(R)- and (S)-fluoxetine were found to be competitive inhibitors of P450 2D6-mediated bufuralol 1'-hydroxylation in vitro, yielding Ki values of 1.38 +/- 0.48 and 0.22 +/- 0.11 microM, respectively. ...Their N-demethylated metabolites were also found to be potent inhibitors (Ki, (R)-norfluoxetine, 1.48 +/- 0.27 microM; (S)-norfluoxetine, 0.31 +/- 0.04 microM). The microsomal (R)- and (S)-fluoxetine N-demethylase activities for 14 human liver samples were on average 29.6 +/- 13.5 and 19.4 +/- 11.8 pmol of product/min/mg of protein, respectively. The individual rates of N-demethylation correlated with microsomal immunodetectable P450 2D6 levels; (R)-fluoxetine, r = 0.64, P < .05; (S)-fluoxetine, r = 0.63, P < .05. However, this correlation was significantly weaker than the excellent correlation obtained for P450 2D6-marker bufuralol 1'-hydroxylase activity and P450 2D6 levels (r = 0.92, P < or = .01). Quinidine, a potent inhibitor of P450 2D6, inhibited the demethylation of each enantiomer by only approximately 20% at a concentration 300 times greater than the Ki determined for the quinidine inhibition of bufuralol 1'-hydroxylase. Furthermore, antiserum recognizing P450 2D6 inhibited 82% of microsomal bufuralol 1'-hydroxylase activity but only 27% of the (R)-fluoxetine N-demethylase activity in the same human liver sample. In summary, these data indicate that the enantiomers of fluoxetine and norfluoxetine are potent inhibitors of P450 2D6 and that P450 forms other than P450 2D6 appear to be responsible for the majority of microsomal fluoxetine N-demethylation.
•After familiarisation, captive cockatiels used substrates in trays as enrichment.•Wood shavings, earth and sand were preferred.•Water was little used and bathing was not observed.•The findings may ...be used to enrich the environment of cockatiels in aviaries.
Most research to enrich the environment of psittacines in captivity has focused on foraging. Little is known about the importance of bathing substrates for enrichment of their environment, despite this being a natural behaviour that is rarely possible in captivity. Twelve captive-bred, adult cockatiels (Nymphicus hollandicus) were housed in groups of four in three aviary replicates. An initial choice test determined preferences for different substrates: earth, sand, wood shavings, shallow and deep water. Each substrate was provided in trays on the floor, together with an empty tray as a control. Positions were rearranged daily following a Latin square design. No bathing behaviours were observed but wood shavings, earth and sand were visited most frequently. Shallow water and the control were visited less frequently than wood shavings, and deep water was visited less than any of the other treatments. Thus alternatives to water were chosen to test the effects of substrates on bird behaviour, in particular flying as the aim was to encourage the birds to visit the substrate. In a changeover design with three one-week periods the behaviour of cockatiels provided with wood shavings, earth or a control were compared. Birds in the Wood shaving and Earth treatments flew more to the ground, compared to the Control treatment. This was more often from the wall and faster in the case of the Wood shavings and more often from their perch in the Earth treatment. However, those in the Control treatment flew more from the perch to the wall, with no net difference in total flying. It is concluded that provision of wood shavings or earth will provide an alternative to flying from the perch to the wall, but did not otherwise affect the behaviour of the birds.
Abstract Study question What is PGT-AO’s impact on implantation and pregnancy rate per embryo transfer, by determining the prevalence and effect of (mosaic) aneuploidies and their segregational ...origin? Summary answer PGT-AO potentially enhances the efficiency of PGT and increases the pregnancy rate per embryo transfer by minimizing transfers with poor outcomes and improving implantation rates. What is known already Demographic factors such as advanced parental age increases risk of aneuploid offspring, driving demand for advanced PGT. Randomized controlled trials revealed that PGT-A does not increase live birth rates after IVF. PGT-A, the most frequent form of PGT, overlooks the mosaic nature and segregational origin of aneuploidies in IVF embryos. This possibly leads to avoiding the transfer of mosaic embryos and reduces the pregnancy rate per cycle. Prompting this study, five embryos transferred based on PGT-M, led to trisomic pregnancies terminated following invasive prenatal diagnosis. Subsequent genome haplarithmisis revealed that these embryos carried (meiotic) trisomies not previously detected by PGT-M. Study design, size, duration In this retrospective study, we included 1944 embryos (816 PGT-M embryos, 323 couples, 224 indications). Currently, 284 have been processed by genome haplarithmisis-based PGT-AO and analyzed to assess if (mosaic) aneuploidies and segregational origin would have altered transfer decisions and subsequent clinical outcomes. We evaluated our novel PGT- A approach, termed PGT-AO, providing a nuanced understanding of early embryonic development in clinical practice and more responsible PGT-A, potentially leading to viable mosaic embryo transfer. Participants/materials, setting, methods The couples were counseled by clinical geneticists at Dutch University Medical Centers (UMCs), in Maastricht, Amsterdam, Utrecht, and Groningen, and enrolled in the diagnostic PGT-M procedure after signing an informed consent form. Embryos (n = 816) eligible for transfer based on absence of the monogenic aberration of interest by PGT-M were analyzed by haplarithmisis-based PGT-AO including parental information. This information allows for the detection of (mosaic) chromosomal abnormalities and their parental and segregational origin. Main results and the role of chance Of 816 included embryos (323 couples, 224 indications), 284 were found to be suitable for transfer by PGT-M and were analyzed by PGT-AO. Of these, 183 were transferred. Of the transferred embryos, 65 (35.5%) had a positive HCG and 48 (26.3%) resulted in a liveborn. 14.6% (7/48) carried abnormalities following our PGT-AO approach. These abnormalities consisted of mitotic mosaic trisomies, mosaic monosomies, and mosaic duplications and a deletion. Of the transferred embryos, 132 (72.1%) did not result in a liveborn and 115 (62.8%) had negative HCG tests. Of the transferred embryos with negative HCG, 38.3% (44/115) contained a total of 90 abnormalities, consisting of 37 monosomies, 35 trisomies, 12 deletions, 2 duplications, 2 UPD and 1 ring chromosome. The 35 trisomies occurred in 20 embryos, of which 9 were of meiotic origin and 5 of mitotic origin, 1 of both meiotic and mitotic, and 5 could not be determined. Based on these preliminary results, PGT-AO can avoid the transfer of embryos with aneuploidy of meiotic origin and non-mosaic status. In contrast, embryos with aneuploidy of mitotic origin are often mosaic and the abnormality may not be uniformly distributed throughout the blastocyst and could potentially be considered for transfer. Limitations, reasons for caution Haplarithmisis relies on the inclusion of parental DNA to phase the embryonic genome and thus determine the segregational origin of aberrations. Additionally, mitosis and meiosis II trisomies cannot be discerned where a crossover event is absent for a chromosome with trisomy. Wider implications of the findings Implementation of PGT-AO will re-define the current embryo selection system. This enhances PGT by increasing pregnancy rate per embryo transfer and minimizing transfers with poor outcomes, disposal of potentially viable embryos, spontaneous pregnancy losses, and termination of aneuploid pregnancies. This reduces the emotional and financial burdens on families and healthcare. Trial registration number Not applicable
The giant Antarctic Octopus
Megaleledone setebos
is the largest Southern Ocean octopod whose ecology is poorly known. Here, we study ontogenetic shifts of habitat and trophic ecology of
M. setebos
...throughout its life cycle by stable isotopic analysis of
δ
13
C and
δ
15
N on its beaks collected from the diet of Antarctic toothfish in Amundsen and Ross Seas (Antarctica). Values of
δ
13
C (from − 24.3 to − 19.4‰) differed between beaks of individuals from different capture locations, thus reflecting the ability of
M. setebos
living in different habitats. Despite sequential sampling along beaks showed a small (< 2.3‰), but significant variation in lower beak’s
δ
13
C values, a relation with
δ
15
N values suggests that such differences are related to changes in the diet with
M. setebos
inhabiting the same area its entire life. Values of
δ
15
N differed between beaks of individuals from different capture locations, suggesting that different habitats of
M. setebos
are associated with different diets. Serial sampling along the beaks (from + 4.2 to + 10.7‰) suggests an ontogenetic change of, at least, one trophic level from juvenile to adult. We also report a capture of two large intact specimens from Dumont D’Urville Sea (Antarctica): a male with 1150 mm of total length and 18,300 g of mass and a female with 1030 mm of total length and 10,061 g of mass. The beaks of these both specimens, confirmed to be of
M. setebos
through genetic analysis, were also used to confirm the identification of
M. setebos
collected from Antarctic toothfish stomachs.
Context. Eta Carinae is a highly eccentric, massive binary system (semimajor axis ~15.5 au) with powerful stellar winds and a phase-dependent wind-wind collision (WWC) zone. The primary star, η Car ...A, is a luminous blue variable (LBV); the secondary, η Car B, is a Wolf-Rayet or O star with a faster but less dense wind. Aperture-synthesis imaging allows us to study the mass loss from the enigmatic LBV η Car. Understanding LBVs is a crucial step toward improving our knowledge about massive stars and their evolution. Aims. Our aim is to study the intensity distribution and kinematics of η Car’s WWC zone. Methods. Using the VLTI-MATISSE mid-infrared interferometry instrument, we perform Br α imaging of η Car’s distorted wind. Results. We present the first VLTI-MATISSE aperture-synthesis images of η Car A’s stellar windin several spectral channels distributed across the Br α 4.052 μm line (spectral resolving power R ~ 960). Our observations were performed close to periastron passage in February 2020 (orbital phase ~ 14.0022). The reconstructed iso-velocity images show the dependence of the primary stellar wind on wavelength or line-of-sight (LOS) velocity with a spatial resolution of 6 mas (~14 au). The radius of the faintest outer wind regions is ~26 mas (~60 au). At several negative LOS velocities, the primary stellar wind is less extended to the northwest than in other directions. This asymmetry is most likely caused by the WWC. Therefore, we see both the velocity field of the undisturbed primary wind and the WWC cavity. In continuum spectral channels, the primary star wind is more compact than in line channels. A fit of the observed continuum visibilities with the visibilities of a stellar wind CMFGEN model (CMFGEN is an atmosphere code developed to model the spectra of a variety of objects) provides a full width at half maximum fit diameter of the primary stellar wind of 2.84 ± 0.06 mas (6.54 ± 0.14 au). We comparethe derived intensity distributions with the CMFGEN stellar wind model and hydrodynamic WWC models.
To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of ...radiation therapy (RT) and/or chemotherapy.
Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen.
Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease.
(1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.
The purpose of this study was to examine intratester, interester, and interdevice reliability of range of motion measurements of the elbow and forearm. Elbow flexion and extension and forearm ...pronation and supination were measured on 38 subjects with elbow, forearm, or wrist disease by 5 testers. Standardized test methods and a randomized order of testing were used to test groups of patients with universal standard goniometers, a computerized goniometer, and a mechanical rotation measuring device. Intratester reliability was high for all 3 measuring devices. Meaningful changes in intratester range of motion measurements taken with a universal goniometer occur with 95% confidence if they are greater than 6° for flexion, 7° for extension, 8° for pronation, and 8° for supination. Intertester reliability was high for flexion and extension measurements with the computerized goniometer and moderate for flexion and extension measurements with the universal goniometer. Meaningful change in interobserver range of motion measurements was expected if the change was greater than 4° for flexion and 6° for extension with the computerized goniometer compared with 10° and 10°, respectively, if the universal goniometer was used. Intertester reliability was high for pronation and supination with all 3 devices. Meaningful change in forearm rotation is characterized by a minimum of 10° for pronation and 11° for supination with the universal goniometer. Reliable measurements of elbow and forearm arm movement are obtainable regardless of the level of experience when standardized methods are used. Measurement error was least for repeated measurements taken by the same tester with the same instrument and most when different instruments were used.
•Social media can reinforce hypes on agro-food sustainability issues.•Social media offer opportunities for the self-organization of food movements.•Social media generate data used for new forms of ...agro-food governance.•Social media form a new force and resource in the governance of agro-food.
Social media bring various stakeholders of the agro-food system together into a new playing field. This article reveals the dynamics of this playing field and the ways in which this can influence the governance of agro-food sustainability. We delineate three pathways that highlight the ways in which social media can have implications for the governance of agro-food sustainability; firstly, Hypes on agro-food sustainability issues, secondly, opportunities for the self-organization of food movements, and thirdly, data for new forms of agro-food governance. We conclude that while mass self-communication on social media forms an emergent force that disrupts agro-food governance, it also generates data that forms a resource for powerful players to regain control.
Aquatic ecosystem management requires knowledge of the links among landscape-level anthropogenic disturbances and aquatic ecosystem properties. With large catchment area to surface area ratios ...(CA:SA), reservoirs often receive substantial terrestrial subsidies and can be particularly sensitive to eutrophication. Reservoir numbers and attendant management problems are increasing, and tools are needed to categorize their eutrophication status. We analyzed a dataset of 109 reservoirs in Ohio (USA) in an effort to classify eutrophication status using landscape-level features and reservoir morphometry. These predictor variables were selected because they are relatively stable and easily measured. We employed regression tree analysis and used a composite eutrophication variable as our response variable. Our regression tree analysis accurately divided 67% of Ohio reservoirs into 4 eutrophication status groups using 3 predictor variables: percentage of catchment area composed of agriculture versus forest; maximum reservoir depth; and CA:SA. We can infer that reservoirs with catchments containing >71% forest will likely be oligotrophic to mesotrophic. For reservoirs with <71% catchment forest, trophic status is determined by the relative extent of catchment row crops and either CA:SA or maximum depth. We applied our regression tree to a subset of reservoirs in the Environmental Protection Agency's National Lakes Assessment (NLA; n = 339 reservoirs). With a few exceptions, we categorized NLA reservoirs by eutrophication status despite their broad geographical range across the contiguous USA. Our results show that a few easily measured, stable parameters can classify reservoir eutrophication status. Models like ours may be useful for broad-scale management decisions.
PDF
