Faculty Bibliography

Clinical microbiology automation is currently limited by the lack of an in-plate culture identification system. Using an inexpensive, printed, disposable colorimetric sensor array (CSA) responsive to the volatiles emitted into plate headspace by microorganisms during growth, we report here that not only the presence but the species of bacteria growing in plate was identified before colonies are visible. In 1894 trials, 15 pathogenic bacterial species cultured on blood agar were identified with 91.0% sensitivity and 99.4% specificity within 3 hours of detection. The results indicate CSAs integrated into Petri dish lids present a novel paradigm to speciate microorganisms, well-suited to integration into automated plate handling systems.

Two amino acids play a key role in the first total synthesis of lycopalhine A. L-glutamic acid serves as a convenient chiral starting material for the 13-step synthesis, and l-proline promotes an unusual 5-endo-trig Mannich cyclization that generates the central pyrrolidine ring of the Lycopodium alkaloid. The bicyclo[3.3.0]octanol moiety of the molecule is formed through an intramolecular aldol addition that may occur spontaneously in nature.

The precise connectivity of somatostatin and parvalbumin cortical interneurons is generated during development. An understanding of how these interneuron classes incorporate into cortical circuitry is incomplete but essential to elucidate the roles they play during maturation. Here, we report that somatostatin interneurons in infragranular layers receive dense but transient innervation from thalamocortical afferents during the first postnatal week. During this period, parvalbumin interneurons and pyramidal neurons within the same layers receive weaker thalamocortical inputs, yet are strongly innervated by somatostatin interneurons. Further, upon disruption of the early (but not late) somatostatin interneuron network, the synaptic maturation of thalamocortical inputs onto parvalbumin interneurons is perturbed. These results suggest that infragranular somatostatin interneurons exhibit a transient early synaptic connectivity that is essential for the establishment of thalamic feedforward inhibition mediated by parvalbumin interneurons.

Hereditary sensory and autonomic neuropathy type III features disturbed proprioception and a marked ataxic gait. We recently showed that joint-angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers, and the absolute error, gradient and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle-matching test (mean matching error +/- SE 8.0 +/- 0.8 degrees , controls 3.0 +/- 0.3 degrees ). Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 +/- 0.7 degrees ) but not in the controls (3.0 +/- 0.2 degrees ). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

Electromagnetic field simulations are increasingly used to assure RF safety of patients during MRI exams. In practice, however, tissue property distribution of the patient being imaged is not known, but may be represented with a pre-existing model. Repeatedly, agreement in transmit magnetic (B1 +) field distributions between two geometries has been used to suggest agreement in heating distributions. Here we examine relative effects of anatomical differences on B1 + distribution, Specific Absorption Rate (SAR) and temperature change (DeltaT). Numerical simulations were performed for a single surface coil positioned adjacent a homogeneous phantom and bovine phantom, each with slight geometric variations, and adjacent two different human body models. Experimental demonstration was performed on a bovine phantom using MR thermometry and B1 + mapping. Simulations and experiments demonstrate that B1 + distributions in different samples can be well correlated, while notable difference in maximum SAR and DeltaT occur. This work illustrates challenges associated with utilizing simulations or experiments for RF safety assurance purposes. Reliance on B1 + distributions alone for validation of simulations and/or experiments with a sample or subject for assurance of safety in another should be performed with caution.

The packing of the title compound, C12H9N7.H2O, is dominated by hydrogen bonding and pi-stacking. Layers parallel to [010] are established by hydrogen bonds involving all amine donor functions and one of the water donor functions, while the remaining water donor function enables the stacking of the layers along [10-1], which is accompanied by pi-stacking. In the molecule, the plane of the central tetra-zine ring forms angles of 5.33 (7) and 19.84 (8) degrees with the adjacent 3-amine-pyridine and pyridine rings, respectively.

PURPOSE: To develop a novel framework for free-breathing MRI called XD-GRASP, which sorts dynamic data into extra motion-state dimensions using the self-navigation properties of radial imaging and reconstructs the multidimensional dataset using compressed sensing. METHODS: Radial k-space data are continuously acquired using the golden-angle sampling scheme and sorted into multiple motion-states based on respiratory and/or cardiac motion signals derived directly from the data. The resulting undersampled multidimensional dataset is reconstructed using a compressed sensing approach that exploits sparsity along the new dynamic dimensions. The performance of XD-GRASP is demonstrated for free-breathing three-dimensional (3D) abdominal imaging, two-dimensional (2D) cardiac cine imaging and 3D dynamic contrast-enhanced (DCE) MRI of the liver, comparing against reconstructions without motion sorting in both healthy volunteers and patients. RESULTS: XD-GRASP separates respiratory motion from cardiac motion in cardiac imaging, and respiratory motion from contrast enhancement in liver DCE-MRI, which improves image quality and reduces motion-blurring artifacts. CONCLUSION: XD-GRASP represents a new use of sparsity for motion compensation and a novel way to handle motions in the context of a continuous acquisition paradigm. Instead of removing or correcting motion, extra motion-state dimensions are reconstructed, which improves image quality and also offers new physiological information of potential clinical value. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc.

We present long-term pulmonary function test outcomes from an ongoing, open-label, multi-center, phase 3 extension study assessing the long-term safety and efficacy of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio syndrome type A. In part 1 of the extension study, patients who were initially randomized to ERT in the original placebo-controlled 24-week study [1] remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two treatment regimens. During part 2, all patients received ERT 2.0 mg/kg/week. Pulmonary function was evaluated as a secondary efficacy endpoint. Changes from the original 24-week study [1] baseline to 72 and 120 weeks are presented. In the 24-week study, non-statistical increases were seen in each dosing group for forced vital capacity (FVC) and maximum voluntary ventilation (MVV) versus placebo [1] and both endpoints continued to improve for the combined patient population during the extension study for up to 120 weeks. MVV increased from baseline by a mean (SE) of 1.78 (0.74) L/min by week 72 and 1.80 (1.04) L/min or 11.04 (4.55) % by week 120. FVC increased from baseline by a mean (SE) of 0.05 (0.01) L by week 72 and 0.08 (0.02) L or 8.6 (1.8) % by week 120. In contrast, matched untreated patients from the MorCAP natural history study [2] showed mean decreases in MVV and FVC over 2 years. In conclusion, long-term ERT causes sustained improvements in pulmonary function in patients with Morquio syndrome type A. References: 1. Hendriksz CJ, Burton B, Fleming TR, et al. J Inherit Metab Dis 2014;37:979-90. 2. Harmatz P, Mengel KE, Giugliani R, et al. Mol Genet Metab 2013;109:54-61. BioMarin Pharmaceutical Inc. sponsored this study.
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The exposome is the assembly and measure of all the exposures of an individual in a lifetime. An individual's exposures begin before birth and include insults from environmental and occupational sources. The associated field is called exposomics, which relies on the application of internal and external exposure assessment methods. Exposomics has not yet been thoroughly applied to the study of kidney stones although much is known about how diet and fluid intake affect nephrolithiasis. Some other novel exposures that may contribute to kidney stones are discussed including use of antibiotics, urbanization and migration to urban heat islands, and occupation. People whose school and jobs limit their access to fluids and adequate bathroom facilities may have higher prevalence of stones. Examples include athletes, teachers, heathcare workers, and cab drivers. Occupational kidney stones have received scant attention and may represent a neglected, and preventable, type of stone. An exposomic-oriented history would include a careful delineation of occupation and activities.