Coastal Blue Carbon Opportunity Assessment for Snohomish Estuary: The Climate Benefits of Estuary Restoration

This report presents the findings of a groundbreaking study that confirms the climate mitigation benefits of restoring tidal wetland habitat in the Snohomish Estuary, located within the nation's second largest estuary: Puget Sound. The study, the first of its kind, finds major climate mitigation benefits from wetland restoration and provides a much needed approach for assessing carbon fluxes for historic drained and future restored wetlands which can now be transferred and applied to other geographie

Three birds with one stone: Tidal wetland restoration, carbon sequestration, and enhancing resilience to rising sea levels in the Snohomish River Estuary, Washington

Recent attention has focused on exploring the carbon storage and sequestration values of tidal wetlands to mitigate greenhouse gas emissions. Efforts are now underway to develop the tools and refine the science needed to bring carbon markets to bear on tidal wetland restoration activities. Effective restoration not only maximizes carbon storage in former tidal wetlands but also, through the accumulation of organic and mineral matter, enhances these systems’ resilience to rising sea levels. To this end, this project focuses on the Snohomish River estuary of the Puget Sound, Washington, which offers a continuum of diked and un-diked wetlands including seasonal floodplains, open mudflats, mature and tidal forests, and salt marsh habitats. In addition, there is strong restoration potential in a suite of ongoing and proposed projects. We report here on the carbon storage pools, long-term sediment accretion rates (100 years), and estimated rates of carbon storage, derived from sediment cores collected at representative sites within the Snohomish estuary during the spring and summer of 2013. We found that natural wetlands (open to tidal exchange and riverine inputs) were accreting at rates that equaled or exceeded current rates of eustatic sea level rise, while formerly, or currently diked wetlands (closed to such exchanges and inputs) revealed marked evidence of subsidence. Restored sites showed evidence of both high rates of sediment accretion (1.61 cm/year) and carbon storage (352 g C/m2/year)

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

White paper: cloud computing in 2013 - what legal commitments can you expect from your provider?

A recent VMWare and Forrester Research annual survey published in November 20121 indicated that cloud computing adoption had increased for Australian business to about 58 per cent, up from 42 percent the previous year. A further 20% of businesses planned to implement cloud solutions within the next 18 months. Cloud adoption was seen as a strategic move with competitive advantage being cited as a major factor by a majority of organisations. In addition to cost savings being a driver for adoption, users are increasingly adopting cloud technologies for the flexibility offered by being able to scale up and down without committing permanently to the underlying infrastructure and applications. While adoption of cloud increases, concerns around privacy, security and availability remain significant for Australian businesses. The purpose of this paper is to consider the extent to which there has been an associated maturation in the terms of provision of cloud services, to take account of these continued concerns. This has been done by reviewing a number of the terms and conditions for cloud providers. A primary focus has been privacy and security together with various other commercial issues which can have a significant practical impact on a business\u27 adoption of a cloud solution. In conducting our survey the authors have also reviewed the similar White Paper co-authored by Mark Vincent in 2011, Cloud Computing Contracts White Paper, A Survey of Terms and Conditions and comment on developments or lack thereof since that time. The cloud contracts comprise some 53 individual contracts and documents from 19 providers. The contracts relate to paid business grade services available in Australia

Letter to the Editor in response to the article by Borg et al

As Australian First Nations people, public health practitioners and academics, we would like to thank Borg et al. for the raising the importance of increasing influenza vaccination rates [1]. The coverage of influenza immunisation in Australian First Nations children is close to 50% in the Northern Territory but is very low in most other states, thus this is a topic worthy of research. We would, however, like to offer an additional interpretation of their study results