Identifying key health system components associated with improved outcomes to inform the reconfiguration of services for adults with rare autoimmune rheumatic diseases : a mixed methods study.

Open Access via the Elsevier agreementPeer reviewe

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p \u3c 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p \u3c 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach

The BLAST Survey of the Vela Molecular Cloud: Physical Properties of the Dense Cores in Vela-D

The Balloon-borne Large-Aperture Submillimeter Telescope (BLAST) carried out a 250, 350 and 500 micron survey of the galactic plane encompassing the Vela Molecular Ridge, with the primary goal of identifying the coldest dense cores possibly associated with the earliest stages of star formation. Here we present the results from observations of the Vela-D region, covering about 4 square degrees, in which we find 141 BLAST cores. We exploit existing data taken with the Spitzer MIPS, IRAC and SEST-SIMBA instruments to constrain their (single-temperature) spectral energy distributions, assuming a dust emissivity index beta = 2.0. This combination of data allows us to determine the temperature, luminosity and mass of each BLAST core, and also enables us to separate starless from proto-stellar sources. We also analyze the effects that the uncertainties on the derived physical parameters of the individual sources have on the overall physical properties of starless and proto-stellar cores, and we find that there appear to be a smooth transition from the pre- to the proto-stellar phase. In particular, for proto-stellar cores we find a correlation between the MIPS24 flux, associated with the central protostar, and the temperature of the dust envelope. We also find that the core mass function of the Vela-D cores has a slope consistent with other similar (sub)millimeter surveys.Comment: Accepted for publication in the Astrophysical Journal. Data and maps are available at http://blastexperiment.info

BLAST: The Mass Function, Lifetimes, and Properties of Intermediate Mass Cores from a 50 Square Degree Submillimeter Galactic Survey in Vela (l = ~265)

We present first results from an unbiased 50 deg^2 submillimeter Galactic survey at 250, 350, and 500 micron from the 2006 flight of the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). The map has resolution ranging from 36 arcsec to 60 arcsec in the three submillimeter bands spanning the thermal emission peak of cold starless cores. We determine the temperature, luminosity, and mass of more than one thousand compact sources in a range of evolutionary stages and an unbiased statistical characterization of the population. From comparison with C^(18)O data, we find the dust opacity per gas mass, kappa r = 0.16 cm^2 g^(-1) at 250 micron, for cold clumps. We find that 2% of the mass of the molecular gas over this diverse region is in cores colder than 14 K, and that the mass function for these cold cores is consistent with a power law with index alpha = -3.22 +/- 0.14 over the mass range 14 M_sun < M < 80 M_sun. Additionally, we infer a mass-dependent cold core lifetime of t_c(M) = 4E6 (M/20 M_sun)^(-0.9) years - longer than what has been found in previous surveys of either low or high mass cores, and significantly longer than free fall or likely turbulent decay times. This implies some form of non-thermal support for cold cores during this early stage of star formation.Comment: Accepted for publication in the Astrophysical Journal. Maps available at http://blastexperiment.info

Phase 1 Study of Two Merozoite Surface Protein 1 (MSP1(42)) Vaccines for Plasmodium falciparum Malaria

OBJECTIVES: To assess the safety and immunogenicity of two vaccines, MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel, targeting blood-stage Plasmodium falciparum parasites. DESIGN: A Phase 1 open-label, dose-escalating study. SETTING: Quintiles Phase 1 Services, Lenexa, Kansas between July 2004 and November 2005. PARTICIPANTS: Sixty healthy malaria-naïve volunteers 18–48 y of age. INTERVENTIONS: The C-terminal 42-kDa region of merozoite surface protein 1 (MSP1(42)) corresponding to the two allelic forms present in FVO and 3D7 P. falciparum lines were expressed in Escherichia coli, refolded, purified, and formulated on Alhydrogel (aluminum hydroxide). For each vaccine, volunteers in each of three dose cohorts (5, 20, and 80 μg) were vaccinated at 0, 28, and 180 d. Volunteers were followed for 1 y. OUTCOME MEASURES: The safety of MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel was assessed. The antibody response to each vaccine was measured by reactivity to homologous and heterologous MSP1(42), MSP1(19), and MSP1(33) recombinant proteins and recognition of FVO and 3D7 parasites. RESULTS: Anti-MSP1(42) antibodies were detected by ELISA in 20/27 (74%) and 22/27 (81%) volunteers receiving three vaccinations of MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel, respectively. Regardless of the vaccine, the antibodies were cross-reactive to both MSP1(42)-FVO and MSP1(42)-3D7 proteins. The majority of the antibody response targeted the C-terminal 19-kDa domain of MSP1(42), although low-level antibodies to the N-terminal 33-kDa domain of MSP1(42) were also detected. Immunofluorescence microscopy of sera from the volunteers demonstrated reactivity with both FVO and 3D7 P. falciparum schizonts and free merozoites. Minimal in vitro growth inhibition of FVO or 3D7 parasites by purified IgG from the sera of the vaccinees was observed. CONCLUSIONS: The MSP1(42)/Alhydrogel vaccines were safe and well tolerated but not sufficiently immunogenic to generate a biologic effect in vitro. Addition of immunostimulants to the Alhydrogel formulation to elicit higher vaccine-induced responses in humans may be required for an effective vaccine

PTF10nvg: An Outbursting Class I Protostar in the Pelican/North American Nebula

During a synoptic survey of the North American Nebula region, the Palomar Transient Factory (PTF) detected an optical outburst (dubbed PTF10nvg) associated with the previously unstudied flat or rising spectrum infrared source IRAS 20496+4354. The PTF R-band light curve reveals that PTF10nvg brightened by more than 5 mag during the current outburst, rising to a peak magnitude of R~13.5 in 2010 Sep. Follow-up observations indicate PTF10nvg has undergone a similar ~5 mag brightening in the K band, and possesses a rich emission-line spectrum, including numerous lines commonly assumed to trace mass accretion and outflows. Many of these lines are blueshifted by ~175 km/s from the North American Nebula's rest velocity, suggesting that PTF10nvg is driving an outflow. Optical spectra of PTF10nvg show several TiO/VO bandheads fully in emission, indicating the presence of an unusual amount of dense (> 10^10 cm^-3), warm (1500-4000 K) circumstellar material. Near-infrared spectra of PTF10nvg appear quite similar to a spectrum of McNeil's Nebula/V1647 Ori, a young star which has undergone several brightenings in recent decades, and 06297+1021W, a Class I protostar with a similarly rich near--infrared emission line spectrum. While further monitoring is required to fully understand this event, we conclude that the brightening of PTF10nvg is indicative of enhanced accretion and outflow in this Class-I-type protostellar object, similar to the behavior of V1647 Ori in 2004-2005.Comment: Accepted to the Astronomical Journal; 21 pages, 11 figures, 6 tables in emulateapj format; v2 fixes typo in abstract; v3 updates status to accepted, adjusts affiliations, adds acknowledgmen

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness