Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

How do atmospheric rivers form?

Identifying the source of atmospheric rivers: Are they rivers of moisture exported from the subtropics or footprints left behind by poleward travelling storms? The term atmospheric river is used to describe corridors of strong water vapor transport in the troposphere. Filaments of enhanced water vapor, commonly observed in satellite imagery extending from the subtropics to the extratropics, are routinely used as a proxy for identifying these regions of strong water vapor transport. The precipitation associated with these filaments of enhanced water vapor can lead to high impact flooding events. However, there remains some debate as to how these filaments form. In this paper we analyse the transport of water vapor within a climatology of wintertime North Atlantic extratropical cyclones. Results show that atmospheric rivers are formed by the cold front which sweeps up water vapor in the warm sector as it catches up with the warm front. This causes a narrow band of high water vapor content to form ahead of the cold front at the base of the warm conveyor belt airflow. Thus, water vapor in the cyclone's warm sector, and not long-distance transport of water vapor from the subtropics, is responsible for the generation of filaments of high water vapor content. A continuous cycle of evaporation and moisture convergence within the cyclone replenishes water vapor lost via precipitation. Thus, rather than representing a direct and continuous feed of moist air from the subtropics into the centre of a cyclone (as suggested by the term atmospheric river), these filaments are, in-fact, the result of water vapor exported from the cyclone and thus they represent the footprints left behind as cyclones travel polewards from subtropics.

An investigation into the relationship between values and commitment: a study of staff in the UK charity sector

Abstract The concept of values “fit” has been a significant theme in the management literature for many years. It is argued that where there is alignment of staff and organizational values a range of positive outcomes are encountered. What is unclear is how this translates into the charity sector. This study explores the phenomenon of values alignment in two UK charities. Questionnaires were used to measure staff values, perceptions of organization values and staff commitment. Drawing on the work of Finegan (2000), an interaction term is used as a proxy for fit. Analyses of data from 286 participants indicated that it was the perceptions of organization values that had the greatest impact on staff commitment. The alignment of staff values and perceptions of organization values only had a degree of effect within one of the charities. This challenges the dominant view on such alignment and the implications of this are discussed. Keywords staff, values fit, commitment, organizational identification

Anxiety and attentional bias in preschool-aged children: an eyetracking study

Extensive research has examined attentional bias for threat in anxious adults and school-aged children but it is unclear when this anxiety-related bias is first established. This study uses eyetracking technology to assess attentional bias in a sample of 83 children aged 3 or 4 years. Of these, 37 (19 female) met criteria for an anxiety disorder and 46 (30 female) did not. Gaze was recorded during a free-viewing task with angry-neutral face pairs presented for 1250 ms. There was no indication of between-group differences in threat bias, with both anxious and non-anxious groups showing vigilance for angry faces as well as longer dwell times to angry over neutral faces. Importantly, however, the anxious participants spent significantly less time looking at the faces overall, when compared to the non-anxious group. The results suggest that both anxious and non-anxious preschool-aged children preferentially attend to threat but that anxious children may be more avoidant of faces than non-anxious children.

Large-scale dynamics associated with clustering of extratropical cyclones affecting Western Europe

Some recent winters in Western Europe have been characterized by the occurrence of multiple extratropical cyclones following a similar path. The occurrence of such cyclone clusters leads to large socio-economic impacts due to damaging winds, storm surges, and floods. Recent studies have statistically characterized the clustering of extratropical cyclones over the North Atlantic and Europe and hypothesized potential physical mechanisms responsible for their formation. Here we analyze 4 months characterized by multiple cyclones over Western Europe (February 1990, January 1993, December 1999, and January 2007). The evolution of the eddy driven jet stream, Rossby wave-breaking, and upstream/downstream cyclone development are investigated to infer the role of the large-scale flow and to determine if clustered cyclones are related to each other. Results suggest that optimal conditions for the occurrence of cyclone clusters are provided by a recurrent extension of an intensified eddy driven jet toward Western Europe lasting at least 1 week. Multiple Rossby wave-breaking occurrences on both the poleward and equatorward flanks of the jet contribute to the development of these anomalous large-scale conditions. The analysis of the daily weather charts reveals that upstream cyclone development (secondary cyclogenesis, where new cyclones are generated on the trailing fronts of mature cyclones) is strongly related to cyclone clustering, with multiple cyclones developing on a single jet streak. The present analysis permits a deeper understanding of the physical reasons leading to the occurrence of cyclone families over the North Atlantic, enabling a better estimation of the associated cumulative risk over Europe.

Equipped to deal with uncertainty in climate and impacts predictions: lessons from internal peer review

The quantification of uncertainty is an increasingly popular topic, with clear importance for climate change policy. However, uncertainty assessments are open to a range of interpretations, each of which may lead to a different policy recommendation. In the EQUIP project researchers from the UK climate modelling, statistical modelling, and impacts communities worked together on ‘end-to-end’ uncertainty assessments of climate change and its impacts. Here, we use an experiment in peer review amongst project members to assess variation in the assessment of uncertainties between EQUIP researchers. We find overall agreement on key sources of uncertainty but a large variation in the assessment of the methods used for uncertainty assessment. Results show that communication aimed at specialists makes the methods used harder to assess. There is also evidence of individual bias, which is partially attributable to disciplinary backgrounds. However, varying views on the methods used to quantify uncertainty did not preclude consensus on the consequential results produced using those methods. Based on our analysis, we make recommendations for developing and presenting statements on climate and its impacts. These include the use of a common uncertainty reporting format in order to make assumptions clear; presentation of results in terms of processes and trade-offs rather than only numerical ranges; and reporting multiple assessments of uncertainty in order to elucidate a more complete picture of impacts and their uncertainties. This in turn implies research should be done by teams of people with a range of backgrounds and time for interaction and discussion, with fewer but more comprehensive outputs in which the range of opinions is recorded.

High-frequency water quality monitoring in an urban catchment: hydrochemical dynamics, primary production and implications for the Water Framework Directive

This paper describes the hydrochemistry of a lowland, urbanised river-system, The Cut in England, using in situ sub-daily sampling. The Cut receives effluent discharges from four major sewage treatment works serving around 190,000 people. These discharges consist largely of treated water, originally abstracted from the River Thames and returned via the water supply network, substantially increasing the natural flow. The hourly water quality data were supplemented by weekly manual sampling with laboratory analysis to check the hourly data and measure further determinands. Mean phosphorus and nitrate concentrations were very high, breaching standards set by EU legislation. Though 56% of the catchment area is agricultural, the hydrochemical dynamics were significantly impacted by effluent discharges which accounted for approximately 50% of the annual P catchment input loads and, on average, 59% of river flow at the monitoring point. Diurnal dissolved oxygen data demonstrated high in-stream productivity. From a comparison of high frequency and conventional monitoring data, it is inferred that much of the primary production was dominated by benthic algae, largely diatoms. Despite the high productivity and nutrient concentrations, the river water did not become anoxic and major phytoplankton blooms were not observed. The strong diurnal and annual variation observed showed that assessments of water quality made under the Water Framework Directive (WFD) are sensitive to the time and season of sampling. It is recommended that specific sampling time windows be specified for each determinand, and that WFD targets should be applied in combination to help identify periods of greatest ecological risk. This article is protected by copyright. All rights reserved.

Infrared and millimetre-wave scintillometry in the suburban environment – Part 1: Structure parameters

Scintillometry, a form of ground-based remote sensing, provides the capability to estimate surface heat fluxes over scales of a few hundred metres to kilometres. Measurements are spatial averages, making this technique particularly valuable over areas with moderate heterogeneity such as mixed agricultural or urban environments. In this study, we present the structure parameters of temperature and humidity, which can be related to the sensible and latent heat fluxes through similarity theory, for a suburban area in the UK. The fluxes are provided in the second paper of this two-part series. A millimetre-wave scintillometer was combined with an infrared scintillometer along a 5.5 km path over northern Swindon. The pairing of these two wavelengths offers sensitivity to both temperature and humidity fluctuations, and the correlation between wavelengths is also used to retrieve the path-averaged temperature–humidity correlation. Comparison is made with structure parameters calculated from an eddy covariance station located close to the centre of the scintillometer path. The performance of the measurement techniques under different conditions is discussed. Similar behaviour is seen between the two data sets at sub-daily timescales. For the two summer-to-winter periods presented here, similar evolution is displayed across the seasons. A higher vegetation fraction within the scintillometer source area is consistent with the lower Bowen ratio observed (midday Bowen ratio < 1) compared with more built-up areas around the eddy covariance station. The energy partitioning is further explored in the companion paper.

Infrared and millimetre-wave scintillometry in the suburban environment – Part 2: Large-area sensible and latent heat fluxes

A millimetre-wave scintillometer was paired with an infrared scintillometer, enabling estimation of large-area evapotranspiration across northern Swindon, a suburban area in the UK. Both sensible and latent heat fluxes can be obtained using this "two-wavelength" technique, as it is able to provide both temperature and humidity structure parameters, offering a major advantage over conventional single-wavelength scintillometry. The first paper of this two-part series presented the measurement theory and structure parameters. In this second paper, heat fluxes are obtained and analysed. These fluxes, estimated using two-wavelength scintillometry over an urban area, are the first of their kind. Source area modelling suggests the scintillometric fluxes are representative of 5–10 km2. For comparison, local-scale (0.05–0.5 km2) fluxes were measured by an eddy covariance station. Similar responses to seasonal changes are evident at the different scales but the energy partitioning varies between source areas. The response to moisture availability is explored using data from 2 consecutive years with contrasting rainfall patterns (2011–2012). This extensive data set offers insight into urban surface-atmosphere interactions and demonstrates the potential for two-wavelength scintillometry to deliver fluxes over mixed land cover, typically representative of an area 1–2 orders of magnitude greater than for eddy covariance measurements. Fluxes at this scale are extremely valuable for hydro-meteorological model evaluation and assessment of satellite data products

Memo test: standardisation of computerised assessment of auditory verbal short-term memory

Short-term memory (STM) impairments are prevalent in adults with acquired brain injuries. While there are several published tests to assess these impairments, the majority require speech production, e.g. digit span (Wechsler, 1987). This feature may make them unsuitable for people with aphasia and motor speech disorders because of word finding difficulties and speech demands respectively. If patients perceive the speech demands of the test to be high, the may not engage with testing. Furthermore, existing STM tests are mainly ‘pen-and-paper’ tests, which can jeopardise accuracy. To address these shortcomings, we designed and standardised a novel computerised test that does not require speech output and because of the computerised delivery it would enable clinicians identify STM impairments with greater precision than current tests. The matching listening span tasks, similar to the non-normed PALPA 13 (Kay, Lesser & Coltheart, 1992) is used to test short-term memory for serial order of spoken items. Sequences of digits are presented in pairs. The person hears the first sequence, followed by the second sequence and s/he decides whether the two sequences are the same or different. In the computerised test, the sequences are presented in live voice recordings on a portable computer through a software application (Molero Martin, Laird, Hwang & Salis 2013). We collected normative data from healthy older adults (N=22-24) using digits, real words (one- and two-syllables) and non-words (one- and two- syllables). Their performance was scored following two systems. The Highest Span system was the highest span length (e.g. 2-8) at which a participant correctly responded to over 7 out of 10 trials at the highest sequence length. Test re-test reliability was also tested in a subgroup of participants. The test will be available as free of charge for clinicians and researchers to use.

The aims of early years outdoor education in England: a conceptual and empirical investigation

This paper explores the place of aims in the early years foundation stage outdoor environment in England. Through examining the writing of academics, various themes are identified, and constructed into possible aims. These themes/aims are compared to an empirical study of early years teachers’ attitudes. Data was collected by questionnaire from schools within the University of Reading partnership. There was general agreement between experts and teachers as to the aims. While some respondents were able to explain what the aims of outdoor activity were, a significant number were unable to identify aims; further, a significant number did not distinguish between approach/practice and aims. A lack of understanding and agreement as to what the aims are may indicate teachers are unsure about the purpose of outdoor education for young children. A result of this study is to agree and make explicit the aims for outdoor education in the early years.

What is outside? The early years foundation stage in England: outdoor facilities, organisation and staff attitudes

The purpose of this paper is to report on the facilities available, organisation of, and staff attitudes to early years outdoor education from schools within the south east of England, focusing on provision for children aged three to five. One component of the successful education of the child involves providing an ‘environment for learning’, including the facilities, layout and routines. This paper presents findings concerning the type and variety of facilities available outside; the various styles of organisation of the space; staff attitudes about: their roles, their aims for the environment, children’s behaviour and learning, and perceived drawbacks to practice. This paper draws on empirical data collected from schools within the University of Reading partnership. The findings suggest that although all early years settings must adhere to the statutory framework there are a range of facilities available, and there are a number of ways this environment is organised. Further there appears to be uncertainty about the adult role outside and the aims for activities. The conclusions drawn indicate that staff do not appear to be linking their aims for outdoor education to the facilities provided or to their actions outside. This means there is not a clear link between what staff provide outside and the declared ambitions for learning. This study is important as all educators need to be certain about their aims for education to ensure best outcomes for children. The implications of these findings for early years teachers are that they need to be able to articulate their aims for outdoor education and to provide the correct facilities to achieve these aims. Finally this study was undertaken to raise debate, posit questions and to ascertain the parameters for further research about the early years outdoor environment.

Advances in the stochastic modelling of satellite-derived rainfall estimates using a sparse calibration dataset

As satellite technology develops, satellite rainfall estimates are likely to become ever more important in the world of food security. It is therefore vital to be able to identify the uncertainty of such estimates and for end users to be able to use this information in a meaningful way. This paper presents new developments in the methodology of simulating satellite rainfall ensembles from thermal infrared satellite data. Although the basic sequential simulation methodology has been developed in previous studies, it was not suitable for use in regions with more complex terrain and limited calibration data. Developments in this work include the creation of a multithreshold, multizone calibration procedure, plus investigations into the causes of an overestimation of low rainfall amounts and the best way to take into account clustered calibration data. A case study of the Ethiopian highlands has been used as an illustration.