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Indicators based on nutrient-biota relationships in streams can inform water quality restoration and protection programs. Bacterial assemblages could be particularly useful indicators of nutrient effects because they are species-rich, important contributors to ecosystem processes in streams, and responsive to rapidly changing conditions. Here, we sampled 25 streams weekly (12–14 times each) and used 16S rRNA gene metabarcoding of periphyton-associated bacteria to quantify the effects of total phosphorus (TP) and total nitrogen (TN). Threshold indicator taxa analysis identified assemblage-level changes and amplicon sequence variants (ASVs) that increased or decreased with increasing TP and TN concentrations (i.e., low P, high P, low N, and high N ASVs). Boosted regression trees confirmed that relative abundances of gene sequence reads for these four indicator groups were associated with nutrient concentrations. Gradient forest analysis complemented these results by using multiple predictors and random forest models for each ASV to identify portions of TP and TN gradients at which the greatest changes in assemblage structure occurred. Synthesized statistical results showed bacterial assemblage structure began changing at 24 µg TP/L with the greatest changes occurring from 110 to 195 µg/L. Changes in the bacterial assemblages associated with TN gradually occurred from 275 to 855 µg/L. Taxonomic and phylogenetic analyses showed that low nutrient ASVs were commonly Firmicutes, Verrucomicrobiota, Flavobacteriales, and Caulobacterales, Pseudomonadales, and Rhodobacterales of Proteobacteria, whereas other groups, such as Chitinophagales of Bacteroidota, and Burkholderiales, Rhizobiales, Sphingomonadales, and Steroidobacterales of Proteobacteria comprised the high nutrient ASVs. Overall, the responses of bacterial ASV indicators in this study highlight the utility of metabarcoding periphyton-associated bacteria for quantifying biotic responses to nutrient inputs in streams.

Interest in developing periphytic diatom and bacterial indicators of nutrient effects continues to grow in support of the assessment and management of stream ecosystems and their watersheds. However, temporal variability could confound relationships between indicators and nutrients, subsequently affecting assessment outcomes. To document how temporal variability affects measures of diatom and bacterial assemblages obtained from DNA metabarcoding, we conducted weekly periphyton and nutrient sampling from July to October 2016 in 25 streams in a 1293 km

Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics. Here, we present our results from a pilot study investigating global proteomic profiles of leukemic cells obtained at diagnosis from 16 pediatric AML patients using a robust TMT-LC/LC-MS/MS platform. The proteome profiles were compared among patients with or without core binding factor (CBF) translocation indicated by a t(8, 21) or inv(16) cytogenetic abnormality, minimal residual disease status at the end of the first cycle of chemotherapy (MRD1), and in vitro chemosensitivity of leukemic cells to cytarabine (Ara-C LC50). Our results established proteomic differences between CBF and non-CBF AML subtypes, providing insights to AML subtypes physiology, and identified potential druggable proteome targets such as THY1 (CD90), NEBL, CTSF, COL2A1, CAT, MGLL (MAGL), MACROH2A2, CLIP2 (isoform 1 and 2), ANPEP (CD13), MMP14, and AK5.

Although it is quite challenging to image and analyze the spatial distribution of bioaerosols in a confined space, a three-dimensional (3D) modeling system based on the planar laser-induced fluorescence (PLIF) technique is proposed in this paper, which is designed to analyze the temporal and spatial variations of bioaerosol particles in a confined chamber. The system employs a continuous planar laser source to excite the fluoresce, and a scientific complementary metal oxide semiconductor (sCMOS) camera to capture images of 2048 × 2048 pixels at a frame rate of 12 Hz. While a sliding platform is moving back and forth on the track, a set of images are captured at different positions for 3D reconstruction. In this system, the 3D reconstruction is limited to a maximum measurement volume of about 50 cm × 29.7 cm × 42 cm, with a spatial resolution of about 0.58 mm × 0.82 mm × 8.33 mm, and a temporal resolution of 5 s. Experiments were carried out to detect the PLIF signals from fluorescein aerosols in the chamber, and then 3D reconstruction was used to visualize and analyze the diffusion of aerosol particles. The results prove that the system can be applied to clearly reconstruct the 3D distribution and record the diffusion process of aerosol particles in a confined space.

Since microRNA-92a (miR-92a) and microRNA-21 (miR-21) are crucial biomarkers for colorectal cancer (CRC), monitoring miR-92a and miR-21 in serum is very significant for the early diagnosis of CRC. In this work, we developed a simple and sensitive fluorescent biosensor for the detection of miR-92a and miR-21 based on the quenching ability of Prussian blue nanoparticles (PBNPs) to fluorophores. Carboxyl fluorescein (FAM)-modified ssDNA (P-92a) and Cyanine 5 (Cy5)-modified ssDNA (P-21) were completely complementary to miR-92a and miR-21 separately. They were adsorbed on PBNPs surface by the binding of PO

AIMS This study investigates enteric viruses in wastewater during an outbreak of acute hepatitis caused by hepatitis A virus (HAV) in a large metropolitan area. Emphasis is given to caliciviruses and HAV. METHODS AND RESULTS Metagenomic analysis was performed to characterize enteric viruses excreted by the population of Detroit MI, during a hepatitis A outbreak that occurred in 2017 and 2018. Additionally, HAV, norovirus GII, and sapovirus were quantified, using qPCR, in 54 untreated wastewater samples collected over the course of 4 months. Correlation analysis was performed to identify associations between the number of disease cases and HAV concentrations in wastewater. HAV obtained the highest relative abundance among other enteric viruses detected in wastewater metagenomes. Metagenomic analysis also detected several other enteric viruses including astrovirus, enterovirus and hepatitis E virus. Average sapovirus concentrations of 1·36 × 106 gc l-1 were significantly greater than norovirus GII concentrations (2·94 × 104 gc l-1 ). Additionally, norovirus GI and GII along with sapovirus GI.1 were detected using metagenomics. HAV loads in wastewater were significantly correlated with the number of disease cases reported 1 week after wastewater sampling. CONCLUSIONS Surveying untreated wastewater is a promising method for detecting early signs of hepatitis A outbreaks and for routine environmental monitoring of enteric viruses circulating in the environment. SIGNIFICANCE AND IMPACT OF THE STUDY Authors demonstrate the usefulness of metagenomics for genogrouping and enteric viral surveillance.

NUP98 fusion oncoproteins (FO) are drivers in pediatric leukemias and many transform hematopoietic cells. Most NUP98 FOs harbor an intrinsically disordered region from NUP98 that is prone to liquid–liquid phase separation (LLPS) in vitro. A predominant class of NUP98 FOs, including NUP98–HOXA9 (NHA9), retains a DNA-binding homeodomain, whereas others harbor other types of DNA- or chromatin-binding domains. NUP98 FOs have long been known to form puncta, but long-standing questions are how nuclear puncta form and how they drive leukemogenesis. Here we studied NHA9 condensates and show that homotypic interactions and different types of heterotypic interactions are required to form nuclear puncta, which are associated with aberrant transcriptional activity and transformation of hematopoietic stem and progenitor cells. We also show that three additional leukemia-associated NUP98 FOs (NUP98–PRRX1, NUP98–KDM5A, and NUP98–LNP1) form nuclear puncta and transform hematopoietic cells. These findings indicate that LLPS is critical for leukemogenesis by NUP98 FOs. Significance: We show that homotypic and heterotypic mechanisms of LLPS control NUP98–HOXA9 puncta formation, modulating transcriptional activity and transforming hematopoietic cells. Importantly, these mechanisms are generalizable to other NUP98 FOs that share similar domain structures. These findings address long-standing questions on how nuclear puncta form and their link to leukemogenesis. This article is highlighted in the In This Issue feature, p. 873

Viruses are linked to a multitude of human illnesses and can disseminate widely in urbanized environments causing global adverse impacts on communities and healthcare infrastructures. Wastewater-based epidemiology was employed using metagenomics and quantitative polymerase chain reaction (qPCR) assays to identify enteric and non-enteric viruses collected from a large urban area for potential public health monitoring and outbreak analysis. Untreated wastewater samples were collected from November 2017 to February 2018 (n = 54) to evaluate the diversity of human viral pathogens in collected samples. Viruses were classified into virus types based on primary transmission routes and reviewed against viral associated diseases reported in the catchment area. Metagenomics detected the presence of viral pathogens that cause clinically significant diseases reported within the study area during the sampling year. Detected viruses belong to the Adenoviridae, Astroviridae, Caliciviridae, Coronaviridae, Flaviviridae, Hepeviridae, Herpesviridae, Matonaviridae, Papillomaviridae, Parvoviridae, Picornaviridae, Poxviridae, Retroviridae, and Togaviridae families. Furthermore, concentrations of adenovirus, norovirus GII, sapovirus, hepatitis A virus, human herpesvirus 6, and human herpesvirus 8 were measured in wastewater samples and compared to metagenomic findings to confirm detected viral genus. Hepatitis A virus obtained the greatest average viral load (1.86 × 107 genome copies/L) in wastewater samples compared to other viruses quantified using qPCR with a 100% detection rate in metagenomic samples. Average concentration of sapovirus (1.36 × 106 genome copies/L) was significantly greater than norovirus GII (2.94 × 104 genome copies/L) indicating a higher burden within the study area. Findings obtained from this study aid in evaluating the utility of wastewater-based epidemiology for identification and routine monitoring of various viruses in large communities. This methodology has the potential to improve public health responses to large scale outbreaks and viral pandemics., Graphical abstract Image 1, Highlights • Optimized sequence alignment and qPCR identified the presence of important viral pathogens. • Detected viral pathogens in wastewater associated with reported clinically significant diseases. • Wastewater-based epidemiology can be used for identification of viral outbreaks.

We present a dual-channel mobile lidar system based on laser-induced fluorescence (LIF) for real-time standoff detection and concentration distribution analysis of tryptophan. The system employs an ultraviolet laser excitation source and signal detectors for receiving fluorescence signals within two different wavelength bands. The performed experiments measured tryptophan aerosols at two different standoff distances. Moreover, distilled water and ethanol solutions were also detected for comparison. The results show that the system can detect LIF signals of tryptophan, give early warnings, locate the diffusion sources, and monitor the variation of the aerosol concentration distribution in real time.

Cytarabine has been an integral part of acute myeloid leukemia (AML) chemotherapy for over four decades. However, development of resistance and high rates of relapse is a significant impediment in successfully treating AML. We performed a genome-wide association analysis (GWAS) and identified 113 (83 after adjusting for Linkage Disequilibrium) SNPs associated with in vitro cytarabine chemosensitivity of diagnostic leukemic cells from a cohort of 50 pediatric AML patients (p

Background: Few studies have analyzed the benefit of limb amputations in children with metastatic osteosarcoma and limited life span. Objective: We studied outcomes of limb amputations in children with metastatic osteosarcoma. Design: We performed a retrospective review of patients who underwent limb amputations (January 1995-June 2015) and died within 1 year of surgery. Setting/Participants: We studied 12 patients with osteosarcoma at a single institution. Measurements: Data on mobility, pain, and emotional and psychological well-being were retrieved from medical records from 1 month before surgery to 6 months after surgery. Results: Of the 12 patients (7 females and 5 males; median age at surgery 13 years [range, 7-20 years]) meeting study criteria, 3 patients and 9 patients had primary osteosarcoma in upper and lower limbs, respectively. Mobility improved postamputation in 8 bedridden/wheelchair-bound patients. Postamputation, emotional, and psychological well-being improved for 9 patients, 3 patients had persistent psychological and/or emotional symptoms, and no patient experienced signs of regret. Daily mean pain scores were significantly lower at 1 week (median 3 [range, 0-6]; P = .03) and 3 months (median 0 [range, 0-8]; P = .02) postsurgery than at 1 week presurgery (median 5.5 [range, 0-10]). Morphine consumption (mg/kg/d) showed a trend toward higher values at 1 week (median 0.2 [range, 0-7.6]; P = .6) and 3 months (median 0.2 [range, 0-0.5]; P = .3) postsurgery than at 1 week presurgery (median 0.1 [range, 0-0.5]). Conclusions: Patients undergoing limb amputations had reduced pain and improved mobility and emotional and psychological well-being. Amputations are likely to benefit children with limited life expectancy.

Communities throughout the United States are developing and implementing watershed management plans to address nonpoint sources of pollution and meet Total Maximum Daily Load (TMDL) requirements. Once a TMDL is established, a watershed management plan is developed and implemented to reduce contaminant sources and attain TMDL goals. Developing an effective TMDL and remediation plan should take into account fluctuation of pollution loadings and the timing of first-flush events. The objective of this study is to investigate the effect of hydrological conditions on microbial pollutant levels at a TMDL site during spring and summer storm events. A total of 64 water samples were collected from Sloan Creek in mid-Michigan in the spring/summer of 2015. All samples were analyzed to quantify concentrations of E. coli, bovine-associated Bacteroides (BoBac) gene markers, and human-associated Bacteroides (HuBac) gene markers. Discharge was the driving force of microbial contaminant loading in the studied water body. E. coli concentrations had significant strong correlation with precipitation and discharge, and BoBac concentrations were positively related to discharge. E. coli, BoBac and HuBac patterns suggested first-flush phenomena occurred during summer storms. E. coli permit exceedance rates increased from 31% before first-flush, to 100% during and after first-flush in the summer. The resulting information may help develop a plan for restoring impaired waters and establish the maximum amount of pollutants that the body of water can receive during different hydrological conditions.

Purpose To preliminarily assess the potential prognostic value of various fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters before, during, and after neoadjuvant chemotherapy (NCT). Materials and Methods Thirty-four patients with osteosarcoma were enrolled prospectively from 2008 to 2012 and underwent FDG PET/computed tomography (CT) imaging before (baseline scan), during (interim scan) and after NCT (posttherapy scan). The study was approved by the institutional review board and informed consent was received from patients. Maximum and peak standardized uptake value (SUVmax and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Predictive value of FDG PET parameters for event-free survival (EFS) and overall survival (OS) were evaluated. Multivariable Cox regression analysis for EFS and OS was performed by using histologic response and initial presence of metastasis as covariates. Results At baseline scan, SUVpeak, MTV, and TLG were predictive of EFS (P = .006-.03) and OS (P = .001-.03) but not associated with histologic response. At interim and posttherapy scan, SUVmax, SUVpeak, MTV, and TLG were associated with histologic response (P = .0002-.04) and predictive of EFS (P = .004-.02) and OS (P = .001-.03). Multivariable Cox regression analysis revealed that the FDG PET parameters either at baseline, interim, or posttherapy were independently predictive of EFS and OS. In particular, baseline MTV was an independent predictor of EFS (hazard ratio, 5.0 [95% confidence interval {CI}: 1.5, 16.8]) and OS (hazard ratio, 29.4 [95% CI: 2.2, 392.2]). Conclusion SUVpeak, MTV, and TLG either at baseline, interim, or posttherapy were predictive of EFS and OS and may be useful prognostic biomarkers for osteosarcoma. © RSNA, 2018 Online supplemental material is available for this article.

Children with acute myeloid leukemia (AML) have a dismal prognosis due to a high relapse rate; however, the molecular basis leading to relapsed pediatric AML has not yet been fully characterized. To define the spectrum of alterations common at relapse, we performed integrated profiling of 136 relapsed pediatric AML cases with RNA sequencing (RNA-seq), whole-genome sequencing, and target-capture sequencing. In addition to well-characterized fusion oncoproteins, such as those involving KMT2A (n=36, 26.5%) or NUP98 (n=18, 13.2%), we also identified somatic mutations in UBTF (upstream binding transcription factor) in 12 of 136 cases (8.8%) of this relapsed cohort. Somatic alterations of the UBTF gene, which encodes a nucleolar protein that is a component of the RNA Pol I pre-initiation complex to ribosomal DNA promoters, have rarely been observed in AML. In our cohort, all alterations can be described as heterozygous in-frame exon 13 tandem duplications (UBTF-TD), either at the 3' end of exon 13 of UBTF or of the entire exon 13 (Fig. A). As we noticed limited detection in our pipeline as a result of complex secondary indels alongside the duplications, we established a soft-clipped read-based screening method to detect UBTF-TD more efficiently. Applying the screening to RNA-seq data of 417 additional pediatric AMLs from previous studies and our clinical service, we identified 15 additional UBTF-TDs, many of which have not been previously reported. At the amino acid level, UBTF-TDs caused amino acid insertions of variable sizes (15-181 amino acids), duplicating a portion of high mobility group domain 4 (HMG4), which includes short leucine-rich sequences. UBTF-TD AMLs commonly occurred in early adolescence (median age: 12.6, range: 2.4-19.6), and 19 of the total 27 cases had either normal karyotype (n=12) or trisomy 8 (n=7). UBTF-TD is mutually exclusive from other recurrent fusion oncoproteins, such as NUP98 and KMT2A rearrangements (Fig. B), but frequently occurred with FLT3-ITD (44.4%) or WT1 mutations (40.7%). The median variant allele fraction (VAF) of the UBTF-TD was 48.0% (range: 9.7-66.7%). In four cases with data at multiple disease time points, the identical UBTF-TDs were present at high allele fractions at all time points, suggesting that UBTF-TD is a clonal alteration. tSNE analysis of the transcriptome dataset showed that UBTF-TD AMLs share a similar expression pattern with NPM1 mutant and NUP98-NSD1 AML subtypes, including NKX2-3 and HOXB cluster genes (Fig. C) . Altogether, these findings suggest that UBTF-TD is a unique subtype of pediatric AML. To address the impact of UBTF-TD expression in primary hematopoietic cells, we introduced UBTF-TD and UBTF wildtype expression vectors into cord blood CD34+ cells via lentiviral transduction. UBTF-TD expression promotes colony-forming activity and cell growth, yielding cells with a persistent blast-like morphology (Fig. D). Further, transcriptional profiling of these cells demonstrated expression of HOXB genes and NKX2-3, similar to UBTF-TD AMLs in patients, indicating that UBTF-TD is sufficient to induce the leukemic phenotype. To investigate the prevalence of UBTF-TDs in larger de novo AML cohorts, we applied the above UBTF-TD screening method to the available de novo AML cohorts of TCGA (n=151, adult), BeatAML (n=220, pediatric and adult), and AAML1031 (n=1035, pediatric). We identified UBTF-TDs in 4.3% (45/1035) of the pediatric AAML1031 cohort, while the alteration is less common (0.9%: 3/329, p=0.002) in the adult AML cohorts (Fig. E). In the AAML1031 cohort, UBTF-TDs remain mutually exclusive with known molecular subtypes of AML and commonly occur with FLT3-ITD (66.7%) and WT1 (40.0%) mutations and either normal karyotype or trisomy 8. The presence of UBTF-TDs in the AAML1031 cohort is associated with a poor outcome (Fig. F, median overall survival, 2.3 years) and MRD positivity; multivariate analysis revealed that UBTF-TD and WT1 are independent risk factors for overall survival within FLT3-ITD+ AMLs. In conclusion, we demonstrate UBTF-TD defines a unique subtype of AMLs that previously lacked a clear oncogenic driver. While independent of subtype-defining oncogenic fusions, UBTF-TD AMLs are associated with FLT3-ITD and WT1 mutations, adolescent age, and poor outcomes. These alterations have been under-recognized by standard bioinformatic approaches yet will be critical for future risk-stratification of pediatric AML. Figure 1 Figure 1. Disclosures Iacobucci: Amgen: Honoraria; Mission Bio: Honoraria. Miller: Johnson & Johnson's Janssen: Current Employment. Mullighan: Pfizer: Research Funding; Illumina: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Amgen: Current equity holder in publicly-traded company.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized in part by genetic and epigenetic alterations. Cytarabine arabinoside (Ara-C) has been the cornerstone of chemotherapy treatment for patients diagnosed with AML for decades. Following cellular uptake, ara-C is phosphorylated into its active metabolite, ara-CTP, which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in ara-C activation/inactivation pathway (Fig 1A), can impact intracellular abundance of ara-CTP and thus its therapeutic benefit. Recently, deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) was shown to limit the efficacy of ara-C by intracellularly hydrolyzing its active metabolite (PMID: 27991919). Other nucleoside analogs, such as clofarabine, fludarabine, and gemcitabine have also been shown to be substrates of SAMHD1 (PMID:30305425). Among adult AML patients, higher SAMHD1 expression in the leukemic cells has been found to correlate with poor outcome (PMID: 30341277). However, whether genetic variation in SAMHD1 has any impact on the clinical outcomes in pediatric AML patients has not been evaluated in depth. In this study, we looked into 25 single nucleotide polymorphisms (SNPs) within SAMHD1 gene for their association with clinical outcome of newly diagnosed pediatric AML patients in 2 cohorts (multi-site AML02 [NCT00136084, n=167] and AML08 [NCT00703820, n=231] clinical trials). Briefly, genotypes for the 25 SNPs within SAMHD1 genes were obtained from Illumina 2.5 Omni data of AML patients. Association analysis was conducted using logistic regression models comparing minimal residual disease (MRD) positivity after treatment with chemotherapy using an unadjusted model and an adjusted model stratified by initial risk assignment of the patient determined at diagnosis (i.e. low, standard, and high). MRD positivity was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells. Cox proportional hazard models were used to examine the association of the SNPs with EFS and OS and considered three modes of inheritance. Cox regression models were performed with or without adjusting for provisional risk group assignment at time of diagnosis. Significance levels for association of SNP with clinical outcome were set at p < 0.05. Three top SNPs significantly associated with clinical outcomes were all localized in the 3'UTR region of SAMHD1(Fig 1B). Presence of the variant allele of rs7265241 was associated with a lower EFS and OS in both AML02 and AML08 cohorts. Figure 1C shows the results for OS in AML02 (HR = 2.24, 95% CI (1.05-3.55), p=0.02) and AML08 (HR = 1.52, 95% CI (1.04-1.99), p=0.01). Another 3'UTR SNP, rs1291128 was associated with poor OS in AML02 and in the clofarabine plus ara-C treatment arm in AML08 trial. For rs1291141, T allele was associated with higher MRD positivity (OR: 2.12, p=0.01) in AML02 and poor OS (HR = 1.55, 95% CI (1.12-2.14), p=0.008) in AML08(Fig 1D). Consistent with the clinical outcome results, rs1291141 T allele was also associated with higher SAMHD1 expression in the whole blood (p=8.1e-14) and several other tissues in the GTEx database. https://gtexportal.org/home/ Our results suggest that genetic variation in SAMHD1 is associated with clinical outcomes in pediatric AML patients. Future studies are aimed at looking at haplotypes and SNP-SNP combinations to establish the impact SAMHD1 pharmacogenomics on its expression within leukemic cells and subsequent response to nucleoside analogs in AML patients. SAMHD1 has also been implicated as a tumor suppressor; thus, future studies will evaluate its role both as a proliferation regulator and in drug resistance. Acknowledgements: NIH-R01-CA132946 (Lamba and Pounds), University of Florida Opportunity Seed Grant (Lamba), American Lebanese Syrian Associated Charities (ALSAC), and American Society of Hematology Bridge funding (Lamba) funded the study. We thank Drs. Campana, Coustan-Smith, and Raimondi for MRD and cytogenetic data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Mercury (Hg) is one of the most hazardous pollutants, widely distributed in water, atmosphere, and soil, while the Hg contents from different sources are greatly different. Until now, numerous reported methods are only suitable for a kind of sample because they cannot reconcile sensitivity and linear range. In this work, a tail-extensible DNA fluorescent probe for "turn on" detection of Hg2+ with tunable dynamic range and high sensitivity was developed, which was based on segmental hybridization between silver nanoclusters (AgNCs)-covered DNA and different guanine-rich DNAs. By adding adenine-guanine-cytosine (AGC) base repeats as a tail of the guanine-rich DNA, the formation constant of T-Hg2+-T complex was effectively modulated within two orders of magnitude. Based on it, a tunable dynamic range from 0.035 to 0.2 pM to 8.0-120.0 pM was achieved by combining four fluorescent probes with different tail lengths. The Hg2+contents from different sources were successfully measured. This evidenced the proposed sensor's application toward wide-field detection, which is useful for the direct and objective comparison of results from different sources, and therefore providing a way for solving the shortcomings of reported methods for Hg2+ detection. Additionally,this present method is simple, cost-effective and time-saving, ultrasensitive and highly selective, which is favorable for expanding its applications and subsequent mercury pollution control.

The laser-induced fluorescence (LIF) technique, which has been widely used for food testing, can be combined with various algorithms to classify and recognize different kinds of honey. This paper proposes the Kolmogorov–Smirnov test-Gaussian mixture model (KS-GMM) algorithm, which is coupled with the LIF technique to realize accurate classification and recognition of different types of pure honey. The experiments are designed and carried out to obtain a set of LIF spectrum data from various honey and syrup samples. The proposed KS-GMM algorithm is applied for classification and recognition, with GMM, k-nearest neighbor (kNN), and decision tree algorithms as cross-validation methods. By comparing recognition results of training sets containing different amounts of data, it is found that the KS-GMM algorithm exhibits a maximum recognition accuracy of 96.52%. The research results prove that the KS-GMM algorithm outperforms, to the best of our knowledge, the other three algorithms in classifying and recognizing the honey types.

Introduction: Acute Myeloid Leukemia (AML) is a heterogeneous disease with cytogenetic abnormalities and gene mutations that are routinely used in clinical practice to stratify patients into three risk groups: low, intermediate, or high. Core binding factor (CBF) AML with inv(16) and t(8;21) involved in CBFP-MYH11 and RUNX1-RUNX1T1 gene fusions is associated with a better prognosis. Likewise, outcomes are inferior in patients with non-CBF (NCBF) AML. Despite efforts on genomics and transcriptomics to understand the AML heterogeneity, studies focused on proteomic profiles associated with AML cytogenetic features remain limited. Therefore, the objective of this study is to detect proteomic differences in CBF vs. NCBF pediatric AML as well as to identify proteomic markers associated with the therapeutic response after induction treatment. Methods: For this pilot study, we selected 16 patients (6 with CBF-AML and 10 with NCBF-AML) that were treated in the multi-center AML02 clinical trial (NCT00136084). Leukemic cells at diagnosis were used to generate an untargeted global proteomics profile using 16-plex TMT-LC/LC-MS/MS. Overall, 9800 unique proteins were identified and were evaluated for differences between CBF and non-CBF AML using non-parametric rank-sum statistical tests from the R Bioconductor RankProd package. An exploratory analysis was further performed to identify proteins associated with minimal residual disease after induction 1 (MRD1) in the 10 NCBF patients. Given 15 patients also had gene expression levels using Affymetrix U133A microarray available, Spearman's Rho correlation test between transcriptomics and proteomics was also performed. Results and Conclusion: As compared to CBF-AML, we identified 63 upregulated and 49 downregulated proteins (LogFC >1 and FDR 1, p Acknowledgments: This research was supported by NIH R01CA132946 and University of Florida Health Cancer Center Opportunity funds. Citation Format: Nam K. Nguyen, Huiyun Wu, Junmin Peng, Jeffrey E. Rubnitz, Stanley Pounds, Jatinder K. Lamba. Leukemic Cell Proteomic Profiling in Pediatric AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2535.

We have developed a sensitive surface-enhanced Raman scattering (SERS) substrate composed of 60-nm Au@Ag core-shell nanoparticles linked to 360-nm SiO2 sphere base, which experimentally demonstrate...

Concentration – discharge (c-q) hysteresis loops are used to qualitatively understand solute transport pathways to streams. The majority of c-q studies involve non-urban areas in environmental settings such as the subtropics, mountains, and high latitude rivers. Only a few involve urban or urban salted watersheds. In this study, we explore c-q hysteresis plots and pollutographs for a variety of inorganic solutes (Cl−, Na+, K+, SiO2, NO3−), dissolved organic carbon and an indicator of the aromatic fraction (SUVA254), and a microbiological indicator (E. coli) in an urban salted watershed. The major hydrologic events are snow melts. The overarching hypothesis is that the hysteresis behavior can be explained by extending the pathway analysis (i.e., relative importance of storm event water, CSE; groundwater CG; and soil water, CSO) from the Evans-Davis classification scheme that describes six behaviors to account for differences in source locations and the biogeochemical behavior of the solutes along these pathways. Data sets for the years 2013, 2014, and 2015 were assembled from a series of undergraduate and graduate research projects performed over this period. The results of these studies indicate that: 1) Cl− and Na+ exhibit a combination of C2 (CSE > CSO > CG) and C3 (CG > CSE > CSO) behavior during salting season and A1 (CSO > GG > CSE) and A2 (CSO > CSE > CG) behavior in non-salting times; 2) SiO2 shows A3 (CG > CSO > CSE) behavior in all events, 3) K+ changes from C2 to C1 (CSE > CG > CSO) with concentration depletion over subsequent events; 4) NO3− changes from A2 to C1 or C2 with concentration depletion over subsequent events; 5) DOC and SUVA254 exhibit C2 and A1 behavior, respectively; 6) E. coli changes from C2 to A2 over subsequent storms; 7) Cl−and Na+ peak before the rising limb with a slight lag in the Na+ peak and 8) E. coli does not exhibit first-flush behavior. An integrative pollutograph for a snow melt event shows, 1) K+ and DOC peak together three times, unrelated to any additional event such as rain; 2) DOC becomes more aliphatic at its first peak, and 3) NO3− has a concentration decrease at the second DOC/K+ peak and peaks on the declining limb after the third DOC/K+ peak. These observations can be explained in terms of the c-q plots (e.g., importance of event water), environmental behavior (e.g., conservative solute), the nature of the urban landscape (e.g., pavement), and season (e.g., damped microbial activity). We interpret the multiple concentration peaks to indicate water masses originating from different compartments in the watershed are reaching the stream at different times and with different chemistries. These results extend the work of previous studies and may serve to help develop a fingerprint of solute behavior that can be used to more fully explore early season biogeochemical dynamics in an urban, salted, snow-melt dominated watershed.

PURPOSE Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial because children with incomplete resections, metastases, or relapsed disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population. PATIENTS AND METHODS We performed DNA methylation analyses on 48 newly diagnosed ACTs from the International Pediatric Adrenocortical Tumor Registry and 12 pediatric adrenal controls to evaluate for distinct methylation groups. Pediatric methylation data were also compared systematically with the adult ACC cohort from The Cancer Genome Atlas (TCGA). RESULTS Two pediatric ACT methylation groups were identified and showed differences in selected clinicopathologic and outcome characteristics. The A1 group was enriched for CTNNB1 variants and unfavorable outcome. The A2 group was enriched for TP53 germline variants, younger age at onset, and favorable outcome. Pediatric ACT methylation groups were maintained when International Pediatric Adrenocortical Tumor Registry cohort data were combined with TCGA cohort data. The CpG-island hypermethylator phenotype characterizing the TCGA cohort was not identified in the pediatric patients. When methylome findings were combined with independent histopathologic review using the Wieneke criteria, a high-risk population was identified with uniform fatal outcome. CONCLUSION Our results indicate DNA methylation analysis can enhance current diagnostic algorithms. A combination of methylation and histologic classification produced the strongest prediction model and may prove useful in future risk-adapted therapeutic trials.

β-amyloid 1-40 oligomers (Aβ

Pediatric adrenocortical tumors (ACTs) are heterogeneous and have a poor prognosis. Overall survival is around 60%. In pediatric ACT that is managed only with surgery, features associated with adverse outcome include age greater than 3 years, non-functioning tumors, and metastatic (Stage IV) or residual tumor after surgery (Stage III). These factors individually do not account for most treatment failures, however. As current histopathologic classification systems are hindered by poor reproducibility and lack of predictive value, new prognostic markers are critically needed. In adults, methylation profiling can distinguish benign from malignant ACT, but similar data on pediatric ACT have not been reported. We performed DNA methylation profiling (MethylationEPIC BeadChip Array) on 52 pediatric ACTs and 13 normal pediatric adrenocortical tissue samples. The median age of 38 girls and 14 boys was 2.8 years (range, 0.3-17). ACTs were histologically classified as carcinoma (n=29), adenoma (n=10), and indeterminate (n=13). Overall survival was used as a primary endpoint. Unsupervised analysis of the 20,000 most variably methylated probes segregated cases into two distinct subgroups (designated A1 and A2). Differentially methylated genes (q-value 4 years (HR = 16.8, p = 0.008) and A1 methylation group (HR 7.7, p=0.0011) were each significantly correlated with overall survival. A1 subgroup remained significantly associated with overall survival in a series of models that adjusted for features including: clinical diagnosis, histopathologic characteristics, Ki67 index, and advanced stage. Methylation profiling provides prognostic significance that is independent of most current predictive variables, and in the future, may serve as a powerful biomarker in the prognostication of pediatric ACT.

Consolidation therapies for children with intermediate- or high-risk acute myeloid leukemia (AML) are urgently needed to achieve higher cure rates while limiting therapy-related toxicities. We determined if adoptive transfer of natural killer (NK) cells from haploidentical killer immunoglobulin–like receptor (KIR)–human leukocyte antigen (HLA)-mismatched donors may prolong event-free survival in children with intermediate-risk AML who were in first complete remission after chemotherapy. Patients received cyclophosphamide (Day − 7), fludarabine (Days − 6 through − 2), and subcutaneous interleukin-2 (Days − 1, 1, 3, 5, 7, and 9). Purified, unmanipulated NK cells were infused on Day 0, and NK cell chimerism and phenotyping from peripheral blood were performed on Days 7, 14, 21, and 28. As primary endpoint, the event-free survival was compared to a cohort of 55 patients who completed chemotherapy and were in first complete remission but did not receive NK cells. Donor NK cell kinetics were determined as secondary endpoints. Twenty-one patients (median age at diagnosis, 6.0 years [range, 0.1–15.3 years]) received a median of 12.5 × 106 NK cells/kg (range, 3.6–62.2 × 106 cells/kg) without major side effects. All but 3 demonstrated transient engraftment with donor NK cells (median peak donor chimerism, 4% [range, 0–43%]). KIR–HLA-mismatched NK cells expanded in 17 patients (81%) and contracted in 4 (19%). However, adoptive transfer of NK cells did not decrease the cumulative incidence of relapse (0.393 [95% confidence interval: 0.182–0.599] vs. 0.35 [0.209–0.495]; P = .556) and did not improve event-free (60.7 ± 10.9% vs. 69.1 ± 6.8%; P = .553) or overall survival (84.2 ± 8.5% vs. 79.1 ± 6.6%; P = .663) over chemotherapy alone. The lack of benefit may result from insufficient numbers and limited persistence of alloreactive donor NK cells but does not preclude its potential usefulness during other phases of therapy, or in combination with other immunotherapeutic agents. www.clinicaltrials.gov , NCT00703820 . Registered 24 June 2008.

Background and purpose/objective Mirror therapy has not been reported for phantom limb pain (PLP) in pediatric oncology. Our aims are to describe the incidence and duration of PLP post-amputation, the duration of follow-up, pain scores and pain medications, and the differences between a group that received mirror therapy (MT) in addition to the standard treatment and a group that received only the standard treatment (non-MT). Methods A retrospective review of patients' medical records from June 2009 to March 2015 was completed. The demographic characteristics, diagnoses and types of surgery were collected. The incidence and duration of PLP, duration of pain service follow-up, pain medications and pain scores were collected and analyzed using the Wilcoxon rank sum test. Results Of 21 patients who underwent amputations (median age 13 years, range, 8-24 years), most common primary diagnosis osteosarcoma), 18 (85.7%) experienced PLP; 38.9% of them experienced PLP at 1 year post-amputation (11.1% of the MT group and 66.7% of the non-MT group). The MT group and non-MT groups experienced PLP for a mean (± SD) of 246 (± 200) days, and 541 (± 363) days, respectively (p=0.08). The mean (SD) opioid doses (mg/kg/day) in the MT and non-MT groups were 0.81 (± 0.99) and 0.33 (± 0.31), respectively; the mean (SD) gabapentin doses (mg/kg/day) were 40.1 (± 21) for the MT group and 30.5 (± 11.5) for the non-MT group. Conclusion MT in children with cancer-related amputations is associated with lower incidence of PLP at 1 year and shorter duration of PLP.

Background Maintaining long-term central venous catheters (CVCs) in children undergoing chemotherapy can be challenging. Guidewire catheter exchange (GCE) replaces a CVC without repeat venipuncture. This study evaluated the indications, success rate, and complications of GCE in a large cohort of pediatric cancer patients. Procedure Medical records of pediatric cancer patients who underwent GCE at our institution between 2003 and 2013 were retrospectively reviewed. Variables analyzed included gender, age at GCE, primary cancer diagnosis, indication for GCE, absolute neutrophil count (ANC) at GCE, vein used, success rate, and postoperative complications (

β-amyloid 1–40 oligomers (Aβ40O) is considered to be one of the important biomarkers for the diagnosis and treatment of Alzheimer's disease (AD). To explore a method with excellent performance is favorable for measuring the low concentration of Aβ40O in AD patients. Here, we developed a simple and fast method with a double stranded DNA (dsDNA)/graphene oxide (GO) based sensor, which was a fluorescent probe for a highly sensitive detection of Aβ40O down to 0.1 nM with a linear detectable range from 0.1 nM to 40 nM. The proposed sensor effectively reduced non-specific adsorption and improved the specificity of detection because of the covalent conjugation of a binding DNA (bDNA) containing Aβ40O-targeting aptamer (AptAβ) onto GO surface, as well as the optimization of the number of mismatch base pairs of dsDNA. Moreover, AD patients and healthy persons were distinguished by this present method. All advantages of this method are exactly what the clinical detection of AD biomarkers need. This novel aptasensor might pave a way towards the early diagnosis of AD.

Uniportal video-assisted thoracic surgery (VATS) is gaining popularity among thoracic surgeons, but the limited space in the thorax of children makes uniportal VATS difficult to perform. The purpose of this study was to evaluate procedural and outcome differences between a modified uniportal VATS (MU-VATS) and three-port VATS (TP-VATS) for peripheral lung nodule biopsy in pediatric cancer patients.This is an Institutional Review Board-approved retrospective analysis of all consecutive MU-VATS and TP-VATS peripheral lung nodule biopsies performed at a single institution between June 2014 and December 2016. Patients with diffuse lung disease who underwent a lung biopsy were excluded.Over a 30-month period, 22 patients with a median age of 12 years (range, 7-21) underwent MU-VATS or TP-VATS for excisional biopsy of a peripheral lung nodule. MU-VATS lung biopsy was attempted in 11 patients and TP-VATS lung biopsy in the remaining 11. Both groups were comparable with regard to demographics, primary diagnosis, purpose of biopsy, and lung nodule location. MU-VATS demonstrated no difference when compared with TP-VATS lung biopsy in operative time (54 versus 62 min, P = .899), estimated blood loss (14 versus 15 mL, P = .587), pain score (2.8 versus 2.9, P = .717), and discharge day (1.3 versus 1.2 days, P = .572). No difference existed between groups with regard to conversion, need for intraoperative blood transfusion, and duration of chest tube. Complications including pneumothorax (n = 2) and subcutaneous emphysema (n = 1) were only seen in the TP-VATS group.MU-VATS can be safely utilized for biopsy of peripheral lung nodules in pediatric cancer patients without increasing procedural duration, hospitalization, pain scores, or need for intraoperative blood transfusion. Further studies need to evaluate the theoretical cosmetic advantage from a single surgical scar.

The propensity score (PS) method is widely used to estimate the average treatment effect (TE) in observational studies. However, it is generally confined to the binary treatment assignment. In an extension to the settings of a multi-level treatment, Imbens proposed a generalized propensity score which is the conditional probability of receiving a particular level of the treatment given pre-treatment variables. The average TE can then be estimated by conditioning solely on the generalized PS under the assumption of weak unconfounded-ness. In the present work, we adopted this approach and conducted extensive simulations to evaluate the performance of several methods using the generalized PS, including subclassification, matching, inverse probability of treatment weighting (IPTW), and covariate adjustment. Compared with other methods, IPTW had the preferred overall performance. We then applied these methods to a retrospective cohort study of 228,876 pregnant women. The impact of the exposure to different types of the antidepressant medications (no exposure, selective serotonin reuptake inhibitor (SSRI) only, non-SSRI only, and both) during pregnancy on several important infant outcomes (birth weight, gestation age, preterm labor, and respiratory distress) were assessed.

The use of bisphosphonates for pain control in children with cancer is not extensively studied. We retrospectively evaluated 35 children with cancer treated with intravenous bisphosphonates for pain management at a single institution from 1998 through 2015. We analyzed pain scores and opioid and adjuvant medication consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and 4 weeks after administration. We also determined the time interval between diagnosis and first administration of bisphosphonates and duration of life after bisphosphonate administration. Mean pain scores were 2.45 (±2.96) and 0.75 (±1.69) before and 14 days after bisphosphonate administration, respectively ( P = .25), and morphine equivalent doses of opioids were 5.52 (±13.35) and 5.27 (±9.77), respectively ( P = .07). Opioid consumption was significantly decreased at days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration. The median duration of life after first bisphosphonate administration was 80 days, indicating its use late in the course of treatment. Bisphosphonates did not significantly improve pain outcomes at 2 weeks, but opioid consumption was reduced at several time points during the first 3 weeks. The use of bisphosphonates earlier in the course of pediatric oncological disease should be evaluated in prospective investigations.

The analytical formulas for the average intensity distribution of annular vortex beam with aperture in the turbulent atmosphere are derived based on the extended Huygens–Fresnel principle. Under the H-V 5/7 turbulence model, the propagation proprieties of annular vortex beam with aperture are studied, and the influences of the optical topological charge, the propagation distance and the laser wavelength are numerically analyzed.

Waterborne viruses are a significant cause of human disease, especially in developing countries such as Uganda. A total of 15 virus-selective samples were collected at five sites (Bugolobi Wastewater Treatment Plant (WWTP) influent and effluent, Nakivubo Channel upstream and downstream of the WWTP, and Nakivubo Swamp) in July and August 2016. Quantitative PCR and quantitative RT-PCR was performed to determine the concentrations of four human viruses (adenovirus, enterovirus, rotavirus, and hepatitis A virus) in the samples. Adenovirus (1.53*105-1.98*107 copies/L) and enterovirus (3.17*105-8.13*107 copies/L) were found to have the highest concentrations in the samples compared to rotavirus (5.79*101-3.77*103 copies/L) and hepatitis A virus (9.93*102-1.11*104 copies/L). In addition, next-generation sequencing and metagenomic analyses were performed to assess viral diversity, and several human and vertebrate viruses were detected, including Herpesvirales, Iridoviridae, Poxviridae, Circoviridae, Parvoviridae, Bunyaviridae and others. Effluent from the wastewater treatment plant appears to impact surface water, as samples taken from surface water downstream of the treatment plant had higher viral concentrations than samples taken upstream. Temporal fluctuations in viral abundance and diversity were also observed. Continuous monitoring of wastewater may contribute to assessing viral disease patterns at a population level and provide early warning of potential outbreaks using wastewater-based epidemiology methods.

Owing to less conduction and switching power losses, the recently proposed Aalborg inverter has high efficiency within a wide range of input DC voltage for single-phase DC/AC power conversion. In theory, the conduction power losses can be further decreased, if an LLCL-filter is adopted instead of an LCL-filter for a voltage source inverter, mainly due to the reduced inductance. The Aalborg inverter shows the characteristic of a current source inverter, when working in the `boost ' state. Whether the LLCL-filter can meet the control requirement of this type inverter needs to be further explored. In this study, the small signal analysis for the modified-LLCL - filter-based Aalborg inverter is addressed. Through the modelling, it can be proven that compared with the LCL-filter, the modified-LLCL - filter causes no extra control challenge for the Aalborg inverter, and therefore more inductance in the power loop can be safely saved as well as a complete smaller filter size. A 220 V/50 Hz, 2000 W prototype is used to demonstrate the theoretical analysis.

We present a new configuration of the Na laser guide star (LGS) system with the laser source placed on the near space aircraft platform. Model of the Na LGS with the new configuration is established and the working principle is analyzed in detail. Under the rural environment with 23 km visibility and the H-V 5/7 atmospheric turbulent model, performances of the Na LGS with the new configuration and the conventional configuration are calculated, respectively. Results show that performance of the Na LGS can be significantly improved by using the new configuration, the uplink transmittance can be improved from 64.7% to 99.8%, diameter of the Na LGS can be decreased from 3.03 m to 0.36 m, and number of photons received can be improved from 536 photons cm −2 s −1 to 828 photons cm −2 s −1 .

The research on biomarkers has been limited in its effectiveness because biomarker levels can only be measured within the thresholds of assays and laboratory instruments, a challenge referred to as a detection limit (DL) problem. In this paper, we propose a Bayesian approach to the Cox proportional hazards model with explanatory variables subject to lower, upper, or interval DLs. We demonstrate that by formulating the time-to-event outcome using the Poisson density with counting process notation, implementing the proposed approach in the OpenBUGS and JAGS is straightforward. We have conducted extensive simulations to compare the proposed Bayesian approach to the other four commonly used methods and to evaluate its robustness with respect to the distribution assumption of the biomarkers. The proposed Bayesian approach and other methods were applied to an acute lung injury study, in which a panel of cytokine biomarkers was studied for the biomarkers' association with ventilation-free survival.

Introduction: Cytarabine, daunorubicin and etoposide (ADE) are commonly used for remission and intensification of pediatric acute myeloid leukemia (AML). However, development of drug resistance is a major cause of treatment failure. In this study, we performed a comprehensive evaluation of expression levels of genes of pharmacological significance (pharmacokinetic /pharmacodynamic) to ADE and derived a drug response score predictive of treatment outcomes in pediatric AML patients. Methods: This study included 163 cases (median age=8.79 year, range= (0.013-21.1)) with AML enrolled in the multicenter AML02 clinical trial (ClinicalTrials.gov Identifier: NCT00136084) with Affymetrix U133A microarray gene expression and clinical data available. We used a penalized LASSO regression algorithm (glmnet R-package) to fit a cox regression model on diagnostic leukemic cell gene expression levels of 66 genes of pharmacological significance to ADE. We performed 1000 bootstraps of LASSO regression with event free survival (EFS) as the outcome variable and the five genes represented in at least 95% of the models were included to build an ADE-Response Score (ADE-RS) equation. Patients were classified into low or high score groups using recursive portioning implemented in Rpart-R package and evaluated for association with minimal residual disease after induction I (MRD1), EFS and overall survival (OS). ADE response score equation was further validated using RNA-Seq gene-expression data obtained from diagnostic samples of 432 pediatric AML patients enrolled in Children's Oncology Group (COG) AAML0531 and AAML03P1 treatment protocols. Results: After applying LASSO regression, we defined the equation: ADE-RS = (0.128 x DCTD) - (0.0993 x TOP2A) + (0.212 x ABCC1) - (0.113 x MPO) - (0.126 x CBR1) to develop ADE-response score (ADE-RS), followed by classifying patients into low (60%; 98 patients) or high (40%; 65 patients) score groups. Patients in the high ADE-RS group had significantly worse EFS (HR=4.07(2.43-6.84), P < 0.0001; Figure 1A) and OS (HR= 4.54(2.42-8.49), P In a multivariable cox-regression models that included pLSC6-ADE response score groups, MRD1 status, risk groups, WBC at diagnosis and age in AML02 cohort, high pLSC6-ADE score group was found significantly associated with poor EFS (HR=6.02(2.71-13.2), P Discussion: In this study, we defined a pharmacological response score focused on key genes of PK/PD significance to ADE. We further integrated LSC score with the ADE response score to improve our ability to predict treatment outcome in AML patients across different clinical trials. ADE-RS was composed of five genes: DCTD, which is a deaminase, involved in ara-C inactivation; CBR1, a carbonyl reductase involved in inactivation of daunorubicin (DNR); MPO, myeloperoxidase, an etoposide activator; ABCC1, an efflux transporter of DNR and etoposide; and TOP2A, DNA topoisomerase II alpha, which is a target for DNR and etoposide. Integrated pLSC6 and ADE-RS has a potential to predict treatment outcomes using diagnostic gene expression levels and accordingly develop treatment strategies to improve treatment outcome. Figure 1 Disclosures Gruber: Bristol-Myers Squibb: Consultancy. Rubnitz:AbbVie: Research Funding.

Model of an optical system with coherent laser array source and the piston phase optimized by the stochastic parallel gradient descent algorithm is established. With this model, theory of beam propagation through the optical system in turbulent atmosphere is analyzed, and the analytical formulas of the beam average intensity along the propagation path are derived. Strehl ratio of the received beam induced by intensity disorderly distribution and power efficiency of the received beam are introduced to evaluate performance of the optical system. Under the H-V 5/7 atmospheric turbulent model, performance of an optical system with determinate parameters was calculated, and the influences of the propagation distance and the laser wavelength were numerically analyzed, respectively.

Objective The study objective was to assess the impact of dedicated instruction and deliberate practice on fourth-year medical students' proficiency in performing a coronary anastomosis using a porcine heart model, compared with nonsimulator-trained senior general surgery residents. Methods Ten fourth-year medical students were trained to perform a coronary anastomosis using the porcine simulator. Students trained for 4 months using deliberate practice methodology and one-on-one instruction. At the end of the training, each student was filmed performing a complete anastomosis. Eleven senior general surgery residents were filmed performing an anastomosis after a single tutorial. All films were graded by 3 independent cardiac surgeons in a blinded fashion. The primary outcome was the median final score (range, 1-10) of a modified Objective Structured Assessment of Technical Skill scale. The secondary outcome was time to completion in seconds. Statistical analysis used both parametric (Student t test) and nonparametric (Wilcoxon rank-sum) methods. Results The median combined final score for medical students was 3 (interquartile range, 2.3-4.8), compared with 4 (interquartile range, 3.3-5.3) for residents ( P = .102). The overall median individual final scores were 3 (interquartile range, 2-6) for grader 1, 3 (interquartile range, 2-5) for grader 2, and 4 (interquartile range, 3-5) for grader 3. For each individual grader, there was no difference in median final scores between medical students and residents. The mean time to completion was 792.7 seconds (95% confidence interval, 623.4-962) for medical students and 659 seconds (95% confidence interval, 599.1-719) for residents ( P = .118). Conclusions Dedicated instruction of fourth-year medical students with deliberate and distributed practice of microvascular techniques using a porcine end-to-side coronary artery anastomosis simulation model results in performance comparable to that of senior general surgery residents. These results suggest that focused tissue simulator training can compress the learning curve to acquire technical proficiency in comparison with real-time training.

Beam propagation through an optical system with the two-adaptive-optics configuration and beam shaping has been investigated. In theory, we analyzed beam propagation through the optical system in turbulent atmosphere and calculated performance of the optical system under the H-V 5/7 turbulent model, the ITU-R turbulent model, the Shanxi district turbulent model and the Hefei district turbulent model in China, respectively. The theoretical results showed that performance of the optical system can be significantly improved by beam shaping. With ideal adaptive optics correction precision, power efficiency of the received beam can be improved from 81.27% to 92.00%, and the system performance factor can be improved from 0.61 to 0.67 under the H-V 5/7 turbulent model. In experiment, we found an experimental optical system under the laboratory conditions by using two Liquid Crystal Spatial Light Modulators, and carried out the reduced-scale experiment. The experimental results showed that power efficiency of the received beam can be improved from 71.89% to 87.88%, and power proportion in the bucket with 5 pixels radius at the target can be improved from 44.53% to 52.78% by beam shaping.

We present an effective method to improve performances of the optical systems with Cassegrain-telescope receivers by using vortex sources and phase optimizations. A typical model of optical systems with Cassegrain-telescope receivers is established, theory of beam propagation through the optical system is analyzed and principle of the new method is illuminated in detail. We classify the optical systems with Cassegrain-telescope receivers into two types and analyze the system performance evaluating factors: the first type is that the received beam is converted to signals, and power efficiency of the received beam is used as the system performance evaluating factor; the second type is that the received beam is used as a new source for further propagation after being cleaned up, and the product of power efficiency and beam quality (Strehl ratio) of the received beam is used as the system performance evaluating factor. Under the H-V 5/7 turbulent model, performances of the two systems with vortex sources and phase optimized by the stochastic parallel gradient descent algorithm are calculated. Results show that power efficiency of the received beam in the first type optical system can get 97.86, and the system performance evaluating factor of the second type system can be improved from 0.8560 to 0.9398.

Beam propagation through a double-adaptive-optics optical system in turbulent atmosphere has been investigated. A typical model of optical systems with the double-adaptive-optics configuration is established, principles of the two adaptive optics and theory of beam propagation through the optical system in turbulent atmosphere are analyzed. Power efficiency and beam quality (BPF) of the received beam are introduced to evaluate performance of the optical system. Under the H-V 5/7 turbulent model, influences of the two adaptive optics installations are numerically calculated, respectively. Results show that the adaptive optics at the launcher can improve both power efficiency and beam quality of the received beam, the adaptive optics at the receiver can significantly improve beam quality of the received beam. Evolution of the system performance with the increase of adaptive optics correction order is numerically simulated, and results show that the double-adaptive-optics configuration has great advantages in improving beam quality of the received beam in optical systems with beam long-distance propagation through the turbulent atmosphere.

Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups.In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment.Thirty-seven patients underwent 38 definitive surgeries: limb sparing (26, 68.4%) or amputations (12, 31.6%). Localization included lower extremity (30, 81%), upper extremity (6, 16%), or pelvis (1, 3%). Thirty patients (81%) developed NP and 26 of them required NP-specific medications (87.7%). The mean [standard deviation (SD)] duration of NP was 6.5 weeks (7.2) (median 4.4, range 0.3-29.9). All 26 patients (27 surgeries) treated with NP medications received gabapentin, either as single therapy (65.4%) (17 patients, 18 surgeries), dual therapy with gabapentin and amitriptyline (five patients), or triple therapy with gabapentin, amitriptyline, and methadone (four patients). The mean starting (maximum) doses of gabapentin, amitriptyline, and methadone (mg/kg/day) were 20.2 (43.8), 0.5 (0.7), and 0.3 (0.3), respectively. The incidence and duration of NP, duration of treatment, and NP-specific dose regimens were similar in the limb sparing and the amputation groups.NP after definitive surgery for OS is frequently encountered, can persist for a significant time, and NP outcomes are similar in limb sparing and amputation groups.

Biomarkers have the potential to improve our understanding of disease diagnosis and prognosis. Biomarker levels that fall below the assay detection limits (DLs), however, compromise the application of biomarkers in research and practice. Most existing methods to handle non-detects focus on a scenario in which the response variable is subject to detection limit; only a few methods consider explanatory variables when dealing with DLs. We propose a Bayesian approach for generalized linear models with explanatory variables subject to lower, upper, or interval DLs. In simulation studies, we compared the proposed Bayesian approach to four commonly used methods in a logistic regression model with explanatory variable measurements subject to DL. We also applied the Bayesian approach and other four methods in a real study, in which a panel of cytokine biomarkers was studied for their association with acute lung injury (ALI). We found that IL8 was associated with a moderate increase in risk for ALI in the model based on the proposed Bayesian approach.

Improving power coupling efficiency of beam uplink propagation in a relay mirror system is under extensive research in recent years. A typical model of the relay mirror system is established and theory of beam shaping used to improve power coupling efficiency of the relay mirror system is analyzed in detail. A reduced-scale experimental relay mirror system is founded, which has the same Fresnel number as uplink propagation in the relay mirror system with 1.0 m-caliber transmitter and 30 km propagation distance. Phase distribution of the source is optimized by using the stochastic parallel gradient descent algorithm. The experimental results showed that power coupling efficiency of uplink propagation in the reduced-scale relay mirror system was improved from 72.67 to 87.88 % by beam shaping and the bucket power proportion in 5 pixels at the target was improved from 45.49 to 52.78 %.

We propose and demonstrate the wave front correction of a vortex laser beam by using dual phase only liquid crystal spatial light modulators (LC-SLMs) and a stochastic parallel gradient descent (SPGD) algorithm. One phase only LC-SLM is used to generate vortex laser beam by loading spiral phase screen onto the wave front of input quasi-Gaussian beam. The other phase only LC-SLM under SPGD controller based on the subzone control method adaptively compensates the wave front of vortex laser beam. Numerical simulation and experimental results show that after correction, vortex doughnut like beam is focused into a beam with airy disk pattern distribution in the far field. The adaptive corrections of vortex laser beam with different optical topological charges are studied. The results show that the optical topological charge has little influence on adaptive correction. The powers in the main lobe of far field intensity distributions of vortex laser beams with different optical topological charges are all greatly improved by adaptive correction. The technique proposed in this paper can be used in optical communication, relay mirror and atmospheric turbulence correction.

The association of meat intake and meat-derived mutagens with colorectal tumor risk remains unclear. We evaluated this hypothesis in a large colonoscopy-based case–control study. Included in the study were 2,543 patients with polyp [(1,881 with adenomas and 622 with hyperplastic polyp (HPP)] and 3,764 polyp-free controls. Surveys obtained information about meat intake by cooking methods and doneness levels plus other suspected or known risk factors for colorectal tumors. Unconditional logistic regression was used to derive ORs after adjusting for potential confounders. High intake of red meat and processed meat (Ptrend < 0.05), particularly red meat cooked using high-temperature cooking methods (Ptrend ≤ 0.01), was associated with an elevated risk for colorectal polyps. A significant positive association between exposures to meat-derived heterocyclic amines (HCA) and risk of polyps was found for both adenomas and HPPs. Furthermore, the positive association with red meat intake and HCA exposure was stronger for multiple adenomas than for single adenoma as well as for serrated than for nonserrated adenomas. This study supports a role for red meat and meat-derived mutagen exposure in the development of colorectal tumor. Cancer Prev Res; 4(10); 1686–97. ©2011 AACR.

We presented a new method to improve power efficiencies of the optical systems with Cassegrain telescope receivers by using vortex sources with optimized parameters. A typical model of optical systems with Cassegrain telescope receivers was established and power losses in the optical system under the H-V 5/7 turbulence model were analyzed in detail. The calculating results showed that power efficiency of the optical system can be improved from 76.48% to 97.25%. A reduced-scaled experiment was carried out and the experimental results showed that power efficiency of the optical system can be improved from 71.89% to 90.60%.

Purpose: Although most patients with estrogen receptor α (ER)-positive breast cancer initially respond to endocrine therapy, many ultimately develop resistance to antiestrogens. However, mechanisms of antiestrogen resistance and biomarkers predictive of such resistance are underdeveloped. Experimental Design: We adapted four ER+ human breast cancer cell lines to grow in an estrogen-depleted medium. A gene signature of estrogen independence was developed by comparing expression profiles of long-term estrogen-deprived (LTED) cells to their parental counterparts. We evaluated the ability of the LTED signature to predict tumor response to neoadjuvant therapy with an aromatase inhibitor and disease outcome following adjuvant tamoxifen. We utilized Gene Set Analysis (GSA) of LTED cell gene expression profiles and a loss-of-function approach to identify pathways causally associated with resistance to endocrine therapy. Results: The LTED gene expression signature was predictive of high tumor cell proliferation following neoadjuvant therapy with anastrozole and letrozole, each in different patient cohorts. This signature was also predictive of poor recurrence-free survival in two studies of patients treated with adjuvant tamoxifen. Bioinformatic interrogation of expression profiles in LTED cells revealed a signature of MYC activation. The MYC activation signature and high MYC protein levels were both predictive of poor outcome following tamoxifen therapy. Finally, knockdown of MYC inhibited LTED cell growth. Conclusions: A gene expression signature derived from ER+ breast cancer cells with acquired hormone independence predicted tumor response to aromatase inhibitors and associated with clinical markers of resistance to tamoxifen. Activation of the MYC pathway was associated with this resistance. Clin Cancer Res; 17(7); 2024–34. ©2011 AACR.