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The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
ABSTRACT IMPACT: Plasma and CSF are not reliable estimates of drug exposure in tissue compartments relevant for treatment and prevention of infectious diseases. OBJECTIVES/GOALS: Globally, high dose fluconazole is widely used in the management of cryptococcal meningitis. While it is known to readily penetrate into cerebrospinal (CSF), less is known about drug concentrations in brain parenchymal tissues. Similarly, distribution of fluconazole into gynecological tissues has not been robustly characterized. METHODS/STUDY POPULATION: With informed consent from next-of-kin, we conducted autopsies within 24h of death for hospitalized Ugandans receiving fluconazole for treatment or secondary prophylaxis of cryptococcal meningitis. Dosing history was abstracted from medical chart and caregiver interviews. Fluconazole concentrations were determined using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) in plasma, CSF, 10 brain compartments (frontal, parietal, and occipital lobes, corpus callosum, globus pallidus, hippocampus, midbrain, medulla oblongata, spinal cord, and choroid plexus) and 4 female genital compartments (cervix, vagina, ovary, and uterus), depending on tissue availability. Descriptive statistics of tissue to plasma ratios were used to describe concentrations relative to plasma. RESULTS/ANTICIPATED RESULTS: Fluconazole concentrations were measured in available tissues of 21 individuals with detectable fluconazole in plasma. Daily doses of fluconazole were 200 mg (n=4), 400 mg (n=1), 800 mg (n=4), 1200 mg (n=9) or unknown (n=3). CSF concentrations (n=10) ranged from 93-1380% (median 100%) of plasma while brain concentrations (n=3) across all 10 compartments ranged from 45% to 89% (median 69%) of plasma. In the female genital tract, cervical concentrations (n=10) were 9-78% (median 65%) of plasma and in the 2 individuals with available tissue, concentrations in vaginal, ovarian, and uterine tissues were similar to cervix, ranging from 63-105% of plasma. DISCUSSION/SIGNIFICANCE OF FINDINGS: Measuring drug concentrations directly in tissues, the presumed site of action, improves estimates of drug efficacy. While fluconazole concentrations in CSF were similar to plasma, actual brain tissues were consistently lower. Concentrations were similar between upper and lower female genital tracts, but were consistently lower than plasma.
Mme L., 90 ans, était traitée en 3e intention par rispéridone 0,5 mg puis 1 mg durant 7 jours dans le cadre d’un trouble anxieux généralisé décompensé avec agitation. Une rhabdomyolyse et une cytolyse hépatique ont été découvertes fortuitement, associées à des signes cliniques de syndrome malin des neuroleptiques (SMNL) débutant. Les anomalies cliniques et paracliniques ont été résolutives 7 jours après l’arrêt de la rispéridone.
Nous avons réalisé une revue de la littérature sur le SMNL chez le sujet âgé de plus de 65 ans dans la base de données gratuite de Pubmed entre 1985 et 2014.
Parmi les patients retrouvés, la majorité étaient des hommes âgés de plus de 80 ans. Les pathologies traitées étaient représentées pour moitié par des pathologies neurodégénératives. Les différentes classes d’antipsychotiques étaient représentées, avec notamment : halopéridol, dropéridol, chlorpromazine, trifluopérazine, méthotrimeprazine, loxapine, sulpiride ainsi que risperidone et olanzapine. L’augmentation récente des doses semblait être un facteur favorisant. Les délais d’apparition étaient immédiat (< 48 h), précoce (2 à 15 jours), ou tardif (> 15 jours) dans la plupart des cas. Les signes cardinaux du SMNL étaient présents dans la plupart des cas, associés à une augmentation systématique des CPK. On note 50 % de mortalité.
La spécificité chez le sujet âgé semble être une mortalité plus élevée qu’en population générale. Les facteurs de risque tels les pathologies neurodégénératives sont analysés. Les auteurs interrogent le rapport bénéfice/risque de la prescription des antipsychotiques chez la personne âgée.
The YBJ equation (Young & Ben Jelloul, J. Marine Res., vol. 55, 1997, pp. 735–766) provides a phase-averaged description of the propagation of near-inertial waves (NIWs) through a geostrophic flow. YBJ is obtained via an asymptotic expansion based on the limit
is the Burger number of the NIWs. Here we develop an improved version, the YBJ+ equation. In common with an earlier improvement proposed by Thomas, Smith & Bühler (J. Fluid Mech., vol. 817, 2017, pp. 406–438), YBJ+ has a dispersion relation that is second-order accurate in
. (YBJ is first-order accurate.) Thus both improvements have the same formal justification. But the dispersion relation of YBJ+ is a Padé approximant to the exact dispersion relation and with
of order unity this is significantly more accurate than the power-series approximation of Thomas et al. (2017). Moreover, in the limit of high horizontal wavenumber
, the wave frequency of YBJ+ asymptotes to twice the inertial frequency
. This enables solution of YBJ+ with explicit time-stepping schemes using a time step determined by stable integration of oscillations with frequency
. Other phase-averaged equations have dispersion relations with frequency increasing as
(Thomas et al. 2017): in these cases stable integration with an explicit scheme becomes impractical with increasing horizontal resolution. The YBJ+ equation is tested by comparing its numerical solutions with those of the Boussinesq and YBJ equations. In virtually all cases, YBJ+ is more accurate than YBJ. The error, however, does not go rapidly to zero as the Burger number characterizing the initial condition is reduced: advection and refraction by geostrophic eddies reduces in the initial length scale of NIWs so that
increases with time. This increase, if unchecked, would destroy the approximation. We show, however, that dispersion limits the damage by confining most of the wave energy to low
. In other words, advection and refraction by geostrophic flows does not result in a strong transfer of initially near-inertial energy out of the near-inertial frequency band.
The pore structure of vapour deposited ASW is poorly understood, despite its importance to fundamental processes such as grain chemistry, cooling of star forming regions, and planet formation. We studied structural changes of vapour deposited D2O on intra-molecular to 30 nm length scales at temperatures ranging from 18 to 180 K and observed enhanced mobility from 100 to 150 K. An Arrhenius type model describes the loss of surface area and porosity with a common set of kinetic parameters. The low activation energy (428 K) is commensurate with van der Waals forces between nm-scale substructures in the ice. Our findings imply that water porosity will always change with time, even at low temperatures.
Impact craters are the dominant landform on Mercury and range from the largest basins to the smallest young craters. Peak-ring basins are especially prevalent on Mercury, although basins of all forms are far undersaturated, probably the result of the extensive volcanic emplacement of intercrater plains and younger smooth plains between about 4.1 and 3.5 Ga. This chapter describes the geology of the two largest well-preserved basins, Caloris and Rembrandt, and the three smaller Raditladi, Rachmaninoff, and Mozart basins. We describe analyses of crater size–frequency distributions and relate them to populations of asteroid impactors (Late Heavy Bombardment in early epochs and the near-Earth asteroid population observable today during most of Mercury’s history), to secondary cratering, and to exogenic and endogenic processes that degrade and erase craters. Secondary cratering is more important on Mercury than on other solar system bodies and shaped much of the surface on kilometer and smaller scales, compromising our ability to use craters for relative and absolute age-dating of smaller geological units. Failure to find “vulcanoids” and satellites of Mercury suggests that such bodies played a negligible role in cratering Mercury. We describe an absolute cratering chronology for Mercury’s geological evolution as well as its uncertainties.
Despite the lack of another Flagship-class mission such as Cassini–Huygens, prospects for the future exploration of Saturn are nevertheless encouraging. Both NASA and the European Space Agency (ESA) are exploring the possibilities of focused interplanetary missions (1) to drop one or more in situ atmospheric entry probes into Saturn and (2) to explore the satellites Titan and Enceladus, which would provide opportunities for both in situ investigations of Saturn’s magnetosphere and detailed remote-sensing observations of Saturn’s atmosphere. Additionally, a new generation of powerful Earth-based and near-Earth telescopes with advanced instrumentation spanning the ultraviolet to the far-infrared promise to provide systematic observations of Saturn’s seasonally changing composition and thermal structure, cloud structures and wind fields. Finally, new advances in amateur telescopic observations brought on largely by the availability of low-cost, powerful computers, low-noise, large-format cameras, and attendant sophisticated software promise to provide regular, longterm observations of Saturn in remarkable detail.