Ptychographic hyperspectral spectromicroscopy with an extreme ultraviolet high harmonic comb

We demonstrate a new scheme of spectromicroscopy in the extreme ultraviolet (EUV) spectral range, where the spectral response of the sample at different wavelengths is imaged simultaneously. It is enabled by applying ptychographical information multiplexing (PIM) to a tabletop EUV source based on high harmonic generation, where four spectrally narrow harmonics near 30 nm form a spectral comb structure. Extending PIM from previously demonstrated visible wavelengths to the EUV/X-ray wavelengths promises much higher spatial resolution and more powerful spectral contrast mechanism, making PIM an attractive spectromicroscopy method in both the microscopy and the spectroscopy aspects. Besides the sample, the multicolor EUV beam is also imaged in situ, making our method a powerful beam characterization technique. No hardware is used to separate or narrow down the wavelengths, leading to efficient use of the EUV radiation

Quantitative Chemically-Specific Coherent Diffractive Imaging of Buried Interfaces using a Tabletop EUV Nanoscope

Characterizing buried layers and interfaces is critical for a host of applications in nanoscience and nano-manufacturing. Here we demonstrate non-invasive, non-destructive imaging of buried interfaces using a tabletop, extreme ultraviolet (EUV), coherent diffractive imaging (CDI) nanoscope. Copper nanostructures inlaid in SiO2 are coated with 100 nm of aluminum, which is opaque to visible light and thick enough that neither optical microscopy nor atomic force microscopy can image the buried interfaces. Short wavelength (29 nm) high harmonic light can penetrate the aluminum layer, yielding high-contrast images of the buried structures. Moreover, differences in the absolute reflectivity of the interfaces before and after coating reveal the formation of interstitial diffusion and oxidation layers at the Al-Cu and Al-SiO2 boundaries. Finally, we show that EUV CDI provides a unique capability for quantitative, chemically-specific imaging of buried structures, and the material evolution that occurs at these buried interfaces, compared with all other approaches.Comment: 12 pages, 8 figure

Vortioxetine Differentially Modulates MK-801-Induced Changes in Visual Signal Detection Task Performance and Locomotor Activity

Attention impairment is a common feature of Major Depressive Disorder (MDD), and MDD-associated cognitive dysfunction may play an important role in determining functional status among this patient population. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in MDD patients, and may indirectly increase glutamate neurotransmission in brain regions classically associated with attention function. Previous non-clinical research suggests that vortioxetine has limited effects on attention. This laboratory previously found that vortioxetine did not improve attention function in animals impaired by acute scopolamine administration, using the visual signal detection task (VSDT). However, vortioxetine has limited effects on acetylcholinergic neurotransmission, and thus it is possible that attention impaired by other mechanisms would be attenuated by vortioxetine. This study sought to investigate whether acute vortioxetine administration can attenuate VSDT impairments and hyperlocomotion induced by the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. We found that acute vortioxetine administration had no effect on VSDT performance on its own, but potentiated MK-801-induced VSDT impairments. Furthermore, vortioxetine had no effect on locomotor activity on its own, and did not alter MK-801-induced hyperlocomotion. We further investigated whether vortioxetine’s effect on MK-801 could be driven by a kinetic interaction, but found that plasma and brain exposure for vortioxetine and MK-801 were similar whether administered alone or in combination. Thus, it appears that vortioxetine selectively potentiates MK-801-induced impairments in attention without altering its effects on locomotion, and further that this interaction must be pharmacodynamic in nature. A theoretical mechanism for this interaction is discussed

CANDELS: The progenitors of compact quiescent galaxies at z~2

We combine high-resolution HST/WFC3 images with multi-wavelength photometry to track the evolution of structure and activity of massive (log(M*) > 10) galaxies at redshifts z = 1.4 - 3 in two fields of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). We detect compact, star-forming galaxies (cSFGs) whose number densities, masses, sizes, and star formation rates qualify them as likely progenitors of compact, quiescent, massive galaxies (cQGs) at z = 1.5 - 3. At z > 2 most cSFGs have specific star-formation rates (sSFR = 10^-9 yr^-1) half that of typical, massive SFGs at the same epoch, and host X-ray luminous AGN 30 times (~30%) more frequently. These properties suggest that cSFGs are formed by gas-rich processes (mergers or disk-instabilities) that induce a compact starburst and feed an AGN, which, in turn, quench the star formation on dynamical timescales (few 10^8 yr). The cSFGs are continuously being formed at z = 2 - 3 and fade to cQGs by z = 1.5. After this epoch, cSFGs are rare, thereby truncating the formation of new cQGs. Meanwhile, down to z = 1, existing cQGs continue to enlarge to match local QGs in size, while less-gas-rich mergers and other secular mechanisms shepherd (larger) SFGs as later arrivals to the red sequence. In summary, we propose two evolutionary scenarios of QG formation: an early (z > 2), fast-formation path of rapidly-quenched cSFGs that evolve into cQGs that later enlarge within the quiescent phase, and a slow, late-arrival (z < 2) path for SFGs to form QGs without passing through a compact state.Comment: Submitted to the Astrophysical Journal Letters, 6 pages, 4 figure

The political, research, programmatic, and social responses to adolescent sexual and reproductive health and rights in the 25 years since the International Conference on Population and Development

Among the ground-breaking achievements of the International Conference on Population and Development (ICPD) was its call to place adolescent sexual and reproductive health (ASRH) on global health and development agendas. This article reviews progressmade in low- and middle-income countries in the 25 years since the ICPD in six areas central to ASRH-adolescent pregnancy, HIV, child marriage, violence against women and girls, female genital mutilation, and menstrual hygiene and health. It also examines the ICPD's contribution to the progress made. The article presents epidemiologic levels and trends; political, research, programmatic and social responses; and factors that helped or hindered progress. To do so, it draws on research evidence and programmatic experience and the expertise and experiences of a wide number of individuals, including youth leaders, in numerous countries and organizations. Overall, looking across the six health topics over a 25-year trajectory, there has been great progress at the global and regional levels in putting adolescent health, and especially adolescent sexual and reproductive health and rights, higher on the agenda, raising investment in this area, building the epidemiologic and evidence-base, and setting norms to guide investment and action. At the national level, too, there has been progress in formulating laws and policies, developing strategies and programs and executing them, and engaging communities and societies in moving the agenda forward. Still, progress has been uneven across issues and geography. Furthermore, it has raced ahead sometimes and has stalled at others. The ICPD's Plan of Action contributed to the progress made in ASRH not just because of its bold call in 1994 but also because it provided a springboard for advocacy, investment, action, and research that remains important to this day. (C) 2019 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine

A Specialized Odor Memory Buffer in Primary Olfactory Cortex

The neural substrates of olfactory working memory are unknown. We addressed the questions of whether olfactory working memory involves a verbal representation of the odor, or a sensory image of the odor, or both, and the location of the neural substrates of these processes.We used functional magnetic resonance imaging to measure activity in the brains of subjects who were remembering either nameable or unnameable odorants. We found a double dissociation whereby remembering nameable odorants was reflected in sustained activity in prefrontal language areas, and remembering unnameable odorants was reflected in sustained activity in primary olfactory cortex.These findings suggest a novel dedicated mechanism in primary olfactory cortex, where odor information is maintained in temporary storage to subserve ongoing tasks

Recent breast cancer trends among Asian/Pacific Islander, Hispanic, and African-American women in the US: changes by tumor subtype

Abstract available at publisher's website

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5

Background and Objectives KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.Methods We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.Results We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.</p

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Ambidextrie – der organisationale Drahtseilakt. Synergie zwischen Exploration und Exploitation als Voraussetzung für die digitale Transformation

Sich disruptiv verändernde Rahmenbedingungen können dazu führen, dass bisher erfolgreiche Geschäftsmodelle innert weniger Jahren obsolet werden. Geschuldet ist dies einer mangelnden Anpassungsfähigkeit, deren Ursache unter anderem in der sogenannten Pfadabhängigkeit wurzeln kann. Die Pfadabhängigkeit bezeichnet eine Situation, in der die Auswirkungen von stark durch die Vergangenheit geprägten Entscheiden dazu führen, dass die Möglichkeit bzw. Notwendigkeit neuer Geschäftsmodelle nicht erkannt, verpasst oder deren Chancen falsch eingeschätzt werden. Das Ausbrechen aus der Pfadabhängigkeit ist für den Fortbestand von Unternehmen daher von zentraler Bedeutung. Das Konzept der organisationalen Ambidextrie widmet sich dieser Problemstellung. Ambidextrie beschreibt die Fähigkeit eines Unternehmens, einerseits das Kerngeschäft stetig weiterzuentwickeln, gleichzeitig aber auch neue Wege und Denkweisen zu etablieren und so sicherzustellen, dass Veränderungen im Umsystem rechtzeitig erkannt und die sich dadurch bietenden Chancen für die Zukunft genutzt werden. Eine Fähigkeit, die gerade im Zeitalter der Digitalisierung an Wichtigkeit gewinnt