1,973 research outputs found
Anatomical and molecular properties of long descending propriospinal neurons in mice
Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord. LDPNs were retrogradely labelled from the lumbar spinal cord to map cell body locations throughout the cervical and upper thoracic segments. Ipsilateral LDPNs were distributed throughout the dorsal, intermediate and ventral grey matter as well as the lateral spinal nucleus and lateral cervical nucleus. In contrast, contralateral LDPNs were more densely concentrated in the ventromedial grey matter. Retrograde labelling in GlyT2GFP and GAD67GFP mice showed the majority of inhibitory LDPNs project either ipsilaterally or adjacent to the midline. Additionally, we used several transgenic mouse lines to define the developmental provenance of LDPNs and found that V2b positive neurons form a subset of ipsilaterally projecting LDPNs. Finally, a population of Neurobiotin (NB) labelled LDPNs were assessed in detail to examine morphology and plot the spatial distribution of contacts from a variety of neurochemically distinct axon terminals. These results provide important baseline data in mice for future work on their role in locomotion and recovery from SCI
Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E
Purpose This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer. Methods Six patients with locally advanced, potentially resectable esophageal cancer received pemetrexed 500 mg/m 2 and carboplatin AUC = 6 on days 1 and 22 with 5040 centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by esophagectomy as a prelude to a phase II multi-institutional trial. Results Only 1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This patient also experienced a grade 3 depression. Of the remaining 5 patients, three experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and esophagitis). There were no deaths. Incidentally, one patient manifested a complete pathologic response, three a partial pathologic response, and one stable disease. Conclusion These preliminary observations on safety suggest that this regimen can be further studied in this clinical setting
Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals
We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18Â weeks gestation (WG). During early fetal development (11â14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent type II hair cells. As development progressed (15â18 WG), peak outward conductances increased in putative type II hair cells but did not reach amplitudes observed in adult human hair cells. Type I hair cells express a specific low-voltage activating conductance, G(K,L). A similar current was first observed at 15 WG but remained relatively small, even at 18 WG. The presence of a âcollapsingâ tail current indicates a maturing type I hair cell phenotype and suggests the presence of a surrounding calyx afferent terminal. We were also able to record from calyx afferent terminals in 15â18 WG cristae. In voltage clamp, these terminals exhibited fast inactivating inward as well as slower outward conductances, and in current clamp, discharged a single action potential during depolarizing steps. Together, these data suggest the major functional characteristics of type I and type II hair cells and calyx terminals are present by 18 WG. Our study also describes a new preparation for the functional investigation of key events that occur during maturation of human vestibular organs
Deforming glassy polystyrene: Influence of pressure, thermal history, and deformation mode on yielding and hardening
The toughness of a polymer glass is determined by the interplay of yielding, strain softening, and strain hardening. Molecular-dynamics simulations of a typical polymer glass, atactic polystyrene, under the influence of active deformation have been carried out to enlighten these processes. It is observed that the dominant interaction for the yield peak is of interchain nature and for the strain
hardening of intrachain nature. A connection is made with the microscopic cage-to-cage motion. It is found that the deformation does not lead to complete erasure of the thermal history but that differences persist at large length scales. Also we find that the strain-hardening modulus increases with increasing external pressure. This new observation cannot be explained by current theories
such as the one based on the entanglement picture and the inclusion of this effect will lead to an improvement in constitutive modeling
Universal aspects of vacancy-mediated disordering dynamics: the effect of external fields
We investigate the disordering of an initially phase-segregated binary alloy,
due to a highly mobile defect which couples to an electric or gravitational
field. Using both mean-field and Monte Carlo methods, we show that the late
stages of this process exhibit dynamic scaling, characterized by a set of
exponents and scaling functions. A new scaling variable emerges, associated
with the field. While the scaling functions carry information about the field
and the boundary conditions, the exponents are universal. They can be computed
analytically, in excellent agreement with simulation results.Comment: 15 pages, 6 figure
Neoadjuvant chemoradiation compared to neoadjuvant radiation alone and surgery alone for Stage II and III soft tissue sarcoma of the extremities
<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA).</p> <p>Methods</p> <p>We conducted a retrospective chart review of 112 cases.</p> <p>Results</p> <p>Treatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR.</p> <p>Conclusions</p> <p>NCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.</p
Optimal Packings of Superballs
Dense hard-particle packings are intimately related to the structure of
low-temperature phases of matter and are useful models of heterogeneous
materials and granular media. Most studies of the densest packings in three
dimensions have considered spherical shapes, and it is only more recently that
nonspherical shapes (e.g., ellipsoids) have been investigated. Superballs
(whose shapes are defined by |x1|^2p + |x2|^2p + |x3|^2p <= 1) provide a
versatile family of convex particles (p >= 0.5) with both cubic- and
octahedral-like shapes as well as concave particles (0 < p < 0.5) with
octahedral-like shapes. In this paper, we provide analytical constructions for
the densest known superball packings for all convex and concave cases. The
candidate maximally dense packings are certain families of Bravais lattice
packings. The maximal packing density as a function of p is nonanalytic at the
sphere-point (p = 1) and increases dramatically as p moves away from unity. The
packing characteristics determined by the broken rotational symmetry of
superballs are similar to but richer than their two-dimensional "superdisk"
counterparts, and are distinctly different from that of ellipsoid packings. Our
candidate optimal superball packings provide a starting point to quantify the
equilibrium phase behavior of superball systems, which should deepen our
understanding of the statistical thermodynamics of nonspherical-particle
systems.Comment: 28 pages, 16 figure
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An evaluation of CT radiation doses within the Yorkshire Lung Screening Trial
YesObjectives;
To evaluate radiation doses for all low-dose CT scans performed during the first year of a lung screening trial.
Methods;
For all lung screening scans that were performed using a CT protocol that delivered image quality meeting the RSNA QIBA criteria, , radiation dose metrics, participant height, weight, gender and age were recorded. Values of CTDIvol and DLP were evaluated as a function of weight in order to assess the performance of the scan protocol across the participant cohort. Calculated effective doses were used to establish the additional lifetime attributable cancer risks arising from trial scans.
Results;
Median values of CTDIvol, DLP and effective dose (IQR) from the 3521 scans were 1.1mGy (0.70), 42.4mGycm (24.9) and 1.15mSv (0.67), whilst for 60-80kg participants the values were 1.0mGy (0.30), 35.8mGycm (11.4) and 0.97mSv (0.31). A statistically significant correlation between CTDIvol and weight was identified for males (r=0.9123, p<0.001) and females (r=0.9052, p<0.001), however the effect of gender on CTDIvol was not statistically significant (p=0.2328) despite notable differences existing at the extremes of the weight range. The additional lifetime attributable cancer risks from a single scan were in the range 0.001-0.006%.
Conclusions;
Low radiation doses can be achieved across a typical lung screening cohort using scan protocols that have been shown to deliver high levels of image quality. The observed dose levels may be considered as typical values for lung screening scans on similar types of scanner for an equivalent participant cohort.
Advances in Knowledge;
Presentation of typical radiation dose levels for CT lung screening examinations in a large UK trial.
Effective radiation doses can be of the order of 1mSv for standard sized participants.
Lifetime attributable cancer risks resulting from a single LDCT scan did not exceed 0.006%.The Yorkshire Lung Screening Trial is funded by Yorkshire Cancer Research (award reference L403)
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