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The Tagish Lake carbonaceous chondrite exhibits a unique compositional heterogeneity that may be attributed to varying degrees of aqueous alteration within the parent body asteroid. Previous analyses of soluble organic compounds from four Tagish Lake meteorite specimens (TL5b, TL11h, TL11i, TL11v) identified distinct distributions and isotopic compositions that appeared to be linked to their degree of parent body processing (Herd et al., 2011; Glavin et al., 2012; Hilts et al., 2014). In the present study, we build upon these initial observations and evaluate the molecular distribution of amino acids, aldehydes and ketones, monocarboxylic acids, and aliphatic and aromatic hydrocarbons, including compound-specific 13C compositions, for three additional Tagish Lake specimens: TL1, TL4 and TL10a. TL1 contains relatively high abundances of soluble organics and appears to be a moderately altered specimen, similar to the previously analyzed TL5b and TL11h lithologies. In contrast, specimens TL4 and TL10a both contain relatively low abundances of all of the soluble organic compound classes measured, similar to TL11i and TL11v. The organic-depleted composition of TL4 appears to have resulted from a relatively low degree of parent body aqueous alteration. In the case of TL10a, some unusual properties (e.g., the lack of detection of intrinsic monocarboxylic acids and aliphatic and aromatic hydrocarbons) suggests that it has experienced extensive alteration and/or a distinct organic-depleted alteration history. Collectively, these varying compositions provide valuable new insights into the relationships between asteroidal aqueous alteration and the synthesis and preservation of soluble organic compounds.

Compound-specific carbon isotope analysis (δ(13)C) of meteoritic organic compounds can be used to elucidate the abiotic chemical reactions involved in their synthesis. The soluble organic content of the Murchison carbonaceous chondrite has been extensively investigated over the years, with a focus on the origins of amino acids and the potential role of Strecker-cyanohydrin synthesis in the early solar system. Previous δ(13)C investigations have targeted α-amino acid and α-hydroxy acid Strecker products and reactant HCN; however, δ(13)C values for meteoritic aldehydes and ketones (Strecker precursors) have not yet been reported. As such, the distribution of aldehydes and ketones in the cosmos and their role in prebiotic reactions have not been fully investigated. Here, we have applied an optimized O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatization procedure to the extraction, identification and δ(13)C analysis of carbonyl compounds in the Murchison meteorite. A suite of aldehydes and ketones, dominated by acetaldehyde, propionaldehyde and acetone, were detected in the sample. δ(13)C values, ranging from −10.0‰ to +66.4‰, were more (13)C-depleted than would be expected for aldehydes and ketones derived from the interstellar medium, based on interstellar (12)C/(13)C ratios. These relatively (13)C-depleted values suggest that chemical processes taking place in asteroid parent bodies (e.g. oxidation of the IOM) may provide a secondary source of aldehydes and ketones in the solar system. Comparisons between δ(13)C compositions of meteoritic aldehydes and ketones and other organic compound classes were used to evaluate potential structural relationships and associated reactions, including Strecker synthesis and alteration-driven chemical pathways.

PURPOSE Permanent breast seed implantation (PBSI) is a promising radiotherapy technique for early-stage breast cancer, completed in a single visit by permanently implanting 103 Pd seeds using needles inserted through a template and guided by two-dimensional (2D) ultrasound (US). However, operator dependence has been highlighted as a limitation of this procedure. Consequently, we propose and have developed an intraoperative guidance system using three-dimensional (3D) US and an instrumented mechanical arm to provide intraoperative 3D imaging and needle template tracking. METHODS A mechatronic 3D US scanner reconstructs a 3D image from 150 2D images. A tracked mechanical arm mounted to the scanner locates four fiducial points on the template, registering the template to the 3D image. 3D reconstruction was validated for linear and volumetric measurement accuracy using phantoms of known geometry. In vivo breast US image quality was evaluated in a healthy volunteer. The encoded arm was calibrated and validated using a jig with divots at known locations relative to the scanner and the scanner registered to the 3D US image using intersecting strings in a fluid-filled test jig. Template registration accuracy was assessed using a machined test jig. Tracking accuracy was assessed in a liquid medium by comparing tracked and imaged needle tip positions. Finally, the system was used to guide a mock procedure in a patient-specific phantom and micro-CT imaging used to evaluate its accuracy. RESULTS Geometric validation showed median distances within ±1.1% of expected values and volumetric validation showed differences of ≤4.1%. Tracking arm point measurements showed an average error of 0.43 mm and 3D US volume registration showed target registration error ≤0.9 mm. Mean template registration accuracy in each axis of translation/rotation was ≤1.3 mm/1.0°. Mean needle-targeting error was 2.5 mm and 1.6° for needle tips and trajectories, respectively. Mean needle tip and angular errors of the phantom procedure were 2.1 mm and 2.6°. Modeled seed displacement of the phantom procedure showed mean error of 2.6 mm and a maximum of 3.8 mm. CONCLUSIONS A 3D US guidance system for PBSI has been developed. Benchtop performance and image quality in volunteer scans are satisfactory. A phantom PBSI procedure was successfully delivered using the system with maximum seed error within dosimetric benchmarks (

The curation and handling of volatile-bearing astromaterials is of prime importance in current and future plans for sample return missions to targets containing organic compounds, ices, or other volatile components. We report on the specific curation constraints required for the preservation of the Tagish Lake meteorite, a C2 ungrouped chondrite that contains significant concentrations of organic matter, including compounds of prebiotic interest or volatile in character, and which was recovered from a frozen lake surface a few days after its fall. Here, we review the circumstances of the meteorite's handling, its complement of intrinsic and contaminant organic compounds, and an unusual reaction between some of the specimens and the Al foil in which they were enclosed. From our results, we derive the requirements for curation of the meteorite, and describe a specialized facility that enables its curation and handling. The Subzero Facility for Curation of Astromaterials consists of a purified Ar glove box enclosed within a freezer chamber, and enables investigations relevant to curation of samples at or below −10 °C. We provide several recommendations based on insights obtained from the commissioning and initial use of the facility that are relevant to collection of freshly fallen meteorites, curation of volatile-bearing meteorites and other astromaterials, and planning and implementation of curation plans for future sample return missions to volatile-bearing targets.

Purpose: To evaluate multislice computed tomography (CT) scanning for fast and reliable readout of radiation therapy (RT) dose distributions using CT polymer gel dosimetry (PGD) and to establish a baseline assessment of image noise and uniformity in an unirradiated gel dosimeter. Methods: A 16-slice CT scanner was used to acquire images through a 1 L cylinder filled with water. Additional images were collected using a single slice machine. The variability in CT number (N CT ) associated with the anode heel effect was evaluated and used to define a new slice-by-slice background subtraction artifact removal technique for CT PGD. Image quality was assessed for the multislice system by evaluating image noise and uniformity. The agreement in N CT for slices acquired simultaneously using the multislice detector array was also examined. Further study was performed to assess the effects of increasing x-ray tube load on the constancy of measured N CT and overall scan time. In all cases, results were compared to the single slice machine. Finally, images were collected throughout the volume of an unirradiated gel dosimeter to quantify image noise and uniformity before radiation is delivered. Results: Slice-by-slice background subtraction effectively removes the variability in N CT observed across images acquired simultaneously using the multislice scanner and is the recommended background subtraction method when using a multislice CT system. Image noise was higher for the multislice system compared to the single slice scanner, but overall image quality was comparable between the two systems. Further study showed N CT was consistent across image slices acquired simultaneously using the multislice detector array for each detector configuration of the slice thicknesses examined. In addition, the multislice system was found to eliminate variations in N CT due to increasing x-ray tube load and reduce scanning time by a factor of 4 when compared to imaging a large volume using a single slice scanner. Images acquired through an unirradiated, active gel revealed N CT varies between the top and bottom of the 1 L cylinder as well as across the diameter of the cylinder by up to 7 HU. Conclusions: Multislice CT imaging has been evaluated for CT PGD and found to be the superior technique compared to single slice imaging in terms of the time required to complete a scan and the tube load characteristics associated with each scanning method. The implementation of multislice scanning is straightforward and expected to facilitate routine gel dosimetry measurements for complex dose distributions in modern RT centers.

The C2 ungrouped Tagish Lake meteorite preserves a range of lithologies, reflecting variable degrees of parent-body aqueous alteration. Here, we report on soluble organic compounds, including aliphatic and aromatic hydrocarbons, monocarboxylic acids, and amino acids, found within specimens representative of the range of aqueous alteration. We find that differences in soluble organic compounds among the lithologies may be explained by oxidative, fluid-assisted alteration, primarily involving the derivation of soluble organic compounds from macromolecular material. In contrast, amino acids probably evolved from precursor molecules, albeit in parallel with other soluble organic compounds. Our results demonstrate the role of parent-body alteration in the modification of organic matter and generation of prebiotic compounds in the early solar system, and have implications for interpretation of the complement of soluble organic compounds in carbonaceous chondrites.

The distribution and isotopic and enantiomeric compositions of amino acids found in three distinct fragments of the Tagish Lake C2-type carbonaceous chondrite were investigated via liquid chromatography with fluorescence detection and time-of-flight mass spectrometry and gas chromatography isotope ratio mass spectrometry. Large L-enantiomeric excesses (L(sub ee) approximately 43-59%) of the alpha-hydrogen aspartic and glutamic amino acids were measured in Tagish Lake, whereas alanine, another alpha hydrogen protein amino acid, was found to be nearly racemic (D much approximately L) using both techniques. Carbon isotope measurements of D- and L-aspartic acid and 1)- and L-alanine in Tagish Lake fall well outside of the terrestrial range and indicate that the measured aspartic acid enantioenrichment is indigenous to the meteorite. Alternate explanations for the L-excesses of aspartic acid such as interference from other compounds present in the sample, analytical biases, or terrestrial amino acid contamination were investigated and rejected. These results can be explained by differences in the solid-solution phase behavior of aspartic acid, which can form conglomerate enantiopure solids during crystallization, and alanine, which can only form racemic crystals. Amplification of a small initial L-enantiomer excess during aqueous alteration on the meteorite parent body could have led to the large L-enrichments observed for aspartic acid and other conglomerate amino acids in Tagish Lake. The detection of non terrestrial L-proteinogenic amino acid excesses in the Tagish Lake meteorite provides support for the hypothesis that significant enantiomeric enrichments for some amino acids could form by abiotic processes prior to the emergence of life.

Cases in which a child has been falsely reported as missing or abducted can be extremely challenging to the law enforcement agencies responsible for their investigation. In the absence of a witnessed abduction or an obvious crime scene, it is difficult to determine whether a child has actually been abducted or has become a victim of a homicide and a false allegation. The purpose of this study was to examine falsely alleged kidnapping cases and identify successful investigative strategies. Sixty-one adjudicated false allegation cases involving 66 victims were analyzed. The mean age of the victim was 5 years. Victims came from generally unstable, high-risk family situations and were killed primarily by biological parents. Victims were killed because they were unwanted or viewed as an obstacle to a desired goal, or they were victims of abuse or maltreatment that ended in fatality.

Background Respiratory syncytial virus (RSV) is a leading cause of viral infections in immunocompromised hosts and is associated with significant morbidity and mortality. In January 2015, our institution switched from aerosolized to oral ribavirin (RBV) for primary treatment of RSV infection among high-risk immunocompromised adult patients. The objective of the study was to evaluate the clinical and economic outcomes associated with this switch. Methods Retrospective cohort analysis of adult patients diagnosed with RSV infection and treated with RBV between January 1, 2013, and May 31, 2016. Results Of 46 patients, 20 (43%) patients received oral RBV and 26 (57%) received aerosolized RBV. Underlying conditions included lung transplant (n = 22), hematopoietic cell transplant (n = 16), hematological malignancy (n = 5), and structural lung diseases (n = 4). At the time of RSV diagnosis, 42 (91%) were hospitalized, 36 (78%) had clinical and radiographic evidence of lower respiratory tract infection (RTI), 9 (20%) were admitted to the ICU, and 4 (9%) required intubation. There were no differences in clinical outcomes between the 2 groups with regard to adverse events, progression from upper to lower RTI, escalation of care, or 30-day mortality. Three (15%) in the oral group and 1 (4%) in the aerosolized group died within 30 days (P = .33). The cost avoidance attributable to the switch in therapy over 1 year is $1.2 million. Conclusion Oral RBV appears to be a safe and cost-effective alternative to aerosolized RBV for the management of RSV infection in immunocompromised patients. Larger studies are needed to validate the safety and efficacy of this approach.

This study compares prostate localization using three-dimensional ultrasound (3D US) to a standard technique using implanted fiducial markers (FMs) for prostate image guided radiation therapy(IGRT). Two methods to determine prostate position on US were evaluated: Assisted segmentation (prospectively) and manual segmentation (retrospectively). Daily couch shifts to align the prostate into treatment position were measured using each technique. A total of 278 FM couch shifts and 255 and 218 corresponding assisted and manual segmentation US couch shifts were analyzed in each direction: Anterior-posterior, right-left, and superior-inferior. Ninety five percent “limits-of-agreement” (LOA) were used to analyze paired couch shifts and to determine if US can reliably replace FMs. We chose an error tolerance of ± 3 mm for the LOA analysis. For FM vs assisted-segmentation US, 35.3%, 51.0%, and 48.2% of couch shifts (anterior-posterior, right-left, and superior-inferior, respectively) agreed within ± 3 mm . Agreement improved using manual segmentation US (corresponding agreements were 45.3%, 64.1%, and 55.2%), however, results still lie markedly below the 95% we consider to indicate clinical equivalence. Based on these results, our experience indicates US cannot replace FMs for prostate IGRT, using either assisted or manual segmentation. US couch shifts showed considerably greater variability than FM measures and USimage quality is shown to affect agreement. Planning target volume margins for use with the US system were found to be 15.8, 8.7, and 12.5 mm for assisted segmentation and 13.1, 7.6, and 9.8 mm for manual segmentation. Comparison of these margins to those reported in recent studies for use with FMIGRT indicate FMs offer greater sparing of the rectum and bladder than the US system.

X-ray computed tomography (CT) as a method of extracting 3D dose information from irradiated polymer gel dosimeters is showing potential as a practical means to implement gel dosimetry in a radiation therapy clinic. However, the response of CT contrast to dose is weak and noise reduction is critical in order to achieve adequate dose resolutions with this method. Phantom design and CT imaging technique have both been shown to decrease image noise. In addition, image postprocessing using noise reduction filtering techniques have been proposed. This work evaluates in detail the use of the adaptive mean filter for reducing noise in CT gel dosimetry. Filter performance is systematically tested using both synthetic patterns mimicking a range of clinical dose distribution features as well as actual clinical dose distributions. Both low and high signal-to-noise ratio (SNR) situations are examined. For all cases, the effects of filter kernel size and the number of iterations are investigated. Results indicate that adaptive mean filtering is a highly effective tool for noise reduction CT gel dosimetry. The optimum filtering strategy depends on characteristics of the dose distributions and image noise level. For low noise images (SNR approximately 20), the filtered results are excellent and use of adaptive mean filtering is recommended as a standard processing tool. For high noise images (SNR approximately 5) adaptive mean filtering can also produce excellent results, but filtering must be approached with more caution as spatial and dose distortions of the original dose distribution can occur.

This study reports on the effects of x-ray CT dose in CT imaged normoxic polyacrylamide (nPAG) gel dosimeters. The investigation is partitioned into three sections. First, the CT dose absorbed in nPAG is quantified under a range of typical gel CT imaging protocols. It is found that the maximum absorbed CT dose occurs for volumetric imaging and is in the range of 4.6 +/- 0.2 cGy/image. This does scales linearly with image averaging. Second, using Raman spectroscopy, the response of nPAG to CT imaging photon energies (i.e., 120-140 kVp) is established and compared to the well known dose response of nPAG exposed to 6 MV photons. It is found that nPAG exhibits a weaker response (per unit dose) to 140-kVp incident photons as compared to 6 MV incident photons (slopes m6 mv = -0.0374 +/- 0.0006 Gy(-1) and m140 kVp = -0.016 +/- 0.001 Gy(-1)). Finally, using the above data, an induced change in CT number (deltaN(CT)) is calculated for nPAG imaged using a range of gel imaging protocols. It is found that under typical imaging protocols (120-140 kVp, 200 mAs, approximately 16-32 image averages) a deltaN(CT) < 0.2 H is induced in active nPAG dosimeters. This deltaN(CT) is below the current limit of detectability of CT nPAG polymer gel dosimetry. Under expanded imaging protocols (e.g., very high number of image averages) an induced deltaN(CT) of approximately 0.5 H is possible. In these situations the additional polymerization occurring in nPAG due to the imaging process may need to be accounted for.

This study presents a 3D dose mapping of complex dose distributions using an x‐ray computed tomography (CT) polymer gel dosimetry technique. Two polyacrylamide gels (PAGs) of identical composition were irradiated with the same four arc stereotactic treatment to maximum doses of 15 Gy (PAG1) and 8 Gy (PAG2). The PAGs were CT imaged using a previously defined protocol that involves image averaging and background subtraction to improve image quality. For comparison with the planned isodose distribution, the PAG images were converted to relative dose maps using a CT number‐dose calibration curve or simple division. The PAG images were then co‐registered with the planning CT images in the BrainLab® treatment planning software which automatically provides reconstructed sagittal and coronal images for 3D evaluation of measured and planned dose. The hypo‐intense high dose region in both sets of gel images agreed with the planned 80% isodose contour and was shifted by up to 1.5 and 3.0 mm in the axial and reconstructed planes, respectively. This demonstrates the ability of the CT gel technique to accurately localize the high dose region produced by the stereotactic treatment. The resulting agreement of the measured relative dose volume for PAG1 was within 3.0 mm for the 50% and 80% isodose surfaces. However, the dose contrast was too low in PAG2 to allow for accurate definition of measured relative dose surfaces. Thus, a PAG should be irradiated to higher doses if quantitative relative dose information is required. Unfortunately, this implies use of an additional PAG and its CT number dose response since doses greater than 8–10 Gy fall outside the linear regions of the response. PACS number(s): 87.53.–j, 87.57.–s, 87.59.Fm

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Purpose: Uncertainties in target identification can reduce treatment accuracy in permanent breast seed implant (PBSI) brachytherapy. This study evaluates the relationship between seroma visualization and seed placement accuracy. Methods: Spatially co-registered CT and 3D ultrasound (US) images were acquired for 10 patients receiving PBSI. Seromas were retrospectively contoured independently by 3 radiation oncologists on both CT and US and respective consensus volumes were defined, CTVCT and CTVUS. The seroma clarity and inter-user conformity index (CI), as well as inter-modality CI, volume, and positional differences were evaluated. Correlations with seed placement accuracy were then assessed. CTVs were expanded by 1.25cm to create PTVCT and PTVUS and evaluate the conformity with PTVClinical (CTVClinical+1.25cm) used in treatment planning. The change in PTV coincidence by expanding PTVClinical by 0.25cm was determined. Results: CTVUS were a mean 68 ± 12% smaller than CTVCT and generally had improved clarity and inter-user conformity. No correlations between seed displacement and CTVUS-CTVCT positional difference or CI were observed. Greater seed displacements were associated with larger CTVUS-CTVCT volume differences (r=−0.65) and inter-user CT CI (r=−0.74). A median (range) 88% (71–99%) of PTVCT and 83% (69–100%) of PTVUS were contained within PTVClinical. Expanding treatment margins to 1.5cm increased coincidence to 98% (86–100%) and 94% (82–100%), respectively. Conclusions: Differences in seroma visualization impacts seed displacement in PBSI. Reducing dependence on CT by incorporating 3DUS into target identification, or expanding CT-based treatment margins to 1.5cm may reduce or mitigate uncertainties related to seroma visualization.

This review is primarily concerned with the synthesis, structure and fluxional behaviour of cyclic and acyclic chalcogen-nitrogen systems containing phosphorus (V) or phosphorus (III). The cyclic Ph 4 P 2 N 4 S 2 R − and Ph 4 P 2 N 4 S 2− 2 anions (and their selenium analogues) are versatile ligands for both early and late transition metals. Mono-, di-, tri- and tetradentate bonding modes have been established for the eight-membered P 2 N 4 S 2 ring in these inorganic heterocycles. Ligation occurs through sulphur (or selenium) and/or nitrogen, while the coordinatively saturated phosphorus (V) centres serve as an informative probe of fluxional processes. By contrast, coordination occurs exclusively through phosphorus in both the cyclic and acyclic phosphorus (III) systems. In order to provide a background for the discussion of the coordination chemistry of hybrid PN/SN systems, the review begins with a short account of N-bonded complexes of cyclophosphazenes and S 4 N 4 , which is followed by a discussion of metal complexes of the S 4 N 2− 4 dianion. The concluding section of the review describes metal complexes of some related anionic SN ligands. In particular, the alkali metal derivatives of the acyclic [RNS(R′)NR″] − anions and transition metal complexes of the cyclic radical PhCN 2 S 2 are discussed.