bluuebunny/crossref_metadata_2025 huggingface dataset:
Stomatal rings: structure, functions and origin
Authors: Pautov Anatoly , Bauer Svetlana , Ivanova Olga , Krylova Elena , Yakovleva Olga , Sapach Yulia , Pautova Irina
Published: October 2020

Stomatal rings are structural elements of stomata of some flowering plants, being found in various groups of eudicots. The presence of a stomatal ring on a stoma does not depend on stomatal complex types, dimensions of stomata or their density. The guard cells of these stomata lie on the subsidiary cells. The location of the outer ledges on the outer tangential walls of the guard cells and the position of the stomatal rings on the guard cell walls around the outer ledges or on the outer ledges themselves are also among the characteristic features of these stomata. To elucidate the role of the stomatal rings we applied modelling using the finite-element method. The modelling has shown that the outer ledges prevent movements of the outer tangential walls of the guard cells and stimulate movements of the inner tangential walls and the immersion of the opening stomatal pore in the epidermis. Stomatal rings can enhance this effect. They also prevent the movements of the outer ledges and the widening of the stomatal aperture between them during stoma opening. This type of stomata occurs in evergreen plants growing in diverse conditions.
Distinct Laminar and Cellular Patterns of GABA Neuron Transcript Expression in Monkey Prefrontal and Visual Cortices
Authors: Dienel Samuel J , Ciesielski Andrew J , Bazmi Holly H , Profozich Elizabeth A , Fish Kenneth N , Lewis David A
Published: October 2020

The functional output of a cortical region is shaped by its complement of GABA neuron subtypes. GABA-related transcript expression differs substantially between the primate dorsolateral prefrontal cortex (DLPFC) and primary visual (V1) cortices in gray matter homogenates, but the laminar and cellular bases for these differences are unknown. Quantification of levels of GABA-related transcripts in layers 2 and 4 of monkey DLPFC and V1 revealed three distinct expression patterns: 1) transcripts with higher levels in DLPFC and layer 2 [e.g., somatostatin (SST)]; 2) transcripts with higher levels in V1 and layer 4 [e.g., parvalbumin (PV)], and 3) transcripts with similar levels across layers and regions [e.g., glutamic acid decarboxylase (GAD67)]. At the cellular level, these patterns reflected transcript- and cell type-specific differences: the SST pattern primarily reflected differences in the relative proportions of SST mRNA-positive neurons, the PV pattern primarily reflected differences in PV mRNA expression per neuron, and the GAD67 pattern reflected opposed patterns in the relative proportions of GAD67 mRNA-positive neurons and in GAD67 mRNA expression per neuron. These findings suggest that differences in the complement of GABA neuron subtypes and in gene expression levels per neuron contribute to the specialization of inhibitory neurotransmission across cortical circuits.
US Food and Drug Administration (FDA) Emergency Use Authorization: Glass Half Full or Glass Half Empty?
Authors: Guharoy Roy , Krenzelok Edward P
Published: October 2020

Recently, the US Food and Drug Administration (FDA) issued emergency use authorization (EUA) for convalescent plasma (CP) for the treatment of hospitalized patients with coronavirus disease 2019 based on a non–peer-reviewed, open-label, observational study. Issuance of an EUA without a proven randomized, controlled trial (RCT) sets a dangerous precedent since the premature action drives healthcare providers and patients away from RCTs that are essential for determining the efficacy and safety of CP. More caution should have been taken based on what was learned from the recent debacle related to the rescinded EUA of hydroxychloroquine and chloroquine, which were approved initially based on an anecdotal report. The FDA process for determining efficacy and safety must be based solely on data from RCTs in order to sustain public and professional trust for future treatment and vaccine efforts to be successful.
Late Negotiations: Ecopoetry and Kathleen Jamie
Authors: Gillis Alan
Published: October 2020

This essay explores Kathleen Jamie’s ecopoetry, expanding upon previous discussions of her work in this context. Through close readings of key poems, a broader exploration of lyric poetry and ecopoetics is developed. The opening section discusses current debates. While there is agreement with a critical consensus that our environmental catastrophe necessitates new ways of thinking, it is queried whether this, regarding lyric poetry, necessitates rejection of all convention and previous approaches. The main section of the essay then reexamines the work of Jamie, a well-known ecopoet, to scrutinize ways in which an emphasis on close reading and attention to matters of form might allow for a richer understanding than is allowed for in current ecocritical debates.
NCOA3identified as a new candidate to explain autosomal dominant progressive hearing loss
Authors: Salazar-Silva R , Dantas Vitor Lima Goes , Alves Leandro Ucela , Batissoco Ana Carla , Oiticica Jeanne , Lawrence Elizabeth A , Kawafi Abdelwahab , Yang Yushi , Nicastro Fernanda Stávale , Novaes Beatriz Caiuby , Hammond Chrissy , Kague Erika , Mingroni-Netto R C
Published: October 2020

Hearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of near 13 cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C > G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3−/− did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3−/−, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3−/− and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.
A Decolonial Theory of Religion: Race, Coloniality, and Secularity in the Americas
Authors: Yountae An
Published: October 2020

This article offers a transatlantic, decolonial theory (or method for the study) of religion by insisting on the need to resituate the Americas and the transatlantic historical experience as primary sites for theorizing modern religion. Despite the surging interest in decolonial theory, its concrete connection with key topics and issues in the field of religious studies has not been systematically theorized, while decolonial theorists working outside the field of religious studies show little or no interest in the formative role of religion in the constitution of the system of modernity/coloniality. This article seeks to build a cohesive framework for a decolonial theory of religion in conversation with various decolonial, anti-racist thinkers writing from Latin American, Caribbean, and US contexts. By pointing at secularity as a key element of modernity/coloniality, the medium through which religion enacts coloniality, it raises critical questions regarding method and theory in the study of Latin American/Caribbean religions.
Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir
Authors: Pham Hanh T , Alves Brunna M , Yoo Sunbin , Xiao Meng A , Leng Jing , Quashie Peter K , Soares Esmeralda A , Routy Jean-Pierre , Soares Marcelo A , Mesplède Thibault
Published: October 2020

Objectives

The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions.

Methods

Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results.

Results

R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints.

Conclusions

Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.
Fourteen ways of looking back at the Treaty of Versailles†
Authors: Kritsiotis Dino
Published: October 2020

This article examines the idea of the Treaty of Versailles as a readily quantifiable corpus of provisions as set down in a readily identifiable document that was signed at the Palace of Versailles on 28 June 1919. It does so by recalling the pre-history to that peace that stretches as far back as US President Woodrow Wilson’s Fourteen Points of January 1918, for the German Government accepted these Fourteen Points as well as subsequent pronouncements of President Wilson as the basis for the peace that ended the Great War. Through a close engagement with diplomatic correspondence from October and November 1918, the article considers how impressions came to form that a ‘contract’ had been made with the enemy (John Maynard Keynes) by the time of the Armistice of Compiègne of November 1918—an apparent ‘charter for our future activity’ (Harold Nicolson) or a localized lex pacificatoria for its time. The article explores the amenability of each of the Fourteen Points to international normativity and, in its final section, it provides a broader account of how this set of positions shaped Germany’s official response to the draft treaty (‘Observations of the German Delegation on the Conditions of Peace’) that was released in May 1919.
The stratified disc wind of MCG-03-58-007
Authors: Braito V , Reeves J N , Severgnini P , Della Ceca R , Ballo L , Cicone C , Matzeu G A , Serafinelli R , Sirressi M
Published: October 2020

Past Suzaku, XMM–Newton, and NuSTAR observations of the nearby (z = 0.03233) bright Seyfert 2 galaxy MCG-03-58-007 revealed the presence of two deep and blue-shifted iron K-shell absorption line profiles. These could be explained with the presence of two phases of a highly ionized, high column density accretion disc wind outflowing with vout1 ∼ −0.1c and vout2 ∼ −0.2c. Here we present two new observations of MCG-03-58-007: one was carried out in 2016 with Chandra and one in 2018 with Swift. Both caught MCG-03-58-007 in a brighter state ($F_{{\mathrm{2}-10\, keV}} \sim 4 \times 10^{-12}$ erg cm−2 s−1) confirming the presence of the fast disc wind. The multi-epoch observations of MCG-03-58-007 covering the period from 2010 to 2018 were then analysed. These data show that the lower velocity component outflowing with vout1 ∼ −0.072 ± 0.002c is persistent and detected in all the observations, although it is variable in column density in the range NH ∼ 3–8 × 1023 cm−2. In the 2016 Swift observation we detected again the second faster component outflowing with vout2 ∼ −0.2c, with a column density ($N_{\mbox{H}}=7.0^{+5.6}_{-4.1}\times 10^{23}$ cm−2), similar to that seen during the Suzaku observation. However during the Chandra observation 2 yr earlier, this zone was not present (NH < 1.5 × 1023 cm−2), suggesting that this faster zone is intermittent. Overall the multi-epochs observations show that the disc wind in MCG-03-58-007 is not only powerful, but also extremely variable, hence placing MCG-03-58-007 among unique disc winds such as the one seen in the famous QSO PDS456. One of the main results of this investigation is the consideration that these winds could be extremely variable, sometime appearing and sometime disappearing; thus to reach solid and firm conclusions about their energetics multiple observations are mandatory.
UV line-driven disc wind as the origin of UltraFast Outflows in AGN
Authors: Mizumoto Misaki , Nomura Mariko , Done Chris , Ohsuga Ken , Odaka Hirokazu
Published: October 2020

UltraFast Outflows (UFOs) are observed in some active galactic nuclei (AGN), with blueshifted and highly ionized Fe-K absorption features. AGN typically have an ultraviolet (UV-) bright accretion flow, so UV line driving is an obvious candidate for launching these winds. However this mechanism requires material with UV opacity, in apparent conflict with the observed high-ionization state of the wind. In this paper, we synthesize the X-ray energy spectra resulting from different lines of sight through a state of the art radiation hydrodynamics UV line-driven disc wind simulation. We demonstrate that there are some lines of sight that only intercept highly ionized and fast outflowing material. The cooler material required for the UV line driving acceleration is out of the line of sight, close to the disc, shielded from the X-rays by a failed wind. We fit these simulated wind spectra to data from the archetypal UFO source PG 1211+143 and show that they broadly reproduce the depth and velocity of the iron absorption lines seen. This directly demonstrates that UV line driving is a viable mechanism to launch even the fastest UFOs. We simulate microcalorimeter observations of this wind and show that their high-energy resolution can resolve the detailed structure in the wind and recover the wind energetics when combined with models that correctly estimate the line formation radius of the wind. New data from microcalorimeters will pave the way for physical predictions of AGN wind feedback in cosmological simulations.
The quiescent fraction of isolated low surface brightness galaxies: observational constraints
Authors: Prole D J , van der Burg R F J , Hilker M , Spitler L R
Published: October 2020

Understanding the formation and evolution of low surface brightness galaxies (LSBGs) is critical for explaining their wide-ranging properties. However, studies of LSBGs in deep photometric surveys are often hindered by a lack of distance estimates. In this work, we present a new catalogue of 479 LSBGs, identified in deep optical imaging data from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP). These galaxies are found across a range of environments, from the field to groups. Many are likely to be ultra-diffuse galaxies (UDGs). We see clear evidence for a bimodal population in colour–Sérsic index space, and split our sample into red and blue LSBG populations. We estimate environmental densities for a sub-sample of 215 sources by statistically associating them with nearby spectroscopic galaxies from the overlapping GAMA spectroscopic survey. We find that the blue LSBGs are statistically consistent with being spatially randomized with respect to local spectroscopic galaxies, implying they exist predominantly in low-density environments. However, the red LSBG population is significantly spatially correlated with local structure. We find that $26\pm 5{{\ \rm per\ cent}}$ of isolated, local LSBGs belong to the red population, which we interpret as quiescent. This indicates that high environmental density plays a dominant, but not exclusive, role in producing quiescent LSBGs. Our analysis method may prove to be very useful, given the large samples of LSB galaxies without distance information expected from e.g. the Vera C. Rubin observatory (aka LSST), especially in combination with upcoming comprehensive wide-field spectroscopic surveys.
Broad He i 1.08-µm absorption from the obscurer in the active galaxy NGC 5548
Authors: Wildy Conor , Landt Hermine , Ward Martin J , Czerny Bożena , Kynoch Daniel
Published: October 2020

The nucleus of the active galaxy NGC 5548 was the target of two intensive spectroscopic monitoring campaigns at X-ray, ultraviolet (UV), and optical frequencies in 2013/2014. These campaigns detected the presence of a massive obscuration event. In 2016/2017, Landt et al. conducted a near-IR spectroscopic monitoring campaign on NGC 5548 and discovered He i  1.08-μm absorption. Here, we decompose this absorption into its components and study its time variability. We attribute the narrow He  i absorption lines to the warm absorber (WA) and, as for the newly appeared low-ionization WA lines in the UV, their presence is most likely due to a reduction in ionization parameter caused by the obscurer. The observed variability of the narrow He i absorption is consistent with what is expected for the WA. Most importantly, we also detect fast, broad He i absorption, which we attribute to the obscurer. This He i broad absorption, which is indicative of a high column density gas, is unsaturated and variable on time-scales of a few months. The observed variability of the obscurer is mainly due to changes in ionization, although density changes also play a role. We test the physical cycle model of Dehghanian et al. which proposes that helium recombination can account for how the obscurer influences the physics of the WA gas. Our results support their model, but also indicate that the reality might be more complex.
Photometric redshifts for galaxies in the Subaru Hyper Suprime-Cam and unWISE and a catalogue of identified clusters of galaxies
Authors: Wen Z L , Han J L
Published: October 2020

We first present a catalogue of photometric redshifts for 14.68 million galaxies derived from the 7-band photometric data of Hyper Suprime-Cam Subaru Strategic Program and the Wide-field Infrared Survey Explorer using the nearest-neighbour algorithm. The redshift uncertainty is about 0.024 for galaxies of z ≤ 0.7, and steadily increases with redshift to about 0.11 at z ∼ 2. From such a large data set, we identify 21 661 clusters of galaxies, among which 5537 clusters have redshifts z > 1 and 642 clusters have z > 1.5, significantly enlarging the high redshift sample of galaxy clusters. Cluster richness and mass are estimated, and these clusters have an equivalent mass of M500 ≥ 0.7 × 1014 M⊙. We find that the stellar mass of the brightest cluster galaxies (BCGs) in each richness bin does not significantly evolve with redshift. The fraction of star-forming BCGs increases with redshift, but does not depend on cluster mass.
Similar but different: the varied landscape of Onfp/Oef stars variability
Authors: Rauw Gregor , Nazé Yaël
Published: October 2020

The Oef category gathers rapidly rotating and evolved O-stars displaying a centrally reversed He ii λ 4686 emission line. The origin of the variability of their photospheric and wind spectral lines is debated, with rotational modulation or pulsations as the main contenders. To shed new light on this question, we analysed high-quality and high-cadence Transiting Exoplanet Survey Satellite photometric time series for five Oef stars. We also collected a new time series of spectra for one target (λ Cep) which had been the subject of specific debates in the last years. These observations reveal the variety of Oef behaviours. While space-based photometric data reveal substantial red noise components in all targets, only ζ Pup seems to display a long-lived periodicity. In our sample, stars exhibit a dominant signal at low frequencies but it appears relatively short-lived. This is reminiscent of rotational modulations by transient photospheric spots, though this scenario is challenged by the case of HD 14 442, whose 1.230 d−1 signal significantly exceeds the critical rotational frequency. In parallel, no evidence of persistent p mode non-radial pulsations is found in either photometry or spectroscopy of the stars, only temporary excitation of g mode pulsations could offer an alternative explanation for the dominant signals. Finally, the revised luminosities of the stars using GAIA-DR2 show that they are not all supergiants as ζ Pup. The question then arises whether the Oef peculiarity denotes a homogeneous class of objects after all.
Probing the CGM of low-redshift dwarf galaxies using FIRE simulations
Authors: Li Fei , Rahman Mubdi , Murray Norman , Hafen Zachary , Faucher-Giguère Claude-André , Stern Jonathan , Hummels Cameron B , Hopkins Philip F , El-Badry Kareem , Kereš Dušan
Published: October 2020

Observations of ultraviolet (UV) metal absorption lines have provided insight into the structure and composition of the circumgalactic medium (CGM) around galaxies. We compare these observations with the low-redshift (z ≤ 0.3) CGM around dwarf galaxies in high-resolution cosmological zoom-in runs in the FIRE-2 (Feedback In Realistic Environments) simulation suite. We select simulated galaxies that match the halo mass, stellar mass, and redshift of the observed samples. We produce absorption measurements using trident for UV transitions of C iv, O vi, Mg ii, and Si iii. The FIRE equivalent width (EW) distributions and covering fractions for the C iv ion are broadly consistent with observations inside 0.5Rvir, but are underpredicted for O vi, Mg ii, and Si iii. The absorption strengths of the ions in the CGM are moderately correlated with the masses and star formation activity of the galaxies. The correlation strengths increase with the ionization potential of the ions. The structure and composition of the gas from the simulations exhibit three zones around dwarf galaxies characterized by distinct ion column densities: the discy interstellar medium, the inner CGM (the wind-dominated regime), and the outer CGM (the IGM accretion-dominated regime). We find that the outer CGM in the simulations is nearly but not quite supported by thermal pressure, so it is not in hydrostatic equilibrium, resulting in halo-scale bulk inflow and outflow motions. The net gas inflow rates are comparable to the star formation rate of the galaxy, but the bulk inflow and outflow rates are greater by an order of magnitude, with velocities comparable to the virial velocity of the halo. These roughly virial velocities (${\sim } 100 \, \rm km\, s^{-1}$) produce large EWs in the simulations. This supports a picture for dwarf galaxies in which the dynamics of the CGM at large scales are coupled to the small-scale star formation activity near the centre of their haloes.
High-resolution spectroscopy of the hot Am star HR 3383
Authors: Wahlgren G M , Nielsen K E , Leckrone D S
Published: October 2020

We present the spectrum analysis of the hot Am star HR 3383 (A1 Vm). Hubble Space Telescope STIS and Nordic Optical Telescope SOFIN data are modelled with synthetic spectra, and abundances are investigated for 78 elements. Most light elements up through oxygen show deficiencies, compared to solar abundances, followed by the general trend of increasing abundance enhancement with atomic number that levels off at a 30-fold enhancement at the lanthanide group and heavier elements. The derived element distribution is generally consistent with what is observed in other hot Am stars. Abundances for HR 3383 are also similar to what is seen for the cooler HgMn stars, with the exception of the platinum-group elements that generally show dramatic enhancements in the HgMn stars. Current theory and calculations are able to predict most observed abundances and abundance trends through the iron group. The large number of derived element abundances in this study provides a constraint for theoretical calculations attempting to explain the heavy element abundances in chemically peculiar stars. This paper includes a comprehensive description of spectral lines useful for an abundance analysis of late B and A type stars, and comments are provided on the atomic data. New data for hyperfine structure components for three lines in Lu iii and a single line in Lu ii are presented, based on laboratory spectra. In addition to the stellar spectrum, lines from the interstellar medium are noted for several of the strongest Fe ii ultraviolet transitions.
New Drugs, New Indications for Various Cancers
Authors: Aschenbrenner Diane S.
Published: October 2020

Gemtuzumab ozogamicin (Mylotarg) is now approved to treat newly diagnosed CD33-positive acute myeloid leukemia in pediatric patients ages one month and older. The drug is given in combination with standard chemotherapy.

Lurbinectedin (Zepzelca) has been granted accelerated approval to treat adults with metastatic small cell lung cancer who have disease progression on or after platinum-based chemotherapy.

Pembrolizumab (Keytruda) has received a new indication to treat unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. It is the first immunotherapy approved for this use as a first-line, sole treatment.

A new indication for selinexor (Xpovio), granted under accelerated approval, is to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two different systemic therapies.
Improving Equitable Access to Cervical Cancer Screening and Management
Authors: Kiser Lisa Heidi , Butler Judith
Published: October 2020

Background:

Each year, 13,000 women in the United States are diagnosed with cervical cancer and 4,000 die from it. Moreover, 8 million women 21 to 65 years of age haven't had a Pap test in five years. Hispanic women have the highest incidence of cervical cancer and are less likely to be screened or return for care. Migrant women can face additional barriers to cervical cancer screening, including federal prohibitions against their participation in public health insurance exchanges and nonemergency Medicaid.

Purpose:

Improving cervical cancer screening rates was identified as a priority in a federally qualified health center when only 40% of eligible women were properly screened in 2016. Forty-five percent of the population the clinic serves is uninsured and 60% are Hispanic. The aim of this quality improvement project was to have 75% of the women 21 to 65 years of age who sought care at this clinic during the 60-day project period receive Pap test eligibility screening, enrollment in a state and federal screening program, and case management.

Methods:

Four rapid plan–do–study–act cycles were used. Tests of change included team engagement, patient engagement, eligibility screening, and case log management. Data were analyzed using run charts to evaluate the impact of interventions on outcomes. The interventions consisted of team meetings, a patient engagement tool, an eligibility screening tool, and case log management.

Results:

Among the women who completed care at the clinic during the 60-day project period, 80% were uninsured and 86% were Hispanic. A total of 87% of women received effective care, which consisted of same-day Well Woman Health Care Program enrollment and a same-day Pap test or an appointment to return for a well-woman visit.

Conclusion:

A multicomponent approach led to underserved women receiving equitable access to cervical cancer screening and timely enrollment in a cervical cancer screening program.
Baloxavir Effective in Preventing Influenza in Household Contacts
Authors: Rosenberg Karen
Published: October 2020

According to this study:

A single oral dose of baloxavir is safe and highly effective in preventing influenza in household contacts of index patients.
Ecological Momentary Assessment in Hearing Research: Current State, Challenges, and Future Directions
Authors: Holube Inga , von Gablenz Petra , Bitzer Jörg
Published: October 2020

Common methods to assess hearing deficits and the benefit of hearing devices include retrospective questionnaires and speech tests under controlled conditions. As typically applied, both approaches suffer from serious limitations regarding their ecological validity. An alternative approach rapidly gaining widespread use is ecological momentary assessment (EMA), which employs repeated assessments of individual everyday situations. Smartphones facilitate the implementation of questionnaires and rating schemes to be administered in the real life of study participants or customers, during or shortly after an experience. In addition, objective acoustical parameters extracted from head- or body-worn microphones and/or settings from the hearing aid’s signal processing unit can be stored alongside the questionnaire data. The advantages of using EMA include participant-specific, context-sensitive information on activities, experienced challenges, and preferences. However, to preserve the privacy of all communication partners and bystanders, the law in many countries does not allow audio recordings, limiting the information about environmental acoustics to statistical data such as, for example, levels and averaged spectra. Other challenges for EMA are, for example, the unsupervised handling of the equipment, the trade-off between the accuracy of description and the number of similar listening situations when performing comparisons (e.g., with and without hearing aids), the trade-off between the duration of recording intervals and the amount of data collected and analyzed, the random or target-oriented reminder for subjective responses, as well as the willingness and ability of the participants to respond while doing specific tasks. This contribution reviews EMA in hearing research, its purpose, current applications, and possible future directions.
Potential of Augmented Reality Platforms to Improve Individual Hearing Aids and to Support More Ecologically Valid Research
Authors: Mehra Ravish , Brimijoin Owen , Robinson Philip , Lunner Thomas
Published: October 2020

An augmented reality (AR) platform combines several technologies in a system that can render individual “digital objects” that can be manipulated for a given purpose. In the audio domain, these may, for example, be generated by speaker separation, noise suppression, and signal enhancement. Access to the “digital objects” could be used to augment auditory objects that the user wants to hear better. Such AR platforms in conjunction with traditional hearing aids may contribute to closing the gap for people with hearing loss through multimodal sensor integration, leveraging extensive current artificial intelligence research, and machine-learning frameworks. This could take the form of an attention-driven signal enhancement and noise suppression platform, together with context awareness, which would improve the interpersonal communication experience in complex real-life situations. In that sense, an AR platform could serve as a frontend to current and future hearing solutions. The AR device would enhance the signals to be attended, but the hearing amplification would still be handled by hearing aids. In this article, suggestions are made about why AR platforms may offer ideal affordances to compensate for hearing loss, and how research-focused AR platforms could help toward better understanding of the role of hearing in everyday life.
Current Approaches to Fertility Preservation
Authors: HUMPHREYS MEREDITH , JOHNSTONE ERICA , LETOURNEAU JOSEPH M.
Published: October 2020

The 5 principal reasons a patient may consider fertility preservation are: treatment for cancer that may affect fertility, treatment for nonmalignant medical conditions that may affect fertility, planned indications, planned gender-affirming hormone therapy or surgery, or in the setting of genetic conditions that may increase the risks of premature ovarian insufficiency or early menopause. This paper will focus on describing who may consider preserving their fertility, how to provide the best clinical evaluation of those seeking fertility preservation, and current and future fertility preservation techniques. Last, we will highlight a need to continue to expand access to fertility preservation technologies.
Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines
Authors: Barcelos Isabella , Shadiack Edward , Ganetzky Rebecca D. , Falk Marni J.
Published: October 2020

Purpose of review

Primary mitochondrial disease is a highly heterogeneous but collectively common inherited metabolic disorder, affecting at least one in 4300 individuals. Therapeutic management of mitochondrial disease typically involves empiric prescription of enzymatic cofactors, antioxidants, and amino acid and other nutrient supplements, based on biochemical reasoning, historical experience, and consensus expert opinion. As the field continues to rapidly advance, we review here the preclinical and clinical evidence, and specific dosing guidelines, for common mitochondrial medicine therapies to guide practitioners in their prescribing practices.

Recent findings

Since publication of Mitochondrial Medicine Society guidelines for mitochondrial medicine therapies management in 2009, data has emerged to support consideration for using additional therapeutic agents and discontinuation of several previously used agents. Preclinical animal modeling data have indicated a lack of efficacy for vitamin C as an antioxidant for primary mitochondrial disease, but provided strong evidence for vitamin E and N-acetylcysteine. Clinical data have suggested L-carnitine may accelerate atherosclerotic disease. Long-term follow up on L-arginine use as prophylaxis against or acute treatment for metabolic strokes has provided more data supporting its clinical use in individuals with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and Leigh syndrome. Further, several precision therapies have been developed for specific molecular causes and/or shared clinical phenotypes of primary mitochondrial disease.

We provide a comprehensive update on mitochondrial medicine therapies based on current evidence and our single-center clinical experience to support or refute their use, and provide detailed dosing guidelines, for the clinical management of mitochondrial disease. The overarching goal of empiric mitochondrial medicines is to utilize therapies with favorable benefit-to-risk profiles that may stabilize and enhance residual metabolic function to improve cellular resiliency and slow clinical disease progression and/or prevent acute decompensation.
Pediatric delirium: epidemiology and outcomes
Authors: Siegel Elana J. , Traube Chani
Published: October 2020

Purpose of review

Delirium is a frequent complication of serious medical illness in children. The purpose of this review is to highlight recent data on the epidemiology and outcomes related to pediatric delirium, and discuss prevention strategies.

Recent findings

Delirium rates in the pediatric ICU are greater than 25%. Delirium in children is associated with prolonged mechanical ventilation and hospital length of stay, increased costs, and excess mortality. Pediatric delirium may affect postdischarge cognition and quality of life. Recent initiatives targeting universal screening, early mobilization, and minimization of benzodiazepine-based sedation have shown reduction in delirium prevalence.

Widespread screening is needed in critically ill children to detect and mitigate delirium. The identification of modifiable risk factors has provided an opportunity for delirium prevention. Large-scale longitudinal studies are needed to investigate the long-term sequelae of delirium in children.
Reducing Unplanned Extubations in a Level IV Neonatal Intensive Care Unit: The Elusive Benchmark
Authors: Mahaseth Maheshwar , Woldt Eunice , Zajac Mary Ellen , Mazzeo Brande , Basirico Jennie , Natarajan Girija
Published: October 2020

Introduction:

Unplanned extubation (UE) is a common adverse event in the neonatal intensive care unit (NICU). At our level IV NICU, we initiated a quality improvement project in 2012 to reduce UE rates from 7.47 to below 100 intubated days. We describe the strategies used.

Methods:

Multiple plan-do-study-act cycles were performed to address key drivers. Important interventions focused on staff education, consistent use of a new endotracheal (ET) tube securing device, 2 providers during bedside activities, documentation of ET tube position, and targeted sedation. Process measures included immediate root cause analyses for UE events and the use of the endotracheal tube securing device. The primary outcome was the UE rate per 100 intubated days.

Results:

Over a nearly 6-year study period, quarterly UE rates decreased from 7.19 to 0.66 per 100 intubated days. The proportion of neonates requiring reintubation remained stable (64%–76%). Rates of root cause analysis completion and use of the ET securing device were more than 90% in the last 3 years of the study. The majority (61%) of UE events occurred in infants with birth weights greater than 2 kg, and 46% of infants had a prior UE. UE was associated with desaturation (50%), bradycardia (22%), and the need for resuscitation (7%).

Conclusions:

This quality improvement effort in a level IV NICU achieved a reduction in UE rates to below 1 per 100 intubated days after more than 5 years. Consistency in practices and widespread communication with the staff was critical to the effort.
Coming Together to Save Babies: Our Institution’s Quality Improvement Collaborative to Improve Infant Safe Sleep Practices
Authors: Macklin Jamie R. , Bagwell Gail , Denny Sarah A. , Goleman Jane , Lloyd Julia , Reber Kris , Stoverock Linda , McClead Richard E.
Published: October 2020

Introduction:

Many hospitalized infants are not observed in an American Academy of Pediatrics-recommended safe sleep environment, which can translate to unsafe sleep practices at home. We implemented this collaborative to reduce our county’s sleep-related death rate by improving infant safe sleep practices in the freestanding children’s hospital setting and increasing safe sleep screening and education in our clinics and emergency departments (EDs).

Methods:

Physicians from our institution’s primary care clinics, EDs, neonatal intensive care units, and general inpatient units created and led multidisciplinary safe sleep teams. Teams have used standardized data tools to collect information on infant patient ages and sleep position and environment, both in the hospital and at home. Based on audit data, teams have implemented multiple Plan-Do-Study-Act cycles during this collaborative. We have calculated changes in safe sleep practices in the hospital and changes in screening and education on safe sleep behaviors over time.

Results:

Our teams have significantly increased compliance with safe sleep practices in the inpatient and neonatal intensive care unit settings (P < 0.01). We have also increased screening and education on appropriate safe sleep behaviors by ED and primary care providers (P < 0.01). Our county’s sleep-related death rate has not significantly decreased during the collaborative.

Conclusions:

Our collaborative has increased American Academy of Pediatrics-recommended safe sleep practices in our institution, and we decreased sleep-related deaths in our primary care network. We have created stronger ties to our community partners working to decrease infant mortality rates. More efforts will be needed, both within and outside of our institution, to lower our community’s sleep-related death rate.
Long-Term Orthognathic Considerations in the Pierre Robin Sequence Patient
Authors: Pfaff Miles J. , De Leon Fransia , Le Laura , Haveles Christos , Liu Claire , Berthiaume Emily , Ayeroff Julia R. , Wilson Libby F. , Lee Justine C.
Published: October 2020

Background:

One of the arguments against early intervention for micrognathia in Pierre Robin sequence is the concept that the growth of the mandible will eventually “catch up.” Long-term growth of the mandible and occlusal relationships of conservatively managed Pierre Robin sequence patients remain unknown. In this study, the authors evaluated the orthognathic surgery requirements for Pierre Robin sequence patients at skeletal maturity.

Methods:

Orthognathic surgical requirements of conservatively managed Pierre Robin sequence and isolated cleft patients (aged ≥13 years) at two institutions were reviewed and analyzed using t test, chi-square test, and Fisher’s exact test. Values of p < 0.05 were considered statistically significant.

Results:

Of the Pierre Robin sequence patients (n = 64; mean age ± SD, 17.9 ± 2.9 years), 65.6 percent were syndromic (primarily Stickler and velocardiofacial syndrome), 96.9 percent had a cleft palate, and 39.1 percent required orthognathic surgery at skeletal maturity. Nonsyndromic and syndromic Pierre Robin sequence patients demonstrated no differences in occlusal relationships or mandibular surgery frequency. The majority of Pierre Robin sequence patients requiring mandibular advancement had a class II occlusion. Comparison of Pierre Robin sequence patients to isolated cleft palate patients (n = 17) revealed a comparable frequency of orthognathic surgery between the two; however, Pierre Robin sequence patients did require mandibular advancement surgery at a greater frequency than cleft palate patients (p = 0.006).

Conclusions:

The present study found that 39.1 percent of conservatively managed Pierre Robin sequence patients required orthognathic surgery at skeletal maturity, of which the vast majority required mandibular advancement for class II malocclusion. These data suggest that mandibular micrognathia in conservatively managed Pierre Robin sequence patients may not resolve over time and may require surgical intervention.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis
Authors: Ge Yirong , Tan Sihai , Bi Jing , Rao Mei , Yu Yuli , Tian Lidan
Published: October 2020

Neuroblastoma is an important problem in children. Long noncoding RNAs (lncRNAs) exhibit important roles in tumorigenicity of neuroblastoma. However, the role and mechanism of lncRNA small nucleolar RNA host gene 16 (SNHG16) in neuroblastoma tumorigenicity remain poorly understood. Forty-six neuroblastoma samples and 28 normal tissues were harvested. The levels of SNHG16, microRNA-15b-5p (miR-15b-5p), and phosphoribosyl pyrophosphate synthetase 1 (PRPS1) were detected via quantitative reverse transcription PCR or western blot. Cell proliferation as well as cycle distribution were measured via 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell metastasis was investigated via epithelial–mesenchymal transition or transwell assay. The target relationship of miR-15b-5p and SNHG16 or PRPS1 was explored via starBase and dual-luciferase reporter assay. The role of SNHG16 in neuroblastoma in vivo was analyzed using a xenograft model. We found SNHG16 and PRPS1 levels were increased in neuroblastoma tissues and cells. SNHG16 knockdown inhibited cell proliferation, increased the cell cycle distribution at G0/G1 phase, and decreased the cells at S phase. SNHG16 overexpression caused an opposite effect. SNHG16 silence suppressed neuroblastoma cell metastasis. PRPS1 knockdown constrained cell proliferation and metastasis and regulated cell cycle distribution. miR-15b-5p was sponged by SNHG16 and directly targeted PRPS1. miR-15b-5p knockdown or PRPS1 overexpression mitigated the influence of SNHG16 silence on cell cycle, proliferation, and metastasis. SNHG16 knockdown reduced xenograft tumor growth. In conclusion, SNHG16 downregulation suppressed neuroblastoma tumorigenicity by regulating cell cycle, proliferation, and metastasis via miR-15b-5p/PRPS1 axis.
High-resolution analogue of time-domain phonon spectroscopy in the transmission electron microscope
Authors: VandenBussche Elisah J. , Flannigan David J.
Published: October 2020

Femtosecond photoexcitation of semiconducting materials leads to the generation of coherent acoustic phonons (CAPs), the behaviours of which are linked to intrinsic and engineered electronic, optical and structural properties. While often studied with pump-probe spectroscopic techniques, the influence of nanoscale structure and morphology on CAP dynamics can be challenging to resolve with these all-optical methods. Here, we used ultrafast electron microscopy (UEM) to resolve variations in CAP dynamics caused by differences in the degree of crystallinity in as-prepared and annealed GaAs lamellae. Following
in situ
femtosecond photoexcitation, we directly imaged the generation and propagation dynamics of hypersonic CAPs in a mostly amorphous and, following an
in situ
photothermal anneal, a mostly crystalline lamella. Subtle differences in both the initial hypersonic velocities and the asymptotic relaxation behaviours were resolved via construction of space-time contour plots from phonon wavefronts. Comparison to bulk sound velocities in crystalline and amorphous GaAs reveals the influence of the mixed amorphous-crystalline morphology on CAP dispersion behaviours. Further, an increase in the asymptotic velocity following annealing establishes the sensitivity of quantitative UEM imaging to both structural and compositional variations through differences in bonding and elasticity. Implications of extending the methods and results reported here to elucidating correlated electronic, optical and structural behaviours in semiconducting materials are discussed.

This article is part of a discussion meeting issue ‘Dynamic
in situ
microscopy relating structure and function'.
Biological physics by high-speed atomic force microscopy
Authors: Casuso Ignacio , Redondo-Morata Lorena , Rico Felix
Published: October 2020

While many fields have contributed to biological physics, nanotechnology offers a new scale of observation. High-speed atomic force microscopy (HS-AFM) provides nanometre structural information and dynamics with subsecond resolution of biological systems. Moreover, HS-AFM allows us to measure piconewton forces within microseconds giving access to unexplored, fast biophysical processes. Thus, HS-AFM provides a tool to nourish biological physics through the observation of emergent physical phenomena in biological systems. In this review, we present an overview of the contribution of HS-AFM, both in imaging and force spectroscopy modes, to the field of biological physics. We focus on examples in which HS-AFM observations on membrane remodelling, molecular motors or the unfolding of proteins have stimulated the development of novel theories or the emergence of new concepts. We finally provide expected applications and developments of HS-AFM that we believe will continue contributing to our understanding of nature, by serving to the dialogue between biology and physics.

This article is part of a discussion meeting issue ‘Dynamic
in situ
microscopy relating structure and function’.