With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, ...and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore cross-cutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.
The purpose of this study was to examine the effects of PPAR-gamma agonist rosiglitazone, relative to sulfonylureas, on circulating levels of adiponectin and the prothrombotic factor, plasminogen ...activator inhibitor (PAI)-1, in type 2 diabetic patients, and to investigate, in animal models, whether the antithrombotic action of rosiglitazone was mediated through adiponectin.
Our clinical study (n=64) showed that after 24-week add-on therapy, the rosiglitazone group had a greater mean reduction in plasma PAI-1 levels (25%, versus 12% in sulfonylurea group, P=0.002). Stepwise multiple linear regression analysis identified the reduction in plasma fasting glucose and the rise in adiponectin levels to be independently associated with the reduction in PAI-I concentration in the rosiglitazone-treated patients. Rosiglitazone (20 mg/kg/d) reduced adipose tissue PAI-1 mRNA expression and its plasma levels in wild-type C57 mice with diet-induced obesity (P<0.001), but this suppressive effect was attenuated in adiponectin knockout mice. Adenovirus-mediated overexpression of adiponectin led to a significant suppression of adipose tissue PAI-1 expression and its circulating concentrations in db/db diabetic mice. Our in vitro study demonstrated that recombinant adiponectin directly inhibited PAI-1 production in 3T3-L1 adipocytes.
The antithrombotic effect of rosiglitazone is mediated, at least in part, through the suppressive effect of adiponectin on PAI-1 production.
This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral ...transmission to the infant.
A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020-February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes.
Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 5.4 vs. 31.1 5.3 years; mean standard deviation (SD);
< .001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval CI: 1.00, 1.21;
= 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58;
= 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50;
= 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62;
< 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33;
= 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period.
These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission.
· SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes.. · The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy.. · The proportion of vertical transmission from mother to fetus was 0.3%.
Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have ...been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class exhibits potent viral entry inhibition against H1N1 A/California/04/2009 (CA09) virus. LPAF-a class antibodies derive from the HV2-70 gene and contain a “Tyr-Gly-Asp”-motif, which occludes the HA-sialic acid binding site as revealed by a co-crystal structure with HA. Both germline-reverted and mature LPAF antibodies potently neutralize CA09 virus and have nanomolar affinities for CA09 HA. Moreover, increased frequencies for LPFA-a class antibodies are observed in humans after a single vaccination. Overall, this work highlights the identification of a multidonor class of head-directed influenza-neutralizing antibodies and delineates the mechanism of their recurrent elicitation in humans.
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•Analysis of HV2-70-derived antibodies reveals basis for a multidonor “LPAF-a” class•LPAF-a.01 antibody inserts extended CDR H3 into influenza sialic acid-binding site•Germline-reverted LPAF-a class antibodies have nanomolar affinity for CA09 antigen•Increased frequency of LPAF-a class antibodies in humans after CA09 vaccination
Multidonor influenza-neutralizing antibodies targeting hemagglutinin-head regions may have vaccine utility. Cheung et al. report a HV2-70-derived multidonor class, the “LPAF-a” antibody class, which targets the hemagglutinin head and can be commonly observed in humans after a single vaccination. Recurrent elicitation is attributed to tight binding between hemagglutinin and germline LPAF-a class antibodies.
Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy ...and dosing is needed.
To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.
Multicenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019.
People were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week's dose, or placebo.
The primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 none to 10 being worst or most intense) using the mean score at baseline (from days -3 to -1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day -1) to the mean step count from week 3 (from days 19 to 21).
Among the 160 people randomized, 156 were included in the primary analyses (median age, 72 years IQR, 67 to 78 years; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -0.3 95% CI, -0.9 to 0.4) or between the 16 mg/d of morphine group and the placebo group (mean difference, -0.3 95%, CI, -1.0 to 0.4). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -1453 95% CI, -3310 to 405), between the 16 mg/d of morphine group and the placebo group (mean difference, -1312 95% CI, -3220 to 596), between the 24 mg/d of morphine group and the placebo group (mean difference, -692 95% CI, -2553 to 1170), or between the 32 mg/d of morphine group and the placebo group (mean difference, -1924 95% CI, -47 699 to 921).
Among people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness.
ClinicalTrials.gov Identifier: NCT02720822.
The role of an atomic-layer thick periodic Y–O array in inducing the epitaxial growth of single-crystal hexagonal YAlO3 perovskite (H-YAP) films was studied using high-angle annular dark-field and ...annular bright-field scanning transmission electron microscopy in conjunction with a spherical aberration-corrected probe and in situ reflection high-energy electron diffraction. We observed the Y–O array at the interface of amorphous atomic layer deposition (ALD) sub-nano-laminated (snl) Al2O3/Y2O3 multilayers and GaAs(111)A, with the first film deposition being three cycles of ALD-Y2O3. This thin array was a seed layer for growing the H-YAP from the ALD snl multilayers with 900 °C rapid thermal annealing (RTA). The annealed film only contained H-YAP with an excellent crystallinity and an atomically sharp interface with the substrate. The initial Y–O array became the bottom layer of H-YAP, bonding with Ga, the top layer of GaAs. Using a similar ALD snl multilayer, but with the first film deposition of three ALD-Al2O3 cycles, there was no observation of a periodic atomic array at the interface. RTA of the sample to 900 °C resulted in a non-uniform film, mixing amorphous regions and island-like H-YAP domains. The results indicate that the epitaxial H-YAP was induced from the atomic-layer thick periodic Y–O array, rather than from GaAs(111)A.
Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, and is currently in clinical trials. Preclinical studies have established ...antitumor activity of rhApo2L/TRAIL in models of epithelial cancers; however, efficacy in non-Hodgkin lymphoma (NHL) models is not well studied. Of 7 NHL cell lines tested in vitro, rhApo2L/TRAIL stimulated apoptosis in BJAB, Ramos RA1, and DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types of NHL, augmented rhApo2L/TRAIL-induced caspase activation in Ramos RA1 and DoHH2 but not BJAB or SC-1 cells, through modulation of intrinsic rather than extrinsic apoptosis signaling. In vivo, rhApo2L/TRAIL and rituximab cooperated to attenuate or reverse growth of tumor xenografts of all 4 of these cell lines. Depletion of natural killer (NK) cells or serum complement substantially reduced combined efficacy against Ramos RA1 tumors, suggesting involvement of antibodydependent cell- and complement-mediated cytotoxicity. Both agents exhibited greater activity against disseminated than subcutaneous BJAB xenografts, and worked together to inhibit or abolish disseminated tumors and increase survival. Moreover, rhApo2L/TRAIL helped circumvent acquired rituximab resistance of a Ramos variant. These findings provide a strong rationale for clinical investigation of rhApo2L/TRAIL in combination with rituximab as a novel strategy for NHL therapy.
This study aims to compare radiographic healing rates of Austin bunionectomies in smokers, nonsmokers, and secondhand smokers. Delayed bone healing has been linked to cigarette smoking previously, ...but no study is known to have examined smoking in relation to elective foot surgery. We hypothesized that smoking will delay bone healing after elective foot surgery. Surgical patients were placed into 1 of 3 cigarette smoking–related groups. Nicotine dependence was measured by the standardized modified Fagerström est and a urine cotinine test. Bone healing was determined via examination of postsurgical radiographs. Outcomes were assessed with 1-way analyses of variance. Forty-six patients were prospectively evaluated. There were 17 smokers, 12 secondhand smokers, and 17 nonsmokers. Healing time after Austin bunionectomy was 69 days (SD = 26.0), 120 days (SD = 55.3), and 78 days (SD = 19.1) in nonsmokers, smokers, and secondhand smokers, respectively. It was noted that as urine cotinine number increased, the healing time also increased (Pearson correlation = –.314, P < .01). The same was noted with the score associated with the Fagerström questionnaire, showing an increase in healing time with an increase in score (Pearson correlation = –.128, P < .05). The osteotomy of a smoker took 1.73 times longer to reach radiographic bone consolidation than that of a nonsmoker. This equates to a 42% increase in time to bone healing in the smoking patient. Increased healing time was also correlated to increased urine cotinine and a higher Fagerström number. Smoking is shown to delay radiographic healing. Level of Clinical Evidence: 2
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