Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Losartan Blocks Osteosarcoma-Elicited Monocyte Recruitment, and Combined With the Kinase Inhibitor Toceranib, Exerts Significant Clinical Benefit in Canine Metastatic Osteosarcoma.

PURPOSE: There is increasing recognition that progress in immuno-oncology could be accelerated by evaluating immune-based therapies in dogs with spontaneous cancers. Osteosarcoma (OS) is one tumor for which limited clinical benefit has been observed with the use of immune checkpoint inhibitors. We previously reported the angiotensin receptor blocker losartan suppressed metastasis in preclinical mouse models through blockade of CCL2-CCR2 monocyte recruitment. Here we leverage dogs with spontaneous OS to determine losartan's safety and pharmacokinetics associated with monocyte pharmacodynamic endpoints, and assess its antitumor activity, in combination with the kinase inhibitor toceranib. PATIENTS AND METHODS: CCL2 expression, monocyte infiltration, and monocyte recruitment by human and canine OS tumors and cell lines were assessed by gene expression, ELISA, and transwell migration assays. Safety and efficacy of losartan-toceranib therapy were evaluated in 28 dogs with lung metastatic OS. Losartan PK and monocyte PD responses were assessed in three dose cohorts of dogs by chemotaxis, plasma CCL2, and multiplex cytokine assays, and RNA-seq of losartan-treated human peripheral blood mononuclear cells. RESULTS: Human and canine OS cells secrete CCL2 and elicit monocyte migration, which is inhibited by losartan. Losartan PK/PD studies in dogs revealed that a 10-fold-higher dose than typical antihypertensive dosing was required for blockade of monocyte migration. Treatment with high-dose losartan and toceranib was well-tolerated and induced a clinical benefit rate of 50% in dogs with lung metastases. CONCLUSIONS: Losartan inhibits the CCL2-CCR2 axis, and in combination with toceranib, exerts significant biological activity in dogs with metastatic osteosarcoma, supporting evaluation of this drug combination in patients with pediatric osteosarcoma. See related commentary by Weiss et al., p. 571.

Canine Non-Angiogenic, Non-Myogenic Splenic Stromal Sarcoma: a Retrospective Clinicopathological Analysis and Investigation of Podoplanin as a Marker of Tumour Histogenesis.

Splenic stromal sarcomas are rarely reported tumours that were previously grouped as non-angiomatous, non-lymphomatous mesenchymal neoplasms of the canine spleen. Highly variable survival times have been reported probably due to their heterogeneous nature. The purpose of this study was to assess the outcome and prognostic factors in dogs with splenic stromal sarcoma after treatment by splenectomy. Clinical data were collected retrospectively and histopathology was reviewed for 47 patients. Histological classification, based on morphology in haematoxylin and eosin-stained sections, in conjunction with immunolabelling of macrophage scavenger receptor-A (CD204), desmin, factor VIII-related antigen and smooth muscle actin ,yielded diagnoses of undifferentiated stromal sarcoma (n = 22), complex nodular hyperplasia (CNH, n = 9), sarcoma arising from benign complex nodular hyperplasia (n = 3), histiocytic sarcoma (n = 3), haemangiosarcoma (n = 1) and leiomyosarcoma (n = 1). Four samples were excluded from analysis due to extensive necrosis. An anti-podoplanin (PDPN) antibody was validated on canine tissue and used to assess expression of this protein as a potential indicator of the tissue of origin of the neoplasms (28/42 tumours were positive). There was a statistically significant difference in survival time between patients with stromal sarcoma (sarcoma from benign CNH and undifferentiated stromal sarcoma) and CNH (178 d versus 637 d, respectively; P = 0.027). Dogs with stromal sarcomas and high mitotic count (≥9 per 10 high-power fields) had a significantly shorter survival time (67 d versus 439 d; P = 0.01). Clinical diagnosis of splenic tumours should include evaluation for the presence of benign nodular hyperplasia morphology and immunohistochemistry to exclude more aggressive malignancies where adjuvant therapy is recommended. As in humans, PDPN may be an effective marker for stromal sarcomas of the canine spleen and immunopositivity suggests a fibroblastic reticular or follicular dendritic cell origin.

The Mare: A Pertinent Model for Human Assisted Reproductive Technologies?

Although there are large differences between horses and humans for reproductive anatomy, follicular dynamics, mono-ovulation, and embryo development kinetics until the blastocyst stage are similar. In contrast to humans, however, horses are seasonal animals and do not have a menstrual cycle. Moreover, horse implantation takes place 30 days later than in humans. In terms of artificial reproduction techniques (ART), oocytes are generally matured in vitro in horses because ovarian stimulation remains inefficient. This allows the collection of oocytes without hormonal treatments. In humans, in vivo matured oocytes are collected after ovarian stimulation. Subsequently, only intra-cytoplasmic sperm injection (ICSI) is performed in horses to produce embryos, whereas both in vitro fertilization and ICSI are applied in humans. Embryos are transferred only as blastocysts in horses. In contrast, four cells to blastocyst stage embryos are transferred in humans. Embryo and oocyte cryopreservation has been mastered in humans, but not completely in horses. Finally, both species share infertility concerns due to ageing and obesity. Thus, reciprocal knowledge could be gained through the comparative study of ART and infertility treatments both in woman and mare, even though the horse could not be used as a single model for human ART.

Female age and parity in horses: how and why does it matter?

Although puberty can occur as early as 14-15months of age, depending on breed and use, the reproductive career of mares may continue to advanced ages. Once mares are used as broodmares, they will usually produce foals once a year until they become unfertile, and their productivity can be enhanced and/or prolonged through embryo technologies. There is a general consensus that old mares are less fertile, but maternal age and parity are confounding factors because nulliparous mares are usually younger and older mares are multiparous in most studies. This review shows that age critically affects cyclicity, folliculogenesis, oocyte and embryo quality as well as presence of oviductal masses and uterine tract function. Maternal parity has a non-linear effect. Primiparity has a major influence on placental and foal development, with smaller foals at the first gestation that remain smaller postnatally. After the first gestation, endometrial quality and uterine clearance capacities decline progressively with increasing parity and age, whilst placental and foal birthweight and milk production increase. These combined effects should be carefully balanced when breeding mares, in particular when choosing and caring for recipients and their foals.

Contribution of Reproduction Management and Technologies to Genetic Progress in Horse Breeding.

Reproductive technologies aim at improving fertility with the ultimate result of improving genetic selection. In equidae, the respective contribution of different methods of horse management and breeding to genetic progress remain difficult to evaluate as breeding strategies affect the number of offspring per mare or stallion whereas different selection methods (based on pedigree, performance, genomics or progeny's performance) will be applicable at different ages, leading to different accuracy in the estimation of the breeding value. Here, a mathematical model was applied to evaluate theoretical genetic progress depending on breeding conditions in horses. The model showed that for breeding systems ranging from 0.6 to 2 foals/year/mare and from 10 to 150 foals/year for stallions, when selection of the best animals is strictly made by a truncation, the genetic progress is accelerated by (1) increasing the number of offspring per year, (2) the start of reproduction as soon as the age of 2 in both sexes, and (3) reducing the number of years of use for stallions from 10 to 5 years. The calculation showed that using all ways of improvement could provide an increase in genetic progress of up to +270% and +226% in mares and stallions, respectively, above the basal reference situation of 100%. In the Selle Français breed, the observed reproductive management parameters (10 years generation interval, 10 foals/stallion and 0.55 foals/mare) are close to the worst conditions of the model. In addition, the best mares are not selected for breeding. In conclusion, new reproductive technologies, genomic selection, and breeding younger animals will increase genetic gain.

Long-term T-DNA insert stability and transgene expression consistency in field propagated sugarcane.

KEY MESSAGE: This study addresses T-DNA insert stability and transgene expression consistency in multiple cycles of field propagated sugarcane. T-DNA inserts are stable; no transgene rearrangements were observed. AmCYAN1 and PMI protein accumulation levels were maintained. There was no evidence that production of either protein declined across generations and no transgene silencing was observed in three commercial sugarcane varieties through commercially relevant ratooning, propagation-by-setts, and micro-propagation generation processes over 4 years of field testing. Long term transgene expression consistency and T-DNA insert stability can be achieved in sugarcane, suggesting that it is highly probable that transgenic sugarcane can be successfully commercialized. This study addresses T-DNA insert stability and transgene expression consistency in multiple cycles of field propagated sugarcane. These data are critical supporting information needed for successful commercialization of GM sugarcane. Here seventeen transgenic events, containing the AmCYAN1 gene driven by a CMP promoter and the E. coli PMI gene driven by either a CMP or Ubi promoter, were used to monitor T-DNA insert stability and consistency of transgene encoded protein accumulation through commercially relevant ratooning, propagation-by-setts, and micro-propagation generation processes. The experiments were conducted in three commercial sugarcane varieties over 4 years of field testing. DNA gel blot analysis showed that the T-DNA inserts are stable; no transgene rearrangements were observed. Quantitative ELISA showed no evidence of decreasing AmCYAN1 and PMI protein levels across generations and no transgene silencing was observed. These results indicate that long term transgene expression consistency and T-DNA insert stability can be achieved in sugarcane, suggesting that it is highly probable that transgenic sugarcane can be successfully commercialized.

Nitrate and phosphate removal through enhanced bioretention media: mesocosm study.

Bioretention is an evolving type of Green Stormwater Infrastructure (GSI) designed to attenuate peak flows, reduce stormwater volume, and treat stormwater. This article examines the capabilities of a bioretention soil mixture of sand and compost enhanced with aluminum-based drinking water treatment residuals to reduce nutrients from stormwater runoff. Columns with and without a saturation zone and vegetation were compared to examine their role in removing nitrate and ortho-phosphate from stormwater. Results show that utilization of a saturation zone can significantly reduce nitrate in effluent water (71% compared to 33% without a saturated zone), even in a newly constructed system. However, ortho-phosphate reduction was significantly better in the columns without a saturated zone (80%) compared to columns with (67%). Plants did not significantly improve removal. This suggests amendments such as aluminum-based water treatment residuals for phosphorus removal and a saturation zone for nitrogen removal are needed during the initial establishment period.

Accuracy of digital subtraction angiography, computed tomography angiography, and magnetic resonance angiography in grading of carotid artery stenosis in comparison with actual measurement in an in vitro model.

BACKGROUND: The aim of this study was to investigate the accuracy of digital subtraction angiography (DSA), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) in grading of carotid stenosis compared with actual measurement in an in vitro model. METHODS: Various grades of stenosis were created by adhering different amounts of silicone rubber sealant onto the inner wall of clear, radiolucent tubes. After DSA, CTA, and MRA, the tubes were transected with 1-mm interval through the plaques. The cross-sectional areas were digitally photographed, and the percentage of area reduction of every single slide was measured with ImageJ planimetric software. The maximum actual area reduction (AAR) stenosis of each tube was recorded. The differences among DSA, CTA, MRA, and AAR were compared statistically using paired Student t test. RESULTS: Overall, CTA and MRA significantly underestimated the degrees of stenosis compared with AAR (P = 0.001 and P = 0.0009, respectively), and no significant difference was found between DSA and AAR (P = 0.40). In the subgroup with stenosis of <70%, there was no significant difference between DSA, CTA, and MRA versus AAR (P = 0.18, P = 0.16, and P = 0.08, respectively). In the subgroup with severe stenosis of >70%, CTA and MRA significantly underestimated the stenosis versus AAR (P = 0.004, and P = 0.007 respectively), and DSA significantly overestimated the stenosis (P = 0.0007). CONCLUSIONS: This in vitro model study demonstrated that CTA and MRA underestimate the lesions in severe stenosis of >70%. DSA tends to overestimate the disease. The accuracy of DSA is affected by plaque morphology, such as mountain-shaped lesions.

Creating a process to standardize regimen order sets within an electronic health record.

PURPOSE: US Oncology uses regimen order sets in clinical practice to treat patients. However, the process to assure accuracy and upkeep of these order sets has not been described. The purpose of this project was to evaluate the regimens housed in the electronic health record, iKnowMed, to determine their appropriateness and accuracy. MATERIALS AND METHODS: US Oncology conducted an audit of its standardized regimen library. A utilization review compared chemotherapy regimens in the library and consolidated order sets on the basis of past utilization. Next, internal and external clinical pharmacists were contracted to verify the accuracy, dose, duration, and cycle length of regimens. References cited in the regimen library were evaluated. New or updated references or clinical practice standards were added or modified when necessary. US Oncology corporate pharmacists reviewed the recommendations and discussed findings with an oversight committee. Final proposals were voted on before being incorporated into iKnowMed. An internal database tracking system tool for all reviewed recommendations was created to track and communicate needed changes to the electronic health record. RESULTS: Out of 511 regimen order sets, 51 were recommended for removal or consolidation. Of the remaining 460 regimen order sets, all had some administrative changes. Specifically, 75% had title changes, 14% had cycle-related changes, 31% had reference updates, and 13% had dosing updates. CONCLUSION: Electronic health records systems, such as iKnowMed, can provide standardized order sets for a large oncology network. However, the regimens need to be evaluated routinely using standardized procedures to ensure they are accurate and current.

Rhenium ethoxy- and hydroxycarbene complexes with thiophene substituents.

Reaction of mono- and dilithiated thiophene (a), bithiophene (b) and 2,5-dibromothiophene (c) with [Re(2)(CO)(10)] afforded, after subsequent alkylation with triethyloxonium tetrafluoroborate, tetra- and binuclear Fischer carbene complexes, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)X}], n = 1, X = H (1a); n = 2, X = H (1b); n = 1, X = Br (1c); n = 1, X = C(OEt)Re(2)(CO)(9), (2a); n = 2, X = C(OEt)Re(2)(CO)(9) (2b), as major products. The dirhenium acylate intermediates from this reaction not only gave the expected novel ethoxycarbene complexes with alkylation but after rhenium-rhenium bond breaking afforded a number of minor products. The (1)H NMR spectrum of the crude reaction mixture revealed the formation of four metal hydride complexes and aldehydes. Protonation with HBF(4) instead of alkylation with Et(3)OBF(4) significantly increased the yields of the hydride complexes, which enabled the positive identification of three of these complexes. In addition to the known compounds [Re(CO)(5)H] and [Re(3)(CO)(14)H] (3), a unique complex displaying a hydroxycarbene fragment connected to an acyl fragment via an O-H···O hydrogen bond and a Re···H···Re bond linking the two Re centers, [(µ-H){Re(CO)(4)C(OH){C(4)H(2)S}(n)H}{Re(CO)(4)C(O){C(4)H(2)S}(n)H}], n = 1 (4a) or n = 2 (4b), were isolated. The formation of thiophene aldehydes, H{C(O)}(m){C(4)H(2)S}(n)C(O)H (m = 0 or 1 and n = 1 or 2), were observed and the novel monocarbene complexes with terminal aldehyde groups, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)C(O)H}], n = 1 (5a) and n = 2 (5b) could be isolated. A higher yield of 5b was obtained after stirring crystals of 2b in wet THF. The crystal structures of 1a, 2a, 4a and 5b are reported.

Foliar washoff potential and simulated surface runoff losses of trifloxysulfuron in cotton.

The surface runoff potential of trifloxysulfuron {N-[(4,6-dimethoxy-2-pyrimidinyl)carbamoyl]-3-(2,2,2-trifluoroethoy)-pyridin-2-sulfonamide sodium salt} in cotton (Gossypium hirsutum L.) production systems has not been evaluated. The objectives of this study were to (i) determine sorption/desorption coefficients for trifloxysulfuron; (ii) quantify foliar washoff of trifloxysulfuron when applied to cotton at the five-leaf stage; and (iii) determine the surface runoff potential of trifloxysulfuron when applied to cotton at the five-leaf stage and to bare soil. Freundlich sorption and desorption coefficients were 1.15 and 1.22, respectively. Sorption data indicated that trifloxysulfuron was moderately sorbed to soil and that it will be transported primarily in the dissolved phase of surface runoff. Foliar washoff studies revealed that approximately 91% of trifloxysulfuron applied to cotton at the five-leaf stage was available for washoff 72 h after application. Simulated rainfall (7.5 cm h-1) applied 1 day after herbicide application (7.9 g ha-1) resulted in average concentrations of trifloxysulfuron in surface runoff water of 0.8 microg L-1 for bare plots and 1.3 microg L-1 for cotton plots. Cumulative trifloxysulfuron losses in surface runoff from bare plots and cotton plots were 0.13 and 0.21 g ha-1, respectively. These values correspond to fractional losses of 1.7% for bare plots and 2.7% for cotton plots. Greater runoff losses of trifloxysulfuron from cotton plots were attributed to foliar washoff. Trifloxysulfuron runoff losses may be curtailed if the herbicide is applied early postemergence when canopy coverage is minimal, thereby reducing the potential for foliar washoff.