The effect of intraoperative specimen inking on lumpectomy re-excision rates

<p>Abstract</p> <p>Background</p> <p>Lumpectomy re-excision to obtain negative margins is common. We compare the effect of two specimen orientation approaches on lumpectomy re-excision rates.</p> <p>Methods</p> <p>All women undergoing lumpectomy for breast cancer by a single surgeon between 03/2007 - 02/2009 were included. Lumpectomies underwent standard inking (SI) after surgery by a pathologist from 03/2007-02/2008 while intraoperative inking (II) with direct surgeon input was done from 03/2008-02/2009. Rates of margin positivity and re-excision were compared between these methods.</p> <p>Results</p> <p>65 patients were evaluated, reflecting SI in 39 and II in 26 cases. Margin positivity rates of 46% [SI] vs. 23% [II] (p = 0.06) and re-excision rates of 38% [SI] vs. 19% [II] were observed. Residual disease at re-excision was found in 27% [SI] vs. 67% [II] of cases.</p> <p>Conclusions</p> <p>Intraoperative inking in this practice offered a simple way to reduce re-excision rates after lumpectomy and affect an improvement in quality of patient care.</p

Decrements of Muscle Protein Synthesis with Unloading are Not Due to Insufficient Concentrations of Intramuscular Leucine

Skeletal muscle mass and strength play critical roles in quality of life, and significant muscle atrophy contributes to reduced function and can exacerbate some disease states. It is well-known that persistent reductions of mechanical loading in skeletal muscle result in degeneration. Generally, reductions of muscle protein synthesis are, at least in part, a major culprit with muscle loss under these conditions, and numerous countermeasures such as exercise and nutritional supplements, known to stimulate protein synthesis have been designed to maintain muscle mass under those conditions. Amino acid supplementation, particularly with branched-chain amino acids (BCAAs), has been suggested as a countermeasure to deter muscle loss during spaceflight and bed rest, suggesting that these important protein precursors are not sufficiently available to support muscle protein synthesis during mechanical unloading. The purpose of this study was to examine the effect of muscle loading/unloading on the free amino acid pool of skeletal muscle in order to determine if concomitant alterations of the amino acid availability impact known changes in muscle protein synthesis under these conditions. We hypothesized reduced protein synthesis during periods of chronic unloading would be due to rate-limiting concentrations of one or more amino acids in the cytosolic free pool. Specific amino acid concentrations of 29 amino acids commonly found in the skeletal muscle cytosolic free-pool were assessed with high-performance liquid chromatography (HPLC) in gastrocnemius muscles taken from male Sprague Dawley rats that were assigned to various hindlimb unloading groups or ambulatory controls, with and without exercise countermeasures. Of the 29 amino acids tested, only one amino acid (nonessential aspartic acid) displayed an instance of concentrations significantly below control values (p ≤ 0.05). Surprisingly, each of the BCAAs, known agonists of muscle protein synthesis, displayed significant elevations in free-pool concentrations in unloaded muscle, even though muscle protein synthesis, and ultimately muscle mass were diminished. Leucine, a potent stimulant of muscle protein synthesis was over two times higher than the leucine concentrations of control muscles, suggesting that leucine was not sufficient to stimulate protein synthesis under conditions of microgravity. It also indicates that amino acid supplementation as a countermeasure may be ineffective, as circulating levels of available BCAAs are already elevated. These results suggest that additional efforts are required to find a suitable defense against muscle atrophy due to mechanical unloading

Patient prioritization of comorbid chronic conditions in the Veteran population: Implications for patient-centered care

OBJECTIVE: Patients with comorbid chronic conditions may prioritize some conditions over others; however, our understanding of factors influencing those prioritizations is limited. In this study, we sought to identify and elaborate a range of factors that influence how and why patients with comorbid chronic conditions prioritize their conditions. METHODS: We conducted semi-structured, one-on-one interviews with 33 patients with comorbidities recruited from a single Veterans Health Administration Medical Center. FINDINGS: The diverse factors influencing condition prioritization reflected three overarching themes: (1) the perceived role of a condition in the body, (2) self-management tasks, and (3) pain. In addition to these themes, participants described the rankings that they believed their healthcare providers would assign to their conditions as an influencing factor, although few reported having shared their priorities or explicitly talking with providers about the importance of their conditions. CONCLUSION: Studies that advance understanding of how and why patients prioritize their various conditions are essential to providing care that is patient-centered, reflecting what matters most to the individual while improving their health. This analysis informs guideline development efforts for the care of patients with comorbid chronic conditions as well as the creation of tools to promote patient-provider communication regarding the importance placed on different conditions

Active Control of Plasmonic–Photonic Interactions in a Microbubble Cavity

Active control of light–matter interactions using nanophotonic structures is critical for new modalities for solar energy production, cavity quantum electrodynamics (QED), and sensing, particularly at the single-particle level, where it underpins the creation of tunable nanophotonic networks. Coupled plasmonic–photonic systems show great promise toward these goals because of their subwavelength spatial confinement and ultrahigh-quality factors inherited from their respective components. Here, we present a microfluidic approach using microbubble whispering-gallery mode cavities to actively control plasmonic–photonic interactions at the single-particle level. By changing the solvent in the interior of the microbubble, control can be exerted on the interior dielectric constant and, thus, on the spatial overlap between the photonic and plasmonic modes. Qualitative agreement between experiment and simulation reveals the competing roles mode overlap and mode volume play in altering coupling strengths.journal articl

Cosmological Results from High-z Supernovae

The High-z Supernova Search Team has discovered and observed 8 new supernovae in the redshift interval z=0.3-1.2. These independent observations, confirm the result of Riess et al. (1998a) and Perlmutter et al. (1999) that supernova luminosity distances imply an accelerating universe. More importantly, they extend the redshift range of consistently observed SN Ia to z~1, where the signature of cosmological effects has the opposite sign of some plausible systematic effects. Consequently, these measurements not only provide another quantitative confirmation of the importance of dark energy, but also constitute a powerful qualitative test for the cosmological origin of cosmic acceleration. We find a rate for SN Ia of 1.4+/-0.5E-04 h^3/Mpc^3/yr at a mean redshift of 0.5. We present distances and host extinctions for 230 SN Ia. These place the following constraints on cosmological quantities: if the equation of state parameter of the dark energy is w=-1, then H0 t0 = 0.96+/-0.04, and O_l - 1.4 O_m = 0.35+/-0.14. Including the constraint of a flat Universe, we find O_m = 0.28+/-0.05, independent of any large-scale structure measurements. Adopting a prior based on the 2dF redshift survey constraint on O_m and assuming a flat universe, we find that the equation of state parameter of the dark energy lies in the range -1.48-1, we obtain w<-0.73 at 95% confidence. These constraints are similar in precision and in value to recent results reported using the WMAP satellite, also in combination with the 2dF redshift survey.Comment: 50 pages, AAS LateX, 15 figures, 15 tables. Accepted for publication by Astrophysical Journa

Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes

Although microarray analysis has provided information regarding the dynamics of gene expression during development of the mouse lung, no extensive correlations have been made to the levels of corresponding protein products. Here, we present a global survey of protein expression during mouse lung organogenesis from embryonic day E13.5 until adulthood using gel-free two-dimensional liquid chromatography coupled to shotgun tandem mass spectrometry (MudPIT). Mathematical modeling of the proteomic profiles with parallel DNA microarray data identified large groups of gene products with statistically significant correlation or divergence in coregulation of protein and transcript levels during lung development. We also present an integrative analysis of mRNA and protein expression in Nmyc loss- and gain-of-function mutants. This revealed a set of 90 positively and negatively regulated putative target genes. These targets are evidence that Nmyc is a regulator of genes involved in mRNA processing and a repressor of the imprinted gene Igf2r in the developing lung

Imaging and Demography of the Host Galaxies of High-Redshift Type Ia Supernovae

We present the results of a study of the host galaxies of high redshift Type Ia supernovae (SNe Ia). We provide a catalog of 18 hosts of SNe Ia observed with the Hubble Space Telescope (HST) by the High-z Supernova Search Team (HZT), including images, scale-lengths, measurements of integrated (Hubble equivalent) BVRIZ photometry in bands where the galaxies are brighter than m ~ 25 mag, and galactocentric distances of the supernovae. We compare the residuals of SN Ia distance measurements from cosmological fits to measurable properties of the supernova host galaxies that might be expected to correlate with variable properties of the progenitor population, such as host galaxy color and position of the supernova. We find mostly null results; the current data are generally consistent with no correlations of the distance residuals with host galaxy properties in the redshift range 0.42 < z < 1.06. Although a subsample of SN hosts shows a formally significant (3-sigma) correlation between apparent V-R host color and distance residuals, the correlation is not consistent with the null results from other host colors probed by our largest samples. There is also evidence for the same correlations between SN Ia properties and host type at low redshift and high redshift. These similarities support the current practice of extrapolating properties of the nearby population to high redshifts pending more robust detections of any correlations between distance residuals from cosmological fits and host properties.Comment: 35 pages, 12 figures, 4 tables, accepted for publication in A

Glacial sedimentation, fluxes and erosion rates associated with ice retreat in Petermann Fjord and Nares Strait, north-west Greenland

Petermann Fjord is a deep (>1000 m) fjord that incises the coastline of north-west Greenland and was carved by an expanded Petermann Glacier, one of the six largest outlet glaciers draining the modern Greenland Ice Sheet (GrIS). Between 5 and 70 m of unconsolidated glacigenic material infills in the fjord and adjacent Nares Strait, deposited as the Petermann and Nares Strait ice streams retreated through the area after the Last Glacial Maximum. We have investigated the deglacial deposits using seismic stratigraphic techniques and have correlated our results with high-resolution bathymetric data and core lithofacies. We identify six seismo-acoustic facies in more than 3500 line kilometres of sub-bottom and seismic-reflection profiles throughout the fjord, Hall Basin and Kennedy Channel. Seismo-acoustic facies relate to bedrock or till surfaces (Facies I), subglacial deposition (Facies II), deposition from meltwater plumes and icebergs in quiescent glacimarine conditions (Facies III, IV), deposition at grounded ice margins during stillstands in retreat (grounding-zone wedges; Facies V) and the redeposition of material downslope (Facies IV). These sediment units represent the total volume of glacial sediment delivered to the mapped marine environment during retreat. We calculate a glacial sediment flux for the former Petermann ice stream as 1080–1420 m3 a−1 per metre of ice stream width and an average deglacial erosion rate for the basin of 0.29–0.34 mm a−1. Our deglacial erosion rates are consistent with results from Antarctic Peninsula fjord systems but are several times lower than values for other modern GrIS catchments. This difference is attributed to fact that large volumes of surface water do not access the bed in the Petermann system, and we conclude that glacial erosion is limited to areas overridden by streaming ice in this large outlet glacier setting. Erosion rates are also presented for two phases of ice retreat and confirm that there is significant variation in rates over a glacial–deglacial transition. Our new glacial sediment fluxes and erosion rates show that the Petermann ice stream was approximately as efficient as the palaeo-Jakobshavn Isbræ at eroding, transporting and delivering sediment to its margin during early deglaciation

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma (MM) cells. This phase 2 study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory MM

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p