2,412 research outputs found

    Future precipitation projections over central and southern Africa and the adjacent Indian Ocean: what causes the changes and the uncertainty?

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    Future projections of precipitation at regional scales are vital to inform climate change adaptation activities. Therefore, is it important to quantify projected changes and associated uncertainty, and understand model processes responsible. This paper addresses these challenges for Southern Africa and adjacent Indian Ocean focusing on the local wet season. Precipitation projections for the end of the 21st century indicate a pronounced dipole pattern in the CMIP5 multi-model mean. The dipole indicates future wetting (drying) to the north (south) of the climatological axis of maximum rainfall, implying a northward shift of the ITCZ and South Indian Ocean Convergence Zone, and therefore not consistent with a simple ‘wet-get-wetter’ pattern. This pattern is most pronounced in early Austral summer suggesting a later and shorter wet season over much of southern Africa. Using a decomposition method we determine physical mechanisms underlying this dipole pattern of projected change, and the associated inter-model uncertainty. The projected dipole pattern is largely associated with the dynamical component of change indicative of shifts in the location of convection. Over the Indian Ocean, this apparent northward shift in the ITCZ may reflect the response to changes in the north-south SST gradient over the Indian Ocean, consistent with a ‘warmest-get-wetter’ mechanism. Over land subtropical drying is relatively robust, particularly in the early wet season. This has contributions from dynamical shifts in location of convection, which may be related to regional SST structures in the Southern Indian Ocean, and the thermodynamic decline in relative humidity. Implications for understanding and potentially constraining uncertainty in projections are discussed

    Optic radiation structure and anatomy in the normally developing brain determined using diffusion MRI and tractography

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    The optic radiation (OR) is a component of the visual system known to be myelin mature very early in life. Diffusion tensor imaging (DTI) and its unique ability to reconstruct the OR in vivo were used to study structural maturation through analysis of DTI metrics in a cohort of 90 children aged 5–18 years. As the OR is at risk of damage during epilepsy surgery, we measured its position relative to characteristic anatomical landmarks. Anatomical distances, DTI metrics and volume of the OR were investigated for age, gender and hemisphere effects. We observed changes in DTI metrics with age comparable to known trajectories in other white matter tracts. Left lateralization of DTI metrics was observed that showed a gender effect in lateralization. Sexual dimorphism of DTI metrics in the right hemisphere was also found. With respect to OR dimensions, volume was shown to be right lateralised and sexual dimorphism demonstrated for the extent of the left OR. The anatomical results presented for the OR have potentially important applications for neurosurgical planning

    Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

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    ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

    The tropical route of quasi-biennial oscillation (QBO) teleconnections in a climate model

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    The influence of the quasi-biennial oscillation (QBO) on tropical climate is demonstrated using 500-year pre-industrial control simulations from the Met Office Hadley Centre model. Robust precipitation responses to the phase of the QBO are diagnosed in the model, which show zonally asymmetric patterns that resemble the El Niño–Southern Oscillation (ENSO) impacts. These patterns are found because the frequency of ENSO events for each QBO phase is significantly different in these simulations, with more El Niño events found under the westerly phase of the QBO (QBOW) and more La Niña events for the easterly phase (QBOE). The QBO–ENSO relationship is non-stationary and subject to decadal variability in both models and observations. In addition, regression analysis shows that there is a QBO signal in precipitation that is independent of ENSO. No evidence is found to suggest that these QBO–ENSO relationships are caused by ENSO modulating the QBO in the simulations. A relationship between the QBO and a dipole of precipitation in the Indian Ocean is also found in models and observations in boreal fall, characterised by a wetter western Indian Ocean and drier conditions in the eastern part for QBOW and the opposite under QBOE conditions. The Walker circulation is significantly weaker during QBOW compared to QBOE, which could explain the observed and simulated zonally asymmetric precipitation responses at equatorial latitudes, as well as the more frequent El Niño events during QBOW. Further work, including targeted model experiments, is required to better understand the mechanisms causing these relationships between the QBO and tropical convection.</p

    Employment mobility in high-technology agglomerations: the cases of Oxfordshire and Cambridgeshire

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    This paper examines labour market behaviour of the highly skilled in high-tech local economies, taking the UK examples of Oxfordshire and Cambridgeshire as case studies. It reports on data from a survey of members of three scientific institutes to compare rates of employee mobility in the two locations and considers the likely explanations and implications of those patterns

    Decoding information in the human hippocampus: a user's guide

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    Multi-voxel pattern analysis (MVPA), or 'decoding', of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus

    GIT2 Acts as a Potential Keystone Protein in Functional Hypothalamic Networks Associated with Age-Related Phenotypic Changes in Rats

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    The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process
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