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Circulating Anti-Müllerian hormone (AMH) is derived from the gonads, and is a mixture of the prohormone (proAMH), which does not bind to AMH receptors, and receptor-competent AMH. The functions of a hormone are partially defined by the factors that control its levels. Ovarian reserve accounts for 55~75% of the woman-to-woman variation in AMH level, leaving over 25% of the biological variation to be explained. Pregnancy has been reported to decrease circulating AMH levels, but the observations are inconsistent, with the effect of pregnancy on the bioactivity of AMH being unknown. We have therefore undertaken a longitudinal study of circulating proAMH and total AMH during pregnancy. Serum samples were drawn at 6-8 gestational time-points (first trimester to post-partum) from 25 healthy women with prior uneventful pregnancies. The total AMH and proAMH levels were measured at each time-point using ELISA. The level of circulating total AMH progressively decreased during pregnancy, in all women (p<0.001). On average, the percentage decline between the first trimester and 36-39 weeks' gestation was 61.5%, with a standard deviation of 13.0% (range 30.4-81.2%). The percentage decline in total AMH levels associated with maternal age (R = -0.53, p = 0.024), but not with the women's first trimester AMH level. The postpartum total AMH levels showed no consistent relationship to the woman's first trimester values (range 31-273%). This raises the possibility that a fundamental determinant of circulating AMH levels is reset during pregnancy. The ratio of proAMH to total AMH levels exhibited little or no variation during pregnancy, indicating that the control of the cleavage/activation of AMH is distinct from the mechanisms that control the total level of AMH., Competing Interests: ISM and MWP have filed a patent pertaining to cleavage-state-specific AMH assays including the proAMH-specific assay used in this manuscript (WO 2014/204327 A1). This does not alter our adherence to PLOS ONE policies on sharing data and materials. CAC, JZ and CAL have declared that no competing interests exist.

In Diffusion Weighted MR Imaging (DWI), the signal is affected by the biophysical properties of neuronal cells and their relative placement, as well as extra-cellular tissue compartments. Typically, microstructural indices, such as fractional anisotropy (FA) and mean diffusivity (MD), are based on a tensor model that cannot disentangle the influence of these parameters. Recently, Neurite Orientation Dispersion and Density Imaging (NODDI) has exploited multi-shell acquisition protocols to model the diffusion signal as the contribution of three tissue compartments. NODDI microstructural indices, such as intra-cellular volume fraction (ICVF) and orientation dispersion index (ODI) are directly related to neuronal density and orientation dispersion, respectively. One way of examining the neurophysiological role of these microstructural indices across neuronal fibres is to look into how they relate to brain function. Here we exploit a statistical framework based on sparse Canonical Correlation Analysis (sCCA) and randomised Lasso to identify structural connections that are highly correlated with resting-state functional connectivity measured with simultaneous EEG-fMRI. Our results reveal distinct structural fingerprints for each microstructural index that also reflect their inter-relationships.

Background: Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population., Methods: Forty-six children with focal epilepsy and 20 controls (6-18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions"), for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions"). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject., Findings: Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance., Conclusions: A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results.

Structural brain networks may be reconstructed from diffusion MRI tractography data and have great potential to further our understanding of the topological organisation of brain structure in health and disease. Network reconstruction is complex and involves a series of processesing methods including anatomical parcellation, registration, fiber orientation estimation and whole-brain fiber tractography. Methodological choices at each stage can affect the anatomical accuracy and graph theoretical properties of the reconstructed networks, meaning applying different combinations in a network reconstruction pipeline may produce substantially different networks. Furthermore, the choice of which connections are considered important is unclear. In this study, we assessed the similarity between structural networks obtained using two independent state-of-the-art reconstruction pipelines. We aimed to quantify network similarity and identify the core connections emerging most robustly in both pipelines. Similarity of network connections was compared between pipelines employing different atlases by merging parcels to a common and equivalent node scale. We found a high agreement between the networks across a range of fiber density thresholds. In addition, we identified a robust core of highly connected regions coinciding with a peak in similarity across network density thresholds, and replicated these results with atlases at different node scales. The binary network properties of these core connections were similar between pipelines but showed some differences in atlases across node scales. This study demonstrates the utility of applying multiple structural network reconstrution pipelines to diffusion data in order to identify the most important connections for further study.

It has been shown that virus infections, often symptomless, significantly limit sweetpotato productivity, especially in regions characterized by low input agricultural systems. In sweetpotatoes, the successful emergence and development of lateral roots (LRs), the main determinant of root architecture, determines the competency of adventitious roots to undergo storage root initiation. This study aimed to investigate the effect of some plant viruses on root architecture attributes during the onset of storage root initiation in 'Beauregard' sweetpotatoes that were grown with or without the presence of nitrogen. In two replicate experiments, virus-tested plants consistently failed to show visible symptoms at 20 days regardless of nitrogen treatment. In both experiments, the severity of symptom development among infected plants ranged from 25 to 118% when compared to the controls (virus tested plants grown in the presence of nitrogen). The presence of a complex of viruses (Sweet potato feathery mottle virus, Sweet potato virus G, Sweet potato virus C, and Sweet potato virus 2) was associated with 51% reduction in adventitious root number among plants grown without nitrogen. The effect of virus treatments on first order LR development depended on the presence or absence of nitrogen. In the presence of nitrogen, only plants infected with Sweet potato chlorotic stunt virus showed reductions in first order LR length, number, and density, which were decreased by 33%, 12%, and 11%, respectively, when compared to the controls. In the absence of nitrogen, virus tested and infected plants manifested significant reductions for all first order LR attributes. These results provide evidence that virus infection directly influences sweetpotato yield potential by reducing both the number of adventitious roots and LR development. These findings provide a framework for understanding how virus infection reduces sweetpotato yield and could lead to the development of novel strategies to mitigate virus effects on sweetpotato productivity.

The ability to assess brain tumor perfusion and abnormalities in the vascular structure in vivo could provide significant benefits in terms of lesion diagnosis and assessment of treatment response. Arterial spin labeling (ASL) has emerged as an increasingly viable methodology for non-invasive assessment of perfusion. Although kinetic models have been developed to describe perfusion in healthy tissue, the dynamic behaviour of the ASL signal in the brain tumor environment has not been extensively studied. We show here that dynamic ASL data acquired in brain tumors displays an increased level of 'biphasic' behaviour, compared to that seen in healthy tissue. A new two-stage model is presented which more accurately describes this behaviour, and provides measurements of perfusion, pre-capillary blood volume fraction and transit time, and capillary bolus arrival time. These biomarkers offer a novel contrast in the tumor and surrounding tissue, and provide a means for measuring tumor perfusion and vascular structural abnormalities in a fully non-invasive manner.

Graph representations of brain connectivity have attracted a lot of recent interest, but existing methods for dividing such graphs into connected subnetworks have a number of limitations in the context of neuroimaging. This is an important problem because most cognitive functions would be expected to involve some but not all brain regions. In this paper we outline a simple approach for decomposing graphs, which may be based on any measure of interregional association, into coherent "principal networks". The technique is based on an eigendecomposition of the association matrix, and is closely related to principal components analysis. We demonstrate the technique using cortical thickness and diffusion tractography data, showing that the subnetworks which emerge are stable, meaningful and reproducible. Graph-theoretic measures of network cost and efficiency may be calculated separately for each principal network. Unlike some other approaches, all available connectivity information is taken into account, and vertices may appear in none or several of the subnetworks. Subject-by-subject "scores" for each principal network may also be obtained, under certain circumstances, and related to demographic or cognitive variables of interest.

Objectives: To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified., Patients and Methods: Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed., Results: Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r = -0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores., Conclusions: Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.

Background: Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain., Objective: Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years., Design/methods: The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998-2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning., Results: At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk., Conclusions: Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.

Parkinson's disease (PD) results in movement and sensory impairments that can be reduced by familiar music. At present, it is unclear whether the beneficial effects of music are limited to lessening the bradykinesia of whole body movement or whether beneficial effects also extend to skilled movements of PD subjects. This question was addressed in the present study in which control and PD subjects were given a skilled reaching task that was performed with and without accompanying preferred musical pieces. Eye movements and limb use were monitored with biomechanical measures and limb movements were additionally assessed using a previously described movement element scoring system. Preferred musical pieces did not lessen limb and hand movement impairments as assessed with either the biomechanical measures or movement element scoring. Nevertheless, the PD patients with more severe motor symptoms as assessed by Hoehn and Yahr (HY) scores displayed enhanced visual engagement of the target and this impairment was reduced during trials performed in association with accompanying preferred musical pieces. The results are discussed in relation to the idea that preferred musical pieces, although not generally beneficial in lessening skilled reaching impairments, may normalize the balance between visual and proprioceptive guidance of skilled reaching.