119 research outputs found

    Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration

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    Objective: To assess the contribution of in utero magnetic resonance (iuMR) imaging in fetuses diagnosed with either agenesis of the corpus callosum or hypogenesis of the corpus callosum (grouped as failed commissuration) on antenatal ultrasonography (USS) from the MERIDIAN cohort. Methods: We report a sub-group analysis of fetuses with failed commissuration diagnosed on USS (with or without ventriculomegaly) from the MERIDIAN study who had iuMR imaging within 2 weeks of USS and outcome reference data were available. The diagnostic accuracy of USS and iuMR are reported as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Results: 79 fetuses with failed commissuration are reported (55 with agenesis and 24 with hypogenesis as the USS diagnoses). The diagnostic accuracy for detecting ‘failed commissuration’ as a group label was 34.2% for USS and 94.9% for iuMR (difference = 60.7%, 95% confidence interval 47.6% to 73.9%, p < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for USS and 87.5% for iuMR whilst the diagnostic accuracy for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for USS and 92.7% for iuMR. There was a statistically significant improvement in ‘appropriate’ diagnostic confidence when using iuMR imaging as assessed by a score-based weighted average’ method (p < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after iuMR imaging and its overall effect on clinical management was ‘significant’, ‘major’ or ‘decisive’ in 35/79 cases (44.3%). Conclusions: Our data suggests that any woman whose fetus has failed commissuration as the only intracranial finding detected on USS should have iuMR imaging for further evaluation

    Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

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    Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

    Creation of a Queryable Toxicology Database Available to Forensic Pathologists

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    Acromioclavicular Joint Reconstruction

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    Our technique for acromioclavicular joint reconstruction provides a variation on coracoclavicular ligament reconstruction to also include acromioclavicular ligament reconstruction. An oblique acromial tunnel is drilled, and the medial limb of the gracilis graft, after being crossed and passed beneath the coracoid and through the clavicle, is passed through this acromial tunnel and sutured to the trapezoid graft limb after appropriate tensioning. Tenodesis screws are not placed in the bone tunnels to avoid graft fraying, and initial forces on the graft are offloaded with braided absorbable sutures passed around the clavicle

    Sinonasal Phosphaturic Mesenchymal Tumor: Case Report and Systematic Review

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    We report a case of sinonasal phosphaturic mesenchymal tumor (PMT) and conduct a systematic review of the literature to highlight a unique paraneoplastic syndrome associated with PMT. We used English language publications from Medline and Cochrane databases (1970–2013) as data sources. A systematic review of the literature was conducted. All reported cases of head and neck PMTs were included. The presence or absence of the associated paraneoplastic syndrome was noted. We found 33 cases of PMT in the head and neck reported in the literature, 17 of which occurred in the sinonasal area. Approximately 5% of all PMTs are located in the head and neck. Just greater than half are concentrated in the sinonasal area, and the remaining involve various bony and soft tissue structures of the head and neck. PMT is sometimes associated with a paraneoplastic syndrome of tumor-induced (oncogenic) osteomalacia (TIO) causing bone pain, muscle weakness, and pathologic fractures. We present the 18th reported case of sinonasal PMT. A smooth mucosa-covered midline intraseptal mass filling the posterior nasal cavity with destruction and erosion of the skull base was found in an adult male. The patient underwent successful endoscopic resection with wide negative margins and is without recurrence at 24-month follow-up. PMT is a benign, locally aggressive tumor with rare malignant transformation. Knowledge of the bony invasion and destruction caused by this tumor is essential in planning surgical resection with wide negative margins. Familiarity with the associated TIO is essential to investigate for and manage any associated bony morbidity
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