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ABSTRACTAttosecond photoelectron spectroscopy has opened up for studying light–matter interaction on ultrafast time scales. It is often performed with interferometric experimental setups that require outstanding stability. We demonstrate and characterize in detail an actively stabilized, versatile, high spectral resolution attosecond beamline based on a Mach-Zehnder interferometer. The active stabilization keeps the interferometer ultra-stable for several hours with an RMS stability of 13 as and a total pump-probe delay scanning range of [Formula: see text] fs. A tunable femtosecond laser source to drive high-order harmonic generation allows for precisely addressing atomic and molecular resonances. Furthermore, the interferometer includes a spectral shaper in 4f-geometry in the probe arm as well as a tunable bandpass filter in the pump arm, which offer additional high flexibility in terms of tunability as well as narrowband or polychromatic probe pulses. We demonstrate the capabilities of the beamline via experiments using several variants of the RABBIT (reconstruction of attosecond beating by two photon transitions) technique. In this setup, the temporal-spectral resolution of photoelectron spectroscopy can reach a new level of accuracy and precision.

IntroductionAs the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function and protect against the onset of chronic disease, whereas sleep deprivation has been linked to cognitive impairment and the onset of depression and dementia.ObjectivesHere, we aim to identify and explore mechanistic links between several sleep parameters, depressive symptoms and cognition in a cohort of middle-aged adults.MethodsWe investigated data from the PREVENT dementia programme via structural equation modeling to illustrate links between predictor variables, moderator variables, and two cognitive constructs (i.e., Executive Function and Memory).ResultsOur model demonstrated that sleep quality, and total hours of sleep were related to participants' depressive symptoms, and that, participant apathy was related to higher scores on the Epworth Sleepiness and Lausanne NoSAS Scales. Subsequently, depressive symptoms, but not sleep or apathy ratings, were associated with Executive Function.ConclusionsWe provide evidence for an indirect relationship between sleep and cognition mediated by depressive symptoms in a middle-aged population. Our results provide a base from which cognition, dementia onset, and potential points of intervention, may be better understood.

Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for >30 mature types and several developmental intermediates. We used this dataset to engineer transgenic driver lines, enabling specific experimental access to a subset of RGC types. Expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.

Abstract Similar to x-ray imaging, THz imaging will require high power and high resolution to advance relevant applications. Previously demonstrated THz imaging usually experiences one or several difficulties in insufficient source power, poor spectral tunability, or limited resolution from a low-wavelength source. A short-wavelength radiation source in the 5–10 THz is relatively scarce. Although a shorter wavelength improves imaging resolution, widely used imaging sensors, such as microbolometers, Schottky diodes, and photoconductive antennas, are usually not sensitive to detect radiation with frequencies above 5 THz. The radiation power of a high-frequency source becomes a key factor to realize low-noise and high-resolution imaging by using an ordinary pyroelectric detector. Here, we report a successful development of a fully coherent, tunable, > 100-kW-peak-power parametric source at 5.7 THz. It is then used together with a low-cost pyroelectric detector for demonstrating high-resolution 5.7-THz imaging in comparison with 2-THz imaging. To take advantage of the wavelength tunability of the source, we also report spectrally resolved imaging between 5.55 and 5.87 THz to reveal the spectroscopic characteristics and spatial distribution of a test drug, Aprovel.

Abstract Background Idiopathic normal pressure hydrocephalus (iNPH) is a progressive syndrome affecting gait, incontinence, and cognition in a significant number of older adults. Still, prospective studies on early development of symptoms are scarce. Aim To investigate how neuropsychological functions develop before and in already diagnosed iNPH over a two-year period in a population-based material. Method A sample of 104 participants (median [IQR] 75 [72–80] years old) from the general population underwent CT-imaging and clinical assessment at baseline and follow-up. We used the iNPH symptom scale covering four domains (Neuropsychology, Gait, Balance, Incontinence) and additional tests of executive functions. Morphological signs were rated with the iNPH Radscale. Non-parametric statistics with Bonferroni corrections and a significance-level of p

It has long been suggested that the inverse Fourier transform of neutron scattering data gives access to space- and time-resolved spin-spin correlations. Scheie et al. perform this procedure on high-precision experimental data from a 1D quantum antiferromagnet and uncover new features in short-term quench dynamics.

Abstract Background Levels of the biomarkers amyloid-β 1–42 (Aβ42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers. Methods In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aβ42, tau and p-tau. Results In the total sample VV (Median 140.7 mL) correlated weakly (rs = − 0.17) with Aβ42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aβ42 was only present in the male group (rs = − 0.22, p = 0.038). Further, Aβ42 correlated positively with tau (rs = 0.30, p = 0.004) and p-tau (rs = 0.26, p = 0.012) in males but not in females. Conclusions The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aβ42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.

Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design, setting, and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients). Outcome measurements and statistical analysis: The primary endpoints were 18-mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests. Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42–1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy. Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.

The authors show that micron size fibers comprised of semiconductor and metallic materials can be purified or doped, recrystallized or have the constituents rearranged into a variety of structures with device prospects.

The main estrogen, 17β-estradiol (E2), exerts several beneficial vascular actions through estrogen receptor α (ERα) in endothelial cells. However, the impact of other natural estrogens such as estriol (E3) and estetrol (E4) on arteries remains poorly described. In the present study, we report the effects of E3 and E4 on endothelial healing after carotid artery injuries in vivo. After endovascular injury, which preserves smooth muscle cells (SMCs), E2, E3, and E4 equally stimulated reendothelialization. By contrast, only E2 and E3 accelerated endothelial healing after perivascular injury that destroys both endothelial cells and SMCs, suggesting an important role of this latter cell type in E4’s action, which was confirmed using Cre/lox mice inactivating ERα in SMCs. In addition, E4 mediated its effects independently of ERα membrane-initiated signaling, in contrast with E2. Consistently, RNA sequencing analysis revealed that transcriptomic and cellular signatures in response to E4 profoundly differed from those of E2. Thus, whereas acceleration of endothelial healing by estrogens had been viewed as entirely dependent on endothelial ERα, these results highlight the very specific pharmacological profile of the natural estrogen E4, revealing the importance of dialogue between SMCs and endothelial cells in its arterial protection.

Purpose: This study aims to investigate how to improve the project management (PM) curriculum by evaluating the nature and alignment of learning outcomes in the PM course syllabi with Bloom's Taxonomy framework. Design/methodology/approach: The research methodology for this study is an integrative approach that uses document analysis and content analysis. The data set was selected based on a purposeful sampling method and came from PM course syllabi for classes that were taught during the 2016-2018 academic years. Findings: Results revealed that most of the reviewed PM course syllabi contained learning outcomes although they were written and assessed at the lower levels of Bloom's Taxonomy and knowledge dimensions. The study calls for the academy and industry to partner in improving the PM curriculum to lower the PM talent deficit and increase project success rates. Research limitations/implications: The absence of PM learning outcomes or the presence of poorly written PM learning outcomes in a course implies that the academy should provide professional development programs to help professors learn how to formulate and write specific, measurable, achievable, relevant and timely learning outcomes. The professors should also ensure that the learning outcomes use a type of cognitive taxonomy that is aligned with the appropriate assessments to measure, monitor and guarantee assurance of learning. Practical implications: Academy and industry partners can work collaboratively to provide students with opportunities that expose them to real-world experiential projects, internships and job opportunities while concurrently giving them hands-on practical applications of learned PM knowledge and skills. The society will be well served when the academy is able to produce well-qualified PM personnel capable of successfully carrying out PM activities and lowering the project's failure rates. Social implications: The society will be well served when the academy is able to produce well-qualified PM personnel capable of successfully carrying out PM activities and lowering the project's failure rates. Originality/value: To the researchers' knowledge, this is the first study to specifically investigate the presence and nature of PM learning outcomes in course syllabi. By evaluating the alignment between PM learning outcomes and Bloom's Taxonomy action verbs and cognitive processes, the study provides some exemplars of well-written and measurable learning outcomes that professors can use to inform their PM curriculum through course design or redesign.

Abstract Microfluidics has emerged rapidly over the past 20 years and has been investigated for a variety of applications from life sciences to environmental monitoring. Although continuous-flow microfluidics is ubiquitous, segmented-flow or droplet microfluidics offers several attractive features. Droplets can be independently manipulated and analyzed with very high throughput. Typically, microfluidics is carried out within planar networks of microchannels, namely, microfluidic chips. We propose that fibers offer an interesting alternative format with key advantages for enhanced optical coupling. Herein, we demonstrate the generation of monodisperse droplets within a uniaxial optofluidic Lab-in-a-Fiber scheme. We combine droplet microfluidics with laser-induced fluorescence (LIF) detection achieved through the development of an optical side-coupling fiber, which we term a periscope fiber. This arrangement provides stable and compact alignment. Laser-induced fluorescence offers high sensitivity and low detection limits with a rapid response time making it an attractive detection method for in situ real-time measurements. We use the well-established fluorophore, fluorescein, to characterize the Lab-in-a-Fiber device and determine the generation of $$\sim$$ ∼ 0.9 nL droplets. We present characterization data of a range of fluorescein concentrations, establishing a limit of detection (LOD) of 10 nM fluorescein. Finally, we show that the device operates within a realistic and relevant fluorescence regime by detecting reverse-transcription loop-mediated isothermal amplification (RT-LAMP) products in the context of COVID-19 diagnostics. The device represents a step towards the development of a point-of-care droplet digital RT-LAMP platform.