Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Non-photochemical laser-induced nucleation.

Non-photochemical laser-induced nucleation (NPLIN) is the formation of a new phase from a metastable phase by the action of light on matter. Using millijoule, nanosecond laser pulses at visible and near-infrared wavelengths, it is possible to form the new phase localized in the volume of the beam. In the case of nucleating molecular solids, the laser polarization may have an effect on the particular polymorph that is formed. Despite the huge potential for applications of NPLIN, there is uncertainty regarding the molecular-scale mechanism, and various possible scenarios may well be relevant to nucleation in general and not just NPLIN. In this Perspective, the discovery and phenomenology of NPLIN are described, putative mechanisms are outlined, and some observations on the broader class of nucleation phenomena are given.

Supersaturation dependence of glycine polymorphism using laser-induced nucleation, sonocrystallization and nucleation by mechanical shock.

The nucleation of glycine from aqueous supersaturated solution has been studied using non-photochemical laser-induced nucleation (NPLIN), ultrasound (sonocrystallization), and mechanical shock of sample vials. It was found that at higher supersaturation, samples were more susceptible to nucleation and produced more of the γ-glycine polymorph. The results are described in terms of a mechanism common to all three nucleation methods, involving the induction of cavitation events and pressure shockwaves. The switch in preference from α- to γ-glycine was observed to occur over a narrower range of supersaturation values for NPLIN. We attribute this to induction of cavitation events with higher energies, which result in higher localized pressures and supersaturations. Experiments on NPLIN using circularly versus linearly polarized light showed no evidence for binary polarization switching control of glycine polymorphism.

Polarization independence of laser-induced nucleation in supersaturated aqueous urea solutions.

In a seminal report on laser-induced nucleation in aqueous supersaturated solutions (Phys. Rev. Lett., 1996, 77, 3475) it was noted that needle-shaped crystals of urea were aligned with the direction of the electric field of the linearly polarized laser pulse. The results gave rise to a new mechanism for control of crystal nucleation involving alignment of solute molecules (optical Kerr effect) now commonly known as non-photochemical laser-induced nucleation (NPLIN). Recent theoretical and experimental work has cast doubts on the optical Kerr effect mechanism. In the present letter we present results from digital imaging of urea-crystal growth immediately following laser-induced nucleation. Analysis of the data shows no statistically significant correlation between crystal angle and direction of linear polarization. The results overturn a long-held result that has shaped theoretical and experimental studies of NPLIN.

Effects of nanoparticle heating on the structure of a concentrated aqueous salt solution.

The effects of a rapidly heated nanoparticle on the structure of a concentrated aqueous salt solution are studied using molecular dynamics simulations. A diamond-like nanoparticle of radius 20 Å is immersed in a sodium-chloride solution at 20% above the experimental saturation concentration and equilibrated at T = 293 K and P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is observed that after 2-3 ns, the salt ions are depleted far more than water molecules from a proximal zone 15-25 Å from the nanoparticle surface. This leads to a transient reduction in molality in the proximal zone and an increase in ion clustering in the distal zone. At longer times, ions begin to diffuse back into the proximal zone. It is speculated that the formation of proximal and distal zones, and the increase in ion clustering, plays a role in the mechanism of nonphotochemical laser-induced nucleation.

Laser-induced nucleation of carbon dioxide bubbles.

A detailed experimental study of laser-induced nucleation (LIN) of carbon dioxide (CO2) gas bubbles is presented. Water and aqueous sucrose solutions supersaturated with CO2 were exposed to single nanosecond pulses (5 ns, 532 nm, 2.4-14.5 MW cm(-2)) and femtosecond pulses (110 fs, 800 nm, 0.028-11 GW cm(-2)) of laser light. No bubbles were observed with the femtosecond pulses, even at high peak power densities (11 GW cm(-2)). For the nanosecond pulses, the number of bubbles produced per pulse showed a quadratic dependence on laser power, with a distinct power threshold below which no bubbles were observed. The number of bubbles observed increases linearly with sucrose concentration. It was found that filtering of solutions reduces the number of bubbles significantly. Although the femtosecond pulses have higher peak power densities than the nanosecond pulses, they have lower energy densities per pulse. A simple model for LIN of CO2 is presented, based on heating of nanoparticles to produce vapor bubbles that must expand to reach a critical bubble radius to continue growth. The results suggest that non-photochemical laser-induced nucleation of crystals could also be caused by heating of nanoparticles.

Measurements of large optical rotary dispersion in the adipose eyelid of Atlantic mackerel (Scomber scombrus).

Collagen is the most prevalent of Nature's structural proteins, and is found in the extracellular matrices of animals. The structures of collagen molecules and aggregates are chiral, which leads to the rotation of transmitted, plane-polarized light. Here, it is shown that the concentrations of chiral molecules and aggregates in the optically transparent, adipose eyelid of Atlantic mackerel (Scomber scombrus) can be so high, that plane-polarized light in the visible spectrum is rotated by tens to hundreds of degrees, depending on wavelength (the optical rotatory dispersion (ORD)). This gives rise to intensely coloured images of eyelid samples when illuminated with white light and viewed between crossed polarizers. The ORD in the visible spectrum is measured with monochromatic light sources, and using this dispersion, the variation of optical thickness within a sample (proportional to collagen concentration and path length) is determined. The agreement between observed and simulated white-light images is almost perfect. While collagen provides vital mechanical rigidity to animal tissue, it might also possess optical properties that are useful for vision and camouflage.

Interfacial ion-transfer mechanism for the intense luminescence observed when opening self-seal envelopes.

The unusually intense luminescence (commonly called triboluminescence) observed when opening self-seal envelopes has been studied using spectroscopy. Emissions from gas-phase species due to electrical discharge were observed, which in the case of air consists of vibronic transitions of N(2)(C(3)Π(u)-B(3)Π(g)) in the ultraviolet (UV) region (280-400 nm). However, the major cause of the intense blue luminescence (around 435 nm) is attributed to optical brightening agents added to the white paper. The results suggest that the emission from the brightening agents may be caused by two mechanisms: (i) fluorescence due to excitation by the UV light from the gas discharge and (ii) nonoptically, by electron transfer. The electrical discharge results from contact electrification; we propose a mechanism for the charge transfer involving a net migration of hydroxide anions out of the paper into the wet latex-adhesive during drying.

Non-photochemical laser-induced nucleation of supercooled glacial acetic acid.

Non-photochemical laser-induced nucleation (NPLIN) of glacial acetic acid (GAA) is demonstrated. The fraction of samples nucleated depends linearly on peak laser power density at low powers (<100 MW cm(-2)) with a threshold of (9.0 ± 4.2) MW cm(-2); at higher laser powers the fraction reaches a plateau of 0.75 ± 0.24 (2σ uncertainties). A simple model based on polarizability of pre-nucleating clusters gives a value of the solid-liquid interfacial tension γ(SL) = 15.5 mJ m(-2). It is hoped that the results will stimulate new developments in experimental and theoretical studies of cluster structure and nucleation in liquids.

Deep ultraviolet and visible crystalloluminescence of sodium chloride.

A protocol has been developed for production of intense crystalloluminescence (XTL) from sodium chloride in aqueous solution by selective doping with transition metal salts (Ag(+), Cu(2+), and Dy(3+)). The method was used to record complete, fully dispersed deep UV-visible (200-650 nm) XTL spectra of sodium chloride for the first time. The results show conclusively that the emissions are due to dopant cations in the NaCl lattice, with no evidence for emission directly from NaCl, e.g., by triboluminescence resulting from crystalline fracture. The UV components of the XTL spectrum are attributed to single cation substituents (Ag(+) and Cu(+)), and a strong visible component (~415 nm) of the XTL is attributed to emission from silver-pair centers, (Ag(+))(2). The nature of the electronic transitions of the dopant cations is discussed. The results suggest that the timescale for transformation of a cluster to the crystalline phase is rapid, with efficient relaxation to the lowest excited electronic states of the dopant cation. This transformation is followed by photoemission of the cation in the nascent crystal.

Chiral hide-and-seek: retention of enantiomorphism in laser-induced nucleation of molten sodium chlorate.

We report the observation of non-photochemical laser-induced nucleation (NPLIN) of sodium chlorate from its melt using nanosecond pulses of light at 1064 nm. The fraction of samples that nucleate is shown to depend linearly on the peak power density of the laser pulses. Remarkably, we observe that most samples are nucleated by the laser back into the enantiomorph (dextrorotatory or levorotatory) of the solid prior to melting. We do not observe a significant dependence on polarization of the light, and we put forward symmetry arguments that rule out an optical Kerr effect mechanism. Our observations of retention of chirality can be explained by decomposition of small amounts of the sodium chlorate to form sodium chloride, which provide cavities for retention of clusters of sodium chlorate even 18 °C above the melting point. These clusters remain sub-critical on cooling, but can be activated by NPLIN via an isotropic polarizability mechanism. We have developed a heterogeneous model of NPLIN in cavities, which reproduces the experimental data using simple physical data available for sodium chlorate.

Using the near field optical trapping effect of a dielectric metasurface to improve SERS enhancement for virus detection.

In this paper, we report the effect of optical trapping on the enhancement factor for Raman spectroscopy, using a dielectric metasurface. It was found that a higher enhancement factor (up to 275%) can be obtained in a substrate immersed in water, where particles are freee to move, compared to a dried substrate, where the particles (radius [Formula: see text] nm, refractive index [Formula: see text]) are fixed on the surface. The highest enhancement is obtained at low concentrations because, this case, the particles are trapped preferentially in the regions of highest electric field (hotspots). For high concentrations, it was observed that the hotspots become saturated with particles and that additional particles are forced to occupy regions of lower field. The dielectric metasurface offers low optical absorption compared to conventional gold substrates. This aspect can be important for temperature-sensitive applications. The method shows potential for applications in crystal nucleation, where high solute supersaturation can be achieved near the high-field regions of the metasurface. The high sensitivity for SERS (surface-enhanced Raman spectroscopy) at low analyte concentrations makes the proposed method highly promising for detection of small biological particles, such as proteins or viruses.

Photofragment angular momentum distributions in the molecular frame. II. Single state dissociation, multiple state interference, and nonaxial recoil in photodissociation of polyatomic molecules.

We present an a(q) (k)(s) polarization-parameter model to describe product angular momentum polarization from the one-photon photodissociation of polyatomic molecules in the molecular frame. We make the approximation that the final photofragment recoil direction is unique and described by the molecular frame polar coordinates (alpha,phi(i)), for which the axial recoil approximation is a special case (e.g., alpha=0). This approximation allows the separation of geometrical and dynamical factors, in particular, the expression of the experimental sensitivities to each of the a(q) (k)(s) in terms of the molecular frame polar angles (chi(i),phi(i)) of the transition dipole moment mu(i). This separation is applied to the linearly polarized photodissociation of polyatomic molecules (asymmetric, symmetric, and spherical top molecules are discussed) and to all dissociation mechanisms that satisfy our recoil approximation, including those with nonaxial recoil and multiple state interference, giving important insight into the geometrical properties of the photodissociation mechanism. For example, we demonstrate that the ratio of polarization parameters A(0) (k)(aniso)/A(0) (k)(iso)=beta (where beta is the spatial anisotropy parameter) is an indication that the dynamics can be explained by a single dissociative state. We also show that for asymmetric top photodissociation, the sensitivity to the a(1) (k)(s) parameters, which can arise either from single-surface or multiple-surface interference mechanisms, is nonzero only for components of the transition dipole moments within the v-d plane of the recoil frame.

(2+1) laser-induced fluorescence of spin-polarized hydrogen atoms.

We report the measurement of the spin polarization of hydrogen (SPH) atoms by (2+1) laser-induced fluorescence, produced via the photodissociation of thermal HBr molecules with circularly polarized 193 nm light. This scheme, which involves two-photon laser excitation at 205 nm and fluorescence at 656 nm, offers an experimentally simpler polarization-detection method than the previously reported vacuum ultraviolet detection scheme, allowing the detection of SPH atoms to be performed more straightforwardly, from the photodissociation of a wide range of molecules and from a variety of collision experiments.

Myosin-XVa Controls Both Staircase Architecture and Diameter Gradation of Stereocilia Rows in the Auditory Hair Cell Bundles.

Mammalian hair cells develop their mechanosensory bundles through consecutive phases of stereocilia elongation, thickening, and retraction of supernumerary stereocilia. Many molecules involved in stereocilia elongation have been identified, including myosin-XVa. Significantly less is known about molecular mechanisms of stereocilia thickening and retraction. Here, we used scanning electron microscopy (SEM) to quantify postnatal changes in number and diameters of the auditory hair cell stereocilia in shaker-2 mice (Myo15sh2) that lack both "long" and "short" isoforms of myosin-XVa, and in mice lacking only the "long" myosin-XVa isoform (Myo15∆N). Previously, we observed large mechanotransduction current in young postnatal inner (IHC) and outer (OHC) hair cells of both these strains. Stereocilia counts showed nearly identical developmental retraction of supernumerary stereocilia in control heterozygous, Myo15sh2/sh2, and Myo15∆N/∆N mice, suggesting that this retraction is largely unaffected by myosin-XVa deficiency. However, myosin-XVa deficiency does affect stereocilia diameters. In control, the first (tallest) and second row stereocilia grow in diameter simultaneously. However, the third row stereocilia in IHCs grow only until postnatal day 1-2 and then become thinner. In OHCs, they also grow slower than taller stereocilia, forming a stereocilia diameter gradation within a hair bundle. The sh2 mutation disrupts this gradation and makes all stereocilia nearly identical in thickness in both IHCs and OHCs, with only subtle residual diameter differences. All Myo15sh2/sh2 stereocilia grow postnatally including the third row, which is not a part of normal development. Serial sections with focused ion beam (FIB)-SEM confirmed that diameter changes of Myo15sh2/sh2 IHC and OHC stereocilia resulted from corresponding changes of their actin cores. In contrast to Myo15sh2/sh2, Myo15∆N/∆N hair cells develop prominent stereocilia diameter gradation. Thus, besides building the staircase, the short isoform of myosin-XVa is essential for controlling the diameter of the third row stereocilia and formation of the stereocilia diameter gradation in a hair bundle.

Spatial control of crystal nucleation in agarose gel.

Spatial and temporal control of crystal nucleation is demonstrated by nonphotochemical laser-induced nucleation of an aqueous agarose gel prepared with supersaturated potassium chloride. The location of nucleation was controlled by means of an optical mask; crystals were only observed in the area exposed to near-infrared laser radiation. The dependence of nucleation on laser power was measured, and the results suggest that the agarose gel reduces the effective supersaturation of the aqueous potassium chloride.

Laser detection of spin-polarized hydrogen from HCl and HBr photodissociation: comparison of H- and halogen-atom polarizations.

Thermal HCl and HBr molecules were photodissociated using circularly polarized 193 nm light, and the speed-dependent spin polarization of the H-atom photofragments was measured using polarized fluorescence at 121.6 nm. Both polarization components, described by the a(0)(1)(perpendicular) and Re[a(1)(1)(parallel, perpendicular)] parameters which arise from incoherent and coherent dissociation mechanisms, are measured. The values of the a(0)(1)(perpendicular) parameter, for both HCl and HBr photodissociation, are within experimental error of the predictions of both ab initio calculations and of previous measurements of the polarization of the halide cofragments. The experimental and ab initio theoretical values of the Re[a(1)(1)(parallel, perpendicular)] parameter show some disagreement, suggesting that further theoretical investigations are required. Overall, good agreement occurs despite the fact that the current experiments photodissociate molecules at 295 K, whereas previous measurements were conducted at rotational temperatures of about 15 K.

Preparation of oriented and aligned H(2) and HD by stimulated Raman pumping.

Stimulated Raman pumping has been used to prepare oriented and aligned samples of H(2)(nu=1,J=1,2,3) and HD(nu=1,J=2) under collision-free conditions using the (1,0) S(0), S(1), Q(1), Q(2), and O(3) lines. The M-sublevel anisotropies were interrogated by polarized [2+1] resonance-enhanced multiphoton ionization via the (0,1) O(2), O(3), and S(1) lines of the E,F (1)Sigma(g) (+)-X (1)Sigma(g) (+) system. The optical excitation schemes employed in this study generate highly oriented and aligned molecular ensembles. We show that the H(2)(nu=1,J=2,M=0) and H(2)(nu=1,J=2,M=2) samples retain their initial polarization for greater than 100 ns and are therefore suitable candidates for targets or projectiles in future scattering experiments.

Postpartum Group A Streptococcus Case Series: Reach Out to Infection Prevention!

A series of postpartum Streptococcus pyogenes infections prompted an investigation to rule out potential transmission by a health care worker. None of the hospital staff screened were colonized. All isolates were determined to be unrelated by molecular methods, including whole-genome sequencing. Thus, nosocomial transmission was considered unlikely.

A case of Wohlfahrtiimonas chitiniclastica bacteremia in continental United States.

INTRODUCTION: Wohlfahrtiimonas chitiniclastica has been associated with open wound infections, cellulitis, osteomyelitis, and bacteremia. CASE PRESENTATION: We report the case of a 41 year old woman with history of congenital myelomeningocele, paraplegia and extensive decubitus ulcers that developed W. chitiniclastica bacteremia secondary to an infected ulcer. CONCLUSION: W. chitiniclastica is an emerging human pathogen that can be readily identified by MALDI-TOF or sequencing.