Objectives
We aimed to assess HIV symptoms from the perspective of both patients and HIV specialists and the impact of discontinuing antiretroviral treatment (ART) on symptomology. We gathered ...opinions from HIV specialists and people living with HIV about ideal ART parameters and treatment satisfaction.
Methods
Ex post‐facto cross‐sectional surveys were administered to 502 people living with HIV and 101 HIV clinicians in Spain (18 sites).
Results
The median age of participants with HIV was 43.2 years, 74.5% were male, and 91.6% had an undetectable viral load. The mean time since initiation of ART was 10.2 years. Between 54% and 67% of people living with HIV reported experiencing nervousness or anxiety, sadness, fatigue, sleep problems, or muscle/joint pain during the preceding 4 weeks. However, only 22%–27% of specialists acknowledged the presence of these symptoms. The most bothersome symptoms were related to mental health or the central nervous system. There were significant differences between the burden of symptoms reported by people living with HIV and those acknowledged by specialists. The symptoms that more frequently caused ART discontinuation were depression, dizziness, and sleep problems. Both people living with HIV and specialists prioritized ART efficacy and low toxicity, but their importance ratings differed for 5 of the 11 ART characteristics assessed. People living with HIV rated their satisfaction with ART at a mean (± standard deviation) of 8.9 ± 1.5 out of 10, whereas HIV specialists rated it lower, at 8.3 ± 0.7 (p < 0.001).
Conclusions
Despite advances in HIV care and treatment, a large proportion of patients still experience symptoms. HIV specialists may not be fully aware of these. People living with HIV and HIV specialists are, overall, satisfied with ART. However, the importance they place on different ART characteristics may vary.
Over the past few decades, the life expectancy of people living with HIV has markedly improved due to the advances in HIV diagnosis, linkage to care, and treatment. However, with these advances, a ...new set of challenges has emerged that must be addressed to ensure the long‐term well‐being of people living with HIV. In this article, as part of a wider journal supplement, we explore the unmet needs and challenges across the HIV continuum of care and re‐define what long‐term success looks like to support the healthy ageing of all people affected by HIV.
Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. ...Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus.
We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition.
Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus.
The objective of this work is the evaluation of the risk of suffering a multipactor discharge within an RF electron gun photoinjector. Photoinjectors are a type of source for intense electron beams, ...which are the main electron source for synchrotron light sources, such as free-electron lasers. The analyzed device consists of 1.6 cells and it has been designed to operate at the S -band. Besides, around the RF gun there is an emittance compensation solenoid, whose magnetic field prevents the growth of the electron beam emittance, and thus the degradation of the properties of the beam. The multipactor analysis is based on a set of numerical simulations by tracking the trajectories of the electron cloud in the cells of the device. To reach this aim, an in-house multipactor code was developed. Specifically, two different cases were explored: with the emittance compensation solenoid assumed to be off and with the emittance compensation solenoid in operation. For both the cases, multipactor simulations were carried out exploring different RF electric field amplitudes. Moreover, for a better understanding of the multipactor phenomenon, the resonant trajectories of the electrons and the growth rate of the electrons population are investigated.
X-band RF photoinjector design for the CompactLight project González-Iglesias, D.; Aksoy, A.; Esperante, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2021, Letnik:
1014
Journal Article
Recenzirano
Odprti dostop
RF photoinjectors have been under development for several decades to provide the high-brightness electron beams required for X-ray Free Electron Lasers. This paper proposes a photoinjector design ...that meets the Horizon 2020 CompactLight design study requirements. It consists of a 5.6-cell, X-band (12 GHz) RF gun, an emittance-compensating solenoid and two X-band traveling-wave structures that accelerate the beam out of the space-charge-dominated regime. The RF gun is intended to operate with a cathode gradient of 200 MV/m, and the TW structures at a gradient of 65 MV/m. The shape of the gun cavity cells was optimized to reduce the peak electric surface field. An assessment of the gun RF breakdown likelihood is presented as is a multipacting analysis for the gun coaxial coupler. RF pulse heating on the gun inner surfaces is also evaluated and beam dynamics simulations of the 100MeV photoinjector are summarized.
Abstract Persistent elevated neuronal activity has been identified as the neuronal correlate of working memory. It is generally assumed in the literature and in computational and theoretical models ...of working memory that memory-cell activity is stable and replicable; however, this assumption may be an artifact of the averaging of data collected across trials, and needs experimental verification. In this study, we introduce a classification scheme to characterize the firing frequency trends of cells recorded from the cortex of monkeys during performance of working memory tasks. We examine the frequency statistics and variability of firing during baseline and memory periods. We also study the behavior of cells on individual trials and across trials, and explore the stability of cellular firing during the memory period. We find that cells from different firing-trend classes possess markedly different statistics. We also find that individual cells show substantial variability in their firing behavior across trials, and that firing frequency also varies markedly over the course of a single trial. Finally, the average frequency distribution is wider, the magnitude of the frequency increases from baseline to memory smaller, and the magnitude of frequency decreases larger than is generally assumed. These results may serve as a guide in the evaluation of current theories of the cortical mechanisms of working memory.
In this letter, we evaluate the potential of linear e+e− colliders to measure the top quark mass in radiative events and in a suitable short-distance scheme. We present a calculation of the ...differential cross section for production of a top quark pair in association with an energetic photon from initial state radiation, as a function of the invariant mass of the tt¯ system. This matched calculation includes the QCD enhancement of the cross section around the tt¯ production threshold and remains valid in the continuum well above the threshold. The uncertainty in the top mass determination is evaluated in realistic operating scenarios for the Compact Linear Collider (CLIC) and the International Linear Collider (ILC), including the statistical uncertainty and the theoretical and experimental systematic uncertainties. With this method, the top quark mass can be determined with a precision of 110 MeV in the initial stage of CLIC, with 1 ab−1 at s=380 GeV, and with a precision of approximately 150 MeV at the ILC, with L=4 ab−1 at s=500 GeV. Radiative events allow measurements of the top quark mass at different renormalization scales, and we demonstrate that such a measurement can yield a statistically significant test of the evolution of the MSR mass mtMSR(R) for scales R<mt.
The tumor suppressor p53 is a transcription factor that is frequently inactivated in human tumors. Therefore, restoring its function has been considered an attractive approach to restrain cancer. ...Typically, p53-dependent growth arrest, senescence and apoptosis of tumor cells have been attributed to transcriptional activity of nuclear p53. Notably, wild-type p53 gain-of-function enhances cancer resistance in the mouse, but it also accelerates aging in some models, possibly due to altered p53 activity. Therefore, the emerging evidence of mitochondrial transcription-independent activities of p53 has raised high expectations. Here, we review new developments in transcription-dependent and transcription-independent p53 functions, recent advances in targeting p53 for cancer treatment and the pitfalls of moving from the laboratory research to the clinical setting.
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