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Prion real-time quaking-induced conversion (RT-QuIC) is emerging as the most potent assay for the in vivo diagnosis of Creutzfeldt–Jakob disease (CJD), but its full application, especially as a screening test, is limited by suboptimal substrate availability, reagent costs, and incomplete assay standardization. Therefore, the search for the most informative cerebrospinal fluid (CSF) surrogate biomarker is still of primary importance. We compared the diagnostic accuracy of CSF protein 14-3-3, measured with both western blot (WB) and enzyme-linked immunosorbent assay (ELISA), total (t)-tau and neurofilament light chain protein (NfL) alone or in combination with RT-QuIC in 212 subjects with rapidly progressive dementia in which we reached a highly probable clinical diagnosis at follow-up or a definite neuropathological diagnosis. T-tau performed best as surrogate CSF biomarker for the diagnosis of CJD (91.3% sensitivity and 78.9% specificity). The 14-3-3 ELISA assay demonstrated a slightly higher diagnostic value compared to the WB analysis (76.9% vs. 72.2%), but both methods performed worse than the t-tau assay. NfL was the most sensitive biomarker for all sCJD subtypes (> 95%), including those with low values of t-tau or 14-3-3, but showed the lowest specificity (43.1%). When ELISA-based biomarkers were adopted as screening tests followed by RT-QuIC, t-tau correctly excluded a higher number of non-CJD cases compared to NfL and 14-3-3 ELISA. Our study showed that among the CSF surrogate biomarkers of potential application for the clinical diagnosis of CJD, t-tau performs best either alone or as screening test followed by RT-QuIC as a second-level confirmatory test. [ABSTRACT FROM AUTHOR]

Background: Leucine‐rich kinase 2 (LRRK2)‐linked Parkinson's disease (PD) is clinically indistinguishable from idiopathic PD (IPD). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK2 p.G2019S patients reveal Lewy‐type synucleinopathy as its principal histological substrate. To date no in vivo biomarkers of synucleinopathy have been found in LRRK2 mutation carriers. Objectives: We used real‐time quaking‐induced conversion (RT‐QuIC) technique to assess the presence of alpha‐synuclein (a‐syn) aggregates in cerebrospinal fluid (CSF) of LRRK2 p.G2019S carriers. Methods: CSF samples of 51 subjects were analyzed: 15 LRRK2 p.G2019S PD, 10 IPD, 16 LRRK2 p.G2019S nonmanifesting carriers (NMC) and 10 healthy controls. The presence of parkinsonism and prodromal symptoms was assessed in all study subjects. Results: Forty percent (n = 6) LRRK2‐PD, and 18.8% (n = 3) LRRK2‐NMC had a positive a‐syn RT‐QuIC response. RT‐QuIC detected IPD with 90% sensitivity and 80% specificity. No clinical differences were detected between LRRK2‐PD patients with positive and negative RT‐QuIC. A positive RT‐QuIC result in LRRK2‐NMC occurred in a higher proportion of subjects meeting the Movement Disorder Society research criteria for prodromal PD. Interpretation: RT‐QuIC detects a‐syn aggregation in CSF in a significant number of patients with LRRK2‐PD, but less frequently than in IPD. A small percentage of LRRK2‐NMC tested also positive. If appropriately validated in long‐term studies with large number of mutation carriers, and hopefully, postmortem or in vivo confirmation of histopathology, RT‐QuIC could contribute to the selection of candidates to receive disease modifying drugs, in particular treatments targeting a‐syn deposition. [ABSTRACT FROM AUTHOR]

The inadvertent transmission of long incubating, untreatable and fatal neurodegenerative prionopathies, notably iatrogenic Creutzfeldt-Jakob disease, following transplantation of cadaver-derived corneas, pituitary growth, hormones and dura mater, constitutes a historical precedent which has underpinned the application of precautionary principles to modern day advanced cell therapies. To date these have been reflected by geographic or medical history risk-based deferral of tissue donors. Emergent understanding of other prion-like proteinopathies, their potential independence from prions as a transmissible agent and the variable capability of scalably manufacturable stem cells and derivatives to take up and clear or to propagate prions, substantiate further commitment to qualifying neurodegenerative proteinopathy transmission risks. This is especially so for those involving direct or facilitated access to a recipient's brain or connected visual or nervous system such as for the treatment of stroke, retinal and adult onset neurodegenerative diseases, treatments for which have already commenced. In this review, we assess the prospective global dissemination of advanced cell therapies founded on transplantation or exposure to allogeneic human cells, recap lessons learned from the historical precedents of CJD transmission and review recent advances and current limits in understanding of prion and other neurodegenerative disease prion-like susceptibility and transmission. From these we propose grounds for a reassessment of the risks of emergent advanced cell therapies to transmit neuroproteinopathies and suggestions to ACT developers and regulators for risk mitigation and extension of criteria for deferrals. [ABSTRACT FROM AUTHOR]

The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) can be difficult, but the real-time quaking-induced conversion (RT-QuIC) assays have made a considerable impact on its clinical diagnosis. This technique exploits the ability of the misfolded pathological form of prion protein (PrPSc) found in cerebrospinal fluid (CSF) to induce conversion of normal PrP to the misfolded form, which subsequently aggregates. The formation of these aggregates of misfolded PrP is monitored in real time using fluorescent dyes. The current sensitivity of CSF RT-QuIC undertaken at the UK National CJD Research & Surveillance Unit is 92% and the specificity is 100%. The interpretation of the RT-QuIC traces is affected by the presence of raised CSF red and white cells counts and elevated total protein concentrations. We recommend that CSF samples for RT-QuIC analysis are clear and colourless with a white cell count of <10 x10^6/L and have a total protein concentration of <1 g/L. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper, which follows an earlier paper published in this journal, is to explore the shape and nature of plural policing through the lens of New Right ideology. It aims to reinforce the understanding that policy is driven by both neoliberalism and neoconservatism, not simply the former. In policy terms, it uses the vehicle of a faith-based initiative – the Street Pastors – to consider how the strategic line of plural policing may be shifting.Design/methodology/approach The research that informs this paper spans 2012 to the present day incorporating a multi-method evaluation, an ongoing observation with informal interviews, and two e-mail surveys directed at university students in Plymouth and Cardiff. In addition, the authors carried out a critical analysis of a research report produced by van Steden and a documentary analysis of national newspaper reports of Street Pastor activities.Findings In a previous paper, the authors provided evidence to support the contention of Jones and Lister (2015) that there has been a shift in the landscape of plural policing. The Street Pastors initiative is a movement from "policing by the state" towards "policing from below". The authors suggest here that there may be evidence to speculate that another shift might occur from "policing from below" to "policing through the state". Ultimately, the authors contend, such shifts reflect and serve the dominance of New Right ideology in social and public policy.Research limitations/implications The research limitations of this paper are twofold. First, the surveys had very small sample sizes and so the results should be treated with caution. The authors have underlined this in detail where necessary. Second, it is informed by a series of related though discrete research activities. However, the authors regard this as a strength also, as the findings are consistent across the range. The implications relate to the way in which policy designed to encourage partnership might lead to off-loading public responsibilities on the one hand, while allowing co-option on the other hand.Social implications The practical implications are indivisible from the social implications in the authors' view. The neoliberal and neoconservative dimensions of the current dominant ideology are using local initiatives to save public money and reify disciplinary features of social and public policy.Originality/value The originality of this research relates to the way it was conducted, drawing together the products of discrete but related activities. It adds to the growing research landscape involving the Street Pastors, an important faith-based, publicly backed initiative. But more importantly, it underlines how the two dimensions of New Right ideology come together in practice. The example of the Street Pastors indicates, through the lens of plural policing, how voluntary and local initiatives are being used to refocus the priorities of social and public policy. [ABSTRACT FROM AUTHOR]

Background: Inherited prion diseases are rare autosomal dominant disorders associated with diverse clinical presentations. All are associated with mutation of the gene that encodes prion protein (PRNP). Homozygous mutations with atypical clinical phenotypes have been described but are extremely rare.Case Presentation: A Chinese patient presented with a rapidly progressive cognitive and motor disorder in the clinical spectrum of sCJD. Investigations strongly suggested a diagnosis of CJD. He was found to carry a homozygous mutation at PRNP codon 200 (E200D), but there was no known family history of the disorder. The estimated allele frequency of E200D in East Asian populations is incompatible with it being a highly penetrant mutation in the heterozygous state.Conclusion: In our view the homozygous PRNP E200D genotype is likely to be causal of CJD in this patient. Homotypic PrP interactions are well known to favour the development of prion disease. The case is compatible with recessively inherited prion disease. [ABSTRACT FROM AUTHOR]

No-take marine reserves can be powerful management tools, but only if they are well designed and effectively managed. We review how ecological guidelines for improving marine reserve design can be adapted based on an area’s unique evolutionary, oceanic, and ecological characteristics in the Gulf of California, Mexico. We provide ecological guidelines to maximize benefits for fisheries management, biodiversity conservation and climate change adaptation. These guidelines include: representing 30% of each major habitat (and multiple examples of each) in marine reserves within each of three biogeographic subregions; protecting critical areas in the life cycle of focal species (spawning and nursery areas) and sites with unique biodiversity; and establishing reserves in areas where local threats can be managed effectively. Given that strong, asymmetric oceanic currents reverse direction twice a year, to maximize connectivity on an ecological time scale, reserves should be spaced less than 50-200 km apart depending on the planktonic larval duration of target species; and reserves should be located upstream of fishing sites, taking the reproductive timing of focal species in consideration. Reserves should be established for the long term, preferably permanently, since full recovery of all fisheries species is likely to take > 25 years. Reserve size should be based on movement patterns of focal species, although marine reserves > 10 km long are likely to protect ~ 80% of fish species. Since climate change will affect species’ geographic range, larval duration, growth, reproduction, abundance, and distribution of key recruitment habitats, these guidelines may require further modifications to maintain ecosystem function in the future. [ABSTRACT FROM AUTHOR]

Aim: Use a fishery‐independent metric to model and map regional‐scale fishing impact, and demonstrate how this metric assists with modelling current and potential fish biomass to support coral‐reef management. We also examine the relative importance of anthropogenic and natural factors on fishes at biogeographical scales. Location: Reefs of five jurisdictions in Micronesia. Methods: A subset of 1,127 fish surveys (470 surveys) was used to calculate site‐specific mean parrotfish lengths (a proxy for cumulative fishing impact), which were modelled against 20 biophysical and anthropogenic variables. The resulting model was extrapolated to each 1 ha reef cell in the region to generate a fishing impact map. The remaining data (657 surveys) were then used to model fish biomass using 15 response variables, including fishing impact. This model was used to map estimated current regional fish standing stocks and, by setting fishing impact to 0, potential standing stocks. Results: Human population pressure and distance to port were key anthropogenic variables predicting fishing impact. Total fish biomass was negatively correlated with fishing, but the influence of natural gradients of primary productivity, sea surface temperature, habitat quality and larval supply was regionally more important. Main conclusions: Mean parrotfish length appears to be a useful fishery‐independent metric for modelling Pacific fishing impact, but considering environmental covariates is critical. Explicitly modelling fishing impact has multiple benefits, including generation of the first large‐scale map of tropical fishing impacts that can inform conservation planning. Using fishing impact data to map current and potential fish stocks provides further benefits, including highlighting the relative importance of fishing on fish biomass and identifying key biophysical variables that cause maximum potential biomass to vary significantly across the region. Regional‐scale maps of fishing, fish standing stocks and the potential benefits of protection are likely to lead to improved conservation outcomes during reserve network planning. [ABSTRACT FROM AUTHOR]

Objective: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis.Methods: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics).Results: Patients with an alternative diagnosis and those with sCJD were of similar age, sex and frequency of dementia but CJD mimics had a longer clinical history. Myoclonus, rigidity and hallucinations were more frequent in patients with sCJD but these features were not helpful in classifying individual patients. Alzheimer's disease, dementia with Lewy bodies and genetic neurodegenerative disorders were alternative diagnoses in more than half of the CJD mimic cases, and 10% had an immune-mediated encephalopathy; lymphoma, hepatic encephalopathy and progressive multifocal leukoencephalopathy were seen more than once. Diffusion-weighted MRI was the most useful readily available test to classify cases correctly (92% CJD, 2% CJD mimics). The CSF cell count, 14-3-3 protein detection and S100B were of limited value. A positive CSF RT-QuIC test, introduced during the course of the study, was found in 89% of tested CJD cases and 0% CJD mimics.Conclusion: The combination of diffusion-weighted MRI analysis and CSF RT-QuIC allowed a perfect classification of sCJD versus its mimics in this study. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the need for certification in hospitality; and specifically to see if professional certifications are valued when earned at the college level and brought to the workplace when hired. There were 79 online surveys completed by hospitality industry professionals at the level of hiring manager. The results of the study showed that there is value in completing certificates while in college, before entering the hospitality workforce. Such certifications as ServSafe, Alcohol Awareness, and Guest Service Professional, were found important when applying to hospitality industry related positions after earning a 4-year degree. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of personality types on consumer complaint channels. Respondents completed a survey that depicted four service failure scenarios, each with 11 possible courses of action. The three personality factors measured against the complaint behavior were locus of control, the California Psychological Inventory measure of sociability and Cattell’s 16 personality factors of relaxed versus tense. Factor analysis revealed three complaint channel dimensions: active, passive, and delayed. Sociability produced more active and less passive complaint behavior. Locus of control interacted with relaxed versus tense on the use of passive and delayed complaints. The findings have implications for recognizing and resolving customer complaints for different personality types. [ABSTRACT FROM AUTHOR]

Wearing her Jersey in Autumn It was a polo neck, black and warm. It smelt like him. An item without autonomy too much like this town. Too much like slipping [...]