DETECTION OF MORPHINE AND ITS ANALOGUES USING ENZYMATIC HYDROLYSIS

The invention relates to a method for hydrolyzing drug glucuronic acid conjugates present in mammalian body fluids, the conjugates being derived from a narcotic analgesic, antagonist, or agonist-antagonist whose metabolism includes conjugation with glucuronic acid. The method comprises incubating the body fluid sample at from about 60 to about 70° C., for at least about 1 hour, with 3-glucuronidase derived from Patella vulgata, and substantially increases the sensitivity of chromatographic techniques for the detection of morphine and its analogues

Harmonization-enriched domain adaptation with light fine-tuning for multiple sclerosis lesion segmentation

Deep learning algorithms utilizing magnetic resonance (MR) images have demonstrated cutting-edge proficiency in autonomously segmenting multiple sclerosis (MS) lesions. Despite their achievements, these algorithms may struggle to extend their performance across various sites or scanners, leading to domain generalization errors. While few-shot or one-shot domain adaptation emerges as a potential solution to mitigate generalization errors, its efficacy might be hindered by the scarcity of labeled data in the target domain. This paper seeks to tackle this challenge by integrating one-shot adaptation data with harmonized training data that incorporates labels. Our approach involves synthesizing new training data with a contrast akin to that of the test domain, a process we refer to as "contrast harmonization" in MRI. Our experiments illustrate that the amalgamation of one-shot adaptation data with harmonized training data surpasses the performance of utilizing either data source in isolation. Notably, domain adaptation using exclusively harmonized training data achieved comparable or even superior performance compared to one-shot adaptation. Moreover, all adaptations required only minimal fine-tuning, ranging from 2 to 5 epochs for convergence

Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR

Retrieving C and O Abundance of HR 8799 c by Combining High- and Low-Resolution Data

The formation and evolution pathway for the directly-imaged multi-planetary system HR 8799 remains mysterious. Accurate constraints on the chemical composition of the planetary atmosphere(s) are key to solving the mystery. We perform a detailed atmospheric retrieval on HR 8799~c to infer the chemical abundances and abundance ratios using a combination of photometric data along with low- and high-resolution spectroscopic data (R$\sim$20-35,000). We specifically retrieve [C/H], [O/H], and C/O and find them to be 0.55$^{+0.36}_{-0.39}$, 0.47$^{+0.31}_{-0.32}$, and 0.67$^{+0.12}_{-0.15}$ at 68\% confidence. The super-stellar C and O abundances, yet a stellar C/O ratio, reveal a potential formation pathway for HR 8799~c. Planet c, and likely the other gas giant planets in the system, formed early on (likely within $\sim$1 Myr), followed by further atmospheric enrichment in C and O through the accretion of solids beyond the CO iceline. The enrichment either preceded or took place during the early phase of the inward migration to the planet current locations.Comment: 19 pages, 6 figures, 3 tables, accepted to AAS journal

Retrieving the C and O Abundances of HR 7672~AB: a Solar-Type Primary Star with a Benchmark Brown Dwarf

A benchmark brown dwarf (BD) is a BD whose properties (e.g., mass and chemical composition) are precisely and independently measured. Benchmark BDs are valuable in testing theoretical evolutionary tracks, spectral synthesis, and atmospheric retrievals for sub-stellar objects. Here, we report results of atmospheric retrieval on a synthetic spectrum and a benchmark BD -- HR 7672~B -- with \petit. First, we test the retrieval framework on a synthetic PHOENIX BT-Settl spectrum with a solar composition. We show that the retrieved C and O abundances are consistent with solar values, but the retrieved C/O is overestimated by 0.13-0.18, which is $\sim$4 times higher than the formal error bar. Second, we perform retrieval on HR 7672~B using high spectral resolution data (R=35,000) from the Keck Planet Imager and Characterizer (KPIC) and near infrared photometry. We retrieve [C/H], [O/H], and C/O to be $-0.24\pm0.05$, $-0.19\pm0.04$, and $0.52\pm0.02$. These values are consistent with those of HR 7672~A within 1.5-$\sigma$. As such, HR 7672~B is among only a few benchmark BDs (along with Gl 570~D and HD 3651~B) that have been demonstrated to have consistent elemental abundances with their primary stars. Our work provides a practical procedure of testing and performing atmospheric retrieval, and sheds light on potential systematics of future retrievals using high- and low-resolution data.Comment: 29 pages, 17 figures, 5 tables, resubmitted to AAS journals after first revisio

A Clear View of a Cloudy Brown Dwarf Companion from High-Resolution Spectroscopy

Direct imaging studies have mainly used low-resolution spectroscopy ($R\sim20-100$) to study the atmospheres of giant exoplanets and brown dwarf companions, but the presence of clouds has often led to degeneracies in the retrieved atmospheric abundances (e.g. C/O, metallicity). This precludes clear insights into the formation mechanisms of these companions. The Keck Planet Imager and Characterizer (KPIC) uses adaptive optics and single-mode fibers to transport light into NIRSPEC ($R\sim35,000$ in $K$ band), and aims to address these challenges with high-resolution spectroscopy. Using an atmospheric retrieval framework based on petitRADTRANS, we analyze KPIC high-resolution spectrum ($2.29-2.49~\mu$m) and archival low-resolution spectrum ($1-2.2~\mu$m) of the benchmark brown dwarf HD 4747 B ($m=67.2\pm1.8~M_{\rm{Jup}}$, $a=10.0\pm0.2$ au, $T_{\rm eff}\approx1400$ K). We find that our measured C/O and metallicity for the companion from the KPIC high-resolution spectrum agree with that of its host star within $1-2\sigma$. The retrieved parameters from the $K$ band high-resolution spectrum are also independent of our choice of cloud model. In contrast, the retrieved parameters from the low-resolution spectrum are highly sensitive to our chosen cloud model. Finally, we detect CO, H$_2$O, and CH$_4$ (volume mixing ratio of log(CH$_4$)=$-4.82\pm0.23$) in this L/T transition companion with the KPIC data. The relative molecular abundances allow us to constrain the degree of chemical disequilibrium in the atmosphere of HD 4747 B, and infer a vertical diffusion coefficient that is at the upper limit predicted from mixing length theory.Comment: 33 pages, 16 figures, Accepted to Ap

What Every Business Student Needs to Know About Information Systems

Whether Information Systems should or should not be part of the core business school curriculum is a recurring discussion in many universities. In this article, a task force of 40 prominent information systems scholars address the issue. They conclude that information systems is absolutely an essential body of knowledge for business school students to acquire as well as a key element of the business school\u27s long-run strategic positioning within the university. Originally prepared in response to draft accreditation guidelines prepared by AACSB International, the article includes a compilation of the concepts that the authors believe to be the core information systems knowledge that all business school students should be familiar with

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes

BACKGROUND: Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours. METHODS: Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score. RESULTS: Patients with BRCAm tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCAwt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice® HRD score was observed in BRCAm and BRCAwt tumours with BRCA1 methylation. Patients without BRCAm tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCAm patients.CONCLUSIONS: Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1/2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCAm