32 research outputs found

    Seizure prediction : ready for a new era

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    Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

    Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

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    Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts’ maps could uncover functionally and clinically related genes.Molecular Psychiatry advance online publication, 31 May 2016; doi:10.1038/mp.2016.84

    Dynamics of a vertical cavity quantum cascade phonon laser structure

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    Driven primarily by scientific curiosity, but also by the potential applications of intense sources of coherent sound, researchers have targeted the phonon laser (saser) since the invention of the optical laser over 50 years ago. Here we fabricate a vertical cavity structure designed to operate as a saser oscillator device at a frequency of 325 GHz. It is based on a semiconductor superlattice gain medium, inside a multimode cavity between two acoustic Bragg reflectors. We measure the acoustic output of the device as a function of time after applying electrical pumping. The emission builds in intensity reaching a steady state on a timescale of order 0.1 μs. We show that the results are consistent with a model of the dynamics of a saser cavity exactly analogous to the models used for describing laser dynamics. We also obtain estimates for the gain coefficient, steady-state acoustic power output and efficiency of the device

    Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy

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    Importance A functional area associated with the piriform cortex, termed area tempestas, has been implicated in animal studies as having a crucial role in modulating seizures, but similar evidence is limited in humans. Objective To assess whether removal of the piriform cortex is associated with postoperative seizure freedom in patients with temporal lobe epilepsy (TLE) as a proof-of-concept for the relevance of this area in human TLE. Design, Setting, and Participants This cohort study used voxel-based morphometry and volumetry to assess differences in structural magnetic resonance imaging (MRI) scans in consecutive patients with TLE who underwent epilepsy surgery in a single center from January 1, 2005, through December 31, 2013. Participants underwent presurgical and postsurgical structural MRI and had at least 2 years of postoperative follow-up (median, 5 years; range, 2-11 years). Patients with MRI of insufficient quality were excluded. Findings were validated in 2 independent cohorts from tertiary epilepsy surgery centers. Study follow-up was completed on September 23, 2016, and data were analyzed from September 24, 2016, through April 24, 2018. Exposures Standard anterior temporal lobe resection. Main Outcomes and Measures Long-term postoperative seizure freedom. Results In total, 107 patients with unilateral TLE (left-sided in 68; 63.6% women; median age, 37 years [interquartile range {IQR}, 30-45 years]) were included in the derivation cohort. Reduced postsurgical gray matter volumes were found in the ipsilateral piriform cortex in the postoperative seizure-free group (n = 46) compared with the non–seizure-free group (n = 61). A larger proportion of the piriform cortex was resected in the seizure-free compared with the non–seizure-free groups (median, 83% [IQR, 64%-91%] vs 52% [IQR, 32%-70%]; P < .001). The results were seen in left- and right-sided TLE and after adjusting for clinical variables, presurgical gray matter alterations, presurgical hippocampal volumes, and the proportion of white matter tract disconnection. Findings were externally validated in 2 independent cohorts (31 patients; left-sided TLE in 14; 54.8% women; median age, 41 years [IQR, 31-46 years]). The resected proportion of the piriform cortex was individually associated with seizure outcome after surgery (derivation cohort area under the curve, 0.80 [P < .001]; external validation cohorts area under the curve, 0.89 [P < .001]). Removal of at least half of the piriform cortex increased the odds of becoming seizure free by a factor of 16 (95% CI, 5-47; P < .001). Other mesiotemporal structures (ie, hippocampus, amygdala, and entorhinal cortex) and the overall resection volume were not associated with outcomes. Conclusions and Relevance These results support the importance of resecting the piriform cortex in neurosurgical treatment of TLE and suggest that this area has a key role in seizure generation

    Anti-mullerian hormone and cumulative pregnancy outcome in in-vitro fertilization

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    Purpose: To evaluate the role of Anti-mullerian hormone (AMH) in predicting cumulative pregnancy outcome during in-vitro fertilization (IVF) treatment. Methods: Serum AMH levels on day 6 of ovarian stimulation were taken from 180 women undergoing IVF with or without intracytoplasmic sperm injection (ICSI). The main outcome measures were ongoing pregnancy in the fresh cycle, cumulative ongoing pregnancy and ovarian response. Results: There was a trend of higher median AMH levels in subjects achieving ongoing pregnancy in the fresh IVF cycle. The median AMH levels were significantly higher in subjects attaining ongoing pregnancy cumulatively and in subjects showing ovarian hyper-response in the stimulated cycle. Areas under the ROC curves were 0.606 and 0.792 for the prediction of cumulative ongoing pregnancy and ovarian hyper-response respectively. Conclusions: Serum AMH concentration on day 6 of stimulation was significantly higher in subjects who achieved cumulative ongoing pregnancy in IVF compared to those who did not. Serum AMH is a reasonably good predictor of ovarian hyper-response. © 2010 Springer Science+Business Media, LLC.link_to_subscribed_fulltex

    Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3

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    Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital malformation characterised by limb and craniofacial anomalies, caused by heterozygous mutation or deletion of GLI3. We report four boys and a girl who were presented with trigonocephaly due to metopic synostosis, in association with pre- and post-axial polydactyly and cutaneous syndactyly of hands and feet. Two cases had additional sagittal synostosis. None had a family history of similar features. In all five children, the diagnosis of GCPS was confirmed by molecular analysis of GLI3 (two had intragenic mutations and three had complete gene deletions detected on array comparative genomic hybridisation), thus highlighting the importance of trigonocephaly or overt metopic or sagittal synostosis as a distinct presenting feature of GCPS. These observations confirm and extend a recently proposed association of intragenic GLI3 mutations with metopic synostosis; moreover, the three individuals with complete deletion of GLI3 were previously considered to have Carpenter syndrome, highlighting an important source of diagnostic confusion
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