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Coral reefs have been found to produce the sulfur compound dimethyl sulfide (DMS), a climatically relevant aerosol precursor predominantly associated with phytoplankton. Until recently, the role of coral-reef-derived DMS within the climate system had not been quantified. A study preceding the present work found that DMS produced by corals had negligible long-term climatic forcing at the global–regional scale. However, at sub-daily timescales more typically associated with aerosol and cloud formation, the influence of coral-reef-derived DMS on local aerosol radiative effects remains unquantified. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) has been used in this work to study the role of coral-reef-derived DMS at sub-daily timescales for the first time. WRF-Chem was run to coincide with an October 2016 field campaign over the Great Barrier Reef, Queensland, Australia, against which the model was evaluated. After updating and scaling the DMS surface water climatology, the model reproduced DMS and sulfur concentrations well. The inclusion of coral-reef-derived DMS resulted in no significant change in sulfate aerosol mass or total aerosol number. Subsequently, no direct or indirect aerosol effects were detected. The results suggest that the co-location of the Great Barrier Reef with significant anthropogenic aerosol sources along the Queensland coast prevents coral-reef-derived aerosol from having a modulating influence on local aerosol burdens in the current climate.

The Southern Ocean region is one of the most pristine in the world and serves as an important proxy for the pre-industrial atmosphere. Improving our understanding of the natural processes in this region is likely to result in the largest reductions in the uncertainty of climate and earth system models. While remoteness from anthropogenic and continental sources is responsible for its clean atmosphere, this also results in the dearth of atmospheric observations in the region. Here we present a statistical summary of the latitudinal gradient of aerosol (condensation nuclei larger than 10 nm, CN10) and cloud condensation nuclei (CCN at various supersaturations) concentrations obtained from five voyages spanning the Southern Ocean between Australia and Antarctica from late spring to early autumn (October to March) of the 2017/18 austral seasons. Three main regions of influence were identified: the northern sector (40–45∘ S), where continental and anthropogenic sources coexisted with background marine aerosol populations; the mid-latitude sector (45–65∘ S), where the aerosol populations reflected a mixture of biogenic and sea-salt aerosol; and the southern sector (65–70∘ S), south of the atmospheric polar front, where sea-salt aerosol concentrations were greatly reduced and aerosol populations were primarily biologically derived sulfur species with a significant history in the Antarctic free troposphere. The northern sector showed the highest number concentrations with median (25th to 75th percentiles) CN10 and CCN0.5 concentrations of 681 (388–839) cm−3 and 322 (105–443) cm−3, respectively. Concentrations in the mid-latitudes were typically around 350 cm−3 and 160 cm−3 for CN10 and CCN0.5, respectively. In the southern sector, concentrations rose markedly, reaching 447 (298–446) cm−3 and 232 (186–271) cm−3 for CN10 and CCN0.5, respectively. The aerosol composition in this sector was marked by a distinct drop in sea salt and increase in both sulfate fraction and absolute concentrations, resulting in a substantially higher CCN0.5/CN10 activation ratio of 0.8 compared to around 0.4 for mid-latitudes. Long-term measurements at land-based research stations surrounding the Southern Ocean were found to be good representations at their respective latitudes; however this study highlighted the need for more long-term measurements in the region. CCN observations at Cape Grim (40∘39′ S) corresponded with CCN measurements from northern and mid-latitude sectors, while CN10 observations only corresponded with observations from the northern sector. Measurements from a simultaneous 2-year campaign at Macquarie Island (54∘30′ S) were found to represent all aerosol species well. The southernmost latitudes differed significantly from both of these stations, and previous work suggests that Antarctic stations on the East Antarctic coastline do not represent the East Antarctic sea-ice latitudes well. Further measurements are needed to capture the long-term, seasonal and longitudinal variability in aerosol processes across the Southern Ocean.

Cloud–radiation interactions over the Southern Ocean are not well constrained in climate models, in part due to uncertainties in the sources, concentrations, and cloud-forming potential of aerosol in this region. To date, most studies in this region have reported measurements from fixed terrestrial stations or a limited set of instrumentation and often present findings as broad seasonal or latitudinal trends. Here, we present an extensive set of aerosol and meteorological observations obtained during an austral summer cruise across the full width of the Southern Ocean south of Australia. Three episodes of continental-influenced air masses were identified, including an apparent transition between the Ferrel atmospheric cell and the polar cell at approximately 64∘ S, and accompanied by the highest median cloud condensation nuclei (CCN) concentrations, at 252 cm−3. During the other two episodes, synoptic-scale weather patterns diverted air masses across distances greater than 1000 km from the Australian and Antarctic coastlines, respectively, indicating that a large proportion of the Southern Ocean may be periodically influenced by continental air masses. In all three cases, a highly cloud-active accumulation mode dominated the size distribution, with up to 93 % of the total number concentration activating as CCN. Frequent cyclonic weather conditions were observed at high latitudes and the associated strong wind speeds led to predictions of high concentrations of sea spray aerosol. However, these modelled concentrations were not achieved due to increased aerosol scavenging rates from precipitation and convective transport into the free troposphere, which decoupled the air mass from the sea spray flux at the ocean surface. CCN concentrations were more strongly impacted by high concentrations of large-diameter Aitken mode aerosol in air masses which passed over regions of elevated marine biological productivity, potentially contributing up to 56 % of the cloud condensation nuclei concentration. Weather systems were vital for aerosol growth in biologically influenced air masses and in their absence ultrafine aerosol diameters were less than 30 nm. These results demonstrate that air mass meteorological history must be considered when modelling sea spray concentrations and highlight the potential importance of sub-grid-scale variability when modelling atmospheric conditions in the remote Southern Ocean.

The Sydney Particle Study involved the comprehensive measurement of meteorology, particles and gases at a location in western Sydney during February–March 2011 and April–May 2012. The aim of this study was to increase scientific understanding of particle formation and transformations in the Sydney airshed. In this paper we describe the methods used to collect and analyse particle and gaseous samples, as well as the methods employed for the continuous measurement of particle concentrations, particle microphysical properties, and gaseous concentrations. This paper also provides a description of the data collected and is a metadata record for the data sets published in Keywood et al. (2016a, https://doi.org/10.4225/08/57903B83D6A5D) and Keywood et al. (2016b, https://doi.org/10.4225/08/5791B5528BD63).

Understanding uncertainty is essential for utilizing atmospheric volatile organic compound (VOC) measurements in robust ways to develop atmospheric science. This study describes an inter-comparison of the VOC data, and the derived uncertainty estimates, measured with three independent techniques (PTR-MS, proton-transfer-reaction mass spectrometry; GC-FID-MS, gas chromatography with flame-ionization and mass spectrometric detection; and DNPH–HPLC, 2,4-dinitrophenylhydrazine derivatization followed by analysis by high-performance liquid chromatography) during routine monitoring as part of the Sydney Particle Study (SPS) campaign in 2012. Benzene, toluene, C8 aromatics, isoprene, formaldehyde and acetaldehyde were selected for the comparison, based on objective selection criteria from the available data. Bottom-up uncertainty analyses were undertaken for each compound and each measurement system. Top-down uncertainties were quantified via the inter-comparisons. In all seven comparisons, the correlations between independent measurement techniques were high with R2 values with a median of 0.92 (range 0.75–0.98) and small root mean square of the deviations (RMSD) of the observations from the regression line with a median of 0.11 (range 0.04–0.23 ppbv). These results give a high degree of confidence that for each comparison the response of the two independent techniques is dominated by the same constituents. The slope and intercept as determined by reduced major axis (RMA) regression gives a different story. The slopes varied considerably with a median of 1.25 and a range of 1.16–2.01. The intercepts varied with a median of 0.04 and a range of −0.03 to 0.31 ppbv. An ideal comparison would give a slope of 1.00 and an intercept of 0. Some sources of uncertainty that are poorly quantified by the bottom-up uncertainty analysis method were identified, including: contributions of non-target compounds to the measurement of the target compound for benzene, toluene and isoprene by PTR-MS as well as the under-reporting of formaldehyde, acetaldehyde and acetone by the DNPH technique. As well as these, this study has identified a specific interference of liquid water with acetone measurements by the DNPH technique. These relationships reported for Sydney 2012 were incorporated into a larger analysis with 61 similar published inter-comparison studies for the same compounds. Overall, for the light aromatics, isoprene and the C1–C3 carbonyls, the uncertainty in a set of measurements varies by a factor of between 1.5 and 2. These uncertainties ( ∼ 50 %) are significantly higher than uncertainties estimated using standard propagation of error methods, which in this case were ∼ 22 % or less, and are the result of the presence of poorly understood or neglected processes that affect the measurement and its uncertainty. The uncertainties in VOC measurements identified here should be considered when assessing the reliability of VOC measurements from routine monitoring with individual, stand-alone instruments; when utilizing VOC data to constrain and inform air quality and climate models; when using VOC observations for human exposure studies; and for comparison with satellite retrievals.

The SAFIRED (Savannah Fires in the Early Dry Season) campaign took place from 29 May until 30 June 2014 at the Australian Tropical Atmospheric Research Station (ATARS) in the Northern Territory, Australia. The purpose of this campaign was to investigate emissions from fires in the early dry season in northern Australia. Measurements were made of biomass burning aerosols, volatile organic compounds, polycyclic aromatic carbons, greenhouse gases, radon, speciated atmospheric mercury and trace metals. Aspects of the biomass burning aerosol emissions investigated included; emission factors of various species, physical and chemical aerosol properties, aerosol aging, micronutrient supply to the ocean, nucleation, and aerosol water uptake. Over the course of the month-long campaign, biomass burning signals were prevalent and emissions from several large single burning events were observed at ATARS.Biomass burning emissions dominated the gas and aerosol concentrations in this region. Dry season fires are extremely frequent and widespread across the northern region of Australia, which suggests that the measured aerosol and gaseous emissions at ATARS are likely representative of signals across the entire region of north Australia. Air mass forward trajectories show that these biomass burning emissions are carried north-west over the Timor Sea and could influence the atmosphere over Indonesia and the tropical atmosphere over the Indian Ocean. Here we present characteristics of the biomass burning observed at the sampling site and provide an overview of the more specific outcomes of the SAFIRED campaign.

The Measurements of Urban, Marine and Biogenic Air (MUMBA) campaign took place in Wollongong, New South Wales (a small coastal city approximately 80 km south of Sydney, Australia) from 21 December 2012 to 15 February 2013. Like many Australian cities, Wollongong is surrounded by dense eucalyptus forest, so the urban airshed is heavily influenced by biogenic emissions. Instruments were deployed during MUMBA to measure the gaseous and aerosol composition of the atmosphere with the aim of providing a detailed characterisation of the complex environment of the ocean–forest–urban interface that could be used to test the skill of atmospheric models. The gases measured included ozone, oxides of nitrogen, carbon monoxide, carbon dioxide, methane and many of the most abundant volatile organic compounds. The aerosol characterisation included total particle counts above 3 nm, total cloud condensation nuclei counts, mass concentration, number concentration size distribution, aerosol chemical analyses and elemental analysis.The campaign captured varied meteorological conditions, including two extreme heat events, providing a potentially valuable test for models of future air quality in a warmer climate. There was also an episode when the site sampled clean marine air for many hours, providing a useful additional measure of the background concentrations of these trace gases within this poorly sampled region of the globe. In this paper we describe the campaign, the meteorology and the resulting observations of atmospheric composition in general terms in order to equip the reader with a sufficient understanding of the Wollongong regional influences to use the MUMBA datasets as a case study for testing a chemical transport model. The data are available from PANGAEA (http://doi.pangaea.de/10.1594/PANGAEA.871982).

The vast majority of Australia's fires occur in the tropical north of the continent during the dry season. These fires are a significant source of aerosol and cloud condensation nuclei (CCN) in the region, providing a unique opportunity to investigate the biomass burning aerosol (BBA) in the absence of other sources. CCN concentrations at 0.5 % supersaturation and aerosol size and chemical properties were measured at the Australian Tropical Atmospheric Research Station (ATARS) during June 2014. CCN concentrations reached over 104 cm−3 when frequent and close fires were burning – up to 45 times higher than periods with no fires. Both the size distribution and composition of BBA appeared to significantly influence CCN concentrations. A distinct diurnal trend in the proportion of BBA activating to cloud droplets was observed, with an activation ratio of 40 ± 20 % during the night and 60 ± 20 % during the day. BBA was, on average, less hygroscopic during the night (κ = 0. 04 ± 0.03) than during the day (κ = 0.07 ± 0.05), with a maximum typically observed just before midday. Size-resolved composition of BBA showed that organics comprised a constant 90 % of the aerosol volume for aerodynamic diameters between 100 and 200 nm. While this suggests that the photochemical oxidation of organics led to an increase in the hygroscopic growth and an increase in daytime activation ratios, it does not explain the decrease in hygroscopicity after midday. Modelled CCN concentrations assuming typical continental hygroscopicities produced very large overestimations of up to 200 %. Smaller, but still significant, overpredictions up to ∼ 100 % were observed using aerosol mass spectrometer (AMS)- and hygroscopicity tandem differential mobility analyser (H-TDMA)-derived hygroscopicities as well as campaign night and day averages. The largest estimations in every case occurred during the night, when the small variations in very weakly hygroscopic species corresponded to large variations in the activation diameters. Trade winds carry the smoke generated from these fires over the Timor Sea, where aerosol–cloud interactions are likely to be sensitive to changes in CCN concentrations, perturbing cloud albedo and lifetime. Dry season fires in northern Australia are therefore potentially very important in cloud processes in this region.

There is a lack of knowledge of how biomass burning aerosols in the tropics age, including those in the fire-prone Northern Territory in Australia. This paper reports chemical characterization of fresh and aged aerosols monitored during the 1-month-long SAFIRED (Savannah Fires in the Early Dry Season) field study, with an emphasis on the chemical signature and aging of organic aerosols. The campaign took place in June 2014 during the early dry season when the surface measurement site, the Australian Tropical Atmospheric Research Station (ATARS), located in the Northern Territory, was heavily influenced by thousands of wild and prescribed bushfires. ATARS was equipped with a wide suite of instrumentation for gaseous and aerosol characterization. A compact time-of-flight aerosol mass spectrometer was deployed to monitor aerosol chemical composition. Approximately 90 % of submicron non-refractory mass was composed of organic material. Ozone enhancement in biomass burning plumes indicated increased air mass photochemistry. The diversity in biomass burning emissions was illustrated through variability in chemical signature (e.g. wide range in f44, from 0.06 to 0.18) for five intense fire events. The background particulate loading was characterized using positive matrix factorization (PMF). A PMF-resolved BBOA (biomass burning organic aerosol) factor comprised 24 % of the submicron non-refractory organic aerosol mass, confirming the significance of fire sources. A dominant PMF factor, OOA (oxygenated organic aerosol), made up 47 % of the sampled aerosol, illustrating the importance of aerosol aging in the Northern Territory. Biogenic isoprene-derived organic aerosol factor was the third significant fraction of the background aerosol (28 %).

BackgroundLiquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors. In this initial feasibility analysis, we identified an exosome gene signature of 445 genes (ExoSig445) from colon cancer patients, including those with PC, that is distinct from healthy controls.MethodsPlasma exosomes from 42 patients with metastatic and non-metastatic colon cancer and 10 healthy controls were isolated and verified. RNAseq analysis of exosomal RNA was performed and differentially expressed genes (DEGs) were identified by the DESeq2 algorithm. The ability of RNA transcripts to discriminate control and cancer cases was assessed by principal component analysis (PCA) and Bayesian compound covariate predictor classification. An exosomal gene signature was compared with tumor expression profiles of The Cancer Genome Atlas.ResultsUnsupervised PCA using exosomal genes with greatest expression variance showed stark separation between controls and patient samples. Using separate training and test sets, gene classifiers were constructed capable of discriminating control and patient samples with 100% accuracy. Using a stringent statistical threshold, 445 DEGs fully delineated control from cancer samples. Furthermore, 58 of these exosomal DEGs were found to be overexpressed in colon tumors.ConclusionsPlasma exosomal RNAs can robustly discriminate colon cancer patients, including patients with PC, from healthy controls. ExoSig445 can potentially be developed as a highly sensitive liquid biopsy test in colon cancer.

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency and heparan sulfate storage on energy homeostasis and metabolism in a mouse model of type IIIa mucopolysaccharidosis (MPS IIIa, Sanfilippo A syndrome). At 12-weeks of age, MPS IIIa mice exhibited fasting and postprandial hypertriglyceridemia compared with wildtype mice, with a reduction of white and brown adipose tissues. Partitioning of dietary [3H]triolein showed a marked increase in intestinal uptake and secretion, whereas hepatic production and clearance of triglyceride-rich lipoproteins did not differ from wildtype controls. Uptake of dietary triolein was also elevated in brown adipose tissue (BAT), and notable increases in beige adipose tissue occurred, resulting in hyperthermia, hyperphagia, hyperdipsia, and increased energy expenditure. Furthermore, fasted MPS IIIa mice remained hyperthermic when subjected to low temperature but became cachexic and profoundly hypothermic when treated with a lipolytic inhibitor. We demonstrated that the reliance on increased lipid fueling of BAT was driven by a reduced ability to generate energy from stored lipids within the depot. These alterations arose from impaired autophagosome-lysosome fusion, resulting in increased mitochondria content in beige and BAT. Finally, we show that increased mitochondria content in BAT and postprandial dyslipidemia was partially reversed upon 5-week treatment with recombinant sulfamidase. We hypothesize that increased BAT activity and persistent increases in energy demand in MPS IIIa mice contribute to the negative energy balance observed in patients with MPS IIIa.

This paper engages with the negotiation of insider and outsider researcher identities in the context of Welsh-English bilingualism in Wales. It aims to develop a reflexive approach to researching bilingualism, foregrounding the actions and experiences of doing bilingual research in a minority language context. Taking data from education and business as our starting point, we present two self-reflexive accounts of how our research identities, specifically our language profiles, (as an L1 British English speaker and an LX English user, both of whom have only limited understanding of Welsh), and positionalities are questioned, (de)legitimised and assessed in our research projects. In light of this, we reflect also on the methodological consequences and decisions that were taken during the research process. Taken together, these two reflective perspectives allow us to generate new theoretical, methodical and analytic understandings of language within the bilingual Welsh-English context specifically and researcher reflexivity more broadly.

This article adopts a gendered take on Family Language Policy (FLP) by questioning the way that gender impacts on the issues faced by refugee woman during and after flight. For this reason, the ethnographically informed research addresses the concerns and experiences of mothers and daughters in the Somali community in Bristol, one of the fastest growing communities in the city but one that remains a 'neglected social group … everywhere present but in many ways invisible' (Wallace & Kahin [2017]. "Somali parents and schooling in Britain" (p. 1). UCL Institute of Education Press.), with little known about their experiences on or after arrival (Warfa et al. [2006]. Post-migration geographical mobility, mental health and health service utilisation among Somali refugees in the UK: A qualitative study. "Health & Place," 12(4), 503-515.). The study of FLP not only contributes to our understanding of the processes of language shift and change, it also sheds light on broader language policy issues at societal levels. Analysis suggests that it is principally mothers who take on the demanding, yet invisible work of FLP in the home and that mis-matched fluency between mothers and daughters results in a fracturing of family relations with the potential for long-term emotional repercussions. The findings have implications for educational and public sector organisations involving immigrant communities.

Objective: The COVID-19 pandemic saw increased loneliness and social isolation among older adults as activities and visitor opportunities for residential communities closed down. Health professional students have limited access to geriatric education in coursework and clinical experiences. The Recreation and Education Network for Elder Wellness (RENEW) programme was created by medical students at Baylor College of Medicine in Houston, Texas, aiming to increase engagement and cross-generational communication with older adults, while also decreasing social isolation and loneliness. Method: The RENEW programme included Zoom sessions with two Houston retirement communities led by student facilitators enrolled in medical, dental, and undergraduate programmes on a variety of topics of interest for the residents. Pre- and post-surveys were sent to participants and requested non-identifying biographical data and included the Revised UCLA Loneliness Scale. Results: Facilitators and participants expressed high satisfaction with the programme. Survey results on the Revised UCLA Loneliness Scale showed that participants had an overall decreased loneliness score after participation in RENEW. Student facilitators reported increased exposure to care of older adults and self-reported confidence in communicating with this population. Conclusions: The RENEW model is a collaborative, bidirectional educational tool for older adults and students with possible applications following the COVID-19 pandemic.

Background and objectivesSafety event reporting systems facilitate identification of system-level targets to improve patient safety. Resident physicians report few safety events despite their role as frontline providers and the frequent occurrence of events. The objective of this study is to increase the number of pediatric resident safety event submissions from 8 consecutive points above and below the baseline period's centerline. The control group showed no sustained change in event submissions.ConclusionsOur improvement process was associated with significant increase in pediatric resident safety event submissions without an increase in the number of submissions categorized as duplicates or nonevents.

BackgroundRecent randomized controlled trials have failed to show a survival difference between adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT) in patients with resected gastric cancer (GC). However, a subset of patients with lymph node (LN) positive disease may still benefit from CRT. Additional evidence is needed to help guide physicians in identifying patients in whom CRT should be considered. Our objective was then to compare survival outcomes based on lymph node ratio (LNR) (ratio of metastatic to harvested LNs) for patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with surgery and either CT or CRT.MethodsThis retrospective population-based study used California Cancer Registry (CCR) data from 2004 to 2013. It included 1,493 patients diagnosed with stage IB-III gastric/GEJ adenocarcinoma and treated with CT or CRT following total or partial gastrectomy. Overall survival (OS) was the primary outcome and GC-specific survival was secondary. Mortality hazards ratios (HR) for these outcomes were computed using propensity score weighted Cox regression models, stratified by LNR strata categories as 0%, 1-9%, 10-25% and >25%.ResultsOut of 1,493 patients that met inclusion criteria, 462 were treated with CT while 1,031 received CRT. Median follow-up for all subjects was 76 months and median survival was 54 months for CRT and 35 for the CT cohort, P25% [HR =0.67 (95% CI, 0.56-0.80)]. Similar findings were observed for GC-specific survival and for analyses limited to patients that had at least 15 LNs evaluated.ConclusionsLNR appears to be a simple and readily available measure that could be used in treatment planning for resected GC. CRT offers significant survival advantage over CT among patients with high LN disease burden (LNR of ≥10%).

BackgroundBoth perioperative chemotherapy (PC) and adjuvant chemoradiotherapy (CRT) improve survival in resectable gastric cancer; however, these treatments have never been formally compared. Our objective was to evaluate treatment trends and compare survival outcomes for gastric cancer patients treated with surgery and either PC or CRT.MethodsWe performed a retrospective population-based cohort study between 2007 through 2013 using California Cancer Registry data. Patients diagnosed with stage IB-III gastric adenocarcinoma and treated with total or partial gastrectomy were eligible for this study. Based on the type of treatment received, patients were grouped into surgery-only, PC, or CRT. Primary and secondary outcomes were overall survival (OS) and gastric cancer-specific survival (GCCS) respectively. Mortality hazards ratios (HRs) for each of these outcomes were computed using propensity score weighted and covariate-adjusted Cox regression models, stratified by clinical node status.ResultsOf 2,146 patients who underwent surgical resection, 1,067 had surgery-only, while 771 and 308 received PC or CRT, respectively. Median OS was 25, 33, and 52 months for surgery-only, PC, and CRT, respectively; P

In the original version of this article Sarath Sujatha- Bhaskar’s family name was misspelled. It is correct as reflected in this erratum. The original article has also been updated.

Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P

Peritoneal Carcinomatosis (PC) is a late stage manifestation of several gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and often leave patients with only palliative treatment options. For colorectal PC, median survival is approximately five months, and palliative systemic therapy is able to extend this to approximately 12 months. However, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in some patients with limited tumor burden. In well-selected patients undergoing complete cytoreduction, median survival has been reported as high as 63 month. Identifying patients earlier who are either at risk for, or who have recently developed PC may provide them with additional treatment options such as CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an invasive procedures such as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a minimally invasive, accurate, and specific PC screening method needs to be developed. By utilizing circulating PC biomarkers in the serum of patients, a "liquid biopsy," may be able to be generated to allow a tailored treatment plan and early intervention. Exosomes, stable patient-derived nanovesicles present in blood, urine, and many other bodily fluids, show promise as a tool for the evaluation of labile biomarkers. If liquid biopsies can be perfected in PC, manifestations of this cancer may be more effectively treated, thus offering improved survival.

This review discusses the current state of biomarker discovery for the purposes of diagnostics and therapeutic monitoring. We underscore relevant challenges that have defined the gap between biomarker discovery and meaningful clinical use. We highlight recent advancements in and propose a way to think about future biomarker development.

In the introduction to the special issue 'Elite Multilingualism: Discourses, practices, and debates', we focus on 'elite multilingualism' as a means to provide a window into the complex layers and nuances of today's multilingual, mobile and global society. Our aims here are to provide an empirical and conceptual discussion of a growing language-centred elitism. We also aim to expand current scholarship on the construction, valuation and instrumentalisation of multilingualism, and its consequences for the formation of social boundaries and inequalities. We first discuss major concepts such as the notion of elite/ness and multilingualism, commodification, authenticity and hierarchies and the linguistic market in a global knowledge economy. We also discuss the critical sociolinguistic, discourse and ethnographic approaches that frame this special issue and go on to outline the diverse manifestations of elite multilingualism in different educational and social settings. Finally, we conclude by reflecting on the value of the concept of elite multilingualism as a social practice, and argue for the importance of examining the lived experience of multilinguals on the ground.

Canine distemper virus (CDV) is a well-known RNA virus that affects domestic dogs and all families of wild terrestrial carnivores. Spillover infections from wildlife to domestic animals are mitigated by preventive vaccination, but there is limited information on the off-label use of veterinary vaccines for wildlife like raccoons (Procyon lotor). Twenty wild-caught raccoons were inoculated with a commercial recombinant DNA canarypox-vectored CDV vaccine, applying a regimen of two serial doses by SC route with an interval of 25-28 days between doses. The CDV serum virus neutralizing antibody (VNA) baseline titers and the postvaccination titers were measured at fixed time points. Forty percent (8/20) of the wild-caught raccoons had CDV VNA titers of 1:8 or greater upon intake, and all but a single individual were juvenile animals. Approximately one month following the first vaccine dose, 8% (1/12) of raccoons seronegative at baseline had serum CDV VNA titers of 1:24 or greater. Approximately one month following the booster vaccine dose, 67% (8/12) of raccoons seronegative at baseline had serum CDV VNA titers of 1:24 or greater. Among raccoons with CDV VNA titers greater than or equal to 1:8 at baseline, 13% (1/8) demonstrated a fourfold or greater rise in titer one month after the first vaccine dose, whereas 38% (3/8) reached the same threshold one month after the booster dose. The presence of naturally acquired CDV VNA in juvenile raccoons at the time of vaccination may have interfered with the humoral VNA response. A regimen of at least two serially administered SC vaccine doses may be immunogenic for raccoons, but further investigation of alternative routes, regimens, and CDV vaccine products is also warranted for this species. [ABSTRACT FROM AUTHOR]

Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism.

Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic function, while reductions in Rheb function compromised synapse development. Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor complex 1, and requires wishful thinking, a bone morphogenetic protein receptor critical for functional synapse expansion. In the visual system, loss of Tsc1 in the developing retina disrupted axon guidance independently of cellular growth. Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed those phenotypes. These findings show that Tsc-mediated control of axon guidance and synapse assembly occurs via growth-independent signaling mechanisms, and suggest that Tor complex 2, a regulator of actin organization, is critical in these aspects of neuronal development.

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint. [ABSTRACT FROM AUTHOR]

This article reports on an ethnographic study carried out in three interrelated sites: two contrasting secondary schools and a Youth-Club (the principal focus of this article), in an area of southwest Wales. This article highlights the incongruence between the language at home and the language of the school and posits that the relationship between language use at school and in the wider community needs to be problematised and questioned far more than has been done thus far. This study questions whether school-based ideologies and school-based practices are re-negotiated or contested on the margins of education and whether this re-negotiation and contestation plays an important role in whether a young person chooses to use Welsh or English outside of school. It will be argued that recreational spaces, even though loosely connected to schools as institutions, function as more open spaces where institutional ideologies are actively reworked and renegotiated, either through choosing to use English or by mixing and blending different aspects of linguistic resources, or by re-negotiating and questioning which version of Welshness is more valuable, "the removed and authentic" (as seen at the Welsh school) or the "new and hybrid" as seen at the Youth-Club.

It is well established that Hensen's nodes can induce the formation of supernumerary digits after grafting into the anterior margin of the developing limb bud. The recent finding that distinct mesodermal cell populations are segregated within the node has made it possible to isolate different prospective cell types in an attempt to correlate digit-inducing ability with cell fate. We find that the prospective notochord cells contained within Hensen's node are able to induce supernumerary digits, whereas presumptive somite cells cannot. This early difference in inducing ability persists into later stages of development: epithelial somites are unable to induce while notochord from all lengths of the neuraxis continues to induce. Using probes to retinoic acid receptor-beta 2 and sonic hedgehog (shh) we find no evidence to support the idea that inducing tissues generate extra digits by releasing retinoic acid into adjacent limb tissue but find that the inducing ability of a tissue correlates with its expression of shh.