Introducing willingness-to-pay for noise changes into transport appraisal: an application of benefit transfer.

Numerous research studies have elicited willingness-to-pay values for transport-related noise, however, in many industrialised countries including the UK, noise costs and benefits are still not incorporated into appraisals for most transport projects and policy changes (Odgaard et al, 2005; Grant-Muller et al, 2001). This paper describes the actions recently taken in the UK to address this issue, comprising: primary research based on the city of Birmingham; an international review of willingness-to-pay evidence; development of values using benefit transfers over time and locations; and integration with appraisal methods. Amongst the main findings are: that the willingness-to-pay estimates derived for the UK are broadly comparable with those used in appraisal elsewhere in Europe; that there is a case for a lower threshold at 1 45dB(A)Leq,18hr1 rather than the more conventional 55dB(A); and that values per dB(A) increase with the noise level above this threshold. There are significant issues over the valuation of rail versus road noise, the neglect of non-residential noise and the valuation of high noise levels in different countries. Conclusions are drawn regarding the feasibility of noise valuation based on benefit transfers in the UK and elsewhere, and future research needs in this field are discussed

Management implications of climate change effect on fisheries in Western Australia Part 1: Environmental change and risk assessment FRDC: Project No. 2010/535

Objectives: 1. Assess future climate change effects on Western Australia’s marine environment using a suite of IPCC model projections, downscaled to the key shelf regions and the spatial and temporal scales relevant for key fisheries 2. Examine the modeled shelf climate change scenarios on fisheries and implications of historic and future climate change effects 3. Review management arrangements to examine their robustness to possible effects of climate chang

Management implications of climate change effect on fisheries in Western Australia Part 2: Case studies FRDC Project No. 2010/535

The Western Rock Lobster Panulirus cygnus (George) is taken by commercial and recreational fishers throughout its geographic range along the lower west coast of Western Australia. It is fished by three managed fisheries; West Coast Rock Lobster Managed Fishery (WCRLMF), Augusta–Windy Harbour Managed Fishery and the South Coast Crustacean Fisheries. The WCRLMF is the largest fishery encompassing most of the Western Rock Lobster’s (WRL) geographic range (Figure 1.1.1), including the most productive regions and is Australia’s largest single-species fishery worth $200–400 million annually

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

Simple Summary: One of the reasons that pancreatic cancer is such a deadly disease is that it is able to evade the body’s usual defence system (the immune system). It has been shown that the population of microorganisms in the human gut (the gut microbiome) plays a role in regulating the human immune system. This article outlines the ways in which the gut microbiome influences the immune system in pancreatic cancer both within the bloodstream (systemic) and around the pancreatic tumour itself (local). These are important mechanisms because greater understanding of these will direct the development of future treatments for pancreatic cancer. It is possible that some of these treatment options will target the gut microbiome in order to boost the immune system’s response to pancreatic cancer. Abstract: The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients

Uncertainty and Surprise Jointly Predict Musical Pleasure and Amygdala, Hippocampus, and Auditory Cortex Activity

Listening to music often evokes intense emotions [1, 2]. Recent research suggests that musical pleasure comes from positive reward prediction errors, which arise when what is heard proves to be better than expected [3]. Central to this view is the engagement of the nucleus accumbens—a brain region that processes reward expectations—to pleasurable music and surprising musical events [4, 5, 6, 7, 8]. However, expectancy violations along multiple musical dimensions (e.g., harmony and melody) have failed to implicate the nucleus accumbens [9, 10, 11], and it is unknown how music reward value is assigned [12]. Whether changes in musical expectancy elicit pleasure has thus remained elusive [11]. Here, we demonstrate that pleasure varies nonlinearly as a function of the listener’s uncertainty when anticipating a musical event, and the surprise it evokes when it deviates from expectations. Taking Western tonal harmony as a model of musical syntax, we used a machine-learning model [13] to mathematically quantify the uncertainty and surprise of 80,000 chords in US Billboard pop songs. Behaviorally, we found that chords elicited high pleasure ratings when they deviated substantially from what the listener had expected (low uncertainty, high surprise) or, conversely, when they conformed to expectations in an uninformative context (high uncertainty, low surprise). Neurally, we found using fMRI that activity in the amygdala, hippocampus, and auditory cortex reflected this interaction, while the nucleus accumbens only reflected uncertainty. These findings challenge current neurocognitive models of music-evoked pleasure and highlight the synergistic interplay between prospective and retrospective states of expectation in the musical experience

The yeast Batten disease orthologue Btn1 controls endosome–Golgi retrograde transport via SNARE assembly

Btn1 controls endosome–Golgi retrograde sorting by regulating SNARE phosphorylation and assembly

Thunderclap: Exploring Vulnerabilities in Operating System IOMMU Protection via DMA from Untrustworthy Peripherals

Direct Memory Access (DMA) attacks have been known for many years: DMA-enabled I/O peripherals have complete access to the state of a computer and can fully compromise it including reading and writing all of system memory. With the popularity of Thunderbolt 3 over USB Type-C and smart internal devices, opportunities for these attacks to be performed casually with only seconds of physical access to a computer have greatly broadened. In response, commodity hardware and operating-system (OS) vendors have incorporated support for Input-Output Memory Management Units (IOMMUs), which impose memory protection on DMA, and are widely believed to protect against DMA attacks. We investigate the state-of-the-art in IOMMU protection across OSes using a novel I/O security research platform, and find that current protections fall short when faced with a functional network peripheral that uses its complex interactions with the OS for ill intent, and demonstrate compromises against macOS, FreeBSD, and Linux, which notionally utilize IOMMUs to protect against DMA attackers. Windows only uses the IOMMU in limited cases and remains vulnerable. Using Thunderclap, an open-source FPGA research platform we built, we explore a number of novel exploit techniques to expose new classes of OS vulnerability. The complex vulnerability space for IOMMU-exposed shared memory available to DMA-enabled peripherals allows attackers to extract private data (sniffing cleartext VPN traffic) and hijack kernel control flow (launching a root shell) in seconds using devices such as USB-C projectors or power adapters. We have worked closely with OS vendors to remedy these vulnerability classes, and they have now shipped substantial feature improvements and mitigations as a result of our work.DARPA I2O FA8750-10-C-0237 ("CTSRD") DARPA MTO HR0011- 18-C-0016 ("ECATS") Arm Ltd Google Inc This work was also supported by EPSRC EP/R012458/1 (“IOSEC”)

Interplay in galectin expression predicts patient outcomes in a spatially restricted manner in PDAC

BACKGROUND: Galectins (Gal's) are a family of carbohydrate-binding proteins that are known to support the tumour microenvironment through their immunosuppressive activity and ability to promote metastasis. As such they are attractive therapeutic targets, but little is known about the cellular expression pattern of galectins within the tumour and its neighbouring stromal microenvironment. Here we investigated the cellular expression pattern of Gals within pancreatic ductal adenocarcinoma (PDAC).METHODS: Galectin gene and protein expression were analysed by scRNAseq (n=4) and immunofluorescence imaging (n=19) in fibroblasts and epithelial cells of pancreatic biopsies from PDAC patients. Galectin surface expression was also assessed on tumour adjacent normal fibroblasts and cancer associated primary fibroblasts from PDAC biopsies using flow cytometry.RESULTS: scRNAseq revealed higher Gal-1 expression in fibroblasts and higher Gal-3 and -4 expression in epithelial cells. Both podoplanin (PDPN+, stromal/fibroblast) cells and EpCAM+ epithelial cells expressed Gal-1 protein, with highest expression seen in the stromal compartment. By contrast, significantly more Gal-3 and -4 protein was expressed in ductal cells expressing either EpCAM or PDPN, when compared to the stroma. Ductal Gal-4 cellular expression negatively correlated with ductal Gal-1, but not Gal-3 expression. Higher ductal cellular expression of Gal-1 correlated with smaller tumour size and better patient survival. CONCLUSIONS: In summary, the intricate interplay and cell-specific expression patterns of galectins within the PDAC tissue, particularly the inverse correlation between Gal-1 and Gal-4 in ducts and its significant association with patient survival, highlights the complex molecular landscape underlying PDAC and provides valuable insights for future therapeutic interventions.</p

The chemokine receptor CXCR2 and coronavirus-induced neurologic disease.

Inoculation with the neurotropic JHM strain of mouse hepatitis virus (MHV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis in which virus preferentially replicates within glial cells while excluding neurons. Control of viral replication during acute disease is mediated by infiltrating virus-specific T cells via cytokine secretion and cytolytic activity, however sterile immunity is not achieved and virus persists resulting in chronic neuroinflammation associated with demyelination. CXCR2 is a chemokine receptor that upon binding to specific ligands promotes host defense through recruitment of myeloid cells to the CNS as well as protecting oligodendroglia from cytokine-mediated death in response to MHV infection. These findings highlight growing evidence of the diverse and important role of CXCR2 in regulating neuroinflammatory diseases