Zobrazení zdroje stránky Mouritzenjordan8141

Functional activation of human epidermal growth factor receptor 2 (HER2) has been shown to strongly promote carcinogenesis, leading to the investigation of HER2-directed agents in cancers with HER2 genomic alterations. This has been best documented in the context of HER2 gene amplification in breast and gastric/gastroesophageal junction carcinomas for which several HER2-directed agents are available and have become a part of standard treatment regimens. Somatic HER2 gene mutations have been recently described at low frequency in a variety of human cancers and have emerged as a novel predictive biomarker for HER2-directed therapies. [https://www.selleckchem.com/products/abraxane-nab-paclitaxel.html Selleck Abraxane] Preclinical data also indicate that activating HER2 mutations are potent oncogenic drivers in a manner that is analogous to HER2 amplification. HER2 mutations may clinically confer sensitivity to HER2-directed agents as recently shown in a phase II clinical trial with antibody-drug conjugate against HER2 trastuzumab deruxtecan in patients with non-squamous non-small cell lung carcinoma.If universal health coverage (UHC) cannot be achieved without the sexual and reproductive health (SRH) needs of the population being met, what then is the current situation vis-à-vis universal coverage of SRH services, and the extent to which SRH services have been prioritised in national UHC plans and processes? This was the central question that guided this critical review of more than 200 publications between 2010 and 2019. The findings are the following. The Essential Package of Healthcare Services (EPHS) across many countries exclude several critical SRH services (e.g. safe abortion services, reproductive cancers) that are already poorly available. Inadequate international and domestic public funding of SRH services contributes to a sustained burden of out-of-pocket expenditure (OOPE) and inequities in access to SRH services. Policy and legal barriers, restrictive gender norms and gender-based inequalities challenge the delivery and access to quality SRH services. The evidence is mixed as to whether an eecesarias y urgentes. Es imperativo abogar por asignar mayor prioridad a la SSR en el PESS del gobierno y en los presupuestos de salud alineados con los objetivos de SSR y CUS. Se debe priorizar la implementación de mecanismos de financiamiento estable y continuo, que reducirían la proporción de financiamiento de SSR de los gastos corrientes. Las evidencias, que varían desde descriptiva hasta estudios explicativos que facilitan comprender los "cómo" y "por qué" de los procesos y las vías, son esenciales para guiar las acciones relacionadas con políticas y programas.While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.Recent investigations have implicated the parasympathetic branch of the autonomic nervous system in higher-order executive functions. These actions are purported to occur through autonomic nervous system's modulation of the pFC, with parasympathetic activity during wake associated with working memory (WM) ability. Compared with wake, sleep is a period with substantially greater parasympathetic tone. Recent work has reported that sleep may also contribute to improvement in WM. Here, we examined the role of cardiac parasympathetic activity during sleep on WM improvement in healthy young adults. Participants were tested in an operation span task in the morning and evening, and during the intertest period, participants experienced either a nap or wake. We measured high-frequency heart rate variability as an index of cardiac, parasympathetic activity during both wake and sleep. Participants showed the expected boost in parasympathetic activity during nap, compared with wake. Furthermore, parasympathetic activity during sleep, but not wake, was significantly correlated with WM improvement. Together, these results indicate that the natural boost in parasympathetic activity during sleep may benefit gains in prefrontal executive function in young adults. We present a conceptual model illustrating the interaction between sleep, autonomic activity, and prefrontal brain function and highlight open research questions that will facilitate understanding of the factors that contribute to executive abilities in young adults as well as in cognitive aging.Moments of inattention to our surroundings may be essential to optimal cognitive functioning. Here,we investigated the hypothesis that humans spontaneously switch between two opposing attentional states during wakefulness-one in which we attend to the external environment (an "online" state) and one in which we disengage from the sensory environment to focus our attention internally (an "offline" state). We created a data-driven model of this proposed alternation between "online" and "offline" attentional states in human subjects, on a seconds-level timescale. Participants (n = 34) completed a sustained attention to response task while undergoing simultaneous high-density EEG and pupillometry recording and intermittently reporting on their subjective experience. "Online" and "offline" attentional states were initially defined using a cluster analysis applied tomultimodal measures of (1) EEG spectral power, (2) pupil diameter, (3) RT, and (4) self-reported subjective experience. We then developed a classifier that labeled trials as belonging to the online or offline cluster with &gt;95% accuracy, without requiring subjective experience data.