A mindful approach to controlling intrusive thoughts.

Intrusive thoughts of negative experiences can pose a threat to our well-being. To some extent, unwanted memories can be intentionally controlled via an executive control mechanism that downregulates the occurrence of intrusions. Mindfulness training can improve executive control. It is not known whether mindfulness training can be used as an intervention to improve intentional memory control and reduce intrusions. To this end, 148 healthy participants completed a 10-day app-based mindfulness training or an active control task. At baseline, inhibitory control and working memory were assessed as measures of executive functioning. Post-mindfulness training, intrusions were assessed via the Think/No-Think task. It was expected that mindfulness training would reduce intrusions. Furthermore, we hypothesised that this would be moderated by baseline executive functioning. Results revealed that, contrary to our hypothesis, both groups increased equally in dispositional mindfulness between baseline and post-test. As such, our exploratory analysis revealed that higher dispositional mindfulness across both groups resulted in fewer intrusions and enhanced the ability to downregulate intrusions over time. Furthermore, this effect was moderated by inhibitory control at baseline. These results provide insight into factors that can improve the ability to control unwanted memories, which could have considerable implications for treatments in psychopathologies characterized by the frequent occurrence of intrusive thoughts. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 11th March, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/U8SJN .

The START domain potentiates HD-ZIPIII transcriptional activity.

The CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII) transcription factors (TFs) were repeatedly deployed over 725 million years of evolution to regulate central developmental innovations. The START domain of this pivotal class of developmental regulators was recognized over 20 years ago, but its putative ligands and functional contributions remain unknown. Here, we demonstrate that the START domain promotes HD-ZIPIII TF homodimerization and increases transcriptional potency. Effects on transcriptional output can be ported onto heterologous TFs, consistent with principles of evolution via domain capture. We also show the START domain binds several species of phospholipids, and that mutations in conserved residues perturbing ligand binding and/or its downstream conformational readout abolish HD-ZIPIII DNA-binding competence. Our data present a model in which the START domain potentiates transcriptional activity and uses ligand-induced conformational change to render HD-ZIPIII dimers competent to bind DNA. These findings resolve a long-standing mystery in plant development and highlight the flexible and diverse regulatory potential coded within this widely distributed evolutionary module.

The LeVe CPAP System for Oxygen-Efficient CPAP Respiratory Support: Development and Pilot Evaluation.

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments. Technical Development + Testing: The LeVe ("Light") CPAP system was developed using principles of frugal innovation to produce a solution of low complexity and high resource efficiency. The LeVe system exploits the air flow dynamics of electric fan blowers which are inherently suited to delivery of positive pressure at appropriate flow rates for CPAP. Laboratory evaluation demonstrated that performance of the LeVe system was equivalent to other commercially available systems used to deliver CPAP, achieving a 10 cm H2O target pressure within 2.4% RMS error and 50-70% FiO2 dependent with 10 L/min oxygen from a commercial concentrator. Pilot Evaluation: The LeVe CPAP system was tested to evaluate safety and acceptability in a group of ten healthy volunteers at Mengo Hospital in Kampala, Uganda. The study demonstrated that the system can be used safely without inducing hypoxia or hypercapnia and that its use was well-tolerated by users, with no adverse events reported. Conclusions: To provide respiratory support for the high patient numbers associated with the COVID-19 pandemic, healthcare providers require resource efficient solutions. We have shown that this can be achieved through frugal engineering of a CPAP ventilation system, in a system which is safe for use and well-tolerated in healthy volunteers. This approach may also benefit other respiratory conditions which often go unaddressed in Low and Middle Income Countries (LMICs) for want of context-appropriate technology designed for the limited oxygen resources available.

Mutation Spectra of the MRN (MRE11, RAD50, NBS1/NBN) Break Sensor in Cancer Cells.

The MRN complex (MRE11, RAD50, NBS1/NBN) is a DNA double strand break sensor in eukaryotes. The complex directly participates in, or coordinates, several activities at the break such as DNA resection, activation of the DNA damage checkpoint, chromatin remodeling and recruitment of the repair machinery. Mutations in components of the MRN complex have been described in cancer cells for several decades. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) database, we characterized all the reported MRN mutations. This analysis revealed several hotspot frameshift mutations in all three genes that introduce premature stop codons and truncate large regions of the C-termini. We also found through evolutionary analyses that COSMIC mutations are enriched in conserved residues of NBS1/NBN and RAD50 but not in MRE11. Given that all three genes are important to carcinogenesis, we propose these differential enrichment patterns may reflect a more severe pleiotropic role for MRE11.

Identifying Cancer-Relevant Mutations in the DLC START Domain Using Evolutionary and Structure-Function Analyses.

Rho GTPase signaling promotes proliferation, invasion, and metastasis in a broad spectrum of cancers. Rho GTPase activity is regulated by the deleted in liver cancer (DLC) family of bona fide tumor suppressors which directly inactivate Rho GTPases by stimulating GTP hydrolysis. In addition to a RhoGAP domain, DLC proteins contain a StAR-related lipid transfer (START) domain. START domains in other organisms bind hydrophobic small molecules and can regulate interacting partners or co-occurring domains through a variety of mechanisms. In the case of DLC proteins, their START domain appears to contribute to tumor suppressive activity. However, the nature of this START-directed mechanism, as well as the identities of relevant functional residues, remain virtually unknown. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) dataset and evolutionary and structure-function analyses, we identify several conserved residues likely to be required for START-directed regulation of DLC-1 and DLC-2 tumor-suppressive capabilities. This pan-cancer analysis shows that conserved residues of both START domains are highly overrepresented in cancer cells from a wide range tissues. Interestingly, in DLC-1 and DLC-2, three of these residues form multiple interactions at the tertiary structural level. Furthermore, mutation of any of these residues is predicted to disrupt interactions and thus destabilize the START domain. As such, these mutations would not have emerged from traditional hotspot scans of COSMIC. We propose that evolutionary and structure-function analyses are an underutilized strategy which could be used to unmask cancer-relevant mutations within COSMIC. Our data also suggest DLC-1 and DLC-2 as high-priority candidates for development of novel therapeutics that target their START domain.

The impairing effect of acute stress on suppression-induced forgetting of future fears and its moderation by working memory capacity.

Unwanted imaginations of future fears can, to some extent, be avoided. This is achieved by control mechanisms similar to those engaged to suppress and forget unwanted memories. Suppression-induced forgetting relies on the executive control network, whose functioning is impaired after exposure to acute stress. This study investigates whether acute stress affects the ability to intentionally control future fears and, furthermore, whether individual differences in executive control predict a susceptibility to these effects. The study ran over two consecutive days. On day 1, the working memory capacity of one hundred participants was assessed. Thereafter, participants provided descriptions and details of fearful episodes that they imagined might happen in their future. On day 2, participants were exposed to either the stress or no-stress version of the Maastricht Acute Stress Test, after which participants performed the Imagine/No-Imagine task. Here, participants repeatedly imagined some future fears and suppressed imaginings of others. Results demonstrated that, in unstressed participants, suppression successfully induced forgetting of the episodes' details compared to a baseline condition. However, anxiety toward these events did not differ. Acute stress was found to selectively impair suppression-induced forgetting and, further, this effect was moderated by working memory capacity. Specifically, lower working memory predicted a susceptibility to these detrimental effects. These findings provide novel insights into conditions under which our capacity to actively control future fears is reduced, which may have considerable implications for understanding stress-related psychopathologies and symptomatologies characterized by unwanted apprehensive thoughts.

Real-time frequency-encoded spatiotemporal focusing through scattering media using a programmable 2D ultrafine optical frequency comb.

Optical wavefront shaping is a powerful tool for controlling photons in strongly scattering media. Its speed, however, has been the bottleneck for in vivo applications. Moreover, unlike spatial focusing, temporal focusing from a continuous-wave source has rarely been exploited yet is highly desired for nonlinear photonics. Here, we present a novel real-time frequency-encoded spatiotemporal (FEST) focusing technology. FEST focusing uses a novel programmable two-dimensional optical frequency comb with an ultrafine linewidth to perform single-shot wavefront measurements, with a fast single-pixel detector. This technique enables simultaneous spatial and temporal focusing at microsecond scales through thick dynamic scattering media. This technology also enabled us to discover the large-scale temporal shift, a new phenomenon that, with the conventional spatial memory effect, establishes a space-time duality. FEST focusing opens a new avenue for high-speed wavefront shaping in the field of photonics.

Coherent vortex dynamics in a strongly interacting superfluid on a silicon chip.

Quantized vortices are fundamental to the two-dimensional dynamics of superfluids, from quantum turbulence to phase transitions. However, surface effects have prevented direct observations of coherent two-dimensional vortex dynamics in strongly interacting systems. Here, we overcome this challenge by confining a thin film of superfluid helium at microscale on the atomically smooth surface of a silicon chip. An on-chip optical microcavity allows laser initiation of clusters of quasi-two-dimensional vortices and nondestructive observation of their decay in a single shot. Coherent dynamics dominate, with thermal vortex diffusion suppressed by five orders of magnitude. This establishes an on-chip platform with which to study emergent phenomena in strongly interacting superfluids and to develop quantum technologies such as precision inertial sensors.

Giant vortex clusters in a two-dimensional quantum fluid.

Adding energy to a system through transient stirring usually leads to more disorder. In contrast, point-like vortices in a bounded two-dimensional fluid are predicted to reorder above a certain energy, forming persistent vortex clusters. In this study, we experimentally realize these vortex clusters in a planar superfluid: a 87Rb Bose-Einstein condensate confined to an elliptical geometry. We demonstrate that the clusters persist for long time periods, maintaining the superfluid system in a high-energy state far from global equilibrium. Our experiments explore a regime of vortex matter at negative absolute temperatures and have relevance for the dynamics of topological defects, two-dimensional turbulence, and systems such as helium films, nonlinear optical materials, fermion superfluids, and quark-gluon plasmas.

Thermally robust spin correlations between two 85Rb atoms in an optical microtrap.

The complex collisional properties of atoms fundamentally limit investigations into a range of processes in many-atom ensembles. In contrast, the bottom-up assembly of few- and many-body systems from individual atoms offers a controlled approach to isolating and studying such collisional processes. Here, we use optical tweezers to individually assemble pairs of trapped 85Rb atoms, and study the spin dynamics of the two-body system in a thermal state. The spin-2 atoms show strong pair correlation between magnetic sublevels on timescales exceeding one second, with measured relative number fluctuations 11.9 ± 0.3 dB below quantum shot noise, limited only by detection efficiency. Spin populations display relaxation dynamics consistent with simulations and theoretical predictions for 85Rb spin interactions, and contrary to the coherent spin waves witnessed in finite-temperature many-body experiments and zero-temperature two-body experiments. Our experimental approach offers a versatile platform for studying two-body quantum dynamics and may provide a route to thermally robust entanglement generation.

High-speed alignment optimization of digital optical phase conjugation systems based on autocovariance analysis in conjunction with orthonormal rectangular polynomials.

Digital optical phase conjugation (DOPC) enables many optical applications by permitting focusing of light through scattering media. However, DOPC systems require precise alignment of all optical components, particularly of the spatial light modulator (SLM) and camera, in order to accurately record the wavefront and perform playback through the use of time-reversal symmetry. We present a digital compensation technique to optimize the alignment of the SLM in five degrees of freedom, permitting focusing through thick scattering media with a thickness of 5 mm and transport scattering coefficient of 2.5 mm - 1 while simultaneously improving focal quality, as quantified by the peak-to-background ratio, by several orders of magnitude over an unoptimized alignment.

High-speed single-shot optical focusing through dynamic scattering media with full-phase wavefront shaping.

In biological applications, optical focusing is limited by the diffusion of light, which prevents focusing at depths greater than ∼1 mm in soft tissue. Wavefront shaping extends the depth by compensating for phase distortions induced by scattering and thus allows for focusing light through biological tissue beyond the optical diffusion limit by using constructive interference. However, due to physiological motion, light scattering in tissue is deterministic only within a brief speckle correlation time. In in vivo tissue, this speckle correlation time is on the order of milliseconds, and so the wavefront must be optimized within this brief period. The speed of digital wavefront shaping has typically been limited by the relatively long time required to measure and display the optimal phase pattern. This limitation stems from the low speeds of cameras, data transfer and processing, and spatial light modulators. While binary-phase modulation requiring only two images for the phase measurement has recently been reported, most techniques require at least three frames for the full-phase measurement. Here, we present a full-phase digital optical phase conjugation method based on off-axis holography for single-shot optical focusing through scattering media. By using off-axis holography in conjunction with graphics processing unit based processing, we take advantage of the single-shot full-phase measurement while using parallel computation to quickly reconstruct the phase map. With this system, we can focus light through scattering media with a system latency of approximately 9 ms, on the order of the in vivo speckle correlation time.

Focusing light through scattering media by polarization modulation based generalized digital optical phase conjugation.

Optical scattering prevents light from being focused through thick biological tissue at depths greater than ∼1 mm. To break this optical diffusion limit, digital optical phase conjugation (DOPC) based wavefront shaping techniques are being actively developed. Previous DOPC systems employed spatial light modulators that modulated either the phase or the amplitude of the conjugate light field. Here, we achieve optical focusing through scattering media by using polarization modulation based generalized DOPC. First, we describe an algorithm to extract the polarization map from the measured scattered field. Then, we validate the algorithm through numerical simulations and find that the focusing contrast achieved by polarization modulation is similar to that achieved by phase modulation. Finally, we build a system using an inexpensive twisted nematic liquid crystal based spatial light modulator (SLM) and experimentally demonstrate light focusing through 3-mm thick chicken breast tissue. Since the polarization modulation based SLMs are widely used in displays and are having more and more pixel counts with the prevalence of 4 K displays, these SLMs are inexpensive and valuable devices for wavefront shaping.

Enstrophy Cascade in Decaying Two-Dimensional Quantum Turbulence.

We report evidence for an enstrophy cascade in large-scale point-vortex simulations of decaying two-dimensional quantum turbulence. Devising a method to generate quantum vortex configurations with kinetic energy narrowly localized near a single length scale, the dynamics are found to be well characterized by a superfluid Reynolds number Re_{s} that depends only on the number of vortices and the initial kinetic energy scale. Under free evolution the vortices exhibit features of a classical enstrophy cascade, including a k^{-3} power-law kinetic energy spectrum, and constant enstrophy flux associated with inertial transport to small scales. Clear signatures of the cascade emerge for N≳500 vortices. Simulating up to very large Reynolds numbers (N=32 768 vortices), additional features of the classical theory are observed: the Kraichnan-Batchelor constant is found to converge to C^{'}≈1.6, and the width of the k^{-3} range scales as Re_{s}^{1/2}.

Emergent Non-Eulerian Hydrodynamics of Quantum Vortices in Two Dimensions.

We develop a coarse-grained description of the point-vortex model, finding that a large number of planar vortices and antivortices behave as an inviscid non-Eulerian fluid at large scales. The emergent binary vortex fluid is subject to anomalous stresses absent from Euler's equation, caused by the singular nature of quantum vortices. The binary vortex fluid is compressible, and has an asymmetric Cauchy stress tensor allowing orbital angular momentum exchange with the vorticity and vortex density. An analytic solution for vortex shear flow driven by anomalous stresses is in excellent agreement with numerical simulations of the point-vortex model.

Whole genome DNA methylation sequencing of the chicken retina, cornea and brain.

Whole genome bisulfite sequencing (WGBS) analysis of DNA methylation uses massively parallel next generation sequencing technology to characterize global epigenetic patterns and fluctuations throughout a range of tissue samples. Development of the vertebrate retina is thought to involve extensive epigenetic reprogramming during embryogenesis. The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology and retinogenesis, however, there are currently no publicly available data sets describing the developing chicken retinal methylome. Here we used Illumina WGBS analysis to characterize genome-wide patterns of DNA methylation in the developing chicken retina as well as cornea and brain in an effort to further our understanding of retina-specific epigenetic regulation. These data will be valuable to the vision research community for correlating global changes in DNA methylation to differential gene expression between ocular and neural tissues during critical developmental time points of retinogenesis in the chicken retina.

"Inline" Axial Reconstructed CT Scans Provide a Significantly Larger Assessment of C2 Pedicle Diameter for Screw Placement Compared With "Standard" Axial Scans: Implications for Surgical Planning.

STUDY DESIGN: Radiologic analysis. OBJECTIVE: The objective was to compare C2 pedicle diameter and screw feasibility on reconstructed axial computed tomography (CT) cuts created "Inline" (IL) with the intended pedicle screw tract versus unaltered "Standard" (STD) axial cuts. BACKGROUND DATA: Axial CT cuts through the C2 pedicle are commonly evaluated when planning pedicle screw fixation as medial aberrancies of the vertebral artery can significantly narrow pedicle diameter. STD axial CT cuts provided by radiology departments are typically formatted orthogonal to the long axis of the neck or the vertical plumb, which is often not IL with the axis of the intended C2 pedicle screw tract. MATERIALS AND METHODS: A total of 89 cervical spine CT scans obtained by a single radiology department over 2 years (35 male, 54 female; mean age 64.9 y) were reviewed. STD axial cuts were not manipulated but were assessed as provided. IL axial cuts were created along the intended C2 pedicle screw tract using free, open-source DICOM viewer software. Inner and outer pedicle diameters were measured on axial cuts most closely approximating the isthmus of the intended tract. RESULTS: On STD cuts, the mean outer and inner pedicle diameters were 5.05±1.45 and 2.01±1.31 mm, respectively. By contrast, IL measurements yielded significantly larger outer and inner diameters: 5.85±1.78 and 2.68±1.47 mm (P<0.01). IL measurement predicted a higher number of pedicles amenable to insertion of a 3.5 mm screw with safety margins of 1 to 3 mm. CONCLUSIONS: Reformatted IL axial cuts through the intended path of C2 pedicle screws provide significantly larger assessments of C2 pedicle diameter than those obtained on STD cuts. IL measurements predict C2 screw insertion feasibility in a substantially higher number of pedicles. As assessment of IL cuts may alter surgical decision-making at no added cost or radiation exposure, we suggest that they be obtained whenever considering C2 pedicle screw placement.

EMBRYONIC DEVELOPMENT AND A QUANTITATIVE MODEL OF PROGRAMMED DNA ELIMINATION IN MESOCYCLOPS EDAX (S. A. FORBES, 1891) (COPEPODA: CYCLOPOIDA).

The highly programmed fragmentation of chromosomes and elimination of large amounts of nuclear DNA from the presomatic cell lineages (i.e., chromatin diminution), occurs in the embryos of the freshwater zooplankton Mesocyclops edax (S. A. Forbes, 1891) (Crustacea: Copepoda). The somatic genome is reorganized and reduced to a size five times smaller even though the germline genome remains intact. We present the first comprehensive, quantitative model of DNA content throughout embryogenesis in a copepod that possesses embryonic DNA elimination. We used densitometric image analysis to measure the DNA content of polar bodies, germline and somatic nuclei, and excised DNA "droplets." We report: 1) variable DNA contents of polar bodies, some of which do not contain the amount corresponding to the haploid germline genome size; 2) presence of pronuclei in newly laid embryo sacs; 3) gonomeric chromosomes in the second to fourth cleavage divisions and in the primordial germ cell and primordial endoderm cell during the fifth cleavage division; 4) timing of early embryonic cell stages, elimination of DNA, and divisions of the primordial germ cell and primordial endoderm cell at 22°C; and 5) persistence of a portion of the excised DNA "droplets" throughout embryogenesis. DNA elimination is a trait that spans multiple embryonic stages and a knowledge of the timing and variability of the associated cytological events with DNA elimination will promote the study of the molecular mechanisms involved in this trait. We propose the "genome yolk hypothesis" as a functional explanation for the persistence of the eliminated DNA that might serve as a resource during postdiminution cleavage divisions.

Hybridized wavefront shaping for high-speed, high-efficiency focusing through dynamic diffusive media.

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit (typically ?1??mm). To overcome this challenge, wavefront shaping techniques that use a spatial light modulator (SLM) to correct the phase of the incident wavefront have recently been developed. These techniques are able to focus light through scattering media beyond the optical diffusion limit. However, the low speeds of typically used liquid crystal SLMs limit the focusing speed. Here, we present a method using a digital micromirror device (DMD) and an electro-optic modulator (EOM) to measure the scattering-induced aberrations, and using a liquid crystal SLM to apply the correction to the illuminating wavefront. By combining phase modulation from an EOM with the DMD's ability to provide selective illumination, we exploit the DMD's higher refresh rate for phase measurement. We achieved focusing through scattering media in less than 8 ms, which is sufficiently short for certain in vivo applications, as it is comparable to the speckle correlation time of living tissue.

Impact of insurance status on ability to return for outpatient management of pediatric supracondylar humerus fractures.

PURPOSE: Outcomes are excellent following surgical management of displaced supracondylar humerus fractures. Short delays until surgical fixation have been shown to be equivalent to immediate fixation with regards to complications. We hypothesized that insurance coverage may impact access to care and the patient's ability to return to the operating room for outpatient surgery. METHODS: A retrospective review of supracondylar humerus fractures treated at a large urban pediatric hospital from 2008 to 2012 was performed. Fractures were classified by the modified Gartland classification and baseline demographics were collected. Time from discharge to office visits and subsequent surgical fixation was calculated for all type II fractures discharged from the emergency department. Insurance status and primary carrier were collected for all patients. RESULTS: 2584 supracondylar humerus fractures were reviewed, of which 584 were type II fractures. Of the 577 type II fractures with complete records, 383 patients (61 %) were admitted for surgery and the remaining 194 were discharged with plans for outpatient follow-up. There was no difference in insurance status between patients admitted for immediate surgery. Of the 194 patients who were discharged with type 2 fractures after gentle reduction, 59 patients (30.4 %) ultimately underwent surgical fixation. Of these, 42 patients were privately insured (58.3 % of patients with private insurance), 16 had governmental insurance (15.1 %), and 1 was uninsured (6.3 %). Patients with private insurance were 2.46 times more likely to have surgery than patients with public or no insurance (p = 0.005). Of the 135 patients who did not eventually have surgery, 92 (68.1 %) were seen in the clinic. Patients with private insurance were 2.78 times more likely to be seen back in the clinic when compared to publicly insured or uninsured patients (p = 0.0152). CONCLUSIONS: Despite an equivalent number of privately insured and publicly insured patients undergoing immediate surgery for type II fractures, those with public or no insurance who were discharged were 2.46 times less likely to obtain outpatient surgery when compared to privately insured patients. Patient insurance status and the ability to follow up in a timely manner should be assessed at the time of initial evaluation in the emergency department. Level of evidence Level 3.