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Background: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.Methods/design: This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71 years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73).Discussion: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials. [ABSTRACT FROM AUTHOR]

Background: Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood.Methods: We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume.Results: Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P= .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1α level (P= .0003) and CSF IL-1β level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005).Conclusions: A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis. [ABSTRACT FROM AUTHOR]

This research examines the commuting behavior of workers who have recently moved to or within rural areas in England. While internal migration and commuting are often examined separately, the present study sees them as interrelated, hence the term ‘migration-commuting nexus.’ This study uses the ASHE data in the first longitudinal study of changes in residence and subsequent changes (or lack thereof) of place of work. In particular, this study examines persistence and change of commuting distance status, the time trend of such changes, and their association with recent rural migration and with socioeconomic attributes of English workers. [ABSTRACT FROM AUTHOR]

Tree-ring chronologies form the backbone of high-resolution palaeoclimatology. However, their number declines drastically prior to medieval times, and only a few such records worldwide extend back to the mid-Holocene. Here, we present a collection of more than 400 subfossil yew (Taxus baccata L.) trees excavated from near sea-level peat-rich sediments in the Fenland region of eastern England. The well-preserved yew trunks are between two and eight metres long, often exhibit adventitious root layers, and contain up to 400 rings of highly irregular growth. Combined dendrochronological and radiocarbon dating resulted in two tree-ring width chronologies that comprise 36 and 32 trees, span 413 and 418 years, exhibit mean inter-series correlations (Rbar) of 0.50 and 0.51, and were provisionally dated to 5225−4813 (±4) and 4612−4195 (±6) years cal BP. Together with a total of 63 radiocarbon dates (14C), our subfossil tree-ring evidence suggests that yew establishment (or onset of preservation) began ∼5250 years cal BP and resulted in extensive climax forests between 5200 and 4200 years cal BP. A first stage of yew decline ∼4800−4600 years cal BP was possibly caused by oxygen deprivation from soil wetting, whereas yew disappearance ∼4200 years cal BP is suggested to have been triggered by marine inundation as a consequence of rapid sea-level rise. Both phases of yew decline in eastern England coincide with marked reductions in subfossil oak and pine from peatbogs in Ireland, Germany and the Netherlands. Our results emphasise the potential to develop a dendrochronological network in coastal England for better understanding of larger-scale climate and environmental changes during the mid-Holocene, including the still debated 4.2 ka climate event. Moreover, we expect our subfossil yew chronologies to facilitate the dating of local archaeological remains, refine sea-level reconstructions around the British Isles, and contribute to the international radiocarbon calibration curve IntCal. [Display omitted] • We present >400 subfossil yew (Taxus baccata) trees from eastern England. • Dendrochronological and radiocarbon dating were combined for chronology development. • Two 400-year-long tree-ring chronologies date between 5200 and 4200 years cal BP. • Mid-Holocene woodlands in eastern England were dominated by yew until ∼4.2ka ago. • We hypothesise that yew disappearance around 4.2ka was related to rapid sea-level rise. [ABSTRACT FROM AUTHOR]

• Willowed log jams (∼dams) have been installed frequently to reduce flood risk. • Few studies have assessed pre- and post- installation changes to watercourse flows. • Discharge data shows an average 27.3% reduction on peaks, following installation. • River-reach (0–130 m) wildlife camera photos and levels confirm attenuation. • Willowed log jams re-naturalise flows, locally alleviating floods and droughts. Nature Based Solutions (NBS), including Natural Flood Management (NFM) schemes are becoming an important component of many governmental and organisation responses to increases in flood and aridity risk. NFM structures may take multiple forms to slow, store, disconnect and filter distributed overland flow pathways within a catchment that coalesce to generate a flood-wave downstream and runoff rather than infiltrate groundwaters. To date few studies have conducted observations pre- and post-installation monitoring at river reach-scales, despite widespread and frequent installation, to investigate the efficacy of willowed engineered log jams (WELJs) interventions used in abating flood-flows, through backing-up flood-pulses with consequent reductions in downstream discharges. This paper examines the efficiency, before and after installation of five 1 m high WELJs incorporating 1,000 Bay willow (Salix pentandra) saplings supporting the dead horizontal timber, across a total of 130 linear metres spanning the floodplain of a decommissioned reservoir. One rain gauge, two fixed point time-lapse wildlife cameras and three water level stations were installed: upstream-of, within, and downstream-of all WELJs. The findings demonstrate a substantial reduction is achieved for most events, with an average of 27.3% reduction in peak discharge being achieved post-installation. The time to peak is little impacted, however there is demonstrable evidence of a longer and higher recessional limb to the events. These findings quantify for the first time the role that WELJs can play in a move towards re-naturalisation of water level regimes, with lower peak water flows achieved, and waters released from the river-reach more slowly. Furthermore, baseflow during dry periods is also elevated by 27.1%, offering greater resilience to dry periods and droughts. Consequently, over the river-reach scale (0–130 m), WELJs play an important role in alleviating flood and drought risk through suppressing flood peaks and increasing baseflow during low flows; steps towards improved hydro-morphological quality overall. [ABSTRACT FROM AUTHOR]