Explore the vast range of titles available.

ObjectiveThe International Liaison Committee on Resuscitation has recommended improvements in training for neonatal resuscitation, highlighting the potential role of respiratory function monitors (RFMs). Our objective was to determine whether a manikin-based, standardised face mask ventilation training intervention using an RFM with a simple visual display reduced face mask leak.DesignMulticentre, before and after study. Participants and instructors were blinded to the RFM display during both assessment periods.ParticipantsHealthcare professionals working or training in a hospital providing maternity and neonatal services.InterventionAll participants underwent a training intervention on positive pressure ventilation using a modified, leak-free manikin and RFM. The intervention consisted of a demonstration of optimal face mask ventilation technique, training in RFM interpretation with corrective strategies for common scenarios and a period of deliberate practice. Each participant performed 30 s of positive pressure ventilation blinded to the RFM display before and after training.Main outcome measuresThe primary outcome was face mask leak (%) measured after training. Secondary outcome measures included expired tidal volume, inflating pressures and ventilation rate. Adjustments made to technique during training were an important qualitative outcome.ResultsFour hundred and fourteen participants were recruited over a 13-month period from April 2022, and 412 underwent analysis. Median (IQR) face mask leak before training was 31% (10–69%) compared with 10% (6–18%) after training (p<0.0001). Improvements were noted across all other ventilation parameters.ConclusionStandardised face mask ventilation training using an RFM with simple visual feedback led to a significant reduction in leak.

Growing convergence among mobile computing devices and embedded technology sparks the development and deployment of \"context-aware\" applications, where location is the most essential context. In this paper we present LANDMARC, a location sensing prototype system that uses Radio Frequency Identification (RFID) technology for locating objects inside buildings. The major advantage of LANDMARC is that it improves the overall accuracy of locating objects by utilizing the concept of reference tags. Based on experimental analysis, we demonstrate that active RFID is a viable and cost-effective candidate for indoor location sensing. Although RFID is not designed for indoor location sensing, we point out three major features that should be added to make RFID technologies competitive in this new and growing market. [PUBLICATION ABSTRACT]

The study ofCoNb2O6sits at the confluence of simplicity and complexity: on one hand, the model for Ising chains—the building blocks ofCoNb2O6—in a transverse field can be exactly solved and, thus, serves as an archetype of quantum criticality; on the other hand, the weak but nonzero interchain coupling adds geometric frustration to the stage, substantially complicating the phase diagram. Here we utilize low-temperature specific heat and thermal conductivity measurements to study the low-lying magnetic excitations inCoNb2O6and its spin-1 analogNiNb2O6. The thermal conductivity is found to be suppressed around the quantum critical point, where the specific heat is enhanced due to gapless magnetic excitations, pointing to the localized nature of the latter. These results highlight the predominant role of frustration in determining the quantum critical magnetic excitations of spin chains, which may furthermore underlie the remarkable similarities between the phenomenology of these spin-1/2and spin-1 systems.

The epidermal growth factor receptor (EGFR) is a clinically validated target in head and neck squamous cell carcinoma (HNSCC), where EGFR-blocking antibodies are approved for first-line treatment. However, as with other targeted therapies, intrinsic/acquired resistance mechanisms limit efficacy. In the FaDu HNSCC xenograft model, we show that combined blockade of EGFR and ERBB3 promotes rapid tumor regression, followed by the eventual outgrowth of resistant cells. RNA sequencing revealed that resistant cells express FGFR3-TACC3 fusion proteins, which were validated as drivers of the resistant phenotype by several approaches, including CRISPR-mediated inactivation of FGFR3-TACC3 fusion genes. Interestingly, analysis of signaling in resistant cell lines demonstrated that FGFR3-TACC3 fusion proteins promote resistance by preferentially substituting for EGFR/RAS/ERK signaling rather than ERBB3/PI3K/AKT signaling. Furthermore, although FGFR3-TACC3 fusion proteins promote resistance of additional EGFR-dependent HNSCC and lung cancer cell lines to EGFR blockade, they are unable to compensate for inhibition of PI3K signaling in PIK3CA -mutant HNSCC cell lines. Validation of FGFR3-TACC3 fusion proteins as endogenous drivers of resistance in our screen provides strong evidence that these fusions are capable of substituting for EGFR signaling. Thus, FGFR3-TACC3 fusion proteins may represent a novel mechanism of acquired resistance in EGFR-dependent cancers of multiple cell lineages.

In mammalian cells, endoplasmic reticulum (ER) stress has recently been shown to induce autophagy and the induction requires the unfolded protein response (UPR) signaling pathways. However, little is known whether autophagy regulates UPR pathways and how specific UPR targets might control autophagy. Here, we demonstrated that although ER stress-induced autophagy was suppressed by class III phosphatidylinositol-3′-kinase (PI3KC3) inhibitor 3-methyladenine (3-MA), wortmannin and knockdown of Beclin1 using small interfering RNA (siRNA), only 3-MA suppressed UPR activation. We discovered that the UPR regulator and ER chaperone GRP78/BiP is required for stress-induced autophagy. In cells in which GRP78 expression was knocked down by siRNA, despite spontaneous activation of UPR pathways and LC3 conversion, autophagosome formation induced by ER stress as well as by nutrition starvation was inhibited. GRP78 knockdown did not disrupt PI3KC3–Beclin1 association. However, electron microscopic analysis of the intracellular organelle structure reveals that the ER, a putative membrane source for generating autophagosomal double membrane, was massively expanded and disorganized in cells in which GRP78 was knocked down. ER expansion is known to be dependent on the UPR transcription factor XBP-1. Simultaneous knockdown of GRP78 and XBP-1 recovered normal levels of stress-induced autophagosome formation. Thus, these studies uncover 3-MA as an inhibitor of UPR activation and establish GRP78 as a novel obligatory component of autophagy in mammalian cells.

In natural visually guided behavior, observers must separate relevant information from a barrage of irrelevant information. Many studies have investigated the neural underpinnings of this ability using artificial stimuli presented on blank backgrounds. Natural images, however, contain task-irrelevant background elements that might interfere with the perception of object features. Recent studies suggest that visual feature estimation can be modeled through the linear decoding of task-relevant information from visual cortex. So, if the representations of task-relevant and irrelevant features are not orthogonal in the neural population, then variation in the task-irrelevant features would impair task performance. We tested this hypothesis using human psychophysics and monkey neurophysiology combined with parametrically variable naturalistic stimuli. We demonstrate that (1) the neural representation of one feature (the position of an object) in visual area V4 is orthogonal to those of several background features, (2) the ability of human observers to precisely judge object position was largely unaffected by those background features, and (3) many features of the object and the background (and of objects from a separate stimulus set) are orthogonally represented in V4 neural population responses. Our observations are consistent with the hypothesis that orthogonal neural representations can support stable perception of object features despite the richness of natural visual scenes.

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions ( n =33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study’s 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.

Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat attention deficit hyperactivity disorder (ADHD) and generally to enhance cognition, increases spatially selective visual attention, enhancing visual performance at only the attended location. Further, we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.

Goat production is rapidly expanding in tropical arid and semi-arid regions, yet limited knowledge exists on the feed they consume. This study investigated the in vitro digestibility, volatile fatty acid (VFA) profile, and methane production of 17 browse and eight forage species consumed by goats in Australia (Experiment 1) and tested interactive effects of forages (Avena sativa and Chloris gayana (Reclaimer)) and browses (Owenia acidula and Eucalyptus coolabah) combined in ratios of 25:75, 50:50, and 75:25, respectively (Experiment 2). Among browses, O. acidula exhibited the most favourable fermentation profile with 53.29% digestibility, 90.64 mL of gas/g dry matter (DM), total VFA concentration of 86.81 mM, 14.41 mL methane/ g digested DM, and an acetate to propionate ratio (A:P) of 1.54. Among the forages, A. sativa demonstrated the greatest digestibility (64.25%), total gas (115.02 mL/g DM), and VFA (114.02 mM), and the lowest methane production (19.90 mL/ g digested DM; P < 0.001). The 75:25 and 50:50 combinations of A. sativa: O. acidula resulted in greater DM digestibility (62.75% and 60.72%) and total gas (99.03 and 98.41 mL/g DM), while reducing methane (10.11 and 11.08 mL/ g digested DM), and A:P (1.91 and 2.17), respectively (P < 0.001) highlighting them as promising candidates for silvopasture systems.

ObjectiveIn adult patients with acute respiratory failure, nasal high-flow (NHF) therapy at the time of intubation can decrease the duration of hypoxia. The objective of this pilot study was to calculate duration of peripheral oxygen saturation below 75% during single and multiple intubation attempts in order to inform development of a larger definitive trial.Design and settingThis double-blinded randomised controlled pilot trial was conducted at a single, tertiary neonatal centre from October 2020 to October 2021.ParticipantsInfants undergoing oral intubation in neonatal intensive care were included. Infants with upper airway anomalies were excluded.InterventionsInfants were randomly assigned (1:1) to have NHF 6 L/min, FiO2 1.0 or NHF 0 L/min (control) applied during intubation, stratified by gestational age (<34 weeks vs ≥34 weeks).Main outcome measuresThe primary outcome was duration of hypoxaemia of <75% up to the time of successful intubation,Results43 infants were enrolled (26 <34 weeks and 17 ≥34 weeks) with 50 intubation episodes. In infants <34 weeks’ gestation, median duration of SpO2 of <75% was 29 s (0–126 s) vs 43 s (0–132 s) (p=0.78, intervention vs control). Median duration of SpO2 of <75% in babies ≥34 weeks’ gestation was 0 (0–32 s) vs 0 (0–20 s) (p=0.9, intervention vs control).ConclusionThis pilot study showed that it is feasible to provide NHF during intubation attempts. No significant differences were noted in duration of oxygen saturation of <75% between groups; however, this trial was not powered to detect a difference. A larger, higher-powered blinded study is warranted.