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Background Metaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations. Methods We compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor. Results In our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA , AKT1 , BRAF , and FGFR4 . Conclusion The treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.

Alors que se généralise progressivement l’ouverture des services de réanimation aux visites 24 heures sur 24, la présence des enfants semble encore controversée. Les unités de réanimation chirurgicale du CHU de Caen ont décidé de mettre fin à cette politique restrictive de visites. Cependant, accompagner un enfant face à la mort ou à la maladie ne s’improvise pas. La présence de ce « petit visiteur » est particulièrement stressante pour les familles et les soignants. Elle nécessite donc un encadrement spécifique, plus complexe que celui de l’adulte. En réponse à ce besoin, les équipes de réanimation du CHU de Caen ont développé divers supports (livret et pièce d’accueil, box de réanimation miniature) pour accompagner les enfants et soutenir les équipes soignantes dans cette démarche.

Descriptive sampling is based on a deterministic selection of the input sample values and their random permutation. Descriptive sampling refined is concerned with a block of descriptive samples of prime size. The latter reduces the sampling bias introduced by descriptive sampling and eliminates the problem of descriptive sampling related to the sample size. This paper compares the performance measures, in terms of precision of the estimates for three sampling methods: random sampling, descriptive sampling and refined descriptive sampling. The comparison was made for a production system of the flowshop type by discrete event simulation method.[PUBLICATION ABSTRACT]

The efficacy of foliar sprays with compost water extracts (compost extracts) in reducing the severity of bacterial spot of tomato caused by Xanthomonas vesicatoria was investigated. Extracts prepared from composted cow manure, composted pine bark, an organic farm compost, or composted yard waste, applied as foliar sprays on tomato transplants, resulted in a moderate but statistically significant reduction in the severity of bacterial spot. The population of X. vesicatoria in infected leaves was reduced significantly by extracts prepared from composted cow manure. Efficacy of the water extracts was not affected by oxygen concentrations in the suspension during extraction, compost maturity, or sterilization by filtration or autoclaving. The degree of control provided by foliar sprays with the most effective compost extracts did not differ from that obtained with the plant activator acibenzolar-S-methyl. In the field in two growing seasons, foliar sprays with compost water extracts did not reduce the severity of foliar diseases, including bacterial spot. During the 1997 season, when the severity of bacterial spot in the field was high, foliar sprays with compost water extracts significantly reduced the incidence of bacterial spot on tomato fruit. Amending plot soil with several rates of composted yard waste did not lead to additional control of fruit disease over those only sprayed with extracts. Foliar sprays with a mixture of chlorothalonil and copper hydroxide or with acibenzolar-S-methyl reduced the severity of bacterial spot as well as incidence of spot on fruit.

Recently, there has been a rise in the incidence of neonatal infections among babies born with low birth-weights and under-developed immune systems in neonatal intensive care units (NICUs). There are several risk factors to neonatal infection, the most important of which include the use of medical devices such as nasogastric enteral feeding tubes (NEFTs) and through contamination of infant feeding formula. Therefore, bacterial analysis of feeding tubes used in the NICU is important to identify infection risk factors during neonatal enteral feeding.The aims of this study were (a) to determine the potential risk to neonates posed by ingestion of A. baumannii and Enterobacter spp., in particular E. hormaechei either through feeding tubes, infant formula, or by contaminated milk, (b) to determine whether some of the isolated strains originate from common sources, such as being transferred between the babies within specific neonatal units. Additionally, a longitudinal study for premature twin babies aimed to compare potentially pathogenic E. faecium isolates within and between the feeding tubes and faeces of twin babies over time.PFGE indicated that all of the A. baumannii strains formed two different STs (ST193 and ST113). All ST113 strains were multidrug-resistant and demonstrated an ability to form significant biofilms at 37 °C in infant formula. Tolerance of acidic conditions, desiccation, resistance to human serum and persistence inside macrophages were shown by the majority of strains tested. E. hormaechei strains from feeding tubes exhibited similar behaviour to those isolated from sepsis cases, since both were able to adhere to and invade Caco-2 and HBMEC cell lines. Also, these strains were able to persist and replicate inside macrophages for up to 72 hours.In the longitudinal study, all isolates of E. faecium isolated from preterm infant twins during their hospitalisation in the NICU were typed as ST80, belonging to clonal complex CC17. Furthermore, they were resistant to ampicillin and were found to carry several virulence-associated genes such as esp. All of these strains were found to be essentially the same strain based on their sequence type and genomic analysis and were shown to have high pathogenic potential. These strains isolated from different neonatal locations were indeed the same clone, showing that the bacteria were able to persist and be transferred between the two premature infants in the NICU.This study has provided evidence of colonisation and persistence of opportunistic ESKAPE group pathogens in neonatal feeding tubes, which are important causes of nosocomial infection and dissemination of multidrug-resistant (MDR) strains.

We introduce and study the notions of hyperbolically embedded and very rotating families of subgroups. The former notion can be thought of as a generalization of the peripheral structure of a relatively hyperbolic group, while the latter one provides a natural framework for developing a geometric version of small cancellation theory. Examples of such families naturally occur in groups acting on hyperbolic spaces including hyperbolic and relatively hyperbolic groups, mapping class groups,

Fifty-five organizations in which decision support systems (dss) are used were surveyed to determine how they are supporting dss activity. The findings provide insights about the extent to which dss activity is being supported, which organizational units are providing support, the types and frequency of support provided, the organizational units and management levels that receive support and how often it is provided, and the perceived quality of the support. Typically, dss support is available through between one and four locations in an organization. Personnel working at different levels in their organizations and in different functional areas have distinct patterns of use of dss support services.

The surge in economic and human development has led to increasing concerns about environmental degradation, thus necessitating effective strategies to enhance sustainability and environmental quality. Therefore, this study empirically examines the impact of environmental fiscal policies, environmental technologies, and research and development (R&D) expenditures on achieving environmental sustainability in the G7 countries. Using advanced econometric techniques, including the Cross-Sectionally Augmented Autoregressive Distributed Lags (CS-ARDL) model and the Dynamic Common Correlated Effects (DCCE) approach, the study identifies both short-run and long-run correlations between the aforementioned variables and their impact on greenhouse gas (GHG) emissions. Our findings confirm the inverted U-shaped Kuznets Curve relationship and reinforce the previous literature on the complex dynamics between economic growth and GHG emissions specific to developed countries. The research also supports the effectiveness of well-designed environmental taxes in reducing environmental degradation and GHG emissions, consistent with and extending existing studies in this area. In addition, the study provides empirical evidence of the critical role of environmental technologies and targeted R&D expenditures in improving environmental quality. In terms of policy implications, our research underscores the urgency for policymakers in the G7 countries to fine-tune environmental taxation mechanisms and increase investment in sustainable technological solutions. Specific recommendations include the development of more efficient tax systems that adhere to the polluter-pays principle, as well as financial incentives such as tax credits and subsidies aimed at accelerating green technology adoption and innovation. In doing so, the study seeks to contribute to the broader discourse on environmental policy and sustainable development, providing valuable perspectives for both the academic community and policy actors.

Global Positioning System (GPS) navigation devices and applications have become ubiquitous over the last decade. However, it is unclear whether using GPS affects our own internal navigation system, or spatial memory, which critically relies on the hippocampus. We assessed the lifetime GPS experience of 50 regular drivers as well as various facets of spatial memory, including spatial memory strategy use, cognitive mapping, and landmark encoding using virtual navigation tasks. We first present cross-sectional results that show that people with greater lifetime GPS experience have worse spatial memory during self-guided navigation, i.e. when they are required to navigate without GPS. In a follow-up session, 13 participants were retested three years after initial testing. Although the longitudinal sample was small, we observed an important effect of GPS use over time, whereby greater GPS use since initial testing was associated with a steeper decline in hippocampal-dependent spatial memory. Importantly, we found that those who used GPS more did not do so because they felt they had a poor sense of direction, suggesting that extensive GPS use led to a decline in spatial memory rather than the other way around. These findings are significant in the context of society’s increasing reliance on GPS.

Efficient interconversion of both classical and quantum information between microwave and optical frequency is an important engineering challenge. The optomechanical approach with gigahertz-frequency mechanical devices has the potential to be extremely efficient due to the large optomechanical response of common materials, and the ability to localize mechanical energy into a micron-scale volume. However, existing demonstrations suffer from some combination of low optical quality factor, low electrical-to-mechanical transduction efficiency, and low optomechanical interaction rate. Here we demonstrate an on-chip piezo-optomechanical transducer that systematically addresses all these challenges to achieve nearly three orders of magnitude improvement in conversion efficiency over previous work. Our modulator demonstrates acousto-optic modulation with V π = 0.02 V. We show bidirectional conversion efficiency of 1 0 − 5 with 3.3 μW  red-detuned optical pump, and 5.5 % with 323 μW blue-detuned pump. Further study of quantum transduction at millikelvin temperatures is required to understand how the efficiency and added noise are affected by reduced mechanical dissipation, thermal conductivity, and thermal capacity. Current optomechanical implementations of microwave and optical frequency interconversion are lacking in efficiency and interaction strength. The authors design and demonstrate an on-chip piezo-optomechanical solution which overcomes several technical barriers to reach several orders of magnitude improvement in efficiency.