The intentional or unintentional adulteration of baby formula with drugs of abuse is one of the many increasingly complex samples forensic chemists may have to analyze. This sample type presents a ...challenge because of a complex matrix that can mask the detection of trace drug residues. To enable screening of baby formula for trace levels of drugs, the use of solid‐phase microextraction (SPME) coupled with direct analysis in real‐time mass spectrometry (DART‐MS) was investigated. A suite of five drugs was used as adulterants and spiked into baby formula. Samples were then extracted using SPME fibers which were analyzed by DART‐MS. Development of a proof‐of‐concept method was completed by investigating the effects of the DART gas stream temperature and the linear speed of the sample holder. Optimal values of 350°C and 0.2 mm/s were found. Once the method was established, representative responses and sensitivities for the five drugs were measured and found to be in the range of single ng/mL to hundreds ng/mL. Additional studies found that the presence of the baby formula matrix increased analyte signal (relative to methanolic solutions) by greater than 200%. Comparison of the SPME‐DART‐MS method to a traditional DART‐MS method for trace drug detection found at least a factor of 13 improvement in signal for the drugs investigated. This work demonstrates that SPME‐DART‐MS is a viable technique for the screening of complex matrices, such as baby formula, for trace drug residues and that development of a comprehensive method is warranted.
The tsunami source of the 2021 MW 8.1 Raoul Island earthquake in the Kermadec subduction zone was estimated by inverting the tsunami signals recorded by Deep‐ocean Assessment and Reporting of ...Tsunamis (DART) bottom pressure sensors and coastal tide‐gauges. The main asperity of up to 5 m of slip is located northeastward from the hypocenter, with features compatible with the aftershock distribution and rapid back‐projection analysis. Three earthquakes of MW ∼8 or larger which also produced moderate tsunamis happened in the 20th century in the same portion of the subduction zone. This is the first great tsunamigenic event captured by the new New Zealand DART network in the South West Pacific, which proved valuable to estimate a robust image of the tsunami source. We also show a first proof of concept of the capability of this network to reduce the uncertainty associated with tsunami forecasting and to increase the lead time available for evacuation for future alerts.
Plain Language Summary
We estimated the tsunami source for the 4 March 2021 Raoul Island earthquake (MW 8.1), obtained by inverting tsunami data from tide‐gauges and open ocean Deep‐ocean Assessment and Reporting of Tsunamis (DART) stations. The main asperity of up to 5 m of slip is located northeastward from the hypocenter, with features compatible with the aftershock distribution and rapid back‐projection analysis. This event is important because it was the strongest one of three earthquakes that occurred within hours during the same day. Moreover, it caused the largest of three tsunami that altogether represent a great test for the New Zealand DART new network. The results demonstrate the potential importance of this new DART network for resolving the tsunami source and for early warning purposes as it can reduce the uncertainty of the tsunami forecasts and at the same time increase the lead time available for evacuation.
Key Points
Tsunami source of the 2021 MW 8.1 Raoul Island earthquake by inverting tsunami waveforms
The main slip peaks at 5 m and is located at a depth of ∼20–30 and ∼100 km north of the epicenter
New Deep‐ocean Assessment and Reporting of Tsunamis network was crucial for characterizing the source and will significantly reduce the uncertainty and speed up future warnings
We report the first observations of negative intracloud (IC) dart‐stepped leaders accompanied by regular trains of microsecond‐scale pulses, simultaneously detected by shielded broadband magnetic ...loop antennas and the radio telescope Low Frequency Array (LOFAR). Four investigated pulse trains occurred during complicated IC flashes on 18 June 2021, when heavy thunderstorms hit the Netherlands. The pulses within the trains are unipolar, a few microseconds wide, and with an average inter‐pulse interval of 5–7 μs. The broadband pulses perfectly match energetic, regularly distributed, and relatively isolated bursts of very high frequency sources localized by LOFAR. All trains were generated by negative dart‐stepped leaders propagating at a lower speed than usual dart leaders. They followed channels of previous leaders occurring within the same flash several tens of milliseconds before the reported observations. The physical mechanism remains unclear as to why we observe dart‐stepped leaders, which show mostly regular stepping, emitting energetic microsecond‐scale pulses.
Plain Language Summary
Lightning phenomena inside thunderclouds can be explored using their electromagnetic radiation. To study these processes at small temporal and spatial scales, we combine broadband magnetic loop antennas with the Low Frequency Array (LOFAR) radio telescope. Measurements of broadband antennas acquired during a severe Dutch thunderstorm showed pulse sequences composed of tens microsecond‐scale unipolar pulses, which were surprisingly regularly distributed. Such regular pulse trains have been rarely reported from previous observations. When we thoroughly lined up the timestamps of both simultaneously measuring observational systems, we found that the regular broadband pulses perfectly match with localized isolated bursts of energetic very high frequency radiation detected by LOFAR. The 3D mapping of the radio sources of these bursts allowed us to place the investigated events into the context of the parent intracloud (IC) lightning flash. The results revealed negative IC dart leaders, which propagated along the preconditioned channels originally formed by previous positive or negative IC leaders. Some of these dart leaders then exhibited unusual stepping manifested by the observed regular pulses. We assume that a favorable combination of the conductivity of preexisting lightning channels and the strength of the ambient electric field inside thunderclouds might be needed to trigger this unusual stepping.
Key Points
We observed intracloud negative dart‐stepped leaders producing regular trains of broadband electromagnetic microsecond‐scale pulses
Very High Frequency sources follow channels of previous leaders occurring within the same flash tens of milliseconds before the reported observations
Conductivity of decaying channels and strength of the ambient electric field might act together to trigger this unusual stepping process
DART, the Double Asteroid Redirection Test, successfully impacted asteroid Dimorphos on September 26, 2022, becoming the first mission to demonstrate asteroid deflection. Shared live via a NASA ...broadcast, over a million concurrent viewers around the world watched as the DART spacecraft streamed images to Earth up to the final second before its impact with Dimorphos. In this paper, we share the final phases of the DART encounter and the latest results from the DART Investigation Team's analysis of ground and space-based data. This includes measurements on the amount of deflection that DART imparted on Dimorphos, a determination of the momentum transfer enhancement factor, and results on understanding the geology and surface characteristics of the impact site. The success of the DART mission paves the future for a bold international Planetary Defense program. We also share ideas on bolstering international coordination, developing new technologies that can mitigate different types of asteroid threats, and closing identified gaps in our overall preparedness.
Background
The authors previously reported the results of the nonpancreatic neuroendocrine neoplasm cohort of the SWOG S1609 DART (Dual Anti–CTLA‐4 and Anti–PD‐1 Blockade in Rare Tumors) trial, which ...permitted all histologic grades and had a 44% overall response rate (ORR) among patients with high‐grade disease. Here they sought to validate their findings in a dedicated prospective cohort of high‐grade neuroendocrine neoplasms within S1609.
Methods
A prospective, open‐label, multicenter, phase 2 clinical trial of ipilimumab plus nivolumab was conducted across multiple rare tumor cohorts. The dedicated, high‐grade neuroendocrine neoplasm cohort was examined here. The primary end point was the ORR according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary end points included progression‐free survival (PFS), overall survival (OS), and toxicity.
Results
Nineteen patients with high‐grade neuroendocrine neoplasms (defined by local pathology review) were enrolled in this cohort of S1609. The most common primary sites were unknown primaries (21%), which were followed by the rectum, gastroesophageal junction, cervix, and pancreas (11%). The median number of lines of prior therapy was 1 (range, 0‐3). All patients were microsatellite‐stable. The median Ki‐67 value was 80%. The ORR was 26% (95% confidence interval CI, 11%‐45%), and the clinical benefit rate (stable disease for ≥6 months plus partial responses plus complete responses) was 32% (95% CI, 13%‐57%). The 6‐month PFS rate was 32% (95% CI, 16%‐61%) with a median PFS of 2.0 months (95% CI, 1.8 months to ∞) and a median OS of 8.7 months (95% CI, 6.1 months to ∞). The most common toxicities were fatigue (32%) and rash (26%), and the most common grade 3/4 immune‐related adverse event was rash (15%); there were no events that required treatment discontinuation and no grade 5 events.
Conclusions
Ipilimumab plus nivolumab demonstrated a 26% ORR in patients with high‐grade neuroendocrine neoplasms, with durable responses seen in patients with refractory disease.
Low‐dose ipilimumab with nivolumab results in a 26% overall response rate in high‐grade neuroendocrine neoplasms.
Summary
Uncovering the genetic basis of agronomic traits in wheat landraces is important for ensuring global food security via the development of improved varieties. Here, 723 wheat landraces from 10 ...Chinese agro‐ecological zones were evaluated for 23 agronomic traits in six environments. All accessions could be clustered into five subgroups based on phenotypic data via discriminant function analysis, which was highly consistent with genotypic classification. A genome‐wide association study was conducted for these traits using 52 303 DArT‐seq markers to identify marker‐trait associations and candidate genes. Using both the general linear model and the mixed linear model, 149 significant markers were identified for 21 agronomic traits based on best linear unbiased prediction values. Considering the linkage disequilibrium decay distance in this study, significant markers within 10 cM were combined as a quantitative trait locus (QTL), with a total of 29 QTL identified for 15 traits. Of these, five QTL for heading date, flag leaf width, peduncle length, and thousand kernel weight had been reported previously. Twenty‐five candidate genes associated with significant markers were identified. These included the known vernalization genes VRN‐B1 and vrn‐B3 and the photoperiod response genes Ppd and PRR. Overall, this study should be helpful in elucidating the underlying genetic mechanisms of complex agronomic traits and performing marker‐assisted selection in wheat.
Significance Statement
The genome‐wide associations study is a powerful method to identify marker‐trait associations and dissect the genetic architecture of complex agronomic traits in crops. Here, 723 wheat landraces from 10 agro‐ecological zones in China were evaluated for 23 agronomic traits in multi‐environments. With the use of 52 303 DArT‐seq markers, we identified 149 significant markers for 21 traits, as well as 25 candidate genes for 13 traits. These results could facilitate the utilization of wheat genetic resources in molecular breeding.
Historically, Boswellia resin, commonly known as frankincense, has been used for a variety of applications, including medicinal purposes and in religious ceremonies. These practices continued into ...the modern era, in which the trade of resin has increased dramatically. The genus Boswellia contains many species that are not currently protected by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), but research has found that some of these populations are predicted to decrease by 50 % in the next two decades due to overexploitation (Bongers et al., 2019). This highlights the need for a method that can identify Boswellia resins. In this research, resin from nine different species of Boswellia were collected and analyzed in positive ion mode by Direct Analysis in Real Time Time-of-Flight mass spectrometry (DART TOFMS) by dissolving the resin in methanol to obtain a chemotype devoid of background noise. Chemometric analysis of the data indicated that positive ion spectra from the resins separated the species effectively, indicating that DART TOFMS can be used to identify resins in trade.
•Frankincense resins are economically valuable and have deep historical significance.•Overexploitation of Boswellia populations threatens their survival.•Species identification can provide insight on geographic origin.•Determination of commercial frankincense resins can be accomplished using mass spectrometry.
Dart-thrower’s motion (DTM) is a functional wrist movement from maximum radial extension to maximum ulnar flexion. This study defines a reference range of DTM in a healthy population.
Goniometric ...measurements were collected from both wrists of 200 healthy volunteers. Mean age was 21.1 years (range, 18–25 years), 126 volunteers (63%) were female, and 177 (89%) were right-handed. Volunteers also reported perceived difficulty of performing DTM.
For male subjects, the mean arc of motion was 126° (range, 83°–166°) for dominant and 114° (range, 62°–148°) for nondominant wrists. For female subjects, the mean values were 129° (range, 79°–170°) and 126° (range, 70°–167°), respectively. On multiple regression analysis, female subjects had a significantly increased range of dominant and nondominant arc of motion compared with males. Older subjects had significantly increased dominant but reduced nondominant arc of motion. High inter- and intrarater reliability was observed for goniometric measurement of DTM (intraclass correlation coefficients, 0.93–0.98).
This study quantified a reference range of DTM in normal individuals.
This study provides a reference range for DTM in a young adult population, which may aid clinical comparison of measurements of wrist movement and evaluation of conditions and treatments that impact DTM.
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•Analysis of seed-based toxins and seed mashes completed.•DART-MS or one of its variants a was able to detect all 7 compounds in pure form.•Use of high-temperature IRTD-DART-MS was ...required for detection of large molecules.•PCA of mass spectra of seed mashes containing toxins allows for species identification.
Detection of seed-based toxins is a need for forensic chemists when suspected poisonings occur. The evidence that is found is often physically unidentifiable, as the seeds are mashed to extract the toxin. This work investigates potential strategies for rapid detection of seed-based toxins and seed mashes containing these toxins using chemical signatures obtained by direct analysis in real time mass spectrometry (DART-MS). Seven toxins (digoxin, digitoxin, hypaconitine, hyoscyamine, lanatoside, oleandrin, and scopolamine) and six seeds containing these toxins were studied. While detection of four of the toxins was readily attainable, detection of digoxin, digitoxin, and lanatoside was hindered by the inability to thermally desorb these larger compounds under normal operating conditions. The use of DART-MS variants capable of higher desorption temperatures (thermal desorption (TD)-DART-MS and infrared thermal desorption (IRTD)-DART-MS) enabled detection of these compounds. Detection of toxins from direct analysis of seed mashes and methanolic seed mash extracts was found to be compound and technique dependent. Principal component analysis (PCA) of generated mass spectra enabled differentiation of seed species, even in cases where the toxins were undetectable.
This work highlights the discovered in-situ analytical reaction between primary/secondary alcohols and nitrogenous bases (pyridine, quinoline) that involves the substitution of hydroxyl groups for ...nitrogen-containing charged species and proceeds in an ionization region of Direct Analysis in Real Time mass spectrometry (DART-MS) instrument at gas stream temperature of 150–450 °C. Resulted cations provide strong signals in mass spectra and this ensures high sensitivity of the analysis. Collision induced dissociation of such precursor ions gives rise to characteristic and simple fragmentation mass spectra revealing mainly protonated nitrogenous bases and carbonium cations resulting from the elimination of neutral nitrogen-containing bases. The dependence of signal response on gas stream temperature was elucidated. It was also found that, independently of gas stream temperature, high volatility low-molecular weight alcohols did not demonstrate characteristic DART spectra owing to a high rate of desorption/evaporation which does not provide sufficient probability of the reaction. To the best of our knowledge, this type of specific reactions in a plasma-based source of DART mass spectrometer is reported for the first time. It represents a new and interesting derivatization approach providing a rapid and sensitive complement method for the detection and identification of individual monools of various origin, profiling plant sterols and other steroid alcohols in different matrices.
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•Described novel in-situ reaction between alcohols and nitrogenous bases in DART-MS.•Proposed a new method for the rapid and sensitive detection of monools.•The method applied for profiling of sterols in plant oils and sour creams.
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