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Immediate lymphaticovenular bypass (immediate lymphatic reconstruction [ILR]) at the time of axillary lymph node dissection has emerged as a preventative paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients. These patients are often treated with adjuvant therapies, including radiation. Bioimpedance spectroscopy is a validated tool for trending breast cancer-related lymphedema and identifying subclinical disease. Lymphedema Index (LDEX) values are commonly obtained in ILR patients; however, postoperative trends and relationships with adjuvant treatments are yet to be reported in the literature.After International Review Board approval, 100 consecutive patients underwent axillary lymph node dissection with axillary reverse lymphatic mapping and ILR at a tertiary cancer center. These patients were then followed prospectively in a multidisciplinary lymphedema clinic at 3-month intervals with clinical examination, circumferential limb girth measurements and bioimpedance spectroscopy (LDEX).Seventy-two patients met inclusion for analysis at 3 months, 60 at 6 months, 51 at 9 months, 45 at 12 months, 41 at 15 months, and 22 at 18 months. A majority of the patients included underwent adjuvant radiation. Average LDEX score for patients who developed lymphedema was 3.02 at 3 months, at 29.1 months, 17.8 at 9 months, 15.05 at 12 months, 18.75 at 15 months, and 7.7 at 18 months. Patients who went on to develop lymphedema had a higher LDEX score at 6 months (29.1 vs 3.20, P = 0.1329), which reached a significant difference beginning at 9 months (17.8 vs 3.19, P = 0.0004). All patients who went on to develop lymphedema received adjuvant radiation.These data provide valuable insight guiding follow-up after ILR. Six-month LDEX is much higher in patients who developed lymphedema, all of which underwent adjuvant radiation therapy, which correlates with the time of completion of their treatment. Average LDEX value after this remains significantly higher in this population. Patients who demonstrate this increase in LDEX and received adjuvant radiation are at highest risk to develop lymphedema despite ILR. All patients who developed lymphedema despite ILR had adjuvant radiation, and this is likely a contributing factor. Injury from adjuvant radiation and its impact after ILR is not insignificant and warrants further studies.

The topics of inclusivity and diversity in music education have drawn increased attention to how different minority groups experience music education. Unlike concerns surrounding most gender and race issues, lesbian, gay, bisexual, trans, queer, and other sexual and/or gender minority (LGBTQ+) students and teachers are not always as visibly identifiable as other minority groups and therefore can easily be overlooked. In this literature review, I examine research specific to the LGBTQ+ community, representing an invisible minority group in music classrooms with the aim to raise awareness of the unique obstacles that LGBTQ+ music teachers and students face, so that further discussions engaging music educators might have a stronger knowledge base. Findings suggests that many LGBTQ+ music educators struggle to fully embrace their identity, often having to negotiate professional and personal personalities out of fear or uncertainty. Although music classrooms are often considered safe spaces for LGBTQ+ students, the music curriculum should be more inclusive.

The aims of this study were to examine rates of radial artery access in post-coronary artery bypass grafting (CABG) patients undergoing diagnostic catherization and/or percutaneous coronary intervention (PCI), whether operators with higher procedural volumes and higher percentage radial use were more likely to perform diagnostic catherization and/or PCI via the radial approach in post-CABG patients, and clinical and procedural outcomes in post-CABG patients who undergo diagnostic catherization and/or PCI via the radial or femoral approach.There are limited data comparing outcomes of patients with prior CABG undergoing transradial or transfemoral diagnostic catheterization and/or PCI.Using the National Cardiovascular Data Registry CathPCI Registry, all diagnostic catheterizations and PCIs performed in patients with prior CABG from July 1, 2009, to March 31, 2018 (n = 1,279,058, 1,173 sites) were evaluated. Temporal trends in transradial access were examined, and mortality, bleeding, vascular complications, and procedural metrics were compared between transradial and transfemoral access.The rate of transradial access increased from 1.4% to 18.7% over the study period. Transradial access was associated with decreased mortality (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.75 to 0.91), decreased bleeding (OR: 0.57; 95% CI: 0.51 to 0.63), decreased vascular complications (OR: 0.38; 95% CI: 0.30 to 0.47), increased PCI procedural success (OR: 1.11; 95% CI: 1.06 to 1.16; p 0.0001), and significantly decreased contrast volume across all procedure types. Transradial access was associated with shorter fluoroscopy time for PCI-only procedures but longer fluoroscopy time for diagnostic procedures plus ad hoc PCI and diagnostic procedures only. Operators with a higher rate of transradial access in non-CABG patients were more likely to perform transradial access in patients with prior CABG.The rate of transradial artery access in patients with prior CABG undergoing diagnostic catheterization and/or PCI has increased over the past decade in the United States, and it was more often performed by operators using a transradial approach in non-CABG patients. Compared with transfemoral access, transradial access was associated with improved clinical outcomes in patients with prior CABG.

Radial access combined with hemodynamic support has the limitation of not allowing adequate angiography or delivery of peripheral balloons for managing the femoral access site after removal of the large femoral sheath. We present a case series with use of a novel long 6 French guiding sheath via left radial artery access for angiography of the femoral access site after removal of a large sheath for left ventricular assist device with vascular closure devices.

Breast cancer-related lymphedema is a progressive disease that poses tremendous physical, psychosocial, and financial burden on patients. Immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection is emerging as a potential therapeutic paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients.Eighty-one consecutive patients underwent reverse lymphatic mapping and, when feasible, supermicrosurgical immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection at a tertiary care cancer center. Patients were followed prospectively in a multidisciplinary lymphedema clinic (plastic surgery, certified lymphatic therapy, dietary, case management) at 3-month intervals with clinical examination, circumferential limb girth measurements, and bioimpedance spectroscopy. An institutional control cohort was assessed for the presence of objectively diagnosed and treated breast cancer-related lymphedema. Data were analyzed by a university statistician.Seventy-eight patients met inclusion, and 66 underwent immediate lymphaticovenular anastomosis. Mean follow-up was 250 days. When compared to a retrospective control group, the rate of lymphedema in patients who underwent immediate lymphaticovenular anastomosis was significantly lower (6 percent versus 44 percent; p0.0001). Patients with 6-month follow-up treated with combined adjuvant radiation therapy and chemotherapy had significantly greater risk of developing breast cancer-related lymphedema (p = 0.04) compared to those without combined adjuvant therapy. Arborized anastomotic technique had a statistically shorter operative time than end-to-end anastomosis (p = 0.005).This series of consecutive patients demonstrate a 6 percent incidence of early-onset breast cancer-related lymphedema with immediate lymphaticovenular anastomosis and an increased risk in those undergoing combined adjuvant treatment. These early data represent an encouraging and substantial decrease of breast cancer-related lymphedema in high-risk patients.Therapeutic, III.

Silver mirror durability was evaluated by accelerated testing to elucidate the effects of stress and defects on the extent and mechanisms of corrosion. Coating defects significantly affected the corrosion behavior of the mirrors.

The long-term environmental durability of protected silver mirror coatings is influenced by numerous factors. Here, accelerated environmental exposure testing of model silver mirror coatings illuminated the effects of stress, defects, and layer composition on the extent and mechanisms of corrosion and degradation. Experiments to reduce stress in the highest-stress layers of the mirror coatings revealed that, while stress may affect the extent of corrosion, coating defects and the composition of the mirror layers have the largest influence on corrosion feature development and growth.

Transradial angiography and intervention continues to become increasingly common as an access site for coronary procedures. Since the first "Best Practices" paper in 2013, ongoing trials have shed further light onto the safest and most efficient methods to perform these procedures. Specifically, this document comments on the use of ultrasound to facilitate radial access, the role of ulnar artery access, the utility of non-invasive testing of collateral flow, strategies to prevent radial artery occlusion, radial access for primary PCI and topics that require further study.

Objectives Investigation of novel vertical radiation shield (VRS) in reducing operator radiation exposure. Background Radiation exposure to the operator remains an occupational health hazard in the cardiac catheterization laboratory (CCL). Methods A mannequin simulating an operator was placed near a computational phantom, simulating a patient. Measurement of dose equivalent and Air Kerma located the angle with the highest radiation, followed by a common magnification (8 in.) and comparison of horizontal radiation absorbing pads (HRAP) with or without VRS with two different: CCL, phantoms, and dosimeters. Physician exposure was subsequently measured prospectively with or without VRS during clinical procedures. Results Dose equivalent and Air Kerma to the mannequin was highest at left anterior oblique (LAO)‐caudal angle (p

The problem of localizing a moving target arises in various forms in wireless sensor networks. Deploying multiple sensing receivers and using the time-difference-of-arrival (TDOA) of the target’s emitted signal is widely considered an effective localization technique. Traditionally, TDOA-based algorithms adopt a centralized approach where all measurements are sent to a predefined reference node for position estimation. More recently, distributed TDOA-based localization algorithms have been shown to improve the robustness of these estimates. For target models governed by highly stochastic processes, the method of nonlinear filtering and state estimation must be carefully considered. In this work, a distributed TDOA-based particle filter algorithm is proposed for localizing a moving target modeled by a discrete-time correlated random walk (DCRW). We present a method for using data collected by the particle filter to estimate the unknown probability distributions of the target’s movement model, and then apply the distribution estimates to recursively update the particle filter’s propagation model. The performance of the distributed approach is evaluated through numerical simulation, and we show the benefit of using a particle filter with online model learning by comparing it with the non-adaptive approach.

Hypervelocity impact (HVI) studies are very important for understanding space debris, and play a crucial role in current fragmentation modelling predictions. Both the number and size of orbital debris particles are inputs to different models. The interpretation of optical measurements of orbital debris and the physical sizes of the particles require information on albedo of the particles. While hypervelocity impact experiments at a gun range can offer a realistic representation of the energy of impact and fragmentation, laboratory simulation using laser ablation with a high power laser is appealing because it provides the opportunity to investigate a variety of parameters and couple these to optical albedo measurements of HVI debris in a well-controlled and repeatable environment. Most importantly, laser ablation experiments can be conducted in high-vacuum of 10 -8 Torr, which is representative of the pressure in the Low Earth Orbit (LEO) environment, in contrast to the hypervelocity impact experiments that are typically conducted in low pressure (1-2 Torr) air. Here we compare experiments conducted with laser ablation to hypervelocity impact tests. Specifically, we compare microscopic debris from laboratory ablation with that from the 2014 hypervelocity impact test on DebriSat. Results from microstructure and size distributions of debris collected on witness plates show that laser ablations in low-pressure air offer many similarities to the hypervelocity impact experiments, while ablations in high-vacuum provide critical distinctions relevant to LEO.

A variety of common spacecraft thermal control materials were exposed to a laboratory test designed to simulate the effects of the low-Earth-orbital space-radiation environment. The goal of this test program was to garner performance data on the subject materials, which included two thickness types of old and new rear-surface-silverized fluorinated ethylene propylene Teflon® tape manufactured more than a decade apart, an embossed version of rear-surface-silverized fluorinated ethylene propylene Teflon tape, perforated rear-surface-aluminized Kapton, and a zinc oxide/methyl silicone white paint. In addition to providing high-fidelity data on the end-of-life performance of the materials, the testing revealed that older samples of the rear-surface-silverized fluorinated ethylene propylene Teflon tape showed widely disparate responses and greater solar absorptance increases compared to samples of the same, newly manufactured materials. Samples of the new rear-surface-silverized fluorinated ethylene propylene ...

Rationale Bulk stable isotope analysis (BSIA) of dissolved matter (e.g. dissolved organic carbon, total nitrogen bound (TNb), etc.) is of particular importance since this pool is a prime conduit in the cycling of N and C. Studying the two elemental pools is of importance, as transformation and transport processes of N and C are inextricably linked in all biologically mediated systems. No system able to analyze natural abundance stable carbon and nitrogen isotope composition in aqueous samples (without offline sample preparation) and simultaneously has been reported so far. Extension of the high-temperature combustion (HTC) system, to be capable of measuring TNb stable nitrogen isotope composition, is described in this study. Methods To extend the TOC analyzer to be capable of measuring TNb, modifications from the HTC high-performance liquid chromatography/isotope ratio mass spectrometry (HPLC/IRMS) interface were implemented and expanded. A reduction reactor for conversion of NOx into N2 was implemented into the new developed system. The extension addresses mainly the development of the focusing unit for nitrogen and a degassing device for online separation of TNb from molecular nitrogen (N2) prior to injection. Results The proof of principle of the system was demonstrated with different compound solutions. In this initial testing, the δ15NAIR-N2 values of the tested compounds were determined with precision and trueness of typically ≤0.5‰. Good results (u ≤ 0.5‰) could be achieved down to a TNb concentration of 40 mgN/L and acceptable results (u ≤ 1.0‰) down to 5 mgN/L. In addition, the development resulted in the first system reported to be suitable for simultaneous and direct δ13C and δ15N BSIA of aqueous samples. Conclusions The development resulted in the first system shown to be suitable for both δ13C and δ15N direct BSIA in aqueous samples. This system could open up new possibilities in SIA-based research fields. Copyright © 2016 John Wiley & Sons, Ltd.

The quantitative and isotopic analysis of dissolved matter (e.g. dissolved organic carbon, total dissolved nitrogen, etc.) is of particular importance since this pool is a prime conduit in the cycling of N and C. Studying the two elemental pools simultaneously is of importance, as the transformation and transport processes of N and C are inextricably linked in all biologically mediated systems. Dissolved Carbon concentration and isotopic composition can now be determined routinely through coupling of high temperature combustion (HTC) systems to isotope ratio mass spectrometry (IRMS). However the analysis of δ15N of Total Dissolved Nitrogen is fraught with limitations: low concentration makes lyophilisation followed by EA/IRMS laborious and subject to contamination; wet chemical oxidation-IRMS runs the risk of incomplete conversion and cannot distinguish dissolved N2 from Total Dissolved Nitrogen. Further development of our HTC system lead to the implementation of the δ15N determination which is now coupled into a novel total organic carbon (TOC) analyzing system. An integrated, innovative purge and trap technique (peak focusing) for nitrogen with aluminosilicate adsorber and thermoelectric cooling element based system, in combination with high injection volume (up to 3mL) significantly improves sensitivity. Down to 1ppm and less total nitrogen can be measured with precision of ≤ 0.5‰. To decrease the background caused by physically dissolved nitrogen a new, membrane-based, degasser was designed for online separation of physically dissolved nitrogen. This novel HTC system, “iso TOC cube”, provides an innovative tool with large potential in investigation of biogeochemical carbon and nitrogen cycles.

Objectives Study a novel method using manual pressure on a hemostatic pad and hemoband for ulnar compression as a potential alternative for radial sheath removal. Background The standard for transradial access site (TRA) sheath removal requires an inflatable pressure band over the radial artery and recently a band over the ulnar artery to reduce complications. We present a novel technique using a SoftSeal®-STF hemostatic pad over the radial artery combined with a hemoband over the ulnar artery after sheath removal. Methods All patients had activated clotting time (ACT); sheath removal was performed immediately upon transfer to the recovery room. A hemoband compressed the ulnar artery, radial artery flow was measured using plethysmography and pulse oximetry while direct pressure applied using SoftSeal-STF hemostatic pad for 15 min after radial sheath removed. Radial artery patency was measured using reverse Barbeau test. If radial artery occlusion (RAO) present, patient was asked to return in one month to repeat test. Results Fifty-nine patients were enrolled in the study, one-third with diabetes mellitus, one-third with prior coronary artery bypass surgery, and one-third with history of percutaneous coronary intervention. Mean ACT 261 ± 50 sec, all patients had 4 Fr sheaths and no PCI were performed. Three (6%) patients had minor bleeding requiring use of a pressure band and one (2%) had RAO, which re-canalized at one month. Conclusions Manual pressure of SoftSeal-STF hemostatic pad combined with ulnar compression is a potential alternative to current practice with an inflatable pressure band.

Until recent years there has been no evidence from randomized controlled trials (RCTs) on the efficacy of deep brain stimulation (DBS) for Parkinson's disease (PD). This review and meta-analysis of RCTs describes the efficacy of DBS in improving motor signs, functionality and quality of life of PD patients. Several electronic databases were consulted up to April 2013. RCTs that compared DBS plus medication versus medication (alone or plus sham DBS) in PD patients were included. Outcome measures were motor function, waking time on good functioning without troublesome dyskinesias, levodopa-equivalent dose reduction, medication-induced complications, activities of daily living, health-related quality of life, and neurocognitive and psychiatric effects. Six RCTs (n = 1,184) that compared DBS plus medication versus medication alone were included. The results show that DBS significantly improves patients' symptoms, functionality and quality of life. Effects sizes are intense for the reduction of motor signs and improvement of functionality in the off-medication phase, in addition to the reduction of the required medication dose and its associated complications. Moderate effects were observed in the case of motor signs and time in good functionality in the on-medication phase, in addition to the quality of life. Although the number of RCTs obtained is small, the total sample size is relatively large, confirming the efficacy of DBS in the control of motor signs and improvement of patients' functionality and quality of life. More controlled research is required on the neurocognitive and psychiatric effects of DBS.

Radiation exposure in the cardiac catheterization laboratory (CCL) is a safety risk. In this study, we investigated the impact of a novel sterile Vertical Radiation Shield (VRS) on operator radiation exposure. Prior to a coronary procedure, a dosimeter measured radiation exposure on a mannequin

Background: Heart disease is now considered an inflammatory process targeted primarily by medical therapy on lipid levels. Complementary and alternative medicine searches for novel non-pharmacologic therapy, including pursuing various diets. Animal studies and consumer literature suggest benefits of vinegar on lipid levels and diabetes mellitus. Our nonrandomized pilot study from our group suggested a benefit in raising high-density lipoprotein cholesterol (HDL-C). Based on this data, we conducted a randomized placebo controlled clinical trial to determine the effects of apple cider vinegar intake in those without diabetes mellitus on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, HDL-C, Hemoglobin A1C(Hgb-A1C) and measurement of inflammation with high sensitivity CRP levels (HS-CRP). Methods: A prospective randomized, double blind, placebo-controlled clinical trial consisting of 114 participants was conducted. Participants consumed 30 mL of either apple cider vinegar or placebo for two months. Measurements were collected at baseline, eight and sixteen weeks. The primary endpoint was the change in HDL-C from baseline to eight weeks between the vinegar and placebo groups. Secondary endpoints were change from baseline to eight weeks in TC, LDL-C, triglycerides, Hgb-A1cand HS-CRP. Results: Change in serum HDL-C concentration was not significantly different between the vinegar and control groups after eight weeks of supplementation. Secondary endpoints including TC, LDL-C, Hgb-A1cand HS-CRP were not statistically different at the Bonferroni corrected significance level of 0.01. No significant difference was found regardless of baseline HDL-C levels. Conclusions: We found no significant difference in HDL-C, LDL-C, triglycerides, total cholesterol, or HS-CRP levels with use of vinegar but a trend down of Hgb-A1cin this group of non-diabetic participants. Further investigation is required to define the impact of vinegar in those with diabetes mellitus.

Bulk stable isotope analysis (BSIA) of dissolved matter (e.g. dissolved organic carbon, total nitrogen bound (TNTo extend the TOC analyzer to be capable of measuring TNThe proof of principle of the system was demonstrated with different compound solutions. In this initial testing, the δThe development resulted in the first system shown to be suitable for both δ

Women choose to undergo nipple-areola complex (NAC) reconstruction as part of breast reconstruction following breast cancer treatment. However, the effect of this procedure on psychosocial and sexual well-being is not well studied. The present study aimed to evaluate how NAC reconstruction affects patient satisfaction with regard to psychosocial and sexual well-being.A retrospective chart review was performed for all patients who underwent NAC reconstruction at Magee-Women's Hospital from January 1, 2004 to July 31, 2011. A letter and questionnaire based on the BREAST-Q were mailed to patients to request their participation in the study. Patient satisfaction and health-related quality of life were measured before and after NAC reconstruction.In total, 107 of 328 patients (32.6%) completed the survey. The BREAST-Q scale score for satisfaction with outcome following NAC reconstruction was 85.1 ± 15.8, with higher satisfaction scores for patients with a follow-up of1.5 years than those with a follow-up of2.5 years (82.5 ± 21.7 vs. 69.5 ± 19.5; p 0.01). No significant differences were found in satisfaction with the breast mound before and after NAC reconstruction. Women scored significantly higher on the psychosocial and sexual well-being scales after NAC reconstruction (p 0.002 and 0.00004, respectively).This study indicates that patients are highly satisfied after undergoing NAC reconstruction. Satisfaction with the procedure, however, may decrease over time. NAC reconstruction significantly contributes to patient psychosocial and sexual well-being, and this effect did not change over time. NAC reconstruction improves patient outcomes in those who choose to undergo the procedure.

Background In 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis‐St. Paul. Methods and Results Eleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and P =0.03). Conclusions Early access to the CCL after cardiac arrest due to a shockable rhythm in a selected group of patients is feasible in a large metropolitan area in the United States and is associated with a 65% survival rate to hospital discharge with a good neurological outcome.

M ATERIALS that reside on the exterior of a spacecraft, and are therefore unshielded, are exposed to the entire space environment. In addition to receiving a substantial dose of ionizing radiation from exposure to solar ultraviolet radiation, external spacecraft materials or surfaces can also be subjected to extremely large fluxes of ionizing radiation from the charged-particle environment. In particular, the electron and proton fluxes impart an extremely large dose of ionizing radiation into the surface layers of exposed materials, which generally produces both optical and mechanical degradation through a variety of mechanisms. These effects have been studied for years on many materials, particularly thermal control coatings [1–19]. Any effective simulation of the space environment for the purpose of material evaluation requires accurate modeling of these charged-particle environments. This requires environment models that describe the electron and proton fluxes as a function of particle energy for all particle energies (within reason). The models AE8 [20] and AP8 [21] have been the standards for describing the trapped-particle environments for electrons and protons, respectively, for all orbits. Unfortunately, corresponding and comprehensive engineeringmodels for the plasma environments do not currently exist for all orbits. Generally speaking, the models AE8 andAP8 are referred to as trapped-particle environment models because their intent is to describe the particle fluxes that are essentially trapped in the Van Allen radiation belts. Historically, this has been defined as particle fluxes with energies greater than 40 keV for electrons and 100 keV for protons. Particle populations with energies lower than these limits are referred to as plasma particles, which are not confined to the idealized radiation belts. The AE8 and AP8 models neglect the lower energy ranges of both electron and proton populations for largely historical reasons: Theflight data upon which they are based spanned only limited energy ranges, which resulted in the development of models that started at relatively high energy levels relative to the plasma environments. Particle populations below these energy levels (40 keV for electrons and 100 keV for protons) were either ignored or approximated through crude extrapolation of the model’s flux-energy curves. Although the Advanced Technology Satellite 6 (ATS-6) model [22] has often served to describe plasma electron and proton environments, primarily at geosynchronous Earth orbit (GEO), the model is based on only 45 days of flight data. An excellent review of the temporal and energy coverage of numerous satellite data and space environment models, including AE8, AP8, and ATS-6, is provided in [23]. Use of the plasma-population-deficient models AE8 and AP8 can easily lead to a two-order-of-magnitude underprediction of the energy deposited into the shallow depths of an external spacecraft material. It is important to note that the fluxes of particle populations increase exponentially with decreasing energy; consequently, there are orders-of-magnitude-more particles below the cutoff range of these trapped-particle models. Since these low-energy particles deposit energy and stop in very shallow depths of materials, their large combined fluence results in a tremendous deposition of energy in the surface of materials. Without consideration of the proper plasma environment, the energy deposition in exterior spacecraft materials is incorrectly predicted by energy-deposition codes. Recently,more comprehensive and accuratemodels of the plasmaparticle environments at GEO have been published. These models use a large data set of orbital measurements as their basis and provide themost accurate description of the lower-energy particle population currently available. The Los Alamos National Laboratory Magnetospheric PlasmaAnalyzer (LANL-MPA)model [24] is based onmore than 16 years of orbital measurements and characterizes GEO electron and proton fluxes from about 45 keV down to approximately Received 29 September 2010; revision received 28 April 2011; accepted for publication 23 May 2011. Copyright © 2011 by The Aerospace Corporation. Published by the American Institute of Aeronautics and Astronautics, Inc., with permission. Copies of this paper may be made for personal or internal use, on condition that the copier pay the $10.00 per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923; include the code 0022-4650/11 and $10.00 in correspondence with the CCC. Research Scientist, Materials Science Department, Space Materials Laboratory, 2310 East El Segundo Boulevard, M2-248. Associate of the Technical Staff, Materials Science Department, Space Materials Laboratory, 2310 East El Segundo Boulevard, M2-248. Associate Member of the Technical Staff, Materials Science Department, Space Materials Laboratory, 2310 East El Segundo Boulevard, M2-248. §Distinguished Scientist, Space Materials Laboratory, 2310 East El Segundo Boulevard, M2-248. JOURNAL OF SPACECRAFT AND ROCKETS Vol. 48, No. 6, November–December 2011

Gas chromatography‐combustion‐isotope ratio mass spectrometry (GC‐C‐IRMS) is increasingly applied to food and metabolic studies for stable isotope analysis (δ 13 C), with the quantification of analyte concentration often obtained via a second alternative method. We describe a rapid direct transesterification of triacylglycerides (TAGs) for fatty acid methyl ester (FAME) analysis by GC‐C‐IRMS demonstrating robust simultaneous quantification of amount of analyte (mean r 2 =0.99, accuracy ±2% for 37 FAMEs) and δ 13 C (±0.13‰) in a single analytical run. The maximum FAME yield and optimal δ 13 C values are obtained by derivatizing with 10% (v/v) acetyl chloride in methanol for 1h, while lower levels of acetyl chloride and shorter reaction times skewed the δ 13 C values by as much as 0.80‰ .A Bland‐Altman evaluation of the GC‐C‐IRMS measurements resulted in excellent agreement for pure oils (±0.08‰) and oils extracted from French fries (±0.49‰), demonstrating reliable simultaneous quantification of FAME concentration and δ 13 C values. Thus, we conclude that for studies requiring both the quantification of analyte and δ 13 C data, such as authentication or metabolic flux studies, GC‐C‐IRMS can be used as the sole analytical method.

In the face of mounting clinical demand, and armed with reconstructive techniques that are technically challenging and frequently result in suboptimal patient outcomes, increasing focus is being placed on tissue engineering and regenerative medicine as a potential source of novel skeletal reconstructive approaches. Specifically, evidence is accumulating that highlights the promise of osteoprogenitor cell-based reconstructive strategies to meet the needs of an expanding patient population. Historically, the study of cell and molecular biology guiding physiologic and pathologic skeletal development, as well as endogenous bone regeneration following injury, has provided a wealth of information that lends insight toward potential parallel processes that may regulate the osteogenic differentiation of progenitor cells. Multiple progenitor cell populations are now known to possess a capacity to undergo robust osteogenic differentiation in the presence of appropriate environmental cues (hESC, BMSC, ASC, etc.) Recent investigations have put forth multiple advantages of ASC relative to BMSC. Of note, ASC exist in relative abundance, lack the need for in vitro expansion prior to utilization, and can be harvested with relative ease and reduced donor morbidity. Collectively, these factors, paired with promising in vitro and in vivo observations that speak toward the substantial osteogenic potential of ASC, have spurred enthusiasm to pursue the application of ASC in the maturation of skeletal tissue engineering applications. Yet, elucidating what structural and functional properties of scaffolds designed for ASC-mediated skeletal tissue engineering applications (porosity, pore size, composition, mechanical stability, degradation kinetics, etc.), as well as evolving our understanding and capacity to deliver spatiotemporally specific pro-osteogenic targeted molecular manipulation to progenitor cells, remain important hurdles to clear. The scope of this review encompasses the current state of ongoing investigations along these fronts, as well as what future direction will be critical to the transition of cell-based skeletal tissue engineering strategies to the bedside.

Calvarial bones arise from two embryonic tissues, namely, the neural crest and the mesoderm. In this study we have addressed the important question of whether disparate embryonic tissue origins impart variable osteogenic potential and regenerative capacity to calvarial bones, as well as what the underlying molecular mechanism(s). Thus, by performing in vitro and in vivo studies, we have investigated whether differences exist between neural crest–derived frontal and paraxial mesodermal–derived parietal bone. Of interest, our data indicate that calvarial bone osteoblasts of neural crest origin have superior potential for osteogenic differentiation. Furthermore, neural crest–derived frontal bone displays a superior capacity to undergo osseous healing compared with calvarial bone of paraxial mesoderm origin. Our study identified both in vitro and in vivo enhanced endogenous canonical Wnt signaling in frontal bone compared with parietal bone. In addition, we demonstrate that constitutive activation of canonical Wnt signaling in paraxial mesodermal–derived parietal osteoblasts mimics the osteogenic potential of frontal osteoblasts, whereas knockdown of canonical Wnt signaling dramatically impairs the greater osteogenic potential of neural crest–derived frontal osteoblasts. Moreover, fibroblast growth factor 2 (FGF-2) treatment induces phosphorylation of GSK-3β and increases the nuclear levels of β-catenin in osteoblasts, suggesting that enhanced activation of Wnt signaling might be mediated by FGF. Taken together, our data provide compelling evidence that indeed embryonic tissue origin makes a difference and that active canonical Wnt signaling plays a major role in contributing to the superior intrinsic osteogenic potential and tissue regeneration observed in neural crest–derived frontal bone. © 2010 American Society for Bone and Mineral Research.

Ectopic expression of transcription factors can reprogram somatic cells to a pluripotent state. However, most of the studies used skin fibroblasts as the starting population for reprogramming, which usually take weeks for expansion from a single biopsy. We show here that induced pluripotent stem (iPS) cells can be generated from adult human adipose stem cells (hASCs) freshly isolated from patients. Furthermore, iPS cells can be readily derived from adult hASCs in a feeder-free condition, thereby eliminating potential variability caused by using feeder cells. hASCs can be safely and readily isolated from adult humans in large quantities without extended time for expansion, are easy to maintain in culture, and therefore represent an ideal autologous source of cells for generating individual-specific iPS cells.

Quantitative biomarker analysis is an invaluable tool used routinely by organic geochemists to interpret and explain environmental processes. Since the advent of organic geochemistry, all levels of biomarker methodology from wet chemistry to data interpretation have significantly advanced; however, an important aspect of data analysis has remained constant and that is the expression of biomarkers in terms of mass (e.g., mg gOC−1). We argue that biomarkers are more appropriately expressed in terms of moles (e.g., mmol molOC−1) to better reflect molecular-level distribution of compounds of interest, as well as introducing a chemical consistency for better comparability and transferability between data sets. Using modeled and real data culled from the literature, we demonstrate that the use of moles is not a trivial conversion and that distribution and relative weighting of biomarker data sets are shifted and affect the total data structure. The shift is sometimes strong enough to exert changes in interpretation (e.g., microbial abundance in an estuarine system), alter proxies (e.g., terrestrial-to-aquatic ratio), and potentially influence the use of multivariate statistical methods (e.g., principal components analysis).

Cleft palate is a common birth defect that carries significant biomedical and psychosocial implications throughout the lives of affected children and their families. To date, numerous etiopathogenetic factors have been identified that can lead to isolated and syndromic forms of cleft palate. The management of patients with cleft palate has improved significantly over the last several decades with important surgical advances and an increasingly multidisciplinary approach to patient care. Technological innovations have become focused on improving functional results, with current research and clinical reports of cleft palate reconstruction promising even greater improvements and further “minimalization” of surgery in the future. As part of this evolution, research in tissue engineering approaches for cleft palate reconstruction promise increased functionality, improved aesthetics, fewer complications, and reduced disease burden. The current review discusses several aspects of tissue engineering research that promise innovation in cleft palate repair including distraction osteogenesis, biologic implants, fetal surgery, in utero medical therapy, and prevention.

Children less than 2 years of age are capable of healing large calvarial defects, whereas adults have been found to lack this endogenous ability. In this study, we used microarray analysis to compare genomewide expression patterns during active regeneration after injury with calvaria in skeletally immature and mature mice. Parietal bone defects were created in 6-day-old (juvenile) and 60-day-old (adult) mice using a 4-mm trephine bit (n = 20 mice per age group). The calvarial disc was removed, leaving the underlying dura mater intact. Two weeks after injury, the region of regeneration with the underlying dura mater was harvested, and RNA was extracted for microarray analysis. The 25 most differentially upregulated genes in juvenile regenerates compared with adults were listed, as well as selected bone-related genes. In addition, QRT-PCR confirmation of specific genes was performed for validation. Juvenile regenerates expressed significantly greater amounts of BMP-2, -4, -7, as well as FGF-2 and its receptor FGFR-1. Various other growth factors were also noted to be upregulated, including IGF-2 and Ptn. This corresponded with the increased expression of markers for osteogenic differentiation of Sparc and Oc. Markers of osteoclast activity, Acp5, Ctsk, and Mmp2, were noted to be greater in juvenile regenerates compared with adults. The observation of Mmp14 upregulation, however, highlights the importance of balanced osteoclast-mediated bone resorption for ultimate healing. The 2 most differentially regulated genes, transthyretin (Ttr) and prostaglandin D2 synthase (Ptgds), highlight the potential role of retinoic acid signaling and the prostaglandin axis on skeletal regeneration. These findings underscore the multitude of biomolecular mechanisms at play, allowing juvenile calvaria to heal after injury. The identification of various growth factors and cytokines involved also suggests novel therapeutic strategies for tissue-engineering purposes.

Background: Skeletal defects represent a significant socioeconomic burden to the US healthcare system. Current options for reconstructing osseous deficits have shortcomings. Objective: To review the use of mesenchymal stem cells for skeletal tissue engineering. Methods: We focused on the application of mesenchymal cells in skeletal regeneration, optimization of this technique, tropic effects of multipotent mesenchymal cells, and future directions. Results/conclusion: A number of cell-based modalities have been investigated. We have been interested in the role of adipose-derived stromal cells in bone regeneration and understanding the mechanisms behind osteogenic differentiation of progenitor cells and acceleration of this process. Future clinical applications of multipotent mesenchymal cells will depend on better understanding of the molecular signaling involved in osteogenic differentiation and maintaining pluripotency.

The stable isotope composition of dissolved organic carbon (delta(13)C-DOC) provides powerful information toward understanding carbon sources and cycling, but analytical limitations have precluded its routine measurement in natural samples. Recent interfacing of wet oxidation-based dissolved organic carbon analyzers and isotope ratio mass spectrometers has simplified the measurement of delta(13)C-DOC in freshwaters, but the analysis of salty estuarine/marine samples still proves difficult. Here we describe the coupling of the more widespread high-temperature catalytic oxidation-based total organic carbon analyzer to an isotope ratio mass spectrometer (HTC-IRMS) through cryogenic trapping of analyte gases exiting the HTC analyzer for routine analysis of delta(13)C-DOC in aquatic and marine samples. Targeted elimination of major sources of background CO2 originating from the HTC analyzer allows for the routine measurement of samples over the natural range of DOC concentrations (from 40 microM to over 2000 microM), and salinities (0.1-36 g/kg). Because consensus reference natural samples for delta(13)C-DOC do not exist, method validation was carried out with water-soluble stable isotope standards as well as previously measured natural samples (IAEA sucrose, Suwannee River Fulvic Acids, Deep Sargasso Sea consensus reference material, and St. Lawrence River water) and result in excellent delta(13)C-DOC accuracy (+/-0.2 per thousand) and precision (+/-0.3 per thousand).

Contributions from multidisciplinary investigations have focused attention on the potential of tissue engineering to yield novel therapeutics. Congenital malformations, including cleft palate, craniosynostosis, and craniofacial skeletal hypoplasias represent excellent targets for the implementation of tissue engineering applications secondary to the technically challenging nature and inherent inadequacies of current reconstructive interventions. Apropos to the search for answers to these clinical conundrums, studies have focused on elucidating the molecular signals driving the biologic activity of the aforementioned maladies. These investigations have highlighted multiple signaling pathways, including Wnt, fibroblast growth factor, transforming growth factor-beta, and bone morphogenetic proteins, that have been found to play critical roles in guided tissue development. Furthermore, a comprehensive knowledge of these pathways will be of utmost importance to the optimization of future cell-based tissue engineering strategies. The scope of this review encompasses a discussion of the molecular biology involved in the development of cleft palate and craniosynostosis. In addition, we include a discussion of craniofacial distraction osteogenesis and how its applied forces influence cell signaling to guide endogenous bone regeneration. Finally, this review discusses the future role of cell-based tissue engineering in the treatment of congenital malformations.

Dinosterol (4a,23,24-trimethyl-5a-cholest-22E-en-3b-ol) is frequently used as an alternative to dinoflagellate cyst (dinocyst) counting in paleoceanography to assess dinoflagellate inputs to marine sediments. However, recent studies have shown poor correlation between these two proxies in continental-margin sediments. We reevaluated the relationship and expanded it to include a suite of biogeochemical transformation products of the parent dinosterol (dinosterone, dinostanone, and dinostanol). These dinoflagellate-specific 4a,23,24-trimethyl steroidal species (Sdinosterol) are compared to dinocyst counts in sediments from the western Mexican margin (375– 3,500 m). Samples were taken from subsurface (3–6 cm) and down core (16–27 cm) to reflect widely contrasting organic carbon content and redox conditions. A strong correlation was found between the sum of all dinoflagellate-derived sterols, Sdinosterols, and total dinocyst counts, highlighting the importance of including diagenetic alteration products of the parent molecule when exploiting organic biomarkers in paleoceanographic studies. In low-energy environments and for well-preserved samples, such as those studied in this work, both methods provide robust, internally consistent data, suggesting that when diagenetic transformation products of dinosterol are taken into account, gas chromatography and optical microscopy could be used interchangeably to estimate dinoflagellate inputs to marine sediments.

Patients with chronic kidney disease and acute coronary syndromes are at high risk for both bleeding and ischemic events. This risk increases with the severity of renal insufficiency. Management for acute coronary syndromes in the setting of kidney disease is a paradox; as the benefit of current treatment is high, so is the risk for complications. Patients with chronic renal disease are frequently excluded from randomized clinical trials, and therefore, the optimal treatment strategies are often speculative in this high-risk patient population. Additional research is needed to further refine the optimal management of patients with chronic kidney disease in the setting of acute coronary syndromes.