Aggregate dust particles at comet 67P/Churyumov-Gerasimenko.

Comets are thought to preserve almost pristine dust particles, thus providing a unique sample of the properties of the early solar nebula. The microscopic properties of this dust played a key part in particle aggregation during the formation of the Solar System. Cometary dust was previously considered to comprise irregular, fluffy agglomerates on the basis of interpretations of remote observations in the visible and infrared and the study of chondritic porous interplanetary dust particles that were thought, but not proved, to originate in comets. Although the dust returned by an earlier mission has provided detailed mineralogy of particles from comet 81P/Wild, the fine-grained aggregate component was strongly modified during collection. Here we report in situ measurements of dust particles at comet 67P/Churyumov-Gerasimenko. The particles are aggregates of smaller, elongated grains, with structures at distinct sizes indicating hierarchical aggregation. Topographic images of selected dust particles with sizes of one micrometre to a few tens of micrometres show a variety of morphologies, including compact single grains and large porous aggregate particles, similar to chondritic porous interplanetary dust particles. The measured grain elongations are similar to the value inferred for interstellar dust and support the idea that such grains could represent a fraction of the building blocks of comets. In the subsequent growth phase, hierarchical agglomeration could be a dominant process and would produce aggregates that stick more easily at higher masses and velocities than homogeneous dust particles. The presence of hierarchical dust aggregates in the near-surface of the nucleus of comet 67P also provides a mechanism for lowering the tensile strength of the dust layer and aiding dust release.

A complex matrix characterization approach, applied to cigarette smoke, that integrates multiple analytical methods and compound identification strategies for non-targeted liquid chromatography with high-resolution mass spectrometry.

RATIONALE: For the characterization of the chemical composition of complex matrices such as tobacco smoke, containing more than 6000 constituents, several analytical approaches have to be combined to increase compound coverage across the chemical space. Furthermore, the identification of unknown molecules requiring the implementation of additional confirmatory tools in the absence of reference standards, such as tandem mass spectrometry spectra comparisons and in silico prediction of mass spectra, is a major bottleneck. METHODS: We applied a combination of four chromatographic/ionization techniques (reversed-phase (RP) - heated electrospray ionization (HESI) in both positive (+) and negative (-) modes, RP - atmospheric pressure chemical ionization (APCI) in positive mode, and hydrophilic interaction liquid chromatography (HILIC) - HESI positive) using a Thermo Q Exactive™ liquid chromatography/high-resolution accurate mass spectrometry (LC/HRAM-MS) platform for the analysis of 3R4F-derived smoke. Compound identification was performed by using mass spectral libraries and in silico predicted fragments from multiple integrated databases. RESULTS: A total of 331 compounds with semi-quantitative estimates ≥100 ng per cigarette were identified, which were distributed within the known chemical space of tobacco smoke. The integration of multiple LC/HRAM-MS-based chromatographic/ionization approaches combined with complementary compound identification strategies was key for maximizing the number of amenable compounds and for strengthening the level of identification confidence. A total of 50 novel compounds were identified as being present in tobacco smoke. In the absence of reference MS2 spectra, in silico MS2 spectra prediction gave a good indication for compound class and was used as an additional confirmatory tool for our integrated non-targeted screening (NTS) approach. CONCLUSIONS: This study presents a powerful chemical characterization approach that has been successfully applied for the identification of novel compounds in cigarette smoke. We believe that this innovative approach has general applicability and a huge potential benefit for the analysis of any complex matrices.

Comprehensive chemical characterization of the aerosol generated by a heated tobacco product by untargeted screening.

A suite of untargeted methods has been applied for the characterization of aerosol from the Tobacco Heating System 2.2 (THS2.2), a heated tobacco product developed by Philip Morris Products S.A. and commercialized under the brand name IQOS®. A total of 529 chemical constituents, excluding water, glycerin, and nicotine, were present in the mainstream aerosol of THS2.2, generated by following the Health Canada intense smoking regimen, at concentrations ≥ 100 ng/item. The majority were present in the particulate phase (n = 402), representing more than 80% of the total mass determined by untargeted screening; a proportion were present in both particulate and gas-vapor phases (39 compounds). The identities for 80% of all chemical constituents (representing > 96% of the total determined mass) were confirmed by the use of authentic analytical reference materials. Despite the uncertainties that are recognized to be associated with aerosol-based untargeted approaches, the reported data remain indicative that the uncharacterized fraction of TPM generated by THS2.2 has been evaluated to the fullest practicable extent. To the best of our knowledge, this work represents the most comprehensive chemical characterization of a heated tobacco aerosol to date. Graphical abstract.

Performance Evaluation of a Nontargeted Platform Using Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry Integrating Computer-Assisted Structure Identification and Automated Semiquantification for the Comprehensive Chemical Characterization of a Complex Matrix.

Nontargeted screening methodologies are powerful approaches for comprehensive chemical characterization of complex matrixes. In order to maximize chemical space coverage, three analytical methods using two-dimensional gas chromatography with time-of-flight mass spectrometry for nonpolar, polar, and volatile compounds have been established. The structural identification process was streamlined with an in-house developed computer-assisted structure identification platform, which facilitated the identification of novel compounds and also delivered semiquantitative concentrations for all compounds. Key performance parameters for this nontargeted platform, including chemical space coverage, confidence for structural identification, accuracy of semiquantification, and performance of differential analysis, were evaluated. The automated structural identification process was assessed using a subset of 243 compounds (out of 2990), which were confirmed to be present in cigarette smoke using reference standards. Consistently high true positive identification rates between 88.2% and 96.2% across the different concentration ranges investigated were demonstrated. Accuracy for semiquantification was assessed by comparison with quantitative data from literature, where a maximum 4-fold deviation from available targeted analysis values was estimated.

Impact of sample preparation upon intracellular metabolite measurements in 3D cell culture systems.

INTRODUCTION: Interest in cell culture metabolomics has increased greatly in recent years because of its many potential applications and advantages (e.g., in toxicology). The first critical step for exploring the cellular metabolome is sample preparation. For metabolomics studies, an ideal sample preparation would extract a maximum number of metabolites and would enable reproducible, accurate analysis of a large number of samples and replicates. In addition, it would provide consistent results across several studies over a relatively long time frame. OBJECTIVES: This study was conducted to evaluate the impact of sample preparation strategies on monitoring intracellular metabolite responses, highlighting the potential critical step(s) in order to finally improve the quality of metabolomics studies. METHODS: The sample preparation strategies were evaluated by calculating the sample preparation effect, matrix factor, and process efficiency (PE) for 16 tobacco exposition-related metabolites, including nicotine, nicotine-derived nitrosamine ketone, their major metabolites, and glutathione, using isotopically-labelled internal standards. Samples were analyzed by liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS). RESULTS: A sample drying step increased losses or variability for some selected metabolites. By avoiding evaporation, good sample preparation recovery was obtained for these compounds. For some metabolites, the cell or culture type impacted PE and matrix factor. CONCLUSION: In our sample preparation protocol, the drying-reconstitution step was identified as the main cause of metabolite losses or increased data variability during metabolomics analysis by LC-HRMS. Furthermore, PE was affected by the type of matrix. Isotopologue internal standards fully compensate losses or enhancements.

Prediction Models of Retention Indices for Increased Confidence in Structural Elucidation during Complex Matrix Analysis: Application to Gas Chromatography Coupled with High-Resolution Mass Spectrometry.

Monitoring of volatile and semivolatile compounds was performed using gas chromatography (GC) coupled to high-resolution electron ionization mass spectrometry, using both headspace and liquid injection modes. A total of 560 reference compounds, including 8 odd n-alkanes, were analyzed and experimental linear retention indices (LRI) were determined. These reference compounds were randomly split into training (n = 401) and test (n = 151) sets. LRI for all 552 reference compounds were also calculated based upon computational Quantitative Structure-Property Relationship (QSPR) models, using two independent approaches RapidMiner (coupled to Dragon) and ACD/ChromGenius software. Correlation coefficients for experimental versus predicted LRI values calculated for both training and test set compounds were calculated at 0.966 and 0.949 for RapidMiner and at 0.977 and 0.976 for ACD/ChromGenius, respectively. In addition, the cross-validation correlation was calculated at 0.96 from RapidMiner and the residual standard error value obtained from ACD/ChromGenius was 53.635. These models were then used to predict LRI values for several thousand compounds reported present in tobacco and tobacco-related fractions, plus a range of specific flavor compounds. It was demonstrated that using the mean of the LRI values predicted by RapidMiner and ACD/ChromGenius, in combination with accurate mass data, could enhance the confidence level for compound identification from the analysis of complex matrixes, particularly when the two predicted LRI values for a compound were in close agreement. Application of this LRI modeling approach to matrixes with unknown composition has already enabled the confirmation of 23 postulated compounds, demonstrating its ability to facilitate compound identification in an analytical workflow. The goal is to reduce the list of putative candidates to a reasonable relevant number that can be obtained and measured for confirmation.

The oral iron chelator deferasirox inhibits NF-κB mediated gene expression without impacting on proximal activation: implications for myelodysplasia and aplastic anaemia.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.

Is the sacro-femoral-pubic angle predictive for pelvic tilt in adolescent idiopathic scoliosis patients?

STUDY DESIGN: This was a retrospective radiographic study. OBJECTIVE: The aim of this study was to evaluate the correlation between pelvic tilt (PT) and the sacro-femoral-pubic angle (SFP angle) in AIS patients and to clarify whether the predictability of PT is affected by different curve patterns. SUMMARY OF BACKGROUND DATA: Pelvic retroversion is one of the compensatory mechanisms to maintain upright position and is also tied to health-related quality of life in patients with adolescent idiopathic scoliosis (AIS). However, measurement of spino-pelvic parameters including PT may not be accurate because of difficulty in visualizing femoral heads on lateral radiographs in some patients. MATERIALS AND METHODS: In this study, 101 female AIS patients were recruited. The subjects were divided into 2 groups: thoracic scoliosis (TS) and lumbar scoliosis (LS) group. Long-cassette standing upright radiographs were obtained; PT and SFP angles were measured through digital analysis software (Surgimap Spine Software, New York, NY). The relations between PT and SFP angle were determined by the Pearson correlation coefficient (r). Linear regressions between PT and SFP angle were also performed. RESULTS: The SFP angle was strongly correlated with PT in both groups, and PT could be estimated by the formulas: PT=74.052-0.991×SFP angle in the TS group and PT=65.345-0.881×SFP angle in the LS group. In the TS group, the SFP angle correlated with PT strongly with a Pearson coefficient of 0.65. Whereas in the LS group, the coefficient was weaker than that in the TS group (0.48 vs. 0.65); however, it still showed that PT was significantly associated with SFP. CONCLUSIONS: Given the high correlation between PT and SFP angle, the SFP angle should be considered a reliable alternative option to PT, which has routinely excellent visibility in coronal films in AIS patients. The predictability was more accurate for AIS patients with thoracic curves than with lumbar curves.

Transverse minilaparotomy for open abdominal aortic aneurysm repair.

INTRODUCTION: Traditional open surgical repair for abdominal aortic aneurysm (AAA) is a major procedure with a relatively high risk of perioperative morbidity. This article describes the results of minimally invasive open AAA repair through a transverse left upper quadrant minilaparotomy. METHODS: Between January 2007 and June 2010, 83 consecutive patients (77 men) underwent elective or urgent repair of a nonruptured AAA through a horizontal transperitoneal left upper quadrant minilaparotomy. Postoperatively, patients were fast-tracked through a multidisciplinary recovery program. RESULTS: Repairs were urgent in 15 patients (18%), and 10 (12%) had aortoiliac aneurysms. American Society of Anesthesiologists (ASA) scores 1 to 4 were 3.6%, 44.6%, 42%, and 11%, respectively. Median (range) age was 73 (61-87) years, AAA size was 5.9 (5.1-10) cm, body mass index was 27 (19-39) kg/m(2), operation time was 150 (85-280) minutes, blood loss was 625 (200-4150) mL, critical care bed days was 1 (0-19), and hospital stay was 4 (2-88) days. Four (4.8%) patients returned to the operating theater within the same admission. No patients required conversion to full laparotomy and none had reintervention postdischarge. Two patients (2.4%) died in the hospital, and 18 (21.7%) had postoperative adverse events, ranging from urinary retention to myocardial infarction. New-onset atrial fibrillation was the commonest of these events (11, 13.3%). Respiratory tract infection incidence was low (4.8%). Incisional herniation developed in two patients (2.4%) at a median (range) follow-up of 10 (6-25) months. Correcting for age, cardiac complications were associated with increased odds of hospital stay >4 days (odds ratio [OR], 7.59; 95% confidence interval [CI], 1.12-52.42; P = .014). Correcting for ASA score, advancing age was associated with increased risk of cardiac complications (OR, 1.18; 95% CI, 1.08-1.28; P = .001), whereas AAA screening (patient identified through screening) and maintaining higher intraoperative systolic pressure were both protective (OR, 0.24; 95% CI, 0.07-0.87; P = .018) and (OR, 0.93; 95% CI, 0.89-0.98; P = .009), respectively. CONCLUSION: Left upper quadrant minilaparotomy is a feasible minimally invasive approach to open AAA repair. This technique is associated with low morbidity and mortality and short hospital stay, particularly in patients identified through AAA screening.

Reaction kinetic model for a recent co-produced water treatment technology.

With the increasing demand for fossil based energy and implementation of progressively strict environmental pollution control standards, treatment of a large amount of co-produced waters (CPWs) from fossil based energy production has become increasingly important. Removal of bicarbonate with H2SO4 has been recently studied as a simple and cost-effective method to decrease the alkalinity of CPWs. The present work investigates the kinetics of the reaction between H2SO4 and NaHCO3, which could provide the base for scaling-up the CPW treatment technology. Based on the measured quantity change of the CO2 gas generated from the reaction between H2SO4 and NaHCO3 with time under specified initial reaction conditions, the reaction orders with respect to H2SO4 and NaHCO3 were determined. Experiments were also conducted within the temperature of 15-30 degrees C to find various global rate coefficients of the reaction to calculate the activation energy and the pre-exponential factor of the empirical Arrhenius form of the bicarbonate removal reaction, which are 197.7 kJ/mol and 3.13 x 10(34) (mol(-3.7) x L(3.7) x sec(-1)), respectively.

Pegfilgrastim to support CHOP-14 in elderly patients with non-Hodgkin's lymphoma.

This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61 - 74). Forty-seven per cent of patients received full dose chemotherapy on schedule for all cycles (range 65 - 93). Chemotherapy was delayed in 10 patients and dose reduced in 15 patients. Hematological toxicity was the most common reason for delays and dose reduction. Six of nine patients (67%) achieved a peripheral blood CD34+ count of at least 20 cellsx106 L-1 on day 12 of cycle one. The delivery on schedule of dose-dense CHOP-14 to elderly patients with previously untreated aggressive NHL is safe and efficacious with once per cycle pegfilgrastim support.

Relapsed plasma cell leukaemia presenting with aggressive extramedullary plasmacytomas in the meninges and testis--a missed opportunity for induction CNS prophylaxis.

After initial treatment, a 54-year-old male with plasma cell leukaemia developed extramedullary relapse in the testis and meninges without evidence of bone marrow involvement. We postulate that the central nervous system (CNS) and testis may have served as sanctuary sites for the disease during initial treatment. A role for CNS prophylaxis in plasma cell leukaemia is suggested.

Unanticipated revision surgery in adult spinal deformity: an experience with 815 cases at one institution.

STUDY DESIGN: Retrospective case series. OBJECTIVE: This study reviewed the overall prevalence and indications of revision surgical procedures for adult scoliosis in a single institution. In this largest single-institution series, revision surgery in adult scoliosis was required for a relatively low proportion of cases (7.61%). The main indications were implant breakage, deformity progression, and infection. SUMMARY OF BACKGROUND DATA: Spine fusion is considered as the final therapeutic intervention in the management of adult scoliosis. However, reports on the repeat surgical intervention of adult scoliosis predate the use of advanced instrumentation systems. METHODS: The scoliosis database of our center was searched, and all cases with index spinal fusion surgical procedures performed for adult scoliosis from 1998 to 2011 with the follow-up period of more than 2 years were identified. The clinical data and radiographs of patients were reviewed to provide information on the indication of initial operation and any subsequent revision surgery. A total of 815 patients were identified, with a mean age of 30.49 years (range, 20-76 yr). The mean follow-up periods were 6.4 years (range, 2-15 yr) for the entire cohort and 7.6 years (range, 2.5-12 yr) for the subset of the cohort requiring revision. RESULTS: The patients exhibiting multiple reasons for revision were classified under primary reason and subjected to subsequent analysis. Among the 815 patients, 62 (7.61%) underwent at least 1 revision surgery. The most common reasons for revision were implant breakage (23/62; 37.1%), deformity progression (10/62; 16.1%), and infection (9/62; 14.5%). The other indications were pseudarthrosis (n = 8), implant dislodgement (n = 6), junctional kyphosis (n = 5), and neurological deficit (n = 1). Revision rate was significantly higher in patients older than 40 years (15.23% vs. 5.87%), in patients with degenerative or congenital scoliosis (15.12% vs. 12.82%), or in patients with hybrid constructs (12.12% vs. 5.82%). CONCLUSION: In this largest single-institution series, revision surgery after index spinal fusion in patients with adult scoliosis was required for a relatively low proportion of surgical cases (7.61%). The main indications for revision were implant breakage, deformity progression, and infection.

Vertebral rotatory subluxation in degenerative scoliosis: facet joint tropism is related.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To identify facet tropism as one of the possible risk factors leading to vertebral rotatory subluxation (VRS). SUMMARY OF BACKGROUND DATA: VRS has been considered as one of the prognostic factors for degenerative scoliosis. Although several risk factors of VRS, including age and Cobb angle, have been investigated, few studies exist that have evaluated the correlation between VRS and anatomical structures of the vertebral column. METHODS: This retrospective study recruited 23 patients diagnosed with degenerative lumbar scoliosis with VRS and 20 patients with degenerative scoliosis without VRS. The lateral translation on coronal radiographs was measured and 5 mm was used as the cutoff value to define rotatory subluxation. Computed tomographic scans for facet joints were made for all lumbar levels. The difference between right and left facet angles was recorded as ΔFA. Facet tropism was defined as a difference between the bilateral facet angles of more than 10°. RESULTS: In this study, VRS was most commonly found at the L3-L4 level (49%) and, with decreasing frequency at L2-L3 (24%), L4-L5 (20%), and L1-L2 (7%). On the convex side of the main curve, face joints at levels with VRS were more coronally oriented compared with those at levels without VRS (41.64° ± 11.65° vs. 36.30° ± 10.99°, P = 0.034). ΔFA was also significantly different between levels with and without VRS (P = 0.005). A strong correlation was found between ΔFA and lateral translation, with a coefficient of 0.33 (P < 0.001). In addition, ΔFA and a larger Cobb angle were found to be significantly associated with VRS based on binary regression analysis, with an odds ratio of 4.68 and 2.14, respectively. CONCLUSION: Facet tropism was more significantly observed at levels with VRS. On the convex side of the main curve, facet joints at levels with VRS were more coronally oriented. A larger Cobb angle and severe facet tropism in degenerative scoliosis should be considered to be related to VRS.

Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium.

PURPOSE: Lipofuscin (LF) accumulation within RPE cells is considered pathogenic in AMD. To test whether LF contributes to RPE cell loss in aging and to provide a cellular basis for fundus autofluorescence (AF) we created maps of human RPE cell number and histologic AF. METHODS: Retinal pigment epithelium-Bruch's membrane flat mounts were prepared from 20 donor eyes (10 ≤ 51 and 10 > 80 years; postmortem: ≤4.2 hours; no retinal pathologies), preserving foveal position. Phalloidin-binding RPE cytoskeleton and LF-AF (488-nm excitation) were imaged at up to 90 predefined positions. Maps were assembled from 83,330 cells in 1470 locations. From Voronoi regions representing each cell, the number of neighbors, cell area, and total AF intensity normalized to an AF standard was determined. RESULTS: Highly variable between individuals, RPE-AF increases significantly with age. A perifoveal ring of high AF mirrors rod photoreceptor topography and fundus-AF. Retinal pigment epithelium cell density peaks at the fovea, independent of age, yet no net RPE cell loss is detectable. The RPE monolayer undergoes considerable lifelong re-modeling. The relationship of cell size and AF, a surrogate for LF concentration, is orderly and linear in both groups. Autofluorescence topography differs distinctly from the topography of age-related rod loss. CONCLUSIONS: Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD.

Catalytic regeneration of mercury sorbents.

Traditionally, mercury sorbents are disposed of in landfills, which may lead to contamination of soil and groundwater. In this work, the regeneration of activated carbon (AC) as a mercury sorbent was investigated. The decomposition of HgCl2 on the surface of pure AC was studied, as well as sorbent which has been treated with FeCl3 or NaCl. In all cases, the sorbent is found to be structurally stable through a single regeneration, which is verified through BET, XRD, and XPS analysis. The desorption of mercury from the sorbent is found to follow Henry's law. Additionally, a kinetic analysis suggests that although the presence of activated carbon lowers the energy requirement for the desorption of mercury, it significantly decreases the rate by decreasing the concentration of the HgCl2. FeCl3 and NaCl both promoted the decomposition of HgCl2, but FeCl3 did so more significantly, increasing the rate constants by a factor of 10 and decreasing the activation energy for the decomposition of HgCl2 by 14% to 40%.