalloiso-Mousterian (≥73.3–43.5 ka) to the Neolithic (∼9.3–5.4 ka) cultural phases are analysed. Results indicate that the most arid environment represented by the samples occurred at ∼32 ka, when populations associated with Dabban lithic assemblages were present within the region. Climatic instability increased during oxygen isotope stage 2. Consistent with other palaeoenvironmental investigations in the Gebel Akhdar, there is no evidence for hyper-arid events during the last glacial and surface water, most probably in the form of local springs, was available throughout the time periods considered. Overall, results indicate that different cultural groups occupied the Gebel Akhdar landscape under different climatic conditions, but that climate variations appear to have been of lower magnitude than those that occurred at inland North African locations. These reconstructions provide further support to the theory that the Gebel Akhdar may have served as a refugium for human populations in North Africa during times of global climatic extremes

Not in education, employment and training: pathways from toddler difficult temperament

Background: Youths disengaged from the education system and labour force (i.e. ‘Not in Education, Employment, or Training’ or ‘NEET’) are often at reduced capacity to flourish and thrive as adults. Developmental precursors to NEET status may extend back to temperamental features, though this – and possible mediators of such associations such as attention deficit hyperactivity (ADHD) symptoms and antisocial behaviours (ASB) – have yet to be directly tested. This study investigates if i) difficult temperament in toddlerhood associates with NEET status in adulthood and ii) different subdomains of ADHD (i.e. hyperactivity-impulsivity vs. inattention) in late childhood and ASB in adolescence partially explain this pathway. Methods: Participants were 6,240 mother-child dyads (60.7% female) from the Avon Longitudinal Study of Parents and Children. Mothers reported on their child’s (a) difficult temperament (i.e. mood, intensity and adaptability) at age 2 and (b) ADHD symptoms at ages 8 and 10. Participants reported their own ASB at age 14 and NEET status in adulthood (ages 18, 20, 22 and 23). Results: First, higher levels of difficult temperament in toddlerhood directly associated with an increased probability of being NEET in adulthood. Second, this effect was carried through hyperactivity-impulsivity, but not inattention, in late childhood, and ASB in adolescence; this demonstrates differential contribution to the pathway between the ADHD dimensions, with symptoms of hyperactivity-impulsivity playing a prominent role. Conclusions: Early difficult temperament is a vulnerability factor for NEET status in adulthood. Our findings suggest that one developmental pathway for this vulnerability manifests through increased hyperactivity-impulsivity in childhood and ASB in adolescence. Of note, difficult temperament, as measured here, reflects difficulties in emotional and behavioural self-control (e.g. low adaptability and high intensity negative emotional expressions). Our results, therefore, suggest a prominent developmental role for lack of self-control from toddlerhood onwards in increasing risk for NEET

High-frequency operation of a DC/AC/DC system for HVDC applications

Voltage ratings for HVdc point-to-point connections are not standardized and tend to depend on the latest available cable technology. DC/DC conversion at HV is required for interconnection of such HVdc schemes as well as to interface dc wind farms. Modular multilevel voltage source converters (VSCs), such as the modular multilevel converter (MMC) or the alternate arm converter (AAC), have been shown to incur significantly lower switching losses than previous two- or three-level VSCs. This paper presents a dc/ac/dc system using a transformer coupling two modular multilevel VSCs. In such a system, the capacitors occupy a large fraction of the volume of the cells but a significant reduction in volume can be achieved by raising the ac frequency. Using high frequency can also bring benefits to other passive components such as the transformer but also results in higher switching losses due to the higher number of waveform steps per second. This leads to a tradeoff between volume and losses which has been explored in this study and verified by simulation results with a transistor level model of 30-MW case study. The outcome of the study shows that a frequency of 350 Hz provides a significant improvement in volume but also a penalty in losses compared to 50 Hz

Developmental pathways from toddler difficult temperament to child generalized psychopathology and adult functioning

BACKGROUND: Early difficult temperament and child mental health problems are consistently associated with impaired functioning in adulthood. We examined three potential pathways between difficult temperament in toddlerhood (age 2) and depressive symptoms (ages 21-23) and well-being (age 23): i) direct - early difficult temperament directly associates with these outcomes, ii) mediated - these direct effects are also mediated by a general psychopathology factor in late childhood/early adolescence (GPF; ages 7, 10,and 13), and iii) moderated-mediated - these mediated effects are also moderated by negative (age 42 months) and positive (age 33 months) parenting behaviors. METHODS: The analytic sample included 1892 mother-child dyads (33.4% male children) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers reported on their child's difficult temperament, negative parenting, positive parenting, and child's mental health symptoms. In adulthood, participants reported their own depressive symptoms and well-being (i.e. mental well-being, life satisfaction, happiness). RESULTS: First, early difficult temperament associated directly and positively with depressive symptoms, but negatively with well-being in adulthood. Second, the GPF in late childhood/early adolescence mediated these direct associations. Third, the mediated pathways were not moderated by negative or positive parenting. LIMITATIONS: i) low risk community sample, ii) early risks are based on maternal reports. CONCLUSIONS: Temperament is a risk factor for impaired psychosocial functioning in adulthood, manifested through increased susceptibility to psychopathology in childhood/adolescence. Although more research is needed to test their generalizability, these findings suggest that targeting early difficult temperament may alleviate the risk for later mental health difficulties and may increase general well-being

High-resolution quantitative MRI of multiple sclerosis spinal cord lesions

PURPOSE: Validation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord. METHODS: Four fixed spinal cord samples were imaged first with a 3T clinical MR scanner to identify areas of interest for scanning, and then with a 7T small bore scanner using a multicomponent‐driven equilibrium single‐pulse observation of T(1) and T(2) protocol to produce apparent proton density, T(1), T(2), myelin water, intracellular water, and free‐water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps. RESULTS: Excellent correspondence was found between high‐resolution MR parameter maps and histology, particularly for apparent proton density MRI and myelin basic protein staining. CONCLUSION: High‐resolution quantitative MRI of the spinal cord provides biologically meaningful measures, and could be beneficial to diagnose and track multiple sclerosis lesions in the spinal cord

High-resolution quantitative MRI of multiple sclerosis spinal cord lesions

Purpose: Validation of quantitative MR measuresfor myelin imaging in the postmortem multiple sclerosis spinal cord. Methods: Four fixed spinal cord samples were imaged first with a 3T clinical MR scannerto identify areas of interest forscanning, and then with a 7T small bore scanner using a multicomponent-driven equilibrium single-pulse observation of T1 and T2 protocol to produce apparent proton density, T1, T2, myelin water, intracellular water, and free-water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps. Results: Excellent correspondence was found between high-resolution MR parameter maps and histology, particularly for apparent proton density MRI and myelin basic protein staining. Conclusion: High-resolution quantitative MRI of the spinal cord provides biologically meaningful measures, and could be beneficial to diagnose and track multiple sclerosis lesions in the spinal cord

Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data

Objective: To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans. Methods: We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI-visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG. Results: Seizure-onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG. Significance: Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co-located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery

Microstructural Imaging in Temporal Lobe Epilepsy: Diffusion Imaging Changes Relate to Reduced Neurite Density

Purpose: Previous imaging studies in patients with refractory temporal lobe epilepsy (TLE) have examined the spatial distribution of changes in imaging parameters such as diffusion tensor imaging (DTI) metrics and cortical thickness. Multi-compartment models offer greater specificity with parameters more directly related to known changes in TLE such as altered neuronal density and myelination. We studied the spatial distribution of conventional and novel metrics including neurite density derived from NODDI (Neurite Orientation Dispersion and Density Imaging) and myelin water fraction (MWF) derived from mcDESPOT (Multi-Compartment Driven Equilibrium Single Pulse Observation of T1/T2)] to infer the underlying neurobiology of changes in conventional metrics. / Methods: 20 patients with TLE and 20 matched controls underwent magnetic resonance imaging including a volumetric T1-weighted sequence, multi-shell diffusion from which DTI and NODDI metrics were derived and a protocol suitable for mcDESPOT fitting. Models of the grey matter-white matter and grey matter-CSF surfaces were automatically generated from the T1-weighted MRI. Conventional diffusion and novel metrics of neurite density and MWF were sampled from intracortical grey matter and subcortical white matter surfaces and cortical thickness was measured. / Results: In intracortical grey matter, diffusivity was increased in the ipsilateral temporal and frontopolar cortices with more restricted areas of reduced neurite density. Diffusivity increases were largely related to reductions in neurite density, and to a lesser extent CSF partial volume effects, but not MWF. In subcortical white matter, widespread bilateral reductions in fractional anisotropy and increases in radial diffusivity were seen. These were primarily related to reduced neurite density, with an additional relationship to reduced MWF in the temporal pole and anterolateral temporal neocortex. Changes were greater with increasing epilepsy duration. Bilaterally reduced cortical thickness in the mesial temporal lobe and centroparietal cortices was unrelated to neurite density and MWF. / Conclusions: Diffusivity changes in grey and white matter are primarily related to reduced neurite density with an additional relationship to reduced MWF in the temporal pole. Neurite density may represent a more sensitive and specific biomarker of progressive neuronal damage in refractory TLE that deserves further study