Severe Overlap Research Articles

Multi-Objective Optimized Overlapping Peak Separation Algorithm for Simultaneous Detection of Copper and Cobalt by Ultraviolet-Visible Spectroscopy

In the zinc hydrometallurgy, the excessive impurity ions of copper and cobalt are very harmful to the electrolysis process, which affects product quality and wastes resources. In order to solve the problems of low sensitivity, severe spectral overlap and narrow effective band, an overlapping peak separation algorithm based on multi-objective optimization was proposed for simultaneous detection of copper and cobalt in high concentration zinc solution by ultraviolet-visible spectroscopy. First, according to the characteristics of the spectral signal, the derivative spectroscopy by continuous wavelet transform was used to separate the spectral overlapping peaks of copper and cobalt and shield the zinc interference. Then, taking decomposition scale as decision variable, and the information occupancy and peak separation as the optimization targets, a multi-objective optimization model was established and solved using the particle swarm multi-objective optimization method. Finally, derivative spectroscopy combined with zero-crossing method was used to establish calibration curves for simultaneous detection of copper and cobalt. The experimental results show that the proposed method is suitable for simultaneous detection of trace amounts of copper and cobalt in high concentration zinc solution.

Effect of Genetic Algorithm-Based Wavelength Selection as a Preprocessing Tool on Multivariate Simultaneous Determination of Paracetamol, Orphenadrine Citrate, and Caffeine in the Presence of p-Aminophenol Impurity.

The utilization of selection methods such as genetic algorithm (GA) aims to construct better partial least squares (PLS) and principal component regression (PCR) models than those established from the full-spectrum range. Determination of paracetamol (PAR), orphenadrine citrate (Or.cit), and caffeine (CAF) in the presence of PAR nephrotoxic impurity [p-aminophenol (PAP)]. GA was applied to select the optimum wavelengths used. A calibration set was prepared in which the three drugs, together with PAP, were modeled by multilevel multifactor design. This calibration set was used to build the PLS and PCR models, either with or without preprocessing the data using GA. Results were compared with and without preprocessing, and this revealed that GA can find an optimized combination of spectral wavelengths, yielding a lower root mean square error of prediction as well as a lower number of latent variables used. The results of the two models show that simultaneous determination of the aforementioned drugs can be performed in the concentration ranges of 20-60, 3-11, and 1-9 μg/mL for PAR, Or.cit, and CAF, respectively. The proposed models were applied for the determination of the three drugs in their pharmaceutical formulations, and the results were verified by the standard addition technique. GA can be useful as a wavelength selection tool before applying multivariate PLS and PCR methods. GA gives an improvement in the predictive ability of the models with lower RMSEP and less number of latent variables (LVs). The proposed PLS, PCR, GA-PLS, and GA-PCR spectrophotometric methods were able to determine paracetamol, orphenadrine citrate, and caffeine in the presence of p-aminophenol and severe spectral overlapping.

Operating systems with high performance and organisational performance: the mediating role of creative atmosphere, job satisfaction and moderating role of learning and organisational culture

The purpose of this research was to investigate the impact of operating systems with high performance on organizational performance of SADERAT. The statistical population consisted of 400 employees of SADERAT Bank branches of Tehran City, that the 196 persons were selected as a statistical sample the collected data from the questionnaire were analyzed by structural equation method at two levels of descriptive and inferential. The results show that there is a positive correlation between operating systems with high performance and organization performance through a creative atmosphere and job satisfaction. Also, learning and organizational culture as a moderator on mediating variables of creative atmosphere and job satisfaction in the relationship between high-performance work systems and organizational performance are also affected. Ultimately, the culture and learning of organization due to the severe overlap, were found a weak moderators in this research.

Operating systems with high performance and organisational performance: the mediating role of creative atmosphere, job satisfaction and moderating role of learning and organisational culture

The purpose of this research was to investigate the impact of operating systems with high performance on organizational performance of SADERAT. The statistical population consisted of 400 employees of SADERAT Bank branches of Tehran City, that the 196 persons were selected as a statistical sample the collected data from the questionnaire were analyzed by structural equation method at two levels of descriptive and inferential. The results show that there is a positive correlation between operating systems with high performance and organization performance through a creative atmosphere and job satisfaction. Also, learning and organizational culture as a moderator on mediating variables of creative atmosphere and job satisfaction in the relationship between high-performance work systems and organizational performance are also affected. Ultimately, the culture and learning of organization due to the severe overlap, were found a weak moderators in this research.

Chemometric decomposition of comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry data employing partial modulation in the negative pulse mode

Partial modulation in the negative pulse mode was optimized for comprehensive two-dimensional gas chromatography (GC × GC) coupled to time-of-flight mass spectrometry (TOFMS). With partial modulation in the negative pulse mode, a flow of auxiliary carrier gas is applied through a pulse valve to a T-junction joining the first (1D) and second (2D) dimension columns for nearly all of the modulation period (PM). This results in dilution of the 1D eluate, followed by briefly turning off the pulse valve for a specified pulse width (pw), effectively “injecting” undiluted 1D eluate onto the 2D column. The raw data has the appearance of 2D separations superimposed on top of the 1D separation. While high peak capacity GC × GC data are produced, there are challenges that needed to be addressed regarding the use of chemometrics for analyte decomposition, identification, and quantification. Herein, these data analysis challenges are addressed using multivariate curve resolution - alternating least squares (MCR-ALS). An isothermal separation of a 15-component mixture of similar compounds is obtained in 20 s using a PM = 250 ms and a pw = 6 ms. Various peak overlap situations were purposely produced to facilitate the chemometric method demonstration. The MCR-ALS chromatographic loadings (peak profiles) were used to determine retention times (tR) and width-at-base (Wb) in both separation dimensions. MCR-ALS readily decomposed 1D × 2D regions for analytes with severe 1D overlap if they were fully resolved on 2D. Decomposition was more challenging for analytes severely overlapped on both GC × GC dimensions when their spectra were similar, though ultimately all 15 compounds were successfully decomposed. Additionally, the 2D concentration peak profiles obtained via MCR-ALS are demonstrated to be reliable for identification and quantifiable. The predicted versus prepared concentration values are in good agreement for two representative analytes, with percent deviation values of −5.6% (±2.2%) for 1-hexene, and 1.8% (±3.4%) for 2-pentanone.

Measurements of C2H4 transitions near 1.625 μm and C2H4 concentrations using the WM-DAS method

The linestrengths and the self- and N2- broadening coefficients for 6 absorption transitions of C2H4 located at v5+v9 near 1.625 μm were measured using wavelength modulation direct absorption spectroscopy (WM-DAS) at 300–700 K. The Rautian and Voigt profiles were used to recover the absorbance and calculate the best-fit spectroscopic parameters and their temperature dependence. The transitions 6140.060 and 6140.405 cm−1 with less overlap between neighboring spectral lines were recommended to be used to measure C2H4 concentrations and temperatures. The C2H4 concentrations at 20 kPa and 1 atm were measured using the measured linestrength of the C2H4 transitions. The results show good agreement within 6.7% between the measured concentrations and the actual concentrations (0.5% ˜ 100%) at 20 kPa. However, they only compare well within 5.3% for concentrations less than 20% at atmospheric pressure due to the severe overlap among neighboring spectral lines.

High-resolution trace gas detection by sub-Doppler noise-immune cavity-enhanced optical heterodyne molecular spectrometry: application to detection of acetylene in human breath.

A sensitive high-resolution sub-Doppler detecting spectrometer, based on noise-immune cavity-enhanced optical heterodyne molecular spectrometry (NICE-OHMS), for trace gas detection of species whose transitions have severe spectral overlap with abundant concomitant species is presented. It is designed around a NICE-OHMS instrumentation utilizing balanced detection that provides shot-noise limited Doppler-broadened (Db) detection. By synchronous dithering the positions of the two cavity mirrors, the effect of residual etalons between the cavity and other surfaces in the system could be reduced. An Allan deviation of the absorption coefficient of 2.2 × 10-13 cm-1 at 60 s, which, for the targeted transition in C2H2, corresponds to a 3σ detection sensitivity of 130 ppt, is demonstrated. It is shown that despite significant spectral interference from CO2 at the targeted transition, which precludes Db detection of C2H2, acetylene could be detected in exhaled breath of healthy smokers.

Predicting Carbon Spectrum in Heteronuclear Single Quantum Coherence Spectroscopy for Online Feedback During Surgery.

1H High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) is a reliable technology used for detecting metabolites in solid tissues. Fast response time enables guiding surgeons in real time, for detecting tumor cells that are left over in the excision cavity. However, severe overlap of spectral resonances in 1D signal often render distinguishing metabolites impossible. In that case, Heteronuclear Single Quantum Coherence Spectroscopy (HSQC) NMR is applied which can distinguish metabolites by generating 2D spectra ( 1H- 13C). Unfortunately, this analysis requires much longer time and prohibits real time analysis. Thus, obtaining 2D spectrum fast has major implications in medicine. In this study, we show that using multiple multivariate regression and statistical total correlation spectroscopy, we can learn the relation between the 1H and 13C dimensions. Learning is possible with small sample sizes and without the need for performing the HSQC analysis, we can predict the 13C dimension by just performing 1H HRMAS NMR experiment. We show on a rat model of central nervous system tissues (80 samples, 5 tissues) that our methods achieve 0.971 and 0.957 mean R2 values, respectively. Our tests on 15 human brain tumor samples show that we can predict 104 groups of 39 metabolites with 97 percent accuracy. Finally, we show that we can predict the presence of a drug resistant tumor biomarker (creatine) despite obstructed signal in 1H dimension. In practice, this information can provide valuable feedback to the surgeon to further resect the cavity to avoid potential recurrence.

Conformational Variability of Cyclosporin C Dissolved in Dimethylformamide

Action of biologically active compounds requires proper spatial structure, and sometimes controversial requirements should be fulfilled at the same time. Cyclosporin, widely used to prevent allograft rejection, is an example because it should cross through a cell membrane and form a complex with a target protein inside the cell. This difficulty is overcome by flexibility of the molecule. Cyclosporin A was widely studied, and it is known to have multiple conformations in polar media such as water and methanol. However, detailed characterization of all these conformers is difficult: their lifetime is too long for MD simulations, analysis of NMR spectra is hampered due to severe signal overlap, and IR spectroscopy gives parameters averaged over all conformers. This paper presents characterization of conformational equilibrium of cyclosporin C dissolved in dimethylformamide. High-resolution NMR spectra recorded at 700 MHz allowed distinguishing most of observed amide proton signals. Existence of several intramolecular hydrogen bonds over the whole set of conformers was supposed; in most cases, however, these bonds are disrupted. Kinetics of a conformational transition is evaluated. Obtained results are in agreement with what is known about cyclosporin A, but can give new information on the role of additional H-bond donors (there are six of them in CsC vs. five in CsA) in the observed chain flexibility.

A novel systematic absence of cross peaks-based 2D-COS approach for bilinear data.

A novel approach to use two-dimensional correlation spectroscopy (2D-COS) to analyze bilinear data is proposed. A phenomenon called Systematic Absence of Cross Peaks (SACPs) is observed in a 2D asynchronous spectrum. Two theorems relevant to SACPs have been derived. The SACP-based 2D-COS method has been successfully applied on analyzing bilinear data from mixed samples (including one model system and two real systems). Implicit isolated peaks can be identified and assigned to different components based on characteristic pattern of SACPs even if the time-related profiles of different components are severely overlapped. Based on the results of SACPs, spectra of pure components can be retrieved. Identification of SACPs can still be achieved in the presence of artifacts. Thus, neither noise nor baseline drift can produce significant influence on the results obtained from the approach described in this paper. We have used several well-established chemometric methods, including N-Findr, VCA, and MCR with various initial settings, on two systems that can be successfully solved using the 2D-COS method. The chemometric methods mentioned above cannot provide correct spectra of pure components because of severe problem of rotational ambiguity derived from severe overlapping of the time-related profiles. Only when the information from SACPs in 2D-COS is used as additional constraints in MCR calculation, correct spectra can be obtained. That is to say, the SACP-based 2D-COS method provides intrinsic information which is crucial in the analysis of chromatographic-spectroscopic and analogous data even if the time-related profiles of different components overlap severely.

Simultaneous and fast determination of bisphenol A and diphenyl carbonate in polycarbonate plastics by using excitation-emission matrix fluorescence couples with second-order calibration method.

A new strategy for the determination of bisphenol A (BPA) and diphenyl carbonate (DPC) in polycarbonate plastics has been proposed, combing excitation-emission matrix fluorescence and second-order chemometrics methods. The studied compounds are two of the most frequently used chemical raw materials and intermediates, which is mainly used for bio-chemical products. The method is fast and sensitive as it can avoid tedious pretreatment steps and large amounts of organic solvents consumption. Chemometrics allowed accurate and precise quantification of two target analytes even in the presence of severe spectral overlap, unknown and background interferences, which benefit from "second-order advantages" provided by chemometrics multivariate calibration. Reasonable quantification results were obtained in real plastics samples, with limits of detection for two analytes were 0.04 and 1.18 × 103 ng mL-1 and limits of quantitation were 0.11 and 3.58 × 103 ng mL-1. In addition, the average recoveries for BPA and DPC were 99.35% and 83.50% with relative standard deviation <2.30%. It was proved that the proposed method can be a useful and sensitive tool to the determination of BPA and DPC in different polycarbonate plastics with a simple sample pretreatment at low cost.

Cysteine-ethylation of tissue-extracted membrane proteins as a tool to detect conformational states by solid-state NMR spectroscopy.

Solid-state NMR (ssNMR) is an ideal tool to study structure and dynamics of membrane proteins in their native lipid environment. In principle, ssNMR has no size limitations. However, this feature is rarely exploited as large membrane proteins display severe resonance overlap. In addition, dismal yields from recombinant bacterial expression systems limit severely spectroscopic characterization of membrane proteins. For very large mammalian membrane proteins, extraction from the original organism remains the most viable approach. In this case, NMR-observable nuclei must be introduced post-translationally, but the approaches developed so far are rather scarce. Here, we detail the synthesis and engineering of a reactive 13C-ethylmethanethiosulfonate (13C-EMTS) reagent for the post-translational alkylation of cysteine sidechains of a 110kDa sarcoplasmic reticulum Ca2+-ATPase (SERCA) extracted from rabbit skeletal muscle tissue. When reconstituted into liposomes, it is possible to resolve the resonances of the engineered ethyl groups by magic-angle spinning (MAS) 2D [13C,13C]-DARR experiments. Notably, the ethyl-group modification does not perturb the function of SERCA, yielding well-resolved 13C-13C fingerprints that are used to image its structural states in the catalytic cycle and filtering out overwhelming naturally-abundant 13C nuclei signals arising from the enzyme and lipids. We anticipate that this approach will be used together with 19F NMR to monitor conformational transitions of enzymes and proteins that are difficult to express recombinantly.

A Deep Neural Network Based on an Attention Mechanism for SAR Ship Detection in Multiscale and Complex Scenarios

Synthetic aperture radar (SAR) ship detection based on deep learning has been widely applied in recent years. However, two main obstacles are hindering SAR ship detection. First, the identification of ships in a port is seriously disrupted by the presence of onshore buildings. It is difficult for the existing detection algorithms to effectively distinguish the targets from such a complex background. Additionally, it appears more complicated to accurately locate densely arranged ships. Second, the ships in SAR images exist at a variety of scales due to multiresolution imaging modes and the variety of ship shapes; these pose a much greater challenge to ship detection. To solve the above problems, this paper proposes an object detection network combined with an attention mechanism to accurately locate targets in complex scenarios. To address the diverse scales of ship targets, we construct a loss function that incorporates the generalized intersection over union (GIoU) loss to reduce the scale sensitivity of the network. For the final processing of the results, soft nonmaximum suppression (Soft-NMS) is also introduced into the model to reduce the number of missed detections for ship targets in the presence of severe overlap. The experimental results reveal that the proposed model exhibits excellent performance on the extended SAR ship detection dataset (SSDD) while achieving real-time detection.

Simultaneous determination of antinonin and trifluralin by electrochemical method and net analyte signal interferent modeling

Antinonin and trifluralin are selective herbicides to control the insects and usually used with each other. Simultaneous determination of antinonin and trifluralin has been investigated, using modified carbon paste electrode (CPE) prepared from: graphite, multi-walled carbon nanotubes (MWCNT) and nanomagnetic core-shell (Fe3O4/SiO2). Cyclic voltammetry (CV) and square wave voltammetry (SWV) studies indicated two-oxidation peak for antinonin and one oxidation peak for trifluralin from 0 to +0.6 V. For simultaneous determination of antinonin and trifluralin severe overlap of the voltammogram profiles was observed. It was shown that the electrochemical profile of the analytes changes in the presence of each other. Therefore, results of the analysis of antinonin and trifluralin by H-point standard addition method in their mixtures in water samples were not satisfactory. In order to determine antinonin and trifluralin simultaneously, net analyte signal interferent modeling (NAS-IM) was used. The proposed sensor was found that is able to determine antinonin and trifluralin with a detection limit of 0.3 and 3 nM, respectively. The method was successfully applied for the assay of antinonin and trifluralin simultaneously in water samples.

Characterizing a Population with Severe Manifestations of Sickle Cell Disease Using U.S. Real-World Evidence

BackgroundSickle cell disease (SCD) is a monogenetic disorder, with 300,000 to 400,000 infants born annually with the disease around the world (Kato et al, Nat Rev Dis Primers 2018). SCD is a progressively debilitating and life-threatening disease characterized by hemolytic anemia, painful vaso-occlusive events (VOEs) and persistent vasculopathy that result in significant morbidity, poor quality of life and early mortality. There is significant heterogeneity in clinical manifestations of SCD, given that vaso-occlusion and hemolysis-associated endothelial dysfunction may manifest in any tissue or organ. Severely affected patients may experience a diverse set of complications (Kato et al, Nat Rev Dis Primers 2018). Given the limited research to date in this area, the objectives of this real-world, retrospective study were to 1) identify and describe severely debilitating clinical complications experienced by patients with SCD in the U.S. and 2) examine rates of associated co-morbidities for this cohort.MethodsA retrospective cohort analysis was undertaken utilizing patient-level, de-identified administrative claims data from the Truven Health U.S. MarketScan® Commercial, Medicare Supplemental, and Medicaid Multi-State Databases, for the period from January 1, 2010 to September 30, 2016. SCD patients were identified based on: ≥ 2 separate dates during study period with a medical claim having a SCD diagnosis (based on set of relevant ICD-9 or ICD-10 CM codes) and included in analyses if they had ≥ 2 years of follow-up with continuous plan enrollment. Treatment approaches and clinical outcomes were defined using a pre-specified list of relevant diagnosis and treatment codes. Commonly identified characteristics of severe SCD were assessed for each patient during their 1st 2 years of continuous enrollment during study period. These included 1): having frequent (i.e. ≥ 4) VOEs [i.e. sickle cell crises either distinct from acute chest syndrome (ACS) or unspecified] that require emergency room care or hospitalization, 2) stroke or history of stroke, 3) receiving chronic red blood cell (RBC) transfusions, or 4) ≥ 1 medical encounters for ACS.ResultsA total of 18,740 patients with SCD (56% Female; 61% from Medicaid database; 75% Black [only reported in Medicaid sample]) met the study criteria. Nearly 60% of the cohort were < 20 years old, 73% < 30 years old and only 9% ≥ 50 years old. Over the 2-year follow-up period, 23% of patients had ≥ 1 prescription for hydroxyurea. Table 1 provides a breakdown of patient comorbidities by age group. The most common comorbidities across all evaluated patients were cardiomegaly (12.6%), depression (11.8%), anxiety (7.8%) and osteonecrosis (7.7%). The prevalence of chronic kidney disease (CKD) increased most markedly as patient age increased, with 20% of 55-64-year-olds experiencing CKD. By the age of 35, over half (53.3%) of the SCD patients had at least one of the 13 listed comorbidities; this increased to 74.2% for a subset with 4 years of follow-up available. Thirty-three percent of patients had ≥ 1 inpatient admission for a VOE. Figure 1 shows patient counts for the selected complications of severe SCD, with rates and overlap among subgroups varying between children and adults. Approximately one-third of patients with SCD with multiple hospitalizations/emergency visits due to VOEs also had an ACS event. There was limited overlap in patients with SCD with history of stroke and those with an ACS event; and as expected there was very little overlap in patients with SCD receiving chronic transfusions and those with ≥4 VOEs or those with ACS (as RBC transfusions are prescribed to certain SCD patients to limit symptom impact).ConclusionsBased on this contemporary real-world evidence from the U.S. setting, a substantial proportion of patients with SCD experience a diverse set of severely debilitating complications of the disease, as well as other co-morbidities associated with the disease. The high rate of comorbidities across all age groups and overrepresentation of patients younger than 30 years of age (relative to age distribution of general U.S. population) indicate that patients with SCD still experience significant morbidity and early mortality with current standard medical care. Given the notable heterogeneity of the clinical manifestations of SCD, future treatment approaches should address the root cause of the disease. DisclosuresParamore:bluebird bio: Employment, Equity Ownership. Kong:bluebird bio: Consultancy, Research Funding. Minegishi:bluebird bio: Employment, Equity Ownership. Shi:bluebird bio: Employment, Equity Ownership.

Human Umbilical Cord Derived Mesenchymal Stromal Cells to Treat Steroid-Refractory Acute GvHD III/IV or Overlap Syndrome: Interim Analysis of a Multicenter Phase I/II Study

BackgroundTreatment of patients developing steroid-refractory acute GvHD (SR-aGvHD) after allogeneic hematopoietic cell transplantation (HCT) remains an unmet clinical need and a major therapeutic challenge. Mesenchymal stromal cells (MSC) induce immunosuppression and reduce the inflammatory status initiated by aGvHD. We performed an interim analysis of a multicenter, prospective, non-randomized, phase I/II study, planned to test the safety and activity of human umbilical cord (UC), third-party MSC given sequentially after Pentatostatin for the treatment of SR-aGvHD grade III-IV as well as the overlap syndrome (EUDRACT n. 2012-000582-21), NCT02032446).Patients and MethodsThird-party UC MSC were produced under GMP conditions as previously described (Capelli C et al Cytotherapy, 2011, 13, 786-801). The treatment schedule was based on the sequential administration of Pentostatin, given iv at dose of 1 mg/m^2 for 3 consecutive days, followed by 3 MSC infusions given at weekly intervals. Between October 2013 and May 2018 (range 4.6 years) we enrolled 27 allogeneic HCT adult recipients (22 male) with SR-aGvHD (n 25) or overlap syndrome (n 2), median age 47 years (range 19-62) transplanted from HLA-identical sibling donors (6; 22%), haploidentical donors (2; 7%), unrelated donors (18; 67%) or cord blood (1; 4%). Target organ involvement included skin in 11 cases (44%), gastrointestinal tract (GI) in 23 (92%) and liver in 12 (48%). Nine patients had grade III (33%), 16 patients grade IV (60%) and 2 patients had severe overlap syndrome (7%). Most of patients exhibited multiple organ involvement (n 16, 64%). Patients started MSC therapy at median of 22 days (10-2101) after the onset of aGvHD or overlap syndrome.ResultsThe infusions of UC MSC-infusion were always well tolerated without any immediate or late toxic event. Response to MSC therapy, by day 30 after the final MSC dose, was evaluable in 16 of 27 patients: 7 achieved CR (26%), 6 PR (22%) and 3 NR (11%). Ten patients died before reaching the evaluation time of response: 8 patients for aGvHD and 2 for haematological disease. One patient was lost to follow up after 9 days from the last UC-MSC infusion. Remarkably, the subgroup of patients with single organ involvement (8 GI, 1 liver) were all evaluable showing 6 patients in overall response (67%, 4 RC and 2 PR). No response was observed in 2 cases of severe overlap syndrome. Patients achieving CR had improved longer term OS vs patients in PR/NR (80% vs 50% at 1 year). For patients with grade III and IV SR-aGvHD, CR rates at day 30 were 67% and 31% respectively. During tapering of steroid therapy 4 out of 7 patients that obtained CR had aGvHD recurrence, at median time of 87 days. We observed relapse of underlying malignancy in 5 patients and all died with active disease. At last follow-up 8 out of 27 patients were alive with no GVHD in 5 of them; 14 patients died from TRM: aGvHD or overlap syndrome itself (n=10), infections (n= 2), cGvHD (n= 2). Two patients with uncontrolled GvHD had clinical signs of Transplant Associated Microangiopathy (TAM). A total of 17 reported AE and 12 SAE were registered. In 23 out of 27 patients infectious complications were observed, in most cases virus related (n.25; CMV followed by BK virus and EBV), and fungal infections (3 aspergillus pneumoniae). Blood-stream documented infections (5) and pneumoniae (5) were also observed.ConclusionsThe infusion of cord blood derived MSC proved safe in all cases. As expected in patients with steroid refractory aGvHD, a high rate of infectious complications were observed. When considering that most patients (60 %) had grade IV aGvHD, the response rate and the OS are promising and this warrants not only the completion of this Phase I/II study but also planning a future pivotal trial. DisclosuresNo relevant conflicts of interest to declare.

Multi-View Laser Point Cloud Global Registration for a Single Object.

Global registration is an important step in the three-dimensional reconstruction of multi-view laser point clouds for moving objects, but the severe noise, density variation, and overlap ratio between multi-view laser point clouds present significant challenges to global registration. In this paper, a multi-view laser point cloud global registration method based on low-rank sparse decomposition is proposed. Firstly, the spatial distribution features of point clouds were extracted by spatial rasterization to realize loop-closure detection, and the corresponding weight matrix was established according to the similarities of spatial distribution features. The accuracy of adjacent registration transformation was evaluated, and the robustness of low-rank sparse matrix decomposition was enhanced. Then, the objective function that satisfies the global optimization condition was constructed, which prevented the solution space compression generated by the column-orthogonal hypothesis of the matrix. The objective function was solved by the Augmented Lagrange method, and the iterative termination condition was designed according to the prior conditions of single-object global registration. The simulation analysis shows that the proposed method was robust with a wide range of parameters, and the accuracy of loop-closure detection was over 90%. When the pairwise registration error was below 0.1 rad, the proposed method performed better than the three compared methods, and the global registration accuracy was better than 0.05 rad. Finally, the global registration results of real point cloud experiments further proved the validity and stability of the proposed method.

Evaluation of benchtop NMR Diffusion Ordered Spectroscopy for small molecule mixture analysis

Diffusion Ordered Spectroscopy (DOSY) is an attractive method for analyzing chemical mixtures in the liquid state because it separates spectra by the molecular weight of the associated molecule. It has been compared with hyphenated chromatographic and analytical methods such LC-MS and has broad potential in servicing those same applications including forensics, reaction analysis, quality control, and fraud detection. Benchtop NMR can collect quality spectra on small molecules, however, lacks the chemical shift dispersion of high field instruments, can suffer from spectral overlap common in mixtures, and the diminished sensitivity of the lower field compounds these problems. In this work, we show that existing high field pulse sequences and processing methods perform well at 43 MHz. Spectra from molecular mixtures where the constituents had 20% differences in diffusion coefficients and significant overlap were able to be matched to a bespoke spectral library and identified correctly. In addition, spectra from mixtures with constituents that have severe overlap in the spectrum and differ by 50% in diffusion coefficients were also able to be match and identified correctly. The combination of benchtop NMR and easy implementation of modern pulse sequences and processing show promise of bringing these useful methods to chemistry laboratories in research and industrial environments.

Two-Dimensional Proton Magnetic Resonance Spectroscopy versus J-Editing for GABA Quantification in Human Brain: Insights from a GABA-Aminotransferase Inhibitor Study

Metabolite-specific, scalar spin-spin coupling constant (J)-editing 1H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) 1H MRS technology offers an attractive alternative as it significantly alleviates the problem of severe metabolite signal overlap associated with standard 1D MRS and retains spectroscopic information for all MRS-detectable species. However, for metabolites found at low concentration, a direct, in vivo, comprehensive methods comparison is challenging and has not been reported to date. Here, we document an assessment of comparability between 2D 1H MRS and J-editing methods for measuring GABA in human brain. This clinical study is unique in that it involved chronic administration a GABA-amino transferase (AT) inhibitor (CPP-115), which induces substantial increases in brain GABA concentration, with normalization after washout. We report a qualitative and quantitative comparison between these two measurement techniques. In general, GABA concentration changes detected using J-editing were closely mirrored by the 2D 1H MRS time courses. The data presented are particularly encouraging considering recent 2D 1H MRS methodological advances are continuing to improve temporal resolution and spatial coverage for achieving whole-brain, multi-metabolite mapping.

Radiographic Assessment of the Popliteal Lymph Node to Aid the Differentiation of Canine Stifle Osteosarcoma From Moderate to Severe Stifle Degenerative Joint Disease

Degenerative joint disease of the stifle is a common canine osseous pathology. Early degenerative changes may show mild mineral proliferation of periarticular margins with soft tissue, resulting in joint distension. If the joint is chronically unstable, osseous changes become more complex. Moderate to severe stifle degenerative disease then transitions to a combination of bony proliferation and resorption as subchondral cystic changes develop. The radiographic descriptions of moderate to severe degenerative disease overlap with those of subtle aggressive disease. If this occurs in a location prone to primary bone tumors, like the distal femur, radiographic interpretation becomes difficult. The aim of this study was to evaluate the utility of objectively assessing the popliteal lymph node size and shape on radiographs to differentiate moderate to severe stifle degenerative joint disease from distal femoral or tibial osteosarcoma. Stifle radiographs were acquired for evaluation of pelvic lameness localized to the stifle joint. Dogs with moderate to severe degenerative stifle joint disease were radiographed at 3 time points: prior to surgery for a tibial plateau leveling osteotomy (103), immediately postoperation (103), and at a recheck 6-8 weeks postsurgery (62). Dogs with osteosarcoma were radiographed only at time of diagnosis (42). Length and width gross popliteal lymph node measurements and a ratio of long axis to short axis were compared between groups using nonparametric analysis. No significant difference was determined using a long axis to short axis ratio for the popliteal lymph node to differentiate moderate to severe stifle degenerative joint disease and osteosarcoma (P = .290). The gross measurements of the long axis and short axis of the popliteal lymph node for dogs with osteosarcoma were significantly greater than the degenerative joint disease groups (P = .017, P = .000). Thus, evaluation of a long axis to short axis ratio for popliteal lymph nodes does not provide a clinically useful objective measure in differentiating peristifle osteosarcoma from moderate to severe degenerative disease of the stifle joint. The length and width of the popliteal lymph node differed significantly; however, the clinical difference is minimal.