Multi-campaign ship and aircraft observations of marine cloud condensation nuclei and droplet concentrations.

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates.

Atmospheric concentrations and sources of black carbon over tropical Australian waters.

Black carbon (BC) aerosols significantly contribute to radiative budgets globally, however their actual contributions remain poorly constrained in many under-sampled ocean regions. The tropical waters north of Australia are a part of the Indo-Pacific warm pool, regarded as a heat engine of global climate, and are in proximity to large terrestrial sources of BC aerosols such as fossil fuel emissions, and biomass burning emissions from northern Australia. Despite this, measurements of marine aerosols, especially BC remain elusive, leading to large uncertainties and discrepancies in current chemistry-climate models for this region. Here, we report the first comprehensive measurements of aerosol properties collected over the tropical warm pool in Australian waters during a voyage in late 2019. The non-marine related aerosol emissions observed in the Arafura Sea region were more intense than in the Timor Sea marine region, as the Arafura Sea was subject to greater continental outflows. The median equivalent BC (eBC) concentration in the Arafura Sea (0.66 µg m-3) was slightly higher than that in the Timor Sea (0.49 µg m-3). Source apportionment modelling and back trajectory analysis and tracer studies consistently suggest fossil fuel combustion eBC (eBCff) was the dominant contributor to eBC across the entire voyage region, with biomass burning eBC (eBCbb) making significant additional contributions to eBC in the Arafura Sea. eBCff (possibly from ship emissions or oil and gas rigs and their associated activities) and cloud condensation nuclei (CCN) were robustly correlated in the Timor Sea data, whereas eBCbb positively correlated to CCN in the Arafura Sea, suggesting different sources and atmospheric processing pathways occurred in these two regions. This work demonstrates the substantial impact that fossil fuel and biomass burning emissions can have on the composition of aerosols and cloud processes in the remote tropical marine atmosphere, and their potentially significant contribution to the radiative balance of the rapidly warming Indo-Pacific warm pool.

Treatment of lymphocyte-variant hypereosinophilic syndrome (L-HES): what to consider after confirming the elusive diagnosis.

Lymphocyte-variant hypereosinophilic syndrome (L-HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin-5 (IL-5). Treatment is challenging because L-HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L-HES. In all, 25 studies were selected; two were randomised controlled trials of IL-5 blockade, which included some patients with L-HES, and the rest were observational studies. Corticosteroids are often used as first-line therapy, but patients with L-HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon-alpha (IFN-α), anti-IL-5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T-cell activation and proliferation, or IL-5 directly. Although effective, IFN-α and cyclosporine were commonly reported to cause side-effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti-IL-5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L-HES.

Baseline characterisation of source contributions to daily-integrated PM2.5 observations at Cape Grim using Radon-222.

We discuss 15 years (2000-2015) of daily-integrated PM2.5 samples from the Cape Grim Station. Ion beam analysis and positive matrix factorisation are used to identify six source-type fingerprints: fresh sea salt (57%); secondary sulfate (14%); smoke (13%); aged sea salt (12%); soil dust (2.4%); and industrial metals (1.5%). An existing hourly radon-only baseline selection technique is modified for use with the daily-integrated observations. Results were not significantly different for days on which >20 hours were below the baseline radon threshold compared with days when all 24 hours satisfied the baseline criteria. This relaxed daily baseline criteria increased the number of samples for analysis by almost a factor of two. Two radon baseline thresholds were tested: historic (100 mBq m-3), and revised (50 mBq m-3). Median aerosol concentrations were similar for both radon thresholds, but maximum values were higher for the 100 mBq m-3 threshold. Back trajectories indicated more interaction with southern Australia and the Antarctic coastline for air masses selected with the 100 mBq m-3 threshold. Radon-only baseline selection using the 50 mBq m-3 threshold was more selective of minimal terrestrial influence than a similar recent study using wind direction and back trajectories. The ratio of concentrations between terrestrial and baseline days for the primary sources soil, smoke and industrial metals was 3.4, 2.6, and 5.5, respectively. Seasonal cycles of soil dust had a summer maximum and winter minimum. Seasonal cycles of smoke were of similar amplitude for terrestrial and baseline events, but of completely different shape: peaking in autumn and spring for terrestrial events, compared to summer for baseline conditions. Seasonal cycles of industrial metals had a summer maximum and winter minimum. A significant fraction of the Cape Grim baseline smoke and industrial metal contributions appeared to be derived from long-term transport (>3 weeks since last terrestrial influence).

Atmospheric stability effects on potential radiological releases at a nuclear research facility in Romania: Characterising the atmospheric mixing state.

A radon-based nocturnal stability classification scheme is developed for a flat inland site near Bucharest, Romania, characterised by significant local surface roughness heterogeneity, and compared with traditional meteorologically-based techniques. Eight months of hourly meteorological and atmospheric radon observations from a 60 m tower at the IFIN-HH nuclear research facility are analysed. Heterogeneous surface roughness conditions in the 1 km radius exclusion zone around the site hinder accurate characterisation of nocturnal atmospheric mixing conditions using conventional meteorological techniques, so a radon-based scheme is trialled. When the nocturnal boundary layer is very stable, the Pasquill-Gifford "radiation" scheme overestimates the atmosphere's capacity to dilute pollutants with near-surface sources (such as tritiated water vapour) by 20% compared to the radon-based scheme. Under these conditions, near-surface wind speeds drop well below 1 m s(-1) and nocturnal mixing depths vary from ∼ 25 m to less than 10 m above ground level (a.g.l.). Combining nocturnal radon with daytime ceilometer data, we were able to reconstruct the full diurnal cycle of mixing depths. Average daytime mixing depths at this flat inland site range from 1200 to 1800 m a.g.l. in summer, and 500-900 m a.g.l. in winter. Using tower observations to constrain the nocturnal radon-derived effective mixing depth, we were able to estimate the seasonal range in the Bucharest regional radon flux as: 12 mBq m(-2) s(-1) in winter to 14 mBq m(-2) s(-1) in summer.

Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia.

BACKGROUND/RATIONALE: Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies. METHODS: Large volumes of six working calibrators were prepared from pooled sera with GADA 4.8-493 World Health Organization (WHO) units/ml and IA-2A 2-235 WHO units/ml. Harmonized assay protocols for IA-2A and GADA using (35)S-methionine-labelled in vitro transcribed and translated antigens were developed based on methods in use in three NIDDK laboratories. Antibody thresholds were defined using sera from patients with recent onset type 1 diabetes and healthy controls. To evaluate the impact of the harmonized assay protocol on concordance of IA-2A and GADA results, two laboratories retested stored TEDDY study sera using the harmonized assays. RESULTS: The harmonized assays gave comparable but not identical results in the three laboratories. For IA-2A, using a common threshold of 5 DK units/ml, 549 of 550 control and patient samples were concordantly scored as positive or negative, specificity was greater than 99% with sensitivity 64% in all laboratories. For GADA, using thresholds equivalent to the 97th percentile of 974 control samples in each laboratory, 1051 (97.9%) of 1074 samples were concordant. On the retested TEDDY samples, discordance decreased from 4 to 1.8% for IA-2A (n = 604 samples; P = 0.02) and from 15.4 to 2.7% for GADA (n = 515 samples; P < 0.0001). CONCLUSION: Harmonization of GADA and IA-2A is feasible using large volume working calibrators and common protocols and is an effective approach to ensure consistency in autoantibody measurements.

OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome. EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain-containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.

Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.

PURPOSE: Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN: We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. RESULTS: Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS: Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.