The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO(2)) of mannitol and hypertonic saline (HTS) in ...patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension.
12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO(2) monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO(2), ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously.
42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO(2) (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO(2) (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output.
In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.
Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, widely used as an anesthetic in neonatal pediatrics, is also an illicit drug named Super K or KitKat consumed by teens and young ...adults. In the immature brain, despite several studies indicating that NMDA antagonists are neuroprotective against excitotoxic injuries, there is more and more evidence indicating that these molecules exert a deleterious effect by suppressing a trophic function of glutamate. In the present study, we show using Gad67-GFP mice that prenatal exposure to ketamine during a time-window in which GABAergic precursors are migrating results in (i) strong apoptotic death in the ganglionic eminences and along the migratory routes of GABAergic interneurons; (ii) long-term deficits in interneuron density, dendrite numbers and spine morphology; (iii) a sex-dependent deregulation of γ-aminobutyric acid (GABA) levels and GABA transporter expression; (iv) sex-dependent changes in the response to glutamate-induced calcium mobilization; and (v) the long-term sex-dependent behavioral impairment of locomotor activity. In conclusion, using a preclinical approach, the present study shows that ketamine exposure during cortical maturation durably affects the integration of GABAergic interneurons by reducing their survival and differentiation. The resulting molecular, morphological and functional modifications are associated with sex-specific behavioral deficits in adults. In light of the present data, it appears that in humans, ketamine could be deleterious for the development of the brain of preterm neonates and fetuses of addicted pregnant women.
Integrated circuits (ICs) are a keystone for most critical applications operating in high-level radiation environments, spanning from high-energy nuclear applications up to space applications. The ...long-term reliability of these applications is essential for safe operation. However, the radiation effects for ICs are commonly investigated using fresh circuits, leaving the coupled effect of radiation and aging degradation unknown. This article investigates the impact of negative bias temperature instability (NBTI) aging degradation mechanism on the heavy-ion single event upset (SEU) radiation susceptibility of 28-nm ultra-thin body and buried oxide (UTBB) fully depleted silicon on insulator (FD-SOI) technology using a custom-designed test vehicle. NBTI aging degradation mechanism has been experimentally proven to increase the SEU sensitivity up to <inline-formula> <tex-math notation="LaTeX">2\times </tex-math></inline-formula> for 28-nm UTBB FD-SOI flip-flops. A comprehensive framework is presented to analyze the underlying mechanisms for the impact of NBTI, which includes NBTI aging mechanism modeling, SEU SPICE simulation, TCAD irradiation simulation, and Monte-Carlo simulation of radiation effects. The framework offered a quantitative prediction of the effect of NBTI degradation mechanism on the heavy-ion SEU radiation sensitivity.
This study aimed to determine whether powdery mildew caused by Blumeria graminis is an endemic pathogen of triticale (×Triticosecale: Triticum × Secale), emerging as a result of recent changes in its ...pathogenicity, or whether it is a new pathogen, possibly resulting from hybridization between ff. spp. tritici and secalis. A secondary aim was to consider breeding practices that may have favoured this emergence. Phylogenetic analyses based upon six genes revealed the close relatedness of the novel entity and the ff. spp. tritici and secalis, but the IGS marker finally grouped together the isolates collected on triticale and on wheat, supporting the scenario of a recent host-range expansion from wheat to triticale. Pathotype analyses concluded that virulence spectra of B. graminis infecting triticale were new in comparison to those observed for other reference formae speciales, and lack of fungicide resistance in triticale isolates strengthens the hypothesis of no or little genetic exchange between wheat and triticale populations of powdery mildew. This adaptation may follow the breakdown of plant resistance genes, which are probably not very diverse in current triticale cultivars since this criterion was not considered as a major one until recent years. Moreover, the complex selection and genetics of this hybrid cereal makes it difficult to predict the transmission of powdery mildew resistance genes.
III–V nanostructures have the potential to revolutionize optoelectronics and energy harvesting. For this to become a reality, critical issues such as reproducibility and sensitivity to defects should ...be resolved. By discussing the optical properties of molecular beam epitaxy (MBE) grown GaAs nanomembranes we highlight several features that bring them closer to large scale applications. Uncapped membranes exhibit a very high optical quality, expressed by extremely narrow neutral exciton emission, allowing the resolution of the more complex excitonic structure for the first time. Capping of the membranes with an AlGaAs shell results in a strong increase of emission intensity but also in a shift and broadening of the exciton peak. This is attributed to the existence of impurities in the shell, beyond MBE-grade quality, showing the high sensitivity of these structures to the presence of impurities. Finally, emission properties are identical at the submicron and submillimeter scale, demonstrating the potential of these structures for large scale applications.
Steroid-induced ocular hypertension (OHT) occurs in approximately one third of cases after dexamethasone implant (DEXi) injection. Among these, more than one fifth occur after the third DEXi ...intravitreal injection (IVI). Our goal was to analyze the clinical profiles of these late responders.
A real-life, retrospective, observational study was conducted to assess demographic characteristics and intraocular pressure (IOP) responses in late responders (IOP ≥ 21mmHg, n DEXi ≥ 4). The following parameters were analyzed: IOP 2 months after IVI and number of glaucoma medications needed. The IOP response compared to baseline was defined as low (< +6mmHg), moderate (≤ +15mmHg) or high (> 15mmHg).
Late steroid-induced OHT occurred in 20.8% of cases. Twenty eyes (18 patients) were included. The mean duration of follow-up was 3.8±1.9 years. They received a mean number of 9.5±4.2 IVI. The first OHT peak, measured at 25.3±3.2mmHg (21-31), occurred after 6.8±2.3 IVI. Approximately 65% of OHT spikes occurred between the fourth and sixth IVI; 35% occurred later. At maximum, 1.7±1.0 glaucoma medications and 0.75±0.79 SLT procedures were required to control the OHT, with no filtering surgery required. The ratio of "low," "moderate," and "high" responders was 5%, 85% and 10% respectively.
Late steroid-induced OHT occurs after at least 3 DEXi in one fifth of multi-injected patients, requiring long-term IOP monitoring. This case series identifies mostly moderate responder profiles, whose IOP rise often remains well-controlled with medical management or laser treatment (SLT).
The grey mould fungus Botrytis cinerea causes losses of commercially important fruits, vegetables and ornamentals worldwide. Fungicide treatments are effective for disease control, but bear the risk ...of resistance development. The major resistance mechanism in fungi is target protein modification resulting in reduced drug binding. Multiple drug resistance (MDR) caused by increased efflux activity is common in human pathogenic microbes, but rarely described for plant pathogens. Annual monitoring for fungicide resistance in field isolates from fungicide-treated vineyards in France and Germany revealed a rapidly increasing appearance of B. cinerea field populations with three distinct MDR phenotypes. All MDR strains showed increased fungicide efflux activity and overexpression of efflux transporter genes. Similar to clinical MDR isolates of Candida yeasts that are due to transcription factor mutations, all MDR1 strains were shown to harbor activating mutations in a transcription factor (Mrr1) that controls the gene encoding ABC transporter AtrB. MDR2 strains had undergone a unique rearrangement in the promoter region of the major facilitator superfamily transporter gene mfsM2, induced by insertion of a retrotransposon-derived sequence. MDR2 strains carrying the same rearranged mfsM2 allele have probably migrated from French to German wine-growing regions. The roles of atrB, mrr1 and mfsM2 were proven by the phenotypes of knock-out and overexpression mutants. As confirmed by sexual crosses, combinations of mrr1 and mfsM2 mutations lead to MDR3 strains with higher broad-spectrum resistance. An MDR3 strain was shown in field experiments to be selected against sensitive strains by fungicide treatments. Our data document for the first time the rising prevalence, spread and molecular basis of MDR populations in a major plant pathogen in agricultural environments. These populations will increase the risk of grey mould rot and hamper the effectiveness of current strategies for fungicide resistance management.
A novel highly flexible mixer-based ultra-wideband (UWB) pulse generator is designed. The baseband pulse generator has a controllable pulse width between 200 ps and 8 ns, while the output amplitude ...only varies over 80 mV in this entire range. The mixer is adjustable so that the voltage controlled oscillator leakage can be controlled and minimised. The proposed architecture gives a highly flexible UWB pulse generator for which the characteristics can be adjusted to fit the specifications of different applications and the spectral mask of the country/region of usage.
Radiation-hardening techniques can be extensively used in the design level to improve the robustness of very large-scale integration (VLSI) circuits used in space applications. Accordingly, this work ...analyzes the efficiency of transistor folding layout in improving the single-event transient (SET) robustness of digital circuits. Additionally, diffusion splitting is proposed to reduce the area overhead of multiple-finger designs. Besides increasing threshold linear energy transfer, results show that both techniques can also reduce the overall cross section and the in-orbit SET rate for protons and heavy ions in low-earth orbit (LEO) and international space station (ISS) orbits.
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