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BackgroundNeurofilament light (NfL) is a widely used biomarker for neurodegeneration. NfL is prone to oligomerisation, but available assays do not reveal the exact molecular nature of the protein variant measured. The objective of this study was to develop a homogeneous ELISA capable of quantifying oligomeric NfL (oNfL) in cerebrospinal fluid (CSF).MethodsA homogeneous ELISA, based on the same capture and detection antibody (NfL21), was developed and used to quantify oNfL in samples from patients with behavioural variant frontotemporal dementia (bvFTD, n=28), non-fluent variant primary progressive aphasia (nfvPPA, n=23), semantic variant PPA (svPPA, n=10), Alzheimer’s disease (AD, n=20) and healthy controls (n=20). The nature of NfL in CSF, and the recombinant protein calibrator, was also characterised by size exclusion chromatography (SEC).ResultsCSF concentration of oNfL was significantly higher in nfvPPA (pConclusionsThe homogeneous ELISA and SEC data suggest that most of the NfL in both the calibrator and human CSF is present as a dimer. In CSF, the dimer appears to be truncated. Further studies are needed to determine its precise molecular composition.

A GGGGCC repeat expansion in theWe used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by theWe show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40

Background The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP (Reverse transcription loop-mediated isothermal amplification) testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. Methods Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated and informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing. Results Discussions revealed that high levels of communication, trust and convenience were necessary to ensure people’s engagement with the programme. Participants felt reassured by and pride in taking part in this novel programme. They suggested modifications to reduce the programme’s environmental impact and overcome cultural barriers to participation. Conclusions Participants’ and stakeholders’ motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary. Community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise engagement.

The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly mass RT-LAMP testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. Conversations revealed that high levels of communication, trust and convenience were necessary to ensure people’s engagement with the programme. This suggests community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise these features of the testing. Participants’ and stakeholders’ motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary.

A deep geologic repository at Yucca Mountain (YM), Nevada, for the disposal of spent nuclear fuel and high-level radioactive waste was proposed by the U.S. Department of Energy (DOE). This paper summarizes the historical development of the 2008 YM performance assessment (PA), and explains how the methods and results of the 2008 PA address regulatory requirements specified by the United States Environmental Protection Agency (EPA) and the United States Nuclear Regulatory Commission (NRC). Topics covered include (i) screening of features, events and processes, (ii) development of scenario classes, (iii) descriptions of barrier capability, and (iv) compliance with applicable quantitative standards for individual protection, individual protection following human intrusion, and ground water protection. This article is part of a special issue of Reliability Engineering and System Safety devoted to the 2008 YM PA and provides a brief summary of information presented in detail in multiple articles in this issue and interprets the results in the context of applicable EPA and NRC regulations.

The term ‘Sustainable Development’ is brandished by modern businesses as a marketing ploy used to suggest evidence of ethical conduct, innovative thinking and moral superiority. However, when analysing an organisations’ adoption of sustainable practices, it is often clear—within the UK—that there are few activities that have been undertaken as an ethical stance instead of legal obligation (McCormick in Environmental politics and policy in industrialized countries, MIT, London, 2002). Our hypothesis is that most methodologies and practices for environmental management do not adopt a holistic perspective, causing significant problems in implementation from inadequate structures and communication channels (Espinosa et al. in Eur J Oper Res, 187:636–651, 2008). In particular we consider that most organisations are currently stifled with management hierarchies that prevent informal/social networking, which may be one of the most powerful natural forms for self-organisation. It is proposed that sustainable development requires more efficient communication channels that foster self-organisation and self-regulation as a method for more productive change processes. In this paper, we explain the reasons why meta-systemic principles of self-organisation and distributed network management offer clear criteria to design an environmental management system that operates on the basis of self-controlled individuals and communities.

The Waste Isolation Pilot Plant (WIPP) is a mined, geologic repository operated for the U.S. Department of Energy in New Mexico. Ongoing technical programs at the facility support requirements regarding continued demonstration of compliance with regulations and improvements to operational efficiency. One factor that can be important to performance measurements at WIPP is the volume of fluid flowing into the repository. The objective of the analysis presented in this paper is to address those processes that influence liquid inflow to the waste disposal areas. Simulations focus on the coupling between brine inflow and properties of the proximal damaged zone in the host rock. Calculations show that significant reduction in predicted brine inflow results when two-phase flow properties of the damaged zone are modified relative to baseline values. Results warrant further investigation regarding these properties. The study also indicates that only nominal improvement to predictive capabilities would result from using a fully coupled transient approach to simulate development of damage in the host rock.