Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions

INTRODUCTION: This study investigated alternative pre‐analytical handling of blood for neurofilament light (NfL) analysis where resources are limited. METHOD: Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48‐hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters. RESULTS: Delayed centrifugation (R^{2}= 0.991) and DPS (discovery cohort, R^{2} = 0.954; confirmatory cohort, DPS: R^{2} = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R^{2} = 0.995) and shaking (R^{2} = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS. DISCUSSION: did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS

An update on fluid biomarkers for neurodegenerative diseases: recent success and challenges ahead.

Over the last twenty years, the characterization of Alzheimer's disease (AD) patients has progressed from a description of clinical symptomatology followed by neuropathological findings at autopsy to in vivo pathophysiological signatures using cerebrospinal fluid (CSF) and positron emission tomography (PET). Additionally, CSF biomarkers now reflect synaptic pathology, axonal injury and neuroinflammation. Novel techniques are capable of measuring proteins of pathophysiological importance at femtomolar concentrations in blood (e.g. amyloid, tau species and neurofilaments), which enable screening of large populations in the near future. This will be essential for secondary prevention trials and clinical management. However, common diseases such as dementia with Lewy bodies, Parkinson's disease and frontotemporal dementias, are still without reliable diagnostic biomarkers, although emerging techniques show promising pilot results for some of these diseases. This is likely to change in the next few years, which will be crucial to stratify populations enrolling in clinical trials, since pathologies often coexist

Multistability of free spontaneously-curved anisotropic strips

Multistable structures are objects with more than one stable conformation, exemplified by the simple switch. Continuum versions are often elastic composite plates or shells, such as the common measuring tape or the slap bracelet, both of which exhibit two stable configurations: rolled and unrolled. Here we consider the energy landscape of a general class of multistable anisotropic strips with spontaneous Gaussian curvature. We show that while strips with non-zero Gaussian curvature can be bistable, strips with positive spontaneous curvature are always bistable, independent of the elastic moduli, strips of spontaneous negative curvature are bistable only in the presence of spontaneous twist and when certain conditions on the relative stiffness of the strip in tension and shear are satisfied. Furthermore, anisotropic strips can become tristable when their bending rigidity is small. Our study complements and extends the theory of multistability in anisotropic shells and suggests new design criteria for these structures.Comment: 20 pages, 10 figure

SYSTEMS-2: a randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative (20Gy/5#) or dose escalated treatment (36Gy/6#) will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM

Harms from other people's drinking: an international survey of their occurrence, impacts on feeling safe and legislation relating to their control.

OBJECTIVE: To examine factors associated with suffering harm from another person's alcohol consumption and explore how suffering such harms relate to feelings of safety in nightlife. DESIGN: Cross-sectional opportunistic survey (Global Drug Survey) using an online anonymous questionnaire in 11 languages promoted through newspapers, magazines and social media. SUBJECTS: Individuals (participating November 2014-January 2015) aged 18-34 years, reporting alcohol consumption in the past 12 months and resident in a country providing ≥250 respondents (n=21 countries; 63 725 respondents). MAIN OUTCOME MEASURES: Harms suffered due to others' drinking in the past 12 months, feelings of safety on nights out (on the way out, in bars/pubs, in nightclubs and when travelling home) and knowledge of over-serving laws and their implementation. RESULTS: In the past 12 months, >40% of respondents suffered at least one aggressive (physical, verbal or sexual assault) harm and 59.5% any harm caused by someone drunk. Suffering each category of harm was higher in younger respondents and those with more harmful alcohol consumption patterns. Men were more likely than women to have suffered physical assault (9.2% vs 4.7; p<0.001), with women much more likely to suffer sexual assault or harassment (15.3% vs 2.5%; p<0.001). Women were more likely to feel unsafe in all nightlife settings, with 40.8% typically feeling unsafe on the way home. In all settings, feeling unsafe increased with experiencing more categories of aggressive harm by a drunk person. Only 25.7% of respondents resident in countries with restrictions on selling alcohol to drunks knew about such laws and 75.8% believed that drunks usually get served alcohol. CONCLUSIONS: Harms from others' drinking are a threat to people's health and well-being. Public health bodies must ensure that such harms are reflected in measures of the societal costs of alcohol, and must advocate for the enforcement of legislation designed to reduce such harms

Diffractive Contribution to the Elasticity and the Nucleonic Flux in the Atmosphere

We calculate the average elasticity considering non-diffractive and single diffractive interactions and perform an analysis of the cosmic-ray flux by means of an analytical solution for the nucleonic diffusion equation. We show that the diffractive contribution is important for the adequate description of the nucleonic and hadronic fluxes in the atmosphere.Comment: 10 pages, latex, 2 figures (uuencoded PostScript

British research in accounting and finance (2001–2007): the 2008 research assessment exercise

No abstract available

'I just want a job' : what do we really know about young people in jobs without training?

Over recent years, a central concern of policy has been to drive up post-16 participation rates in full-time education and address the needs of young people not in education, employment or training (NEET). As a result, young people who enter work which is classified as 'without training' at 16/17 have largely been ignored. However, the decision to Raise the Participation Age (RPA) for continuing in learning for all 17-year olds from 2013 and for all 18-year olds from 2015 in England, together with a growing unease about the impact of the current recession on youth unemployment rates, have revived interest in the 'jobs without training' (JWT) group. This paper draws on the findings from two studies: first, a qualitative study in two contrasting local labour markets, of young people in JWT, together with their employers and parents; and second, an evaluation of the Learning Agreement Pilots (LAP), which was the first policy initiative in England targeted at the JWT group. Both studies reveal a dearth of understanding about early labour market entrants and a lack of policy intervention and infrastructure to support the needs of the JWT group throughout the UK. From this, it is concluded that questionable assumptions have been made about the composition and the aspirations of young people in JWT, and their employers, on the basis of little or no evidence. As a consequence, a policy 'quick fix' to satisfy the RPA agenda will not easily be achieved. If the decision to raise the participation age is adopted also by the Welsh and Scottish parliaments, similar challenges may have to be faced

Adverse Childhood Experiences and their impact on health-harming behaviours in the Welsh adult population

This report is one in a series of reports examining the prevalence of Adverse Childhood Experiences (ACEs) in the Welsh adult population and their impact on health and well-being across the life course. Substantial proportions of the Welsh population reported suffering abuse, neglect and other ACEs during their childhood with 47% reporting having experienced at least one ACE and 14% experiencing four or more ACEs. This report focuses on: alcohol use, drug use, violence, sexual behaviour, incarceration, smoking and poor diet