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Modelling the impact of atmospheric turbulence is not often encountered in aircraft noise auralizations despite its relevance to human-ear perception. As sound waves propagating through turbulent media undergo modulations, observable in phase and amplitude fluctuations, the plausibility of aircraft noise auralizations is increased by taking this effect into account. This paper presents an extension of a method first developed by Rietdijk et al., for modelling these fluctuations for spherical sound waves travelling through randomly inhomogeneous media. The extensions of the method presented in this paper are: (1) Height-dependent von Kármán spectra are implemented to model slanted or vertical sound propagation. (2) An overlap-add-method is introduced to model a moving sound source when height-dependent changes of turbulence characteristics are considered. (3) Easier to measure input parameters for the (meteorological) conditions are implemented, like e.g. the day time or relative humidity. The method is integrated into a global framework dedicated to engine noise simulation, propagation and auralization, developed and validated by the German Aerospace Center (DLR). A good match with measured functions of phase and amplitude fluctuations are observed, as well as realistic reproduction of spectrograms, time signals and the psychoacoustic fluctuation strength of the auralizations with respect to real flyovers.

Cochlear implants can restore hearing in people with severe hearing loss and have a significant impact on communication, social integration, self-esteem, and quality of life. However, whether and how much clinical benefit is derived from cochlear implants varies significantly by patient and is influenced by the etiology and extent of hearing loss, medical comorbidities, and preexisting behavioral and psychosocial issues. In patients with underlying psychosis, concerns have been raised that the introduction of auditory stimuli could trigger hallucinations, worsen existing delusions, or exacerbate erratic behavior. This concern has made psychosis a relative contraindication to cochlear implant surgery. This is problematic because there is a lack of data describing this phenomenon and because the psychosocial benefits derived from improvement in auditory function may be a critical intervention for treating psychosis in some patients. The objective of this report is to provide an ethical framework for guiding clinical decision-making on cochlear implant surgery in the hearing impaired with psychosis.

AbstractBackgroundMeckel’s diverticula result from incomplete obliteration and regression of the omphaloenteric duct and are the most common congenital intestinal malformations. Many Meckel’s diverticula remain asymptomatic and are discovered as incidental findings. They present a diagnostic challenge.MethodsWe report the case of a 35-year-old man who presented with an acute abdomen and ileus. Computed tomography of the abdomen showed a mechanical small bowel ileus. There was a calibre jump in the terminal ileum with a round endoluminal definable hyperdense structure of almost 2 cm in diameter.ResultsAn exploratory laparoscopy was performed revealing an inflamed Meckel’s diverticulum with impacted enterolith as the cause of the intestinal obstruction.ConclusionIn symptomatic Meckel’s diverticula, haemorrhage and obstruction are the most common complications. The development of ileus due to a Meckel’s diverticulum with an enterolith is considered extremely rare but should be taken into account.

Siglec-7 regulates immune cell activity and is a promising target for immunomodulation. Here, we report the discovery of novel sialic acid derivatives binding to Siglec-7. Synthesis and affinity measurements are complemented by high-quality models of sialoside–Siglec-7 complexes based on molecular dynamics (MD) simulations on the microsecond time scale. We provide details for the predicted binding modes for the new ligands, e.g., that an extension of the carbon backbone leads to a different molecular interaction pattern with the receptor and the nearby water structure than found for known Siglec-7 ligands. Further on, we uncover some shortcomings of the GLYCAM06 and GAFF2 force fields when used for the simulation of sialoside-based glycomimetics. Our results open new opportunities for the rational design of Siglec-7 inhibitors. In addition, we provide strategies on how to use and visualize MD simulations to describe and investigate sialoside–Siglec complexes in general.

Modern processors use branch prediction and speculative execution to maximize performance. For example, if the destination of a branch depends on a memory value that is in the process of being read, CPUs will try to guess the destination and attempt to execute ahead. When the memory value finally arrives, the CPU either discards or commits the speculative computation. Speculative logic is unfaithful in how it executes, can access the victim's memory and registers, and can perform operations with measurable side effects. Spectre attacks involve inducing a victim to speculatively perform operations that would not occur during correct program execution and which leak the victim's confidential information via a side channel to the adversary. This paper describes practical attacks that combine methodology from side-channel attacks, fault attacks, and return-oriented programming that can read arbitrary memory from the victim's process. More broadly, the paper shows that speculative execution implementations violate the security assumptions underpinning numerous software security mechanisms, such as operating system process separation, containerization, just-in-time (JIT) compilation, and countermeasures to cache timing and side-channel attacks. These attacks represent a serious threat to actual systems because vulnerable speculative execution capabilities are found in microprocessors from Intel, AMD, and ARM that are used in billions of devices. Although makeshift processor-specific countermeasures are possible in some cases, sound solutions will require fixes to processor designs as well as updates to instruction set architectures (ISAs) to give hardware architects and software developers a common understanding as to what computation state CPU implementations are (and are not) permitted to leak. [ABSTRACT FROM AUTHOR]

The article presents Meltdown and discusses its performance, evaluation, and countermeasures. According to the article, Meltdown is an attack which exploits hardware vulnerabilities in the way the processor enforces memory isolation. The authors note that it successfully leaked kernel memory on unpatched operating systems including Linux, Windows, and Android.

Alkyne-based Raman tags have proven their utility for biological imaging. Although the alkynyl stretching mode is a relatively strong Raman scatterer, the detection sensitivity of alkyne-tagged compounds is ultimately limited by the magnitude of the probe’s Raman response. In order to improve the performance of alkyne-based Raman probes, we have designed several tags that benefit from π–π conjugation as well as from additional n−π conjugation with a sulfur linker. We show that the sulfur linker provides additional enhancement and line width narrowing, offering a simple yet effective strategy for improving alkyne-based Raman tags. We validate the utility of various sulfur-linked alkyne tags for cellular imaging through stimulated Raman scattering microscopy.

Multicomponent bioluminescence imaging in vivorequires an expanded collection of tissue-penetrant probes. Toward this end, we generated a new class of near-infrared (NIR) emitting coumarin luciferin analogues (CouLuc-3s). The scaffolds were easily accessed from commercially available dyes. Complementary mutant luciferases for the CouLuc-3 analogues were also identified. The brightest probes enabled sensitive imaging in vivo. The CouLuc-3 scaffolds are also orthogonal to popular bioluminescent reporters and can be used for multicomponent imaging applications. Collectively, this work showcases a new set of bioluminescent tools that can be readily implemented for multiplexed imaging in a variety of biological settings.

AlScN/GaN heterostructures with their high sheet carrier density (ns) in the two-dimensional electron gas (2DEG) have a high potential for high-frequency and high-power electronics. The abruptness of the heterointerface plays a key role in the 2DEG confinement, and the presence of interlayers (AlN, AlGaN) affects nsand electron mobility (μ) and determines the sheet resistance (Rsh). AlScN/GaN heterostructures suitable for high-electron mobility transistors (HEMT) with and without a nominal AlN interlayer were grown by metal–organic chemical vapor deposition (MOCVD) and characterized electrically and structurally to gain a systematic insight into the unintentional formation and control of graded AlGaN interlayers by diffusion of atoms at the heterointerface. The AlN interlayer increases nsfrom 2.52 × 1013cm–2to 3.25 × 1013cm–2and, as calculated by one-dimensional Schrödinger–Poisson simulations, improves the 2DEG confinement. The barrier growth temperature was varied from 900 °C to 1200 °C to investigate the effect of the thermal budget on diffusion. Growth at 900 °C reduces the thickness of the graded AlGaN interlayer and improves the 2DEG confinement, leading to Rshof 211 Ω/sq, nsof 2.98 × 1013cm–2, and μ of 998 cm2/(Vs).

Cell-to-cell communications are critical to biological processes ranging from embryonic development to cancer progression. Several imaging strategies have been developed to capture such interactions, but many are challenging to deploy in thick tissues and other complex environments. Here, we report a platform termed Luminescence to Observe and Track Intercellular Interactions (LOTIIS). The approach features split fragments of a luciferase enzyme that reassemble when target cells come into proximity. One fragment is secreted by “sender” cells, and the complementary piece is secreted by “receiver” cells. Split reporter assembly is facilitated by a single chain variable fragment (scFv)–peptide interaction on the receiver cell, resulting in localized light production. We demonstrate that LOTIIS can rapidly label cells in close proximity in a time- and distance-dependent fashion. The platform is also compatible with bioluminescence resonance energy transfer probes for multiplexed imaging. Collectively, these data suggest that LOTIIS will enable a variety of cellular interactions to be tracked in biological settings.

Pressure-induced structural modifications in silicate melts play a crucial role in controlling dynamic processes in the deep interiors of the Earth and other planets. The correlation between structural and macroscopic properties of silicate liquids (densification, viscosity, chemical differentiation, etc.), however, remains poorly understood. Here we report the evolution of structural modifications and elastic properties of MgSiO3glass to pressures up to ~70 GPa using a combination of experimental techniques, including micro-confocal Raman spectroscopy, angle-dispersive X‑ray scattering, and Brillouin spectroscopy in the diamond-anvil cell. Our combined data set provides consistent and complementary evidence of a series of pressure-induced structural modifications in MgSiO3glass at ~2, ~8, ~20, and ~40 GPa. Based on these results, a structural evolution model for MgSiO3glass is proposed. We also discuss the role of Mg-O component in MgSiO3and Mg2SiO4glasses in controlling pressure-induced structural modifications and mechanical responses in these supercooled liquids.

Bioluminescence imaging with luciferase–luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with phasor analysis, a method commonly used to distinguish spectrally similar fluorophores. We built a camera-based microscope equipped with special optical filters to directly assign phasor locations to unique luciferase–luciferin pairs. Six bioluminescent reporters were easily resolved in live cells, and the readouts were quantitative and instantaneous. Multiplexed imaging was also performed over extended time periods. Bioluminescent phasor further provided direct measures of resonance energy transfer in single cells, setting the stage for dynamic measures of cellular and molecular features. The merger of bioluminescence with phasor analysis fills a long-standing void in imaging capabilities, and will bolster future efforts to visualize biological events in real time and over multiple length scales.

The thermal conductivity of bridgmanite, the primary constituent of the Earth's lower mantle, has been investigated using diamond anvil cells at pressures up to 85 GPa and temperatures up to 3,100 K. We report the results of time‐domain optical laser flash heating and X‐ray Free Electron Laser heating experiments from a variety of bridgmanite samples with different Al and Fe contents. The results demonstrate that Fe or Fe,Al incorporation in bridgmanite reduces thermal conductivity by about 50% in comparison to end‐member MgSiO3at the pressure‐temperature conditions of Earth's lower mantle. The effect of temperature on the thermal conductivity at 28–60 GPa is moderate, well described as k=k300(300/T)a${k={k}_{300}(300/T)}^{a}$, where ais 0.2–0.5. The results yield thermal conductivity of 7.5–15 W/(m × K) in the thermal boundary layer of the lowermost mantle composed of Fe,Al‐bearing bridgmanite. Heat transport from the Earth's core and mantle to the surface drives plate tectonics and is crucial for sustaining the magnetic field which shields the surface from the solar wind. To quantify the heat transport process across the core‐mantle boundary layer, it is important to know thermal conductivity of major constituent minerals of the lower mantle in the region. Bridgmanite, which was called silicate perovskite, is the most abundant mineral in the lower mantle. Here we measured thermal conductivity on lab‐grown bridgmanite with different Fe and Al compositions compressed at the tips of two opposing diamonds to reproduce relevant pressures in the mantle. To obtain thermal conductivity, we applied optical and X‐ray Free Electron Lasers combined with optical spectroscopy and X‐ray diffraction to heat and measure time‐dependent temperature distributions of the sample. Our study provides relevant high pressure‐temperature data sets to better constrain the heat flux across the core‐mantle boundary. We measured thermal conductivity of Fe,Al‐bearing bridgmanite, the most abundant mineral in the Earth's lower mantle, up to 85 GPa and 3,100 KFinite‐element calculations to temperatures obtained from laser flash and X‐ray Free Electron Laser heating measurements are fitted to evaluate temperature effect on conductivityWe assessed pressure, temperature, composition effects on thermal conductivity of bridgmanite at the thermal boundary layer of the lowermost mantle We measured thermal conductivity of Fe,Al‐bearing bridgmanite, the most abundant mineral in the Earth's lower mantle, up to 85 GPa and 3,100 K Finite‐element calculations to temperatures obtained from laser flash and X‐ray Free Electron Laser heating measurements are fitted to evaluate temperature effect on conductivity We assessed pressure, temperature, composition effects on thermal conductivity of bridgmanite at the thermal boundary layer of the lowermost mantle

Coronary obstruction (CO) is a rare but critical complication of transcatheter aortic valve implantation. It is associated with significant morbidity and mortality. This comprehensive review elucidates the evolving landscape of CO risk assessment and management strategies in the contemporary era of transcatheter aortic valve implantation. Drawing upon recent advances in computed tomography angiography, we delve into the nuanced evaluation of anatomic parameters crucial for predicting CO risk. Furthermore, this review explores the utility of interventional and surgical techniques, including chimney stenting and leaflet modification systems, in mitigating CO complications. In summary, this review serves as a practical guide for clinicians navigating the complexities of CO prevention and management in the evolving landscape of transcatheter aortic valve implantation, with the goal of optimizing patient outcomes and ensuring procedural success.

In situ high-pressure and high-temperature X-ray diffraction studies on magnesiochromite, MgCr2O4, and a natural chromite, (Mg,Fe)(Al,Cr)2O4, using a laser-heated diamond-anvil cell technique were performed at pressures to ~45 GPa. Our results on MgCr2O4at ~15 GPa showed temperature-induced dissociation of MgCr2O4to Cr2O3+MgO below ~1500 K and formation of modified ludwigite (mLd)-type Mg2Cr2O5+Cr2O3above ~1500 K. Above 20 GPa, only a single phase with the CaTi2O4-type structure of MgCr2O4was observed at 1400–2000 K. A second-order Birch-Murnaghan fit to pressure-volume data for the CaTi2O4-type phase of MgCr2O4yields zero-pressure volume (V0) = 264.4(8) Å3and bulk modulus (K0) = 185.4(4) GPa, and for the CaTi2O4-type structure of natural (Mg,Fe)(Al,Cr)2O4yields V0= 261(1) Å3and K0= 175.4(2) GPa. A second-order Birch-Murnaghan fit to pressure-volume data of mLd-type Mg2Cr2O5yields V0= 338.9(8) Å3and K0= 186.5(6) GPa. The obtained high-pressure phase relations of chromite spinels can be used as an indicator for shock pressure in impact rocks and meteorites. The bulk moduli of the high-pressure phases of MgCr2O4and FeCr2O4can help develop a thermodynamic model for Mg and Fe end-member spinels in the upper mantle and transition zone.

In our latest communication, we proved experimentally that the ionic surfactant’s surface excess is exclusively determined by the size of the hydrated counterion.[Lunkenheimer, Langmuir,2017, 33, 10216−1022410.1021/acs.langmuir.7b00786]. However, at this stage of research, we were unable to decide whether this does only hold for the two or three lightest ions of lithium, sodium, and potassium, respectively. Alternatively, we could also consider the surface excess of the heavier hydrated alkali ions of potassium, rubidium, and cesium, having practically identical ion size, as being determined by the cross-sectional area of the related anionic extended chain residue. The latter assumption has represented state of art. Searching for reliable experimental results on the effect of the heavier counterions on the boundary layer, we have extended investigations to the amphiphiles’ solutions of concentrations above the critical concentration of micelle formation (cmc).We provided evidence that the super-micellar solutions’ equilibrium surface tension will remain constant provided the required conditions are followed. The related σcmc-value represents a parameter characteristic of the ionic surfactant’s adsorption and micellization behavior. Evaluating the amphiphile’s surface excess obtained from adsorption as a function of the related amphiphile’s σcmc-value enables you to calculate the radius of the hydrated counterion valid in sub- and super-micellar solution likewise. The σcmc-value is directly proportional to the counterion’s diameter concerned. Taking additionally into account the radii of naked ions known from crystal research, we succeeded in exactly discriminating the hydrated alkali ions’ size from each other. There is a distinct sequence of hydration radii in absolute scale following the inequality, Li+> Na+> K+> (NH4)+> Rb+> Cs+. Therefore, we have to extend our model of counterion effectiveness put forward in our previous communication. It represents a general principle of the counterion effect.

Purpose: Trauma-mediated peripheral nerve axon injury invariably involves structural alteration of the axonal plasmalemma cell membrane. Increased axonal membrane permeability to electrolytes results in metabolic stress and axonal degeneration if the axon does not seal. Poloxamer 188 (P188) is a linear multiblock copolymer composed of a hydrophobic polyoxypropylene (POP) block in the middle with polyethylene glycol (PEG) blocks on both ends. The central POP block concentrates at sites of cell membrane disruption and catalyzes sealing of disrupted cellular membranes. We tested the hypothesis that intravenously administered P188 (9800 Da, 0.2 mM) can accelerate distal axon recovery after sciatic nerve crush injury using an established axonotemetic model. Methods: A crush injury was performed on the sciatic nerve of thirty female Sprague-Dawley rats. Rats were randomized to receive either 0.2 mM P188 or Dextran, administered 1 h after crush injury. Compound nerve action potentials (CNAP) and density of neurofilament distal to the point of injury were analyzed on post-crush day (PCD) 4, 14, and 21. Results: A significant improvement in axonal conduction for animals treated with P188 was observed for PCD 4 and PCD 14 (p< 0.01). The segment of axon distal to the site of injury in the P188-treated group demonstrated significant increase in nerve fiber density on PCD4 (p< 0.01). Conclusion: Therefore, a single dose of intravenous P188 administered 1 h after crush injury to rat sciatic nerve resulted in more rapid structural and functional nerve recovery. Lay Summary: Nerve injuries are common in day-to-day physical trauma. On a molecular level, nerve injury is precipitated by damage to the nerve’s cell membrane, which disrupts the delicate balance of the cellular environment and leads to cell death. There are molecules that can repair ruptured cell membranes by inserting themselves into it and effectively resealing the cell. Copolymer P188 is one such molecules which can be injected intravenously and selectively targets injured cell membranes. In this study, we tested the hypothesis that copolymer P188 injected intravenously into rats following peripheral nerve injury could facilitate the functional recovery of the nerve.

Die interprofessionelle Fallbesprechung ist kein Selbstläufer. Sie braucht eine Ko-Konstruktion interprofessioneller Zusammenarbeit in den Einrichtungen als "Räume des Lernens" (Prescher, et al. 2021). Aus einer bildungstheoretischen Perspektive heraus wird der Ansatz eines feldtheoretisch-strukturdynamischen Zugangs beschrieben. Mit Hilfe der Gewissheits-Zustimmungsmatrix nach Stacey (1996) wird der Blick auf ein interprofessionelles Verständnis einer Zusammenarbeit gelegt, bei dem einem Transformationsverständnis als Mehrebenenbegriff gefolgt wird. Transformative Lernprozesse sind dabei sowohl planvoll und gesteuert als auch ungesteuert und systemspezifisch kontingent angelegt. Daraus wird im Beitrag ein Modell eines feldtheoretisch-transformationalen Bildungsprozesses entwickelt, dass die Mikroebene der Selbsttransformation mit der Meso- und Makroebene der Organisation als organisationsspezifisches Prozessmodell zur erfahrungsbetonenden Ko-Konstruktion interprofessioneller Zusammenarbeit verbindet.

Didaktische Modelle sind der Katalysator dafür, unterschiedliche Planungsentscheidungen in der Gestaltung von Unterricht zusammenzuführen und in geschickte didaktische Arrangements zu überführen, die idealerweise kompetenzstiftend sein sollen. Dabei werden immer wieder neue Ansätze entwickelt, bei denen ein kritischer Blick in die Praxis zeigt, dass diese dort nicht ankommen und nicht gelebt werden. Im Beitrag wird daher die alltägliche Lehrpraxis kritisch gewürdigt und herausgearbeitet, dass es sich lohnt, auf die Klassiker der Didaktik zu schauen, weil Modelle wie die Bildungstheoretische und die Lehr-Lerntheoretische Didaktik das Wissen beschreiben, das Lehrer*Innen alltäglich in ihren Schulen und ihrem Unterricht anwenden. Warum? Weil es einfach lebenspraktisch vernünftig erscheint.

Value engineering is a term used by contractors to describe potential cost savings that can be made on a project without adversely affecting quality, performance, or integrity. COst savings are [...]

Gentle and precise tissue dissection reduces collateral tissue damage and preserves its structural quality for optimizing healing. This is particularly true for peripheral nerve neurorrhaphy. Axon regeneration kinetics across the repair is dependent on the amount of intraneural fibrosis. The purpose of this study was to determine whether scalpel blade smoothness was a deterministic factor in the kinetics of postneurorrhaphy peripheral axon regeneration.

Bioluminescence imaging with luciferase–luciferin pairs is routinely used to monitor cellular functions. Multiple targets can be visualized in tandem using luciferases that process unique substrates, but only a handful of such orthogonal probes are known. Multiplexed studies require additional robust, light-emitting molecules. In this work, we report new luciferins for orthogonal imaging that comprise disubstituted cores. These probes were found to be bright emitters with various engineered luciferases. The unique patterns of light output also provided insight into enzyme–substrate interactions necessary for productive emission. Screening studies identified mutant luciferases that could preferentially process the disubstituted analogues, enabling orthogonal imaging with existing bioluminescent reporters. Further mutational analyses revealed the origins of substrate selectivity. Collectively, this work provides insights into luciferase–luciferin features relevant to bioluminescence and expands the number of probes for multicomponent tracking.

ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of the phospholipids are members of the PC family, but only a subset of mainly 16.0-18:1 PC and 16:0-18:2 PC variants are present. To elucidate whether ABCB4 is the key discriminator in this enrichment of specific PC lipids, we used in vitro studies to identify crucial determinants in substrate selection. We demonstrate that PC-lipid moieties alone are insufficient for stimulating ABCB4 ATPase activity, and that at least two acyl chains and the backbone itself are required for a productive interaction. The nature of the fatty acids, like length or saturation has a quantitative impact on the ATPase activity. Our data demonstrate a two-step enrichment and protective function of ABCB4 to mitigate the harsh detergent effect of the bile salts, because ABCB4 can translocate more than just the PC-lipid variants found in bile.

Bioluminescence imaging with luciferase-luciferin pairs is commonly used for monitoring biological processes in cells and whole organisms. Traditional bioluminescent probes are limited in scope, though, as they cannot be easily distinguished in biological environments, precluding efforts to visualize multicellular processes. Additionally, many luciferase-luciferin pairs emit light that is poorly tissue penetrant, hindering efforts to visualize targets in deep tissues. To address these issues, we synthesized a set of π-extended luciferins that were predicted to be red-shifted luminophores. The scaffolds were designed to be rotationally labile such that they produced light only when paired with luciferases capable of enforcing planarity. A luciferin comprising an intramolecular “lock” was identified as a viable light-emitting probe. Native luciferases were unable to efficiently process the analog, but a complementary luciferase was identified via Rosetta-guided enzyme design. The unique enzyme–substrate pair is red-shifted compared to well-known bioluminescent tools. The probe set is also orthogonal to other luciferase-luciferin probes and can be used for multicomponent imaging. Four substrate-resolved luciferases were imaged in a single session. Collectively, this work provides the first example of Rosetta-guided design in engineering bioluminescent tools and expands the scope of orthogonal imaging probes.

Background: Talus secundarius is a very rare accessory bone at the lateral border of the foot. It is attached via a synchondrosis or small synostosis to the lateral aspect of the talar body and has additional facets to the tip of the lateral malleolus and the superior aspect of the calcaneus.Methods: Over a period of 8 years, we have seen 5 patients with 6 cases of talus secundarius with an average age of 17 years at first presentation to the senior author. One ossicle was an incidental finding and completely asymptomatic. In the other 5 cases, the average duration of symptoms was 21 months at that time. In 3 cases, additional accessory bones were seen around the talus.Results: The average size of the ossicles was 18 × 12 × 8 mm. Complete removal resulted in considerable pain reduction without further functional restriction in 4 cases. Two cases (1 asymptomatic, 1 with mild intermittent symptoms) were treated nonoperatively. The average Foot Function Index improved from 22.6 to 4.8 in all patients and from 31.0 to 4.5 in the patients treated with excision for symptomatic talus secundarius (P< .01).Conclusion: The knowledge of accessory bones at the foot is important, as missed diagnosis may lead to prolonged course of pain and unnecessary protection in the affected patients. Resection of symptomatic ossicles substantially reduces pain, but patients have to be counseled that some symptoms may prevail in a congenital deformity.Level of Evidence: Level IV, prospective case series.

The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial showed that, compared with usual care, a structured remote patient management (RPM) intervention done over 12-months reduced the percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause death. The aim of the study was to evaluate whether this clinical benefit seen for the RPM group during the initial 12 month follow-up of the TIM-HF2 trial would be sustained 1 year after stopping the RPM intervention.

Recently, hybrid processing using evaporation and spin-coating has been applied for the fabrication of perovskite silicon tandem solar cells with record power conversion efficiencies (PCEs) of 25.2%. To achieve large area, high-throughput production of solar cells, spray-coating, a well-known scalable method used in the industry, has advantages over spin-coating. Therefore, we apply a hybrid method using the evaporation of PbI2 and spraying of methylammonium iodide (MAI) for the fabrication of perovskite solar cells. This article presents a systematic study of sprayed MAI amount and processing parameters on the performance of solar cells. We find clear correlations between the processing parameters of the sprayed MAI, the crystallinity of CH3NH3PbI3 and the PCE of the resulting PSCs. High crystallinity and morphology of the CH3NH3PbI3 film is achieved using a slow nozzle speed of 30 mm·s-1. An average PCE of 11.6% ± 3.1% (maximum PCE of 14.3%, stabilized PCE of 10%) was achieved with a normalized MAI amount of 3.4, which represent the flow rate of 0.17 ml·min-1, nozzle speed of 30 mm·s-1, MAI concentration of 9 mg·mL-1, and one single spray pass. Moreover, we successfully show a proof-of-concept of this method for the deposition of homogenous perovskite layers on pyramidal textured silicon.

Bioluminescence imaging with luciferase enzymes and luciferin small molecules is a well-established technique for tracking cells and other biological features in rodent models. Despite its popularity, bioluminescence has long been hindered by a lack of distinguishable probes. Here we present a method to rapidly identify new substrate-selective luciferases for multicomponent imaging. Our strategy relies on parallel screening of luciferin analogues with panels of mutant enzymes. The compiled data set is then analyzed in silicoto uncover mutually orthogonal sets. Using this approach, we screened 159 mutant enzymes with 12 luciferins. Thousands of orthogonal pairs were revealed with sufficient selectivity for use in biological environments. Over 100 pairs were validated in vitro, and three were applied in cell and animal models. The parallel screening method is both generalizable and scalable and will streamline the search for larger collections of orthogonal probes.

This article summarizes the contemporary ethics framework for helping to guide physicians in challenging medical decision-making. It provides a definition and a rationale for using the best interest standard, the harm principle, shared decision making, and the patient’s right to an open future. It then applies these principles to a series of common ethical scenarios encountered in clinical practice.

Bioluminescence imaging enables the sensitive tracking of cell populations and the visualization of biological processes in living systems. Bioluminescent luciferase/luciferin pairs with far-red and near-infrared emission benefit from the reduced competitive absorption by blood and tissue while also facilitating multiplexing strategies. Luciferins with extended π-systems, such as AkaLumine and recently reported CouLuc-1 and -3, can be used for bioluminescence imaging in this long wavelength regime. Existing synthetic routes to AkaLumine and similar π-extended compounds require a multistep sequence to install the thiazoline heterocycle. Here we detail the development of a two-step strategy for accessing these molecules via a Horner–Wadsworth–Emmons reaction and cysteine condensation sequence from readily available aldehyde starting materials. We detail an improved synthesis of AkaLumine, as well as the corresponding two-carbon homologues, Tri- and Tetra-AkaLumine. We then extended this approach to prepare coumarin- and naphthalene-derived luciferins. These putative luciferins were tested against a panel of luciferases to identify capable emitters. Of these, an easily prepared naphthalene derivative exhibits photon emission on par with that of the broadly used Akaluc/AkaLumine pair with similar emission maxima. Overall, this chemistry provides efficient access to several bioluminescent probes for a variety of imaging applications.

Dicyanoacetylene (C4N2) is an unusual energetic molecule with alternating triple and single bonds (think miniature, nitrogen-capped carbyne), which represents an interesting starting point for the transformation into extended carbon–nitrogen solids. While pressure-induced polymerization has been documented for a wide variety of related molecular solids, precise mechanistic details of reaction pathways are often poorly understood and the characterization of recovered products is typically incomplete. Here, we study the high-pressure behavior of C4N2and demonstrate polymerization into a disordered carbon–nitrogen network that is recoverable to ambient conditions. The reaction proceeds via activation of linear molecules into buckled molecular chains, which spontaneously assemble into a polycyclic network that lacks long-range order. The recovered product was characterized using a variety of optical spectroscopies, X-ray methods, and theoretical simulations and is described as a predominately sp2network comprising “pyrrolic” and “pyridinic” rings with an overall tendency toward a two-dimensional structure. This understanding offers valuable mechanistic insights into design guidelines for next-generation carbon nitride materials with unique structures and compositions.

Bioluminescence is widely used for real-time imaging in living organisms. This technology features a light-emitting reaction between enzymes (luciferases) and small molecule substrates (luciferins). Photons produced from luciferase–luciferin reactions can penetrate through heterogeneous tissue, enabling readouts of physiological processes. Dozens of bioluminescent probes are now available and many are routinely used to monitor cell proliferation, migration, and gene expression patterns in vivo.

A general method to synthesize substituted butenolides from hydroxymethylcyclopropenones is reported. Functionalized cyclopropenones undergo ring-opening reactions with catalytic amounts of phosphine, forming reactive ketene ylides. These intermediates can be trapped by pendant hydroxy groups to afford target butenolide scaffolds. The reaction proceeds efficiently in diverse solvents and with low catalyst loadings. Importantly, the cyclization is tolerant of a broad range of functional groups, yielding a variety of α- and γ-substituted butenolides.

We report a new ligation of cyclopropeniminium ions with bioorthogonal phosphines. Cyclopropeniminium scaffolds are sufficiently stable in biological media and, unlike related isomers, react with functionalized phosphines via formal 1,2-addition to a π-system. The ligation can be performed in aqueous solution and is compatible with existing bioorthogonal transformations. Such mutually compatible reactions are useful for multicomponent labeling.

I've been getting Sky & Telescope since 1969 and have worked my way up to observing with a 16-inch Newtonian reflector for the last 5 years. Since most of my [...]

Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation. We aimed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population.

Cyclopropenethiones are reported as new bioorthogonal reagents. These motifs react readily with substituted phosphines to provide thiocarbonyl adducts. In some cases, the ligations are >300-fold faster than analogous reactions with bioorthogonal cyclopropenones. Dialkyl cyclopropenethiones are also stable in aqueous buffers and can be used for biomolecule labeling in vitroand in cell lysate. The rapid reactivity and biocompatibility of cyclopropenethiones suggest that they will be useful probes for cellular studies.

ThO2is an important material for understanding the heat budget of Earth’s mantle, as well as the stability of nuclear fuels at extreme conditions. We measured the in situ high-pressure, high-temperature phase behavior of ThO2to ~60 GPa and ~2500 K. It undergoes a transition from the cubic fluorite-type structure (thorianite) to the orthorhombic α-PbCl2cotunnite-type structure between 20 and 30 GPa at room temperature. Prior to the transition at room temperature, an increase in unit-cell volume is observed, which we interpret as anion sub-lattice disorder or pre-transformation “melting” (Boulfelfel et al. 2006). The thermal equation of state parameters for both thorianite [V0= 26.379(7), K0= 204(2), αKT= 0.0035(3)] and the high-pressure cotunnite-type phase [V0= 24.75(6), K0= 190(3), αKT= 0.0037(4)] are reported, holding K0′$\begin{array}{} K_0^{'} \end{array} $fixed at 4. The similarity of these parameters suggests that the two phases behave similarly within the deep Earth. The lattice parameter ratios for the cotunnite-type phase change significantly with pressure, suggesting a different structure is stable at higher pressure.

To find the thermodynamically stable crystal structure of CaSiO3perovskite (CaPv) at high pressure and 300 K, we have conducted synchrotron X-ray diffraction (XRD) on thermally stress-annealed samples in a Ne pressure medium in the diamond-anvil cell at 28–62 GPa. Rietveld refinements of the diffraction patterns are significantly improved in fitting the positions and intensities of the split lines of CaPv if the starting model is a tetragonal perovskite-type structure with the SiO6octahedral rotation around the tetragonal c-axis. The result is in contrast with other previous experiments, but is consistent with first-principles calculations, reconciling the discrepancy between computations and experiments on the crystal structure of CaPv. We attribute the observed difference to the formation of the thermodynamically more stable phase under improved stress conditions in our experiments. Our fitting shows that the bulk modulus of CaPv is 223 ± 6 GPa when its pressure derivative fixed to 4, which is also consistent with first-principles calculations. The previous observations of the diffraction patterns of CaPv inconsistent with the first-principles studies could be due to the formation of a metastable crystal structure of CaPv under elevated deviatoric stresses.