Distribution of tuberculosis in migrant children and young people in Europe: a retrospective database analysis of European data.

OBJECTIVE: The burden of tuberculosis (TB) in migrant children and young people (CYP) is commonly overlooked, despite the increasing incidence of TB in migrant populations in the European region. This study aimed to examine the distribution and disease characteristics of TB among migrant and native-born CYP through analysis of data from the European Centre for Disease Prevention and Control (ECDC) surveillance system (TESSy). STUDY DESIGN: Retrospective database analysis. METHODS: A retrospective database analysis was conducted on all CYP TB cases (0-17 years) reported to TESSy (1995-2017), exploring distribution, site of TB, and presence of MDR-TB using multivariate analysis in R statistical software. RESULTS: Of the 73,176 CYP TB cases reported in the EU/EFTA (1995-2017), 24.4% (n = 17,879) occurred in migrant CYP and 75.6% (n = 55,297) occurred in native-born CYP. Migrant CYP were more likely (P < 0.001) to have pulmonary TB (OR: 1.90; 95% CI: 1.74-2.09) and unsuccessful treatment outcomes (OR: 2.05; 95% CI: 1.74-2.40) compared to native-born CYP. The proportion of extrapulmonary TB, compared to pulmonary TB across total CYP cases was higher than the existing evidence base. CONCLUSIONS: Overall, there were significant differences in the site of TB and treatment outcomes between migrant and native-born CYP. To improve outcomes, TB screening and detection practices should focus on facilitating care in migrant CYP. However, to better understand the implications of these findings on broader TB control, TB among CYP should be addressed more frequently in reports and research.

A novel likely pathogenic CLCN5 variant in Dent's disease.

BACKGROUND: The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. CASE PRESENTATION: A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. CONCLUSIONS: The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

Point-of-care lung ultrasound in patients with COVID-19 - a narrative review.

Ultrasound imaging of the lung and associated tissues may play an important role in the management of patients with COVID-19-associated lung injury. Compared with other monitoring modalities, such as auscultation or radiographic imaging, we argue lung ultrasound has high diagnostic accuracy, is ergonomically favourable and has fewer infection control implications. By informing the initiation, escalation, titration and weaning of respiratory support, lung ultrasound can be integrated into COVID-19 care pathways for patients with respiratory failure. Given the unprecedented pressure on healthcare services currently, supporting and educating clinicians is a key enabler of the wider implementation of lung ultrasound. This narrative review provides a summary of evidence and clinical guidance for the use and interpretation of lung ultrasound for patients with moderate, severe and critical COVID-19-associated lung injury. Mechanisms by which the potential lung ultrasound workforce can be deployed are explored, including a pragmatic approach to training, governance, imaging, interpretation of images and implementation of lung ultrasound into routine clinical practice.

Kaposi's Sarcoma-Associated Herpesvirus LANA Modulates the Stability of the E3 Ubiquitin Ligase RLIM.

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein functions in latently infected cells as an essential participant in KSHV genome replication and as a driver of dysregulated cell growth. In a previous study, we have identified LANA-interacting proteins using a protein array screen. Here, we explore the effect of LANA on the stability and activity of RLIM (RING finger LIM-domain-interacting protein, encoded by the RNF12 gene), a novel LANA-interacting protein identified in that protein screen. RLIM is an E3 ubiquitin ligase that leads to the ubiquitination and degradation of several transcription regulators, such as LMO2, LMO4, LHX2, LHX3, LDB1, and the telomeric protein TRF1. Expression of LANA leads to downregulation of RLIM protein levels. This LANA-mediated RLIM degradation is blocked in the presence of the proteasome inhibitor, MG132. Therefore, the interaction between LANA and RLIM could be detected in coimmunoprecipitation assay only in the presence of MG132 to prevent RLIM degradation. A RING finger mutant RLIM is resistant to LANA-mediated degradation, suggesting that LANA promotes RLIM autoubiquitination. Interestingly, we found that LANA enhanced the degradation of some RLIM substrates, such as LDB1 and LMO2, and prevented RLIM-mediated degradation of others, such as LHX3 and TRF1. We also show that transcription regulation by RLIM substrates is modulated by LANA. RLIM substrates are assembled into multiprotein transcription regulator complexes that regulate the expression of many cellular genes. Therefore, our study identified another way KSHV can modulate cellular gene expression.IMPORTANCE E3 ubiquitin ligases mark their substrates for degradation and therefore control the cellular abundance of their substrates. RLIM is an E3 ubiquitin ligase that leads to the ubiquitination and degradation of several transcription regulators, such as LMO2, LMO4, LHX2, LHX3, LDB1, and the telomeric protein TRF1. Here, we show that the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded LANA protein enhances the ubiquitin ligase activity of RLIM, leading to enhanced RLIM autoubiquitination and degradation. Interestingly, LANA enhanced the degradation of some RLIM substrates, such as LDB1 and LMO2, and prevented RLIM-mediated degradation of others, such as LHX3 and TRF1. In agreement with protein stability of RLIM substrates, we found that LANA modulates transcription by LHX3-LDB1 complex and suggest additional ways LANA can modulate cellular gene expression. Our study adds another way a viral protein can regulate cellular protein stability, by enhancing the autoubiquitination and degradation of an E3 ubiquitin ligase.

Pharmacologic Activation of Lytic Epstein-Barr Virus Gene Expression without Virion Production.

Several therapeutic strategies targeting Epstein-Barr virus (EBV)-associated tumors involve upregulation of viral lytic gene expression. Evidence has been presented that the unfolded protein response (UPR) leads to EBV lytic gene expression. Clofoctol, an antibacterial antibiotic, has been reported to upregulate the UPR in prostate cancer cell lines and to slow their growth. We investigated the effects of clofoctol on an EBV-positive Burkitt lymphoma cell line and confirmed the upregulation of all three branches of the UPR and activation of EBV lytic gene expression. While immediate early, early, and late EBV RNAs were all upregulated, immediate early and early viral proteins but not late viral proteins were expressed. Furthermore, infectious virions were not produced. The use of clofoctol in combination with a protein kinase R-like endoplasmic reticulum kinase inhibitor led to expression of late viral proteins. The effects of clofoctol on EBV lytic protein upregulation were not limited to lymphoid tumor cell lines but also occurred in naturally infected epithelial gastric cancer and nasopharyngeal cancer cell lines. An agent that upregulates lytic viral protein expression but that does not lead to the production of infectious virions may have particular value for lytic induction strategies in the clinical setting.IMPORTANCE Epstein-Barr virus is associated with many different cancers. In these cancers the viral genome is predominantly latent; i.e., most viral genes are not expressed, most viral proteins are not synthesized, and new virions are not produced. Some strategies for treating these cancers involve activation of lytic viral gene expression. We identify an antibacterial antibiotic, clofoctol, that is an activator of EBV lytic RNA and protein expression but that does not lead to virion production.

Use of thoracic ultrasound by physiotherapists: a scoping review of the literature.

BACKGROUND: Use of diagnostic thoracic ultrasound (TUS) in medical professions to examine the pleura, lung parenchyma and diaphragm is gaining in popularity, however the ways in which physiotherapists are using TUS is unclear. OBJECTIVE: The aim of this scoping review is to gain an understanding of the emerging evidence base surrounding physiotherapy use of TUS to inform research and clinical practice. DATA SOURCES: A systematic search was conducted of the following databases: Cochrane, EPPI centre, PROSPERO, Medline, CINAHL, AMED, EMBASE, HMIC, and BNI. STUDY SELECTION: Inclusion criteria: primary research reporting the use of diagnostic TUS; a physiotherapist as part of the study design or as the chief investigator; published in English. SYNTHESIS METHODS: Data regarding demographics, design, type of conditions and anatomical structures investigated and profession leading the TUS of included papers were compiled in a tabular format. RESULTS: Of the 26 included papers, nine studied healthy participants, four studied COPD and four studied critical care patients. Most papers (n=23) involved scanning the diaphragm. In eight studies the physiotherapist operated the TUS. LIMITATIONS: The paper selection process was performed by one author; with no cross-checking by another individual. CONCLUSION: Use of TUS by physiotherapists is an emerging area in both diaphragm and lung diagnostics. A wide range of patient populations may benefit from physiotherapists using TUS. Papers in this review are heterogeneous making any generalisability difficult but does show its potential for varied uses. TUS is an innovative skill in the hands of physiotherapists, but more research is needed.

Listeria monocytogenes Infection in Hairy Cell Leukemia: A Case Report and Literature Review.

Listeria monocytogenes infections have been described in patients with diverse types of malignancy, especially leukemia. We report the case of a 65-year-old man with previously untreated hairy cell leukemia characterized by CD5 positivity and trisomy 12 (3% of blood lymphocytes) who developed bacteremia due to L. monocytogenes serotype 1/2b. We summarize clinical features and treatment of this patient and five previously reported patients with hairy cell leukemia who also had L. monocytogenes infections. All six patients were men. Their mean age at infection diagnosis was 70 y. Three men had undergone splenectomy 4-11 y before they developed L. monocytogenes infection. The central nervous system was the primary site of infection in four men. Bacteremia alone occurred in two other men. At diagnosis of infection, one man was receiving antileukemia chemotherapy and another man was receiving treatment for Kaposi's sarcoma. Two other patients had other comorbid conditions. All six men recovered from their infections.

Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib.IMPORTANCE EBV establishes viral latency in B cells. Activation of the B cell receptor pathway activates lytic viral expression in cell lines. Here we show that drugs that inhibit important kinases in the BCR signaling pathway inhibit activation of lytic viral expression but do not inhibit several other lytic activation pathways. Immunosuppressant drugs such as cyclosporine and tacrolimus but not rapamycin also inhibit BCR-mediated EBV activation. Finally, we show that BCR activation of lytic infection occurs not only in tumor cell lines but also in freshly isolated B cells from patients and that this activation can be blocked by BCR inhibitors.

Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.

Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1). Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR), mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD002411 (http://proteomecentral.proteomexchange.org/dataset/PXD002411).

Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low-dose gemcitabine-induced lytic activation.

The constant presence of the viral genome in Epstein-Barr virus (EBV)-associated gastric cancers (EBVaGCs) suggests the applicability of novel EBV-targeted therapies. The antiviral nucleoside drug, ganciclovir (GCV), is effective only in the context of the viral lytic cycle in the presence of EBV-encoded thymidine kinase (TK)/protein kinase (PK) expression. In this study, screening of the Johns Hopkins Drug Library identified gemcitabine as a candidate for combination treatment with GCV. Pharmacological induction of EBV-TK or PK in EBVaGC-originated tumor cells were used to study combination treatment with GCV in vitro and in vivo. Gemcitabine was found to be a lytic inducer via activation of the ataxia telangiectasia-mutated (ATM)/p53 genotoxic stress pathway in EBVaGC. Using an EBVaGC mouse model and a [125I] fialuridine (FIAU)-based lytic activation imaging system, we evaluated gemcitabine-induced lytic activation in an in vivo system and confirmed the efficacy of gemcitabine-GCV combination treatment. This viral enzyme-targeted anti-tumor strategy may provide a new therapeutic approach for EBVaGCs.

A Screen for Extracellular Signal-Regulated Kinase-Primed Glycogen Synthase Kinase 3 Substrates Identifies the p53 Inhibitor iASPP.

UNLABELLED: The Kaposi's sarcoma-associated herpesvirus (KSHV) LANA protein is essential for the replication and maintenance of virus genomes in latently KSHV-infected cells. LANA also drives dysregulated cell growth through a multiplicity of mechanisms that include altering the activity of the cellular kinases extracellular signal-regulated kinase (ERK) and glycogen synthase kinase 3 (GSK-3). To investigate the potential impact of these changes in enzyme activity, we used protein microarrays to identify cell proteins that were phosphorylated by the combination of ERK and GSK-3. The assays identified 58 potential ERK-primed GSK-3 substrates, of which 23 had evidence for in vivo phosphorylation in mass spectrometry databases. Two of these, SMAD4 and iASPP, were selected for further analysis and were confirmed as ERK-primed GSK-3 substrates. Cotransfection experiments revealed that iASPP, but not SMAD4, was targeted for degradation in the presence of GSK-3. iASPP interferes with apoptosis induced by p53 family members. To determine the importance of iASPP to KSHV-infected-cell growth, primary effusion lymphoma (PEL) cells were treated with an iASPP inhibitor in the presence or absence of the MDM2 inhibitor Nutlin-3. Drug inhibition of iASPP activity induced apoptosis in BC3 and BCBL1 PEL cells but did not induce poly(ADP-ribose) polymerase (PARP) cleavage in virus-negative BJAB cells. The effect of iASPP inhibition was additive with that of Nutlin-3. Interfering with iASPP function is therefore another mechanism that can sensitize KSHV-positive PEL cells to cell death. IMPORTANCE: KSHV is associated with several malignancies, including primary effusion lymphoma (PEL). The KSHV-encoded LANA protein is multifunctional and promotes both cell growth and resistance to cell death. LANA is known to activate ERK and limit the activity of another kinase, GSK-3. To discover ways in which LANA manipulation of these two kinases might impact PEL cell survival, we screened a human protein microarray for ERK-primed GSK-3 substrates. One of the proteins identified, iASPP, showed reduced levels in the presence of GSK-3. Further, blocking iASPP activity increased cell death, particularly in p53 wild-type BC3 PEL cells.

Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma.

Interferon regulatory factor-5 (IRF-5), a member of the mammalian IRF transcription factor family, is regulated by p53, type I interferon and virus infection. IRF-5 participates in virus-induced TLR-mediated innate immune responses and may play a role as a tumor suppressor. It was suppressed in various EBV-infected transformed cells, thus it is valuable to identify the suppression mechanism. We focused on a promoter CpG islands methylation, a kind of epigenetic regulation in EBV-associated Burkitt's lymphomas (BLs) and gastric carcinomas. IRF-5 is not detected in most of EBV-infected BL cell lines due to hypermethylation of IRF-5 distal promoter (promoter-A), which was restored by a demethylating agent, 5-aza-2'-deoxycytidine. Hypomethylation of CpG islands in promoter-A was observed only in EBV type III latent infected BL cell lines (LCL and Mutu III). Similarly, during EBV infection to Akata-4E3 cells, IRF-5 was observed at early time periods (2 days to 8 weeks), concomitant unmethylation of promoter-A, but suppressed in later infection periods as observed in latency I BL cell lines. Moreover, hypermethylation in IRF-5 promoter-A region was also observed in EBV-associated gastric carcinoma (EBVaGC) cell lines or primary gastric carcinoma tissues, which show type I latent infection. In summary, IRF-5 is suppressed by hypermethylation of its promoter-A in most of EBV-infected transformed cells, especially BLs and EBVaGC. EBV-induced carcinogenesis takes an advantage of proliferative effects of TLR signaling, while limiting IRF-5 mediated negative effects in the establishment of EBVaGCs.

Inhibition of NF-kappa B signaling restores responsiveness of castrate-resistant prostate cancer cells to anti-androgen treatment by decreasing androgen receptor-variant expression.

Androgen receptor splicing variants (ARVs) that lack the ligand-binding domain (LBD) are associated with the development of castration-resistant prostate cancer (CRPC), including resistance to the new generation of high-affinity anti-androgens. However, the mechanism by which ARV expression is regulated is not fully understood. In this study, we show that the activation of classical nuclear factor-kappa B (NF-κB) signaling increases the expression of ARVs in prostate cancer (PCa) cells and converts androgen-sensitive PCa cells to become androgen-insensitive, whereas downregulation of NF-κB signaling inhibits ARV expression and restores responsiveness of CRPC to anti-androgen therapy. In addition, we demonstrated that combination of anti-androgen with NF-κB-targeted therapy inhibits efficiently tumor growth of human CRPC xenografts. These results indicate that induction of ARVs by activated NF-κB signaling in PCa cells is a critical mechanism by which the PCa progresses to CRPC. This has important implications as it can prolong the survival of CRPC patients by restoring the tumors to once again respond to conventional androgen-deprivation therapy (ADT).

Determining the biomass fraction of mixed waste fuels: A comparison of existing industry and (14)C-based methodologies.

(14)C analysis of flue gas by accelerator mass spectrometry (AMS) and liquid scintillation counting (LSC) were used to determine the biomass fraction of mixed waste at an operational energy-from-waste (EfW) plant. Results were converted to bioenergy (% total) using mathematical algorithms and assessed against existing industry methodologies which involve manual sorting and selective dissolution (SD) of feedstock. Simultaneous determinations using flue gas showed excellent agreement: 44.8 ± 2.7% for AMS and 44.6 ± 12.3% for LSC. Comparable bioenergy results were obtained using a feedstock manual sort procedure (41.4%), whilst a procedure based on selective dissolution of representative waste material is reported as 75.5% (no errors quoted). (14)C techniques present significant advantages in data acquisition, precision and reliability for both electricity generator and industry regulator.

SOX2 expression in the developing, adult, as well as, diseased prostate.

BACKGROUND: SOX2 is a member of SOX (SRY-related high mobility group box) family of transcription factors. METHODS: In this study, we examined the expression of SOX2 in murine and human prostatic specimens by immunohistochemistry. RESULTS: We found that SOX2 was expressed in murine prostates during budding morphogenesis and in neuroendocrine (NE) prostate cancer (PCa) murine models. Expression of SOX2 was also examined in human prostatic tissue. We found that SOX2 was expressed in 26 of the 30 BPH specimens. In these BPH samples, expression of SOX2 was limited to basal epithelial cells. In contrast, 24 of the 25 primary PCa specimens were negative for SOX2. The only positive primary PCa was the prostatic NE tumor, which also showed co-expression of synaptophysin. Additionally, the expression of SOX2 was detected in all prostatic NE tumor xenograft lines. Furthermore, we have examined the expression of SOX2 on a set of tissue microarrays consisting of metastatic PCa tissues. Expression of SOX2 was detected in at least one metastatic site in 15 of the 24 patients with metastatic castration-resistant PCa; and the expression of SOX2 was correlated with synaptophysin. CONCLUSIONS: SOX2 was expressed in developing prostates, basal cells of BPH, as well as prostatic NE tumors.

Are the Antarctic dipteran, Eretmoptera murphyi, and Arctic collembolan, Megaphorura arctica, vulnerable to rising temperatures?

Polar terrestrial invertebrates are suggested as being vulnerable to temperature change relative to lower latitude species, and hence possibly also to climate warming. Previous studies have shown Antarctic and Arctic Collembola and Acari to possess good heat tolerance and survive temperature exposures above 30 °C. To test this feature further, the heat tolerance and physiological plasticity of heat stress were explored in the Arctic collembolan, Megaphorura arctica, from Svalbard and the Antarctic midge, Eretmoptera murphyi, from Signy Island. The data obtained demonstrate considerable heat tolerance in both species, with upper lethal temperatures ≥35 °C (1 h exposures), and tolerance of exposure to 10 and 15 °C exceeding 56 days. This tolerance is far beyond that required in their current environment. Average microhabitat temperatures in August 2011 ranged between 5.1 and 8.1 °C, and rarely rose above 10 °C, in Ny-Ålesund, Svalbard. Summer soil microhabitat temperatures on Signy Island have previously been shown to range between 0 and 10 °C. There was also evidence to suggest that E. murphyi can recover from high-temperature exposure and that M. arctica is capable of rapid heat hardening. M. arctica and E. murphyi therefore have the physiological capacity to tolerate current environmental conditions, as well as future warming. If the features they express are characteristically more general, such polar terrestrial invertebrates will likely fare well under climate warming scenarios.

Impact of Schmallenberg virus on British sheep farms during the 2011/2012 lambing season.

British sheep farmers were invited to complete a questionnaire about the impact of Schmallenberg virus (SBV) on animal health, welfare and their own emotional wellbeing during the 2011-2012 lambing season, through Defra and Farming Industry websites, letters to farmers who had requested SBV laboratory tests and advertisement at Sheep 2012. The 494 responders included SBV confirmed (positive by RT-PCR) (n=76), SBV suspected by farmer (n=140) or SBV not suspected (n=278). Percentage of barren ewes was similar across SBV groups, however, lamb and ewe losses were higher on responder farms where SBV was confirmed or suspected. The median percentages of all lambs born (and lambs born deformed ) that died within one week of birth was 10.4 per cent (5.5 per cent), 7.0 per cent (2.9 per cent) and 5.3 per cent (0 per cent), respectively, on SBV confirmed, suspected and not suspected farms (P<0.001). Eight to 16 per cent of SBV confirmed or suspected farms reported lamb mortality of ≥40 per cent. Farmer perceived impact was greater where SBV was confirmed or suspected (P<0.001): 25 per cent reported a high impact on emotional wellbeing (4 per cent of SBV not suspected), 13 per cent reported a high impact on flock welfare and financial performance and 6 per cent were less likely to farm sheep next year because of SBV (<2 per cent in SBV not suspected). Overall, SBV impact has been large relative to reported sheep loss.

Neutral polyfluoroalkyl substances in the global atmosphere.

Concentrations of neutral per- and polyfluoroalkyl substances (nPFAS) in the atmosphere are of interest because nPFAS are highly mobile percursors for perfluoroalkyl acids. Two calibration studies in Ontario, Canada and Costa Rica established the feasibility of using XAD 2-resin based passive air samplers (XAD-PAS) to reliably determine long term average air concentrations of nPFAS under temperate and tropical climatic conditions. The temporal and spatial distribution of nPFAS was investigated by analyzing XAD-PAS deployed for one year at between 17 and 46 sites on six continents between 2006 and 2011 as part of the Global Atmospheric Passive Sampling (GAPS) study. Higher levels of fluorotelomer alcohols (FTOHs) compared to fluorinated sulfonamides (FOSAs), and fluorinated sulfonamidoethanols (FOSEs) were observed at all sites. Urban sites had the highest levels of nPFAS compared to rural and remote sites, which is also apparent in a positive correlation of nPFAS levels with the proximity of a sampling site to areas of high population density. Levels of FOSAs and FOSEs tended to decrease during the six years of measurements, whereas an initial decline in the concentrations of FTOHs from 2006 to 2008 did not continue in 2009 to 2011. A comparison of nPFAS levels measured in national XAD-PAS networks in Costa Rica and Botswana revealed that the GAPS sites in Tapanti and the Kalahari are representative of the more remote regions in those countries. XAD-PAS derived absolute nPFAS levels at GAPS sites are lower than those measured using another PAS, but are within the range of levels measured with active air samplers. Agreement of relative nPFAS composition is better between samplers, suggesting that the discrepancy is due to uncertain sampling rates.