Summary Sensitivity and specificity of the modified Duke criteria for native valve endocarditis are both suboptimal, at approximately 80%. Diagnostic accuracy for intracardiac prosthetic ...material-related infection is even lower. Non-invasive imaging modalities could potentially improve diagnosis of infective endocarditis; however, their diagnostic value is unclear. We did a systematic literature review to critically appraise the evidence for the diagnostic performance of these imaging modalities, according to PRISMA and GRADE criteria. We searched PubMed, Embase, and Cochrane databases. 31 studies were included that presented original data on the performance of electrocardiogram (ECG)-gated multidetector CT angiography (MDCTA), ECG-gated MRI,18 F-fluorodeoxyglucose (18 F-FDG) PET/CT, and leucocyte scintigraphy in diagnosis of native valve endocarditis, intracardiac prosthetic material-related infection, and extracardiac foci in adults. We consistently found positive albeit weak evidence for the diagnostic benefit of18 F-FDG PET/CT and MDCTA. We conclude that additional imaging techniques should be considered if infective endocarditis is suspected. We propose an evidence-based diagnostic work-up for infective endocarditis including these non-invasive techniques.
Natural sensory environments, despite strong potential for structuring systems, have been neglected in ecological theory. Here, we test the hypothesis that intense natural acoustic environments shape ...animal distributions and behavior by broadcasting whitewater river noise in montane riparian zones for two summers. Additionally, we use spectrally-altered river noise to explicitly test the effects of masking as a mechanism driving patterns. Using data from abundance and activity surveys across 60 locations, over two full breeding seasons, we find that both birds and bats avoid areas with high sound levels, while birds avoid frequencies that overlap with birdsong, and bats avoid higher frequencies more generally. We place 720 clay caterpillars in willows, and find that intense sound levels decrease foraging behavior in birds. For bats, we deploy foraging tests across 144 nights, consisting of robotic insect-wing mimics, and speakers broadcasting bat prey sounds, and find that bats appear to switch hunting strategies from passive listening to aerial hawking as sound levels increase. Natural acoustic environments are an underappreciated niche axis, a conclusion that serves to escalate the urgency of mitigating human-created noise.
Introduction
The treatment with long-acting injectable antipsychotics (LAIAs) is more and more frequent and it shows advantages regarding adherence, effectiveness and tolerance.
Objectives
To ...describe and compare the profile of patients under treatment with LAIAs in a psychiatric hospital in Portugal.
Methods
An observational and retrospective study was carried out with the collection of data referring to patients hospitalized with a first psychotic episode between 01/01/2019 and 30/06/2022 in a psychiatric hospital in Portugal and the respective evaluation of sociodemographic and clinical data through the information recorded in the clinical files.
Results
During the 42 months of the study, we selected 78 patients who presented psychotic symptoms on admission. Patients with a history of previous psychotic episodes and prescription of antipsychotic therapy prior to hospitalization were excluded.
Of 78 patients hospitalized with a first psychotic episode, 34 - which corresponds to approximately 44% - were discharged with LAIAs.
Patients receiving LAIAs had an average age of 39 years. The average number of days of hospitalization was 28 days; 41% were female (n=14) and 59 were male (n=20); 35% (n=12) consumed psychoactive substances previously on admission to hospital; 62% (n=21) were discharged under the compulsive treatment regimen. Regarding the diagnosis at discharge, based on the international classification of disease-11 (ICD-11), the most common were schizophrenia, psychotic disorder induced by psychoactive substances and acute and transient psychotic disorder.
From the statistical analysis carried out, no correlation was observed between the rate of readmissions and the administration of LAIAs, nor was there any correlation between the rate of readmissions and compulsive outpatient treatment.
Conclusions
Despite what is described in the literature, in the sample under study, the LAIAs were not superior in the variables studied, namely in reducing the readmission rate. Possible explanations for the results obtained may be justified by the size of the sample under study and the follow-up time of the cases.
Disclosure of Interest
None Declared
FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic ...fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated β-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7Tax(R) cells. KIF20A depletion also renders MCF-7 and MCF-7Tax(R) cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.
We present scattered light images of the TW Hya disk performed with the Spectro-Polarimetric High-contrast Exoplanet REsearch instrument in Polarimetric Differential Imaging mode at 0.63, 0.79, 1.24, ...and 1.62 m. We also present H2/H3-band angular differential imaging (ADI) observations. Three distinct radial depressions in the polarized intensity distribution are seen, around 85, 21, and 6 au.21 The overall intensity distribution has a high degree of azimuthal symmetry; the disk is somewhat brighter than average toward the south and darker toward the north-west. The ADI observations yielded no signifiant detection of point sources in the disk. Our observations have a linear spatial resolution of 1-2 au, similar to that of recent ALMA dust continuum observations. The sub-micron-sized dust grains that dominate the light scattering in the disk surface are strongly coupled to the gas. We created a radiative transfer disk model with self-consistent temperature and vertical structure iteration and including grain size-dependent dust settling. This method may provide independent constraints on the gas distribution at higher spatial resolution than is feasible with ALMA gas line observations. We find that the gas surface density in the "gaps" is reduced by 50% to 80% relative to an unperturbed model. Should embedded planets be responsible for carving the gaps then their masses are at most a few 10 . The observed gaps are wider, with shallower flanks, than expected for planet-disk interaction with such low-mass planets. If forming planetary bodies have undergone collapse and are in the "detached phase," then they may be directly observable with future facilities such as the Mid-Infrared E-ELT Imager and Spectrograph at the E-ELT.
Reaction of (XA
2
)U(CH
2
SiMe
3
)
2
(
1
; XA
2
= 4,5-bis(2,6-diisopropylanilido)-2,7-di-
tert
-butyl-9,9-dimethylxanthene) with 1 equivalent of Ph
3
CB(C
6
F
5
)
4
in arene solvents afforded the ...arene-coordinated uranium alkyl cations, (XA
2
)U(CH
2
SiMe
3
)(η
n
-arene)B(C
6
F
5
)
4
{arene = benzene (
2
), toluene (
3
), bromobenzene (
4
) and fluorobenzene (
5
)}. Compounds
2
,
3
, and
5
were crystallographically characterized, and in all cases the arene is π-coordinated. Solution NMR studies of
2-5
suggest that the binding preferences of the (XA
2
)U(CH
2
SiMe
3
)
+
cation follow the order: toluene benzene > bromobenzene > fluorobenzene. Compounds
2-4
generated in C
6
H
5
R (R = H, Me or Br, respectively) showed no polymerization activity under 1 atm of ethylene. By contrast,
5
and
5-Th
(the thorium analogue of
5
) in fluorobenzene at 20 and 70 °C achieved ethylene polymerization activities between 16 800 and 139 200 g mol
−1
h
−1
atm
−1
, highlighting the extent to which common arene solvents such as toluene can suppress ethylene polymerization activity in sterically open f-element complexes. However, activation of (XA
2
)An(CH
2
SiMe
3
)
2
{M = U (
1
) or Th (
1-Th
)} with Ph
3
CB(C
6
F
5
)
4
in
n
-alkane solvents did not afford an active polymerization catalyst due to catalyst decomposition, illustrating the critical role of PhX (X = H, Me, Br or F) coordination for alkyl cation stabilization. Gas phase DFT calculations, including fragment interaction calculations with energy decomposition and ETS-NOCV analysis, were carried out on the cationic portion of
2′-Th
,
2′
,
3′
and
5′
(analogues of
2-Th
,
2
,
3
and
5
with hydrogen atoms in place of ligand backbone methyl and
tert
-butyl groups), providing insight into the nature of actinide-arene bonding, which decreases in strength in the order
2′-Th
>
2′
3′
>
5′
.
Uranium(
iv
) alkyl cations have been prepared, and arene solvent coordination was shown to have a major impact on ethylene polymerization activity. Actinide-arene binding was studied experimentally in the solid state and solution, and computationally.
FOXM1 is implicated in genotoxic drug resistance but its mechanism of action remains elusive. We show here that FOXM1-depletion can sensitize breast cancer cells and mouse embryonic fibroblasts ...(MEFs) into entering epirubicin-induced senescence, with the loss of long-term cell proliferation ability, the accumulation of γH2AX foci, and the induction of senescence-associated β-galactosidase activity and cell morphology. Conversely, reconstitution of FOXM1 in FOXM1-deficient MEFs alleviates the accumulation of senescence-associated γH2AX foci. We also demonstrate that FOXM1 regulates NBS1 at the transcriptional level through an forkhead response element on its promoter. Like FOXM1, NBS1 is overexpressed in the epirubicin-resistant MCF-7Epi(R) cells and its expression level is low but inducible by epirubicin in MCF-7 cells. Consistently, overexpression of FOXM1 augmented and FOXM1 depletion reduced NBS1 expression and epirubicin-induced ataxia-telangiectasia mutated (ATM)phosphorylation in breast cancer cells. Together these findings suggest that FOXM1 increases NBS1 expression and ATM phosphorylation, possibly through increasing the levels of the MRN(MRE11/RAD50/NBS1) complex. Consistent with this idea, the loss of P-ATM induction by epirubicin in the NBS1-deficient NBS1-LBI fibroblasts can be rescued by NBS1 reconstitution. Resembling FOXM1, NBS1 depletion also rendered MCF-7 and MCF-7Epi(R) cells more sensitive to epirubicin-induced cellular senescence. In agreement, the DNA repair-defective and senescence phenotypes in FOXM1-deficent cells can be effectively rescued by overexpression of NBS1. Moreover, overexpression of NBS1 and FOXM1 similarly enhanced and their depletion downregulated homologous recombination (HR) DNA repair activity. Crucially, overexpression of FOXM1 failed to augment HR activity in the background of NBS1 depletion, demonstrating that NBS1 is indispensable for the HR function of FOXM1. The physiological relevance of the regulation of NBS1 expression by FOXM1 is further underscored by the strong and significant correlation between nuclear FOXM1 and total NBS1 expression in breast cancer patient samples, further suggesting that NBS1 as a key FOXM1 target gene involved in DNA damage response, genotoxic drug resistance and DNA damage-induced senescence.
Vascular endothelial growth factor (VEGF) has a central role in breast cancer development and progression, but the mechanisms that control its expression are poorly understood. Breast cancer tissue ...microarrays revealed an inverse correlation between the Forkhead transcription factor Forkhead box class O (FOXO)3a and VEGF expression. Using the lapatinib-sensitive breast cancer cell lines BT474 and SKBR3 as model systems, we tested the possibility that VEGF expression is negatively regulated by FOXO3a. Lapatinib treatment of BT474 or SKBR3 cells resulted in nuclear translocation and activation of FOXO3a, followed by a reduction in VEGF expression. Transient transfection and inducible expression experiments showed that FOXO3a represses the proximal VEGF promoter, whereas another Forkhead member, FOXM1, induces VEGF expression. Chromatin immunoprecipitation and oligonucleotide pull-down assays showed that both FOXO3a and FOXM1 bind a consensus Forkhead response element (FHRE) in the VEGF promoter. Upon lapatinib stimulation, activated FOXO3a displaces FOXM1 bound to the FHRE before recruiting histone deacetylase 2 (HDAC2) to the promoter, leading to decreased histones H3 and H4 acetylation, and concomitant transcriptional inhibition of VEGF. These results show that FOXO3a-dependent repression of target genes in breast cancer cells, such as VEGF, involves competitive displacement of DNA-bound FOXM1 and active recruitment of transcriptional repressor complexes.
In isolated microgrids and remote regions, the challenge of developing reliable and self-sufficient renewable energy systems is amplified due to the lack of grid flexibility options. One of the ...leading solutions to increase renewable energy usage in isolated systems is the commission of energy storage. The current study proposes a novel optimization model that sizes the most cost-efficient renewable power capacity mix of an autonomous microgrid supported by storage technologies. The proposed algorithm considers operational, technical and land-use constraints. The problem is formulated using linear programming, is tested and scrutinized with sets of historical weather, load demand and installation prices data, and is modelled hour-by-hour. The method is applied to Corvo, an island in the Azores archipelago, Portugal. The results obtained exhibit that the proposed approach provides the optimal configuration of the renewable-based microgrid with an LCOE (Levelized Cost of electricity) of 0.21 €/kWh, a value lower than a diesel-based alternative, and while ensuring minimum land area occupation. Furthermore, sensitivity analysis is also presented to examine the effect of variables on the LCOE and PC (present cost) of the system. The present study shows that the developed optimal sizing model can improve electricity planning and facilitate energy transition in distributed power systems.
Abstract
We use data from five stellar occultations observed between 2013 and 2016 to constrain Chariklo’s size and shape, and the ring reflectivity. We consider four possible models for Chariklo ...(sphere, Maclaurin spheroid, triaxial ellipsoid, and Jacobi ellipsoid), and we use a Bayesian approach to estimate the corresponding parameters. The spherical model has a radius
R
= 129 ± 3 km. The Maclaurin model has equatorial and polar radii
and
, respectively, with density
. The ellipsoidal model has semiaxes
,
, and
. Finally, the Jacobi model has semiaxes
a
= 157 ± 4 km,
b
= 139 ± 4 km, and
c
= 86 ± 1 km, and density
. Depending on the model, we obtain topographic features of 6–11 km, typical of Saturn icy satellites with similar size and density. We constrain Chariklo’s geometric albedo between 3.1% (sphere) and 4.9% (ellipsoid), while the ring
I
/
F
reflectivity is less constrained between 0.6% (Jacobi) and 8.9% (sphere). The ellipsoid model explains both the optical light curve and the long-term photometry variation of the system, giving a plausible value for the geometric albedo of the ring particles of 10%–15%. The derived mass of Chariklo of 6–8 × 10
18
kg places the rings close to 3:1 resonance between the ring mean motion and Chariklo’s rotation period.
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