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Background: Large-scale trials of multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theory, reduces cognitive decline over 2 years.Methods: A multi-site, single-blind randomised controlled trial recruiting 704 older adults at high dementia risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Participants are randomised using 1:1 allocation ratio to the APPLE Tree intervention versus control arm (dementia prevention information), stratified by site. The intervention explores and implements strategies to promote healthy lifestyle, increase pleasurable activities and social connections and improve long-term condition self-management. Two facilitators trained and supervised by a clinical psychologist deliver ten, 1-h group video call sessions over 6 months (approximately every fortnight), video-call 'tea breaks' (less structured, facilitated social sessions) in intervening weeks and individual goal-setting phone calls every 2 weeks. From 6 to 12 months, participants meet monthly for 'tea breaks', with those not attending receiving monthly goal-setting phone calls. Participants receive a food delivery, pedometer and website access to cognitive training and information about lifestyle modification. Follow-ups for all outcome measures are at 12 and 24 months. The primary outcome is cognition (Neuropsychological Test Battery (NTB) score) at 24 months. Secondary outcomes are quality of life, cost per quality-adjusted life year (QALY) and wellbeing and lifestyle factors the intervention targets (diet, vascular risk, body weight, activity, sleep, anxiety, depression, social networks and loneliness, alcohol intake and smoking). Participants from purposively selected sites participate in qualitative process evaluation interviews, which will be analysed using thematic analytic methods.Discussion: If effective, the intervention design, involving remote delivery and non-clinical facilitators, would facilitate intervention roll-out to older people with memory concerns.Trial Registration: ISRCTN17325135 . Registration date 27 November 2019. [ABSTRACT FROM AUTHOR]

The equatorial tropics house some of the earliest rock art yet known, and it is weathering at an alarming rate. Here we present evidence for haloclasty (salt crystallisation) from Pleistocene-aged rock art panels at 11 sites in the Maros-Pangkep limestone karsts of southern Sulawesi. We show how quickly rock art panels have degraded in recent decades, contending that climate-catalysed salt efflorescence is responsible for increasing exfoliation of the limestone cave surfaces that house the ~ 45 to 20-thousand-year-old paintings. These artworks are located in the world's most atmospherically dynamic region, the Australasian monsoon domain. The rising frequency and severity of El Niño-induced droughts from anthropogenic climate change (that is, higher ambient temperatures and more consecutive dry days), combined with seasonal moisture injected via monsoonal rains retained as standing water in the rice fields and aquaculture ponds of the region, increasingly provide ideal conditions for evaporation and haloclasty, accelerating rock art deterioration. [ABSTRACT FROM AUTHOR]

Objective: There is limited understanding about how people in the severe stages of Alzheimer's disease (AD) experience and demonstrate awareness. We synthesised all available evidence with the aim of understanding how awareness is preserved or impaired in severe AD and what evidence there is for different levels of awareness according to the levels of awareness framework. Method: A systematic search of the following databases: Embase, PsycINFO, MEDLINE and Web of Science was carried out. A narrative synthesis and analysis was conducted of all included studies. All studies were assessed for quality using the AXIS and CASP tools. Results: Our findings suggest that lower level sensory awareness is relatively maintained in severe AD. Findings for higher level awareness are variable and this may be related to the diversity of methods that have been used to explore awareness in these circumstances. Conclusion: Awareness is complex, heterogeneous and varies significantly between individuals. Environmental and contextual factors have a significant impact on whether awareness is observed in people with severe AD. Adaptation of the environment has the potential to facilitate the expression of awareness while education of caregivers may increase understanding of people with severe AD and potentially improve the quality of care that is received. [ABSTRACT FROM AUTHOR]

Objectives: Awareness can be defined as a response to, or evaluation of, an aspect of one's situation or internal state. Awareness becomes impaired as dementia progresses; however, the exact nature and degree of impairment in advanced dementia remains unclear. The extent to which caregivers understand or make assumptions about the level and nature of awareness in advanced dementia may have a significant impact on their ability to appropriately respond to and care for the person with dementia. This systematic review examines the literature regarding professional caregiver perceptions about awareness in advanced dementia.Design: A systematic search of online literature databases (PsychInfo, Medline, Embase, CINAHL) was conducted up to January 15, 2018, using a range of search terms related to dementia, awareness and caregiver attitudes.Results: The systematic review included a total of 10 qualitative studies that were heterogeneous in aspects of design, including analyses. Narrative synthesis was used to integrate results. Four major themes were identified from review of the papers: how professional caregivers defined awareness; professional caregiver beliefs about what influences the expression of awareness; professional caregiver beliefs around how to assess awareness in advanced dementia; and the perceived impact of episodes of increased awareness on the person with dementia and caregiver. Sub-themes were identified within each of these areas.Conclusion: This review highlights the importance of professional caregiver perceptions of awareness in advanced dementia. Supporting professional caregivers to assess and understand the nature of awareness in advanced dementia would improve their approach to care and outcomes for people with dementia. [ABSTRACT FROM AUTHOR]

Figurative cave paintings from the Indonesian island of Sulawesi date to at least 35,000 years ago (ka) and hand-stencil art from the same region has a minimum date of 40 ka1. Here we show that similar rock art was created during essentially the same time period on the adjacent island of Borneo. Uranium-series analysis of calcium carbonate deposits that overlie a large reddish-orange figurative painting of an animal at Lubang Jeriji Saléh—a limestone cave in East Kalimantan, Indonesian Borneo—yielded a minimum date of 40 ka, which to our knowledge is currently the oldest date for figurative artwork from anywhere in the world. In addition, two reddish-orange-coloured hand stencils from the same site each yielded a minimum uranium-series date of 37.2 ka, and a third hand stencil of the same hue has a maximum date of 51.8 ka. We also obtained uranium-series determinations for cave art motifs from Lubang Jeriji Saléh and three other East Kalimantan karst caves, which enable us to constrain the chronology of a distinct younger phase of Pleistocene rock art production in this region. Dark-purple hand stencils, some of which are decorated with intricate motifs, date to about 21-20 ka and a rare Pleistocene depiction of a human figure—also coloured dark purple—has a minimum date of 13.6 ka. Our findings show that cave painting appeared in eastern Borneo between 52 and 40 ka and that a new style of parietal art arose during the Last Glacial Maximum. It is now evident that a major Palaeolithic cave art province existed in the eastern extremity of continental Eurasia and in adjacent Wallacea from at least 40 ka until the Last Glacial Maximum, which has implications for understanding how early rock art traditions emerged, developed and spread in Pleistocene Southeast Asia and further afield. Uranium-series dating of rock art from Borneo reveals a minimum date for figurative artwork of 40,000 years ago, and a distinct style of parietal art in Southeast Asia at the Last Glacial Maximum.\ [ABSTRACT FROM AUTHOR]

Aim: Few data are available on the optimal long‐term care of early‐stage colorectal cancer survivors, termed survivorship care. We aimed to investigate current practice in the management of patients following treatment for early‐stage colorectal cancer. Method: We performed an internet survey of members of the American Society for Colon and Rectal Surgeons about several aspects of long‐term care, including allocation of clinician responsibility, challenges with transitions to primary care physicians (PCPs), long‐term care plan provision and recommended surgical follow‐up duration. Results: Overall, 251 surgeons responded. Surgeons reported taking primary responsibility for managing adverse surgical effects (93.2%) and surveillance testing (imaging and laboratories 68.6%, endoscopy 82.4%). Barriers to PCP handoffs included patient preference for surgical follow‐up (endorsed by 76.6%) and inadequate communication with PCPs (endorsed by 36.9%). Approximately one‐third of surgeons routinely provide survivorship care plans to PCPs; surgeons who received formal survivorship training were more likely to do so compared to those without such training (OR 3.29, 95% CI 1.57, 6.92). Although only 20.4% of surgeons follow their patients beyond 5 years, individuals in practice longer were more likely to continue long‐term follow‐up than those with ≤ 10 years of experience. Conclusions: This is the largest survey of surgeons regarding long‐term management for early‐stage colorectal cancer and highlights the potential for improved coordination with PCPs and increased implementation of survivorship care plans. [ABSTRACT FROM AUTHOR]

Objective: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia.Method: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning.Results: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance.Conclusion: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan. [ABSTRACT FROM AUTHOR]

We present an inverse method to identify the spatially varying stiffness distributions in 3 dimensions. The method is an extension of the classical Virtual Fields Method-a numerical technique that exploits information from full-field deformation measurements to deduce unknown material properties-in the spatial frequency domain, which we name the Fourier-series-based virtual fields method (F-VFM). Three-dimensional stiffness distributions, parameterised by a Fourier series expansion, are recovered after a single matrix inversion. A numerically efficient version of the technique is developed, based on the Fast Fourier Transform. The proposed F-VFM is also adapted to deal with the challenging situation of limited or even non-existent knowledge of boundary conditions. The three-dimensional F-VFM is validated with both numerical and experimental data. The latter came from a phase contrast magnetic resonance imaging experiment containing material with Poisson's ratio close to 0.5; such a case requires a slightly different interpretation of the F-VFM equations, to enable the application of the technique to incompressible materials. [ABSTRACT FROM AUTHOR]

Background: Interventions that improve cognitive function in Alzheimer's disease are urgently required.Aims: To assess whether a novel cognitive training paradigm based on 'chunking' improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).Method: Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.Results: Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.Conclusions: Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objectives: To review the efficacy of cognitive interventions on improving general cognition in dementia. Method: Online literature databases and trial registers, previous systematic reviews and leading journals were searched for relevant randomised controlled trials. A systematic review, random-effects meta-analyses and meta-regression were conducted. Cognitive interventions were categorised as: cognitive stimulation (CS), involving a range of social and cognitive activities to stimulate multiple cognitive domains; cognitive training (CT), involving repeated practice of standardised tasks targeting a specific cognitive function; cognitive rehabilitation (CR), which takes a person-centred approach to target impaired function; or mixed CT and stimulation (MCTS). Separate analyses were conducted for general cognitive outcome measures and for studies using 'active' (designed to control for non-specific therapeutic effects) and non-active (minimal or no intervention) control groups. Results: 33 studies were included. Significant positive effect sizes (Hedges' g) were found for CS with the mini- mental state examination (MMSE) (g=0.51, 95% CI 0.29 to 0.69; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.65; p=0.019) compared to active controls. Significant benefit was also seen with the Alzheimer's disease Assessment Scale-Cognition (ADAS- Cog) (g=-0.26, 95% CI -0.445 to -0.08; p=0.005). There was no evidence that CT or MCTS produced significant improvements on general cognition outcomes and not enough CR studies for meta-analysis. The lowest accepted minimum clinically important difference was reached in 11/17 CS studies for the MMSE, but only 2/9 studies for the ADAS-Cog. Additionally, 95% prediction intervals suggested that although statistically significant, CS may not lead to benefits on the ADAS-Cog in all clinical settings. Conclusions: CS improves scores on MMSE and ADAS- Cog in dementia, but benefits on the ADAS-Cog are generally not clinically significant and difficulties with blinding of patients and use of adequate placebo controls make comparison with the results of dementia drug treatments problematic. [ABSTRACT FROM AUTHOR]

Distinctive mulberry paintings found in northern Australia, particularly those of the Kimberley region, have been argued to represent some of the oldest surviving rock art on the continent. Significant research efforts continue to focus on resolving the age of these motifs, but comparatively little attention has been given to understanding their physical composition and potential source(s). In a pilot investigation, we conclude that (at least) two mineralogically distinct mulberry pigments occur in Gwion motifs and demonstrate that their major components can be indicatively chemically differentiated, non-invasively. Characterization of a 'quarried' mulberry ochre source demonstrates that these pigments occur locally as natural minerals. [ABSTRACT FROM AUTHOR]

ABSTRACT The virtual fields method (VFM) allows spatial distributions of material properties to be calculated from experimentally determined strain fields. A numerically efficient Fourier-series-based extension to the VFM (the F-VFM) has recently been developed, in which the unknown stiffness distribution is parameterised in the spatial frequency domain rather than in the spatial domain as used in the classical VFM. However, the boundary conditions for the F-VFM are assumed to be well-defined, whereas in practice, the traction distributions on the perimeter of the region of interest are rarely known to any degree of accuracy. In the current paper, we therefore consider how the F-VFM theory can be extended to deal with the case of unknown boundary conditions. Three different approaches are proposed; their ability to reconstruct normalised stiffness distributions and traction distributions around the perimeter from noisy input strain fields is assessed through simulations based on a forward finite element analysis. Finally, a practical example is given involving experimental strain fields from a diametral compression test on an aluminium disc. [ABSTRACT FROM AUTHOR]

We present a new method that combines the fringe projection and the digital image correlation (DIC) techniques on a single hardware platform to simultaneously measure both shape and deformation fields of three-dimensional (3-D) surfaces with complex geometries. The method in its basic form requires only a single camera and single projector, but this can be easily extended to a multi-camera multi-projector system to obtain complete 360° measurements. Multiple views of the surface profile and displacement field are automatically co-registered in a unified global coordinate system, thereby avoiding the significant errors that can arise through the use of statistical point cloud stitching techniques. Experimental results from a two-camera two-projector sensor are presented and compared with results from both a standard stereo-DIC approach and a finite element model. [ABSTRACT FROM AUTHOR]

An experiment to measure granular temperature in a sheared low density granular bed containing a range of sizes of particles has been performed. Using positron emission particle tracking, a single particle was tracked from different size phases. From the coordinate data, the second moment of the velocity fluctuations about the mean flow in each direction was determined. It was found that the larger particles are 'hotter' and that most of the energy is contained in the θ (shearing) direction fluctuations. Evidence was found for Knudsen layer and higher order Burnett effects, suggesting extensions of the Navier-Stokes approaches are necessary to describe heat transport in polydisperse systems. [ABSTRACT FROM AUTHOR]

We study convective motion in vertically vibrated three-dimensional granular beds by comparing the predictions of a model based on a hydrodynamic description to Navier–Stokes order with experimental results obtained using positron emission particle tracking (PEPT). The three-dimensional conservation equations relating mass, momentum and energy are solved using the finite element (FE) method for a viscous vibrofluidized bed by using only observable system parameters such as particle number, size, mass and coefficients of restitution. The mean velocity profiles from the viscous model show reasonable agreement with the experimental results at relatively low altitudes for the range of experimental values studied, though the velocity fields at higher altitudes were systematically underestimated by the model. We confirm that the convection rolls are influenced by the sidewall coefficient of restitution and demonstrate the scaling relationships that operate, where increasing amplitude of vibration leads to a reduction in the angular velocity of the rolls. [ABSTRACT FROM PUBLISHER]

In this paper, we address the behaviour of lacquer coatings similar to that found on the Mazarin Chest, an important Japanese lacquerware artefact currently held by the Victoria and Albert Museum (V&A) in London. The response of Japanese lacquer (urushi) to changes in environmental conditions was investigated by examining the deflection of a glass substrate coated with a thin film of urushi subjected to changes of humidity. This deflection, measured using phase-shifting interferometry, was then used to determine the two in-plane hygral stress components. Results were compared for two sample conditioning regimes--subjected to intense UV ageing and no ageing--each at a range of relative humidity (RH) steps. The changes in humidity were found to cause rapid stress changes in the lacquers, which then relax over much longer time scales. A simple one-dimensional model of the moisture transport and the stress development is shown to be effective in describing the response of the material to changes in environmental RH. [ABSTRACT FROM AUTHOR]

The last 5 years have seen the emergence of a family of optical interferometric techniques that provide deformation measurements throughout three-dimensional (3-D) weakly scattering materials. They include wavelength scanning interferometry (WSI), tilt scanning interferometry (TSI), phase contrast spectral optical coherence tomography (PC SOCT) and hyperspectral interferometry (HSI) and can be thought of as a marriage between the phase sensing capabilities of Phase Shifting Interferometry and the depth-sensing capabilities of Optical Coherence Tomography. It was recently shown that some closely related 3-D optical imaging techniques can be treated as shift-invariant linear filtering operations. In this paper, we extend that work to include WSI, TSI, PC SOCT and HSI as spatial filtering operations and also relate the properties of their transfer functions in the spatial frequency domain to their spatial resolution and phase sensitivity, for depth-resolved displacement measurements. [ABSTRACT FROM AUTHOR]

We present the results of investigations into the strain distributions in the adhesive layers of epoxy-bonded aluminium-aluminium and aluminium-carbon fibre reinforced polymer (Al/CFRP) double-lap shear joints. The area of the adhesive at the end of the overlap region, where high stresses are predicted and failure generally initiates, has been studied at high magnification. 2-D maps of the longitudinal and engineering shear strains in this region have been obtained experimentally by using high magnification moiré interferometry (HMMI). These results have been compared with the strain maps predicted by 3D elastic and elasto-plastic finite element (FE) modelling. Excellent agreement is seen between the experimentally measured and FE-predicted strain distributions, thus validating both methods. In some cases, quantitative comparison of the strains along certain profiles is compromised by noise in the measurements, especially for the Al/CFRP joints, which experienced lower overall strains. The source of such errors is discussed in the paper. [ABSTRACT FROM AUTHOR]

IgA and IgE activity against Teladorsagia circumcincta was investigated in a flock of Texel lambs following natural, mixed nematode infection among lambs. The distribution of IgA activity was similar to a gamma distribution whereas IgE activity was different. Box-Cox analysis demonstrated that X0.25 was a suitable transformation to normalise IgE responses. The transformed IgE activity was under moderate to strong genetic control. Nine different allergens were identified by proteomic analysis. Tropomyosin was selected for further analysis. IgE activity against tropomyosin was moderately heritable and associated with decreased egg counts and with reduced body weight at the time of sampling. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) play a central role in maintenance of immune homeostasis by controlling harmful immune responses to inappropriate antigens and are thought to play a key role in modulating hypersensitivity reactions. Infestation of sheep with Psoroptes ovis results in a pronounced cutaneous hypersensitivity-type response, which appears to be crucial for mite survival. We hypothesize that (i) Tregs are involved in sheep scab lesions and (ii) Treg responses may crucially affect lesion development and subsequent mite survival. Foxp3 is a key transcription factor required for generation and maintenance of Tregs in rodents and humans, and is the most widely used marker for Tregs in these species. In this study, we sequence ovine foxp3 and show that it exhibits a high degree of homology with foxp3 from other species. Using a validated immunohistochemical staining technique, we demonstrate that infestation of sheep with P.  ovis results in an influx of Foxp3+ T cells into the skin. Future work will investigate the regulatory function of ovine Foxp3+ T cells and determine whether the quality of the Treg response to P.  ovis plays a role in individual susceptibility to the mite. [ABSTRACT FROM AUTHOR]

Background Reports of the extent of working memory (WM) impairment in early Alzheimer's disease (AD) have been inconsistent. Using the model of WM proposed by Baddeley, neuropsychological evidence for the impairment of WM in early AD is evaluated. Method Literature searches were performed using Medline, PsycINFO and Embase databases. Individual papers were then examined for additional references not revealed by computerised searches. Results Phonological loop function is intact at the preclinical and early stages of AD, becoming more impaired as the disease progresses. In mild AD, there is impairment on tasks assessing visuospatial sketchpad (VSS) function; however, these tasks also require executive processing by the central executive system (CES). There is evidence that the CES is impaired in mild AD and may be affected in the earlier preclinical stage of the disease. Episodic buffer function may be impaired but further research is required. Conclusions Future research into central executive functioning at the earliest stages of the disease, combined with further longitudinal studies, needs to be carried out. Tasks to assess the proposed functions of the episodic buffer and specific tests of the VSS suitable for AD subjects need to be developed and validated. Learning more about these processes and how they are affected in AD is important in understanding and managing the cognitive deficits seen in the early stages of AD. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sheep scab is caused by the noninvasive mite, Psoroptes ovis , which initiates a profound pro-inflammatory skin response leading to lesion development. To investigate these early events between the skin and the parasite, primary ovine epidermal keratinocyte cultures were generated and challenged with mite derived antigens. The kinetics of the mRNA response of these cells were monitored by microarray. The results indicated that the cells responded within 1 h of challenge, with a significant increase in the pro-inflammatory cytokine IL-8. This result was confirmed by real-time RT-PCR, and showed that IL-8 up-regulation was maximal at 1 h but declined to pre-stimulation levels at 24 and 48 h. The IL-8 mRNA response to mite wash antigens containing secretory and/or excretory proteins was also investigated and compared to the response to whole mite antigen. These studies revealed that the mite wash antigen, at a challenge dose of 10 µg/mL, was markedly more potent and induced significantly higher levels of IL-8 mRNA than the same concentration of whole mite antigen. These results are discussed in relation to mite establishment and survival on the ovine host. [ABSTRACT FROM AUTHOR]

Objective: Forkhead box O (FoxO) transcription factors represent evolutionarily conserved targets of insulin signaling, regulating metabolism and cellular differentiation in response to changes in nutrient availability. Although the FoxO1 isoform is known to play a key role in adipogenesis, its physiological role in differentiated adipose tissue remains unclear.Research Design and Methods: In this study, we analyzed the phenotype of FoxO1 haploinsufficient mice to investigate the role of FoxO1 in high-fat diet-induced obesity and adipose tissue metabolism.Results: We showed that reduced FoxO1 expression protects mice against obesity-related insulin resistance with marked improvement not only in hepatic insulin sensitivity but also in skeletal muscle insulin action. FoxO1 haploinsufficiency also resulted in increased peroxisome proliferator-activated receptor (PPAR)gamma gene expression in adipose tissue, with enhanced expression of PPARgamma target genes known to influence metabolism. Moreover, treatment of mice with the PPARgamma agonist rosiglitazone caused a greater improvement in in vivo insulin sensitivity in FoxO1 haploinsufficient animals, including reductions in circulating proinflammatory cytokines.Conclusions: These findings indicate that FoxO1 proteins negatively regulate insulin action and that their effect may be explained, at least in part, by inhibition of PPARgamma function. [ABSTRACT FROM AUTHOR]

Aim To obtain palaeobotanical evidence enabling evaluation of the viability of the hypothesis that the ‘oriental’ element of the Balkan flora reached south-east Europe from Turkey prior to the Holocene, probably via the Thracian Plain during a late Quaternary glacial stage but no later than the late Weichselian. Location Ezero wetland, northern Thracian Plain, Bulgaria. Methods We undertook analyses of pollen and microspores, plant macrofossils, wood fragments and molluscs recovered from sediments deposited in the Ezero wetland during the late Weichselian and Weichselian late-glacial. Sediment chronology was determined using radiocarbon age estimates. Results Six metres of sediments were recovered from the basin, of which the lower 3 m, extending from c. 15,450 cal yr bp to the early Allerød, was analysed. A major hiatus occurred after c. 13,900 cal yr bp, the overlying sediments being of late Holocene age. Palaeobotanical evidence indicates predominantly open vegetation during the Weichselian late-glacial, although macrofossil remains of woody taxa demonstrate the local presence of patches of wooded steppe and gallery forest. Changes in the composition of the steppe vegetation, and in the nature of the sediments deposited in the basin, indicate changes in climatic conditions, especially in the hydrological regime and in the moisture available to vegetation. After an initially relatively moister phase, the final centuries of the late Weichselian were drier, as was a short interval that may correlate with the Older Dryas. Moister conditions characterize intervals corresponding to the Bølling and Allerød sub-units of the Weichselian late-glacial interstadial. Although the pollen evidence is thus consistent with that from previous studies of this period in south-east Europe and south-west Asia, indicating predominantly open steppe vegetation, the macrofossil evidence indicates the persistent local presence of woody taxa. The woody taxa recorded include Celtis tournefortii-type and Juniperus cf. J. excelsa, two taxa today characteristic of the wooded steppes of Anatolia and members of the ‘oriental’ element of the southern Balkan flora, as well as Rosaceae Subfams. Maloideae and Prunoideae, Alnus and Fraxinus. Main conclusions The late Weichselian vegetation of the northern Thracian Plain included patches of wooded steppe that supported members of the ‘oriental’ element of the modern Balkan flora. The presence of such taxa renders viable the hypothesis that they could have reached south-east Europe from Turkey via the Thracian Plain during glacial times. Such hypotheses in historical biogeography can be evaluated critically using the evidence obtained from plant macrofossil analyses in combination with that from pollen analysis. [ABSTRACT FROM AUTHOR]

Despite the plethora of evidence on the consequences of host nutrition on their immune responses to gastrointestinal parasites, the identity of molecules and mechanisms that drive the manifestations of immunity under nutrient abundance are not yet known. This is partly due to limitations of the methodologies employed to date that have failed to give comprehensive answers. The great advancements in the technological front over the past few years have opened a window of opportunity to identify these effector molecules, to explore both the mechanisms and cellular pathways and to evaluate their importance in the immune response to parasites. The aim of this paper is to present some of the novel, high-throughput technologies that are currently available in immunology and to explore their use in advancing our knowledge in interactions between nutrition and immunity to nematode parasites, with special reference to sheep. In the first part, we introduce the technologies and we discuss advantages and pitfalls of their use. We bring in successful examples of how their employment advanced knowledge and improved our understanding of the mechanisms that regulate immune responses to pathogens (both micro- and macroparasites). In the second part, we focus on the impact of nutrition on the immune response to parasites, and explore how these technologies can be used to advance our knowledge of immunonutritional interactions. We use as our starting point well-established models that have been successfully used to investigate the consequences of nutrition on the manifestations of immunity to parasites, which we further consider in the context of the novel technologies. We conclude by emphasizing the great potential of the described methodologies in unravelling the complex interactions between nutrition and immunity, but we also recommend caution when interpreting the outcomes. [ABSTRACT FROM AUTHOR]

This paper describes an investigation of residual and mechanical strains in aluminium/aluminium (Al/Al) and aluminium/carbon fibre-reinforced polymer (Al/CFRP) adhesively bonded double-lap joints. Residual strains were measured inside the adherends by means of neutron diffraction (ND) and modelled using finite element analysis (FEA). In the Al/Al joints the measured residual strains were negligible, showing good agreement with FE predicted results. However, considerable strains developed in the Al/CFRP joint because of differential thermal contraction of the two materials during joint manufacture. Although considerable scatter was seen in the ND results, the measured and predicted trends showed similar behaviour and were of comparable magnitude. The paper also reports measurements of internal strains in an Al/CFRP joint under tensile load using ND and of surface strains using moiré interferometry (MI). In general, good agreement was observed between FE predictions, surface strains measured with MI and internal strains measured with ND for the loaded Al/CFRP joint. [ABSTRACT FROM AUTHOR]

The three-dimensional conservation equations relating energy and momentum transfer in a vibrated three-dimensional granular bed have been solved numerically by the finite element method. Two closures based on granular kinetic theory were used: one, the standard Fourier law relating heat flux to temperature gradient and the other, including an additional concentration gradient term. Each prediction of the two-dimensional axisymmetric granular temperature and packing fraction fields was compared against a one-dimensional model and three-dimensional experimental results, acquired using the technique of positron emission particle tracking. Both closures resulted in solutions that were in reasonable agreement with the experimental results, but it was found that differences between the predictions of each of the closures were relatively small in comparison to the anisotropy of the experimentally determined temperature distribution. [ABSTRACT FROM AUTHOR]

Tropomyosin is an allergenic, actin-binding protein and a proposed vaccine candidate from several species of parasite. Tropomyosin cDNA, obtained by polymerase chain reaction (PCR) amplification from Dermanyssus gallinae RNA, encoded a predicted protein with 89% and 88% identity to tropomyosins from the ticks Boophilus microplus and Haemaphysalis longicornis, respectively, and 85% identity to the house dust mite (HDM) tropomyosin Der p 10. Mouse antibodies raised against HDM tropomyosin reacted with a band of 38 kDa on Western blots of D. gallinae extract, consistent with the molecular masses of acarine tropomyosins and the putative product of the cDNA encoding D. gallinae tropomyosin. When the same preparation of D. gallinae proteins was used in Western blots with serum from infested hens, the IgY component of the serum bound to a number of mite proteins, but not to tropomyosin, indicating that hens are not directly exposed to this allergen during a natural infestation. Immunolocalization of tropomyosin in mites indicated a ubiquitous distribution of the molecule in mite tissues. Immunolocalization and Western blotting also indicated that poultry red mites ingest host IgY. [ABSTRACT FROM AUTHOR]

Despite the potential benefits offered by vaccination against ectoparasites, there have been few commercial successes with this strategy, in spite of sustained efforts using increasingly sophisticated techniques. This review outlines the progress and challenges offered by recent research into vaccination against some of the major ectoparasites of veterinary importance, and provides an insight into the opportunities arising from our increased understanding of the immunology of host–parasite relationships and the potential for exploitation of this knowledge and that arising from new genomic data provided by expressed sequence tag projects. [ABSTRACT FROM AUTHOR]

It is possible to induce eosinophilia in congenitally athymic rats by infection with the parasite Ascaris suum . Athymic bronchial eosinophilia is associated with increased expression of IL-5 and eotaxin mRNA, and with the presence of residual T cells and mast cells. Anamnestic mastocytosis is particularly pronounced and in this study we examine the relationship between mast cell degranulation and IgE production in athymic rats following infection. Incubation of peritoneal mast cells from athymic rats with anti-IgE induced dose-dependent degranulation, as measured by histamine release. However, the failure of mast cells from infected athymic rats to degranulate following incubation with all but one of the parasite antigens selected confirms the absence of a specific IgE response. In contrast, all agonists induced degranulation in euthymic rats. The only parasite-derived factor to induce histamine release in all mast cells was body fluid, which contains an element capable of inducing IgE-independent degranulation. Furthermore, increased levels of rat mast cell protease II in athymic bronchoalveolar lavage fluid suggest degranulation of mast cells by IgE and allergen independent means in vivo . We believe that the development of eosinophilic lung inflammation in the absence of specific IgE makes this a prototype for investigating the immunological mechanisms underlying nonatopic asthma. [ABSTRACT FROM AUTHOR]

Lymphoid follicles cluster in the terminal rectum of various animal species and of man and hence this site may be important in the development of immune responses to pathogens. For the induction of immune responses at mucosal sites, interplay is required between various cell types performing functions ranging from antigen-sampling cells via antigen-presenting cells to antigen-specific lymphocytes. Therefore, we have characterised the cell populations and relevant functioning of follicle-associated epithelium (FAE) and associated follicles in the terminal portion of rectum in cattle as a representative mammal. Immunohistochemical studies of this region identified immune cell subsets (CD4+, CD8+, WC1+γδ, CD2+, CD21+ and CD40+ cells) characteristic of an immune-inductive site. Examination of FAE identified a subset of cells with structural and functional features of antigen-sampling M-cells. Cells of the FAE and adjacent follicle-associated crypts expressed vimentin and a subset of these cells internalised microparticles, a further attribute of M-cells. The FAE cells were phenotypically heterogeneous and therefore the function and phenotype of these cell subsets requires further characterisation, particularly with respect to their potentially important role in the interaction of hosts with pathogens and the development of immune responses. [ABSTRACT FROM AUTHOR]

Analysis by one-dimensional (1-D) SDS-PAGE/Western blotting of whole mite extract (larval and adult stages) with sheep sera taken 0–84 days after infection with the sheep scab mite,Psoroptes ovisrevealed a progressive IgE antibody response, with a dominant high molecular weight allergen (MW 180 kDa) detected early during infection. Further analysis by two-dimensional (2-D) SDS-PAGE/Western blotting with post-infection sera, revealed a more complex picture with numerous (> 20) IgE reactive spots. Trypsin digest and Maldi-ToF analyses of these spots identified two house dust mite allergen homologues, namely tropomyosin (Der p 10) and paramyosin (Der p 11), and analysis of a third spot indicated an apolipoprotein-like IgE reactive protein (Der p 14). Further 1-D and 2-D SDS/Western blotting, with specific antibodies to the house dust mite allergens Der p 10, 11, and to the IgE reactive peptide of the high molecular weight house dust mite allergen, Der p 14 (vitellogenin/apolipophorin), provided firm evidence for the presence of these three allergens in extracts of thePsoroptesmite. These studies show for the first time that homologues of the house dust mite 10, 11 and 14 group allergens are represented as immunodominant allergens of the sheep scab mite, and may represent important vaccine candidates. [ABSTRACT FROM AUTHOR]

Sixty twin- and 60 single-bearing ewes were used in a 2 X 2 X 2 factorial design incorporating nutritional and shearing-cold exposure treatment (no. =15 per subgroup) to study the effects on periparturient immunity against nematode infection. From week -8 to week -4 relative to parturition, animals grazed ryegrass-white clover pastures at allowances designed to provide either 0.8 (low allowance) or 1.2 (high allowance) of estimated metabolizable energy requirement for a ewe carrying 1.5 lambs. During week-4, half the sheep from each reproductive effort and nutritional group were shorn and exposed to artificial wind and rain for 4 h on each of 4 days consecutively. During the same week, all animals were challenged twice with 1.5 X 104 Teladorsagia circumcincta and 1.5 X 104 Trichostrongylus colubriformis infective third stage larvae to supplement the natural infection from pasture. From week -3 to week + 5 relative to parturition the sheep were run together and offered pasture at rates estimated to enable them to meet their nutrient requirement. Shearing and cold stress reduced ewe body weight (by up to 4.66 kg per sheep), and temporarily reduced the levels of IgA against T. circumcincta (by proportionately 0.24) and T. colubriformis (0.34), and raised faecal egg count (1.6 to 4.4 fold) but did not affect the parasite-specific total antibody levels in the serum. The low allowance during pregnancy was associated with a 6.09-kg decrease in ewe body weight, decrease in the levels of total antibody and of IgA against both T. circumcincta and T. colubriformis, and increased faecal egg count (by 1.5 to 10.6 fold) during pregnancy and lactation. Faecal egg count was consistently higher (up to 8.8 fold) in twin-bearing and rearing ewes than in single-bearing and rearing ewes except during the first 4 weeks of the experiment. A significant effect of litter size on antibody levels was relatively small when compared with short-term changes (reductions)... [ABSTRACT FROM AUTHOR]

The spontaneous formation of cracks in biscuits following baking, also known as checking, is an issue that manufacturers would like to be able to predict and avoid. Unfortunately the mechanisms driving this phenomenon are not well understood. Speckle interferometry was used to study moisture-induced in-plane strain development in biscuits. This sensitive and non-contacting technique for measuring surface displacements has two major advantages over more commonly used methods; firstly, strains can be detected at a far higher sensitivity (down to 2 × 10-6) than previously accessible and secondly the method is a whole-field technique, enabling observation of the development of strain distributions during moisture migration. For biscuits exposed to step changes in humidity, initial strain rates of up to 10-5min-1 were measured, which decreased as the moisture content approached equilibrium, leading to an accumulated strain of ~10-2 after 48 h. Under these conditions, a homogeneous, uniform strain distribution was observed. The data were used to calculate the hygroscopic expansion coefficient, which was linearly related to moisture content and provides the necessary constitutive link between strain and biscuit moisture content needed to model biscuit checking. [ABSTRACT FROM AUTHOR]

Summary Infestation of sheep with the ectoparasitic mite Psoroptes ovis, results in a severe allergic dermatitis. Currently, little is known about the allergens/antigens that stimulate the allergic response. We have isolated an 836-bp cDNA from a P. ovis cDNA library which displays strong homology to cysteine proteases and, in particular, to the group I house dust mite allergens Der p 1, Der f 1 and Eur m 1. The cDNA was expressed in Escherchia coli, fused to a hexahistidine tag and the recombinant protein (Pso o 1) purified using a nickel-affinity column. The recombinant Pso o 1 was tested for recognition by immunoglobulin (Ig)G and IgE in serum from P. ovis naïve and P. ovis infested sheep. Using Western blots, both classes of antibody to Pso o 1 were detected in postinfestation serum. In enzyme-linked immunosorbent assays, a pronounced IgG-antibody response to Pso o 1 was detected in five of five sheep 3 weeks postinfestation. The IgE-antibody response to whole mite extract was poor in four of five animals. However, a marked IgE response occurred in the fifth animal, and IgE anti Pso o 1 was detected in the serum. [ABSTRACT FROM AUTHOR]

Summary The efficacy of two recombinant proteins of Haemonchus contortus was studied in both adult sheep and young lambs. These 15 and 24 kDa excretory/secretory proteins were given combined, either supplemented or not with a glycan-rich insect cell extract. In 9-month-old sheep (trial 1), faecal egg output and worm burden were reduced by 49% and 55%, respectively, after vaccination with rec15/24, and by 46% and 65% after vaccination with rec15/24 and glycan extract. No reduction in egg output or number of worms was found in young lambs using the above recombinant proteins plus glycan-rich extract (trial 2). When trial 1 was repeated (trial 3), the protection could not be reproduced, possibly due to differences in batches of recombinant proteins. In all sheep, independent of their age, rec15/24-specific immunoglobulin (Ig)G1 and IgA titres were present, but 9-month-old protected sheep had significantly higher IgA titres than the lambs. Addition of glycans resulted in lower rec15/24-specific IgG1 and IgA in 9-month-old sheep after challenge. This did not affect the level of protection. A significant negative correlation was found between IgA and worm numbers in protected sheep immunized with rec15/24 supplemented with glycans. Total IgE and rec15/24 specific IgE titres were low. The number of eosinophils, mast cells, sheep mast cell protease (SMCP)+ cells and IgA+ cells did not differ between the protected and unprotected sheep, but the lambs had significantly fewer mast cells independent of their immunization. [ABSTRACT FROM AUTHOR]

Objectives: To assess and improve deployment of a brief test for alcohol misuse: the Paddington Alcohol Test (PAT). Design-Prospective study of the effects of audit feedback.Setting: An urban accident and emergency department.Subjects: Senior house officers (SHO) (n = 13).Outcome Measurements: PAT use and categorisation of patients for each SHO; observational analysis of presenting complaints according to PAT.Results: 1062 of 1737 patients (61.1%) were defined as PAT possible-that is, presented with > or = one complaint listed on the PAT test proforma. In month 1, PAT uptake was poor. PAT use improved significantly when feedback was instituted (p<0.0001). The response to audit and feedback showed marked inter-SHO variation. When feedback was withdrawn (month 4), there was a significant reduction in PAT use (p=0.003). Three other indices of detection followed this trend: (a) number of PAT positive patients identified, (b) proportion of PAT possible patients identified as PAT positive, and (c) number of PAT positive patients referred to the alcoholic health worker. The 10 most common PAT positive categories, accounting for 77% of all PAT positive complaints were: fall > collapse (including "fit", "blackout") > head injury (including "facial injury") > assault (including "domestic violence" and 'other') > nonspecific gastrointestinal problem > "unwell" > psychiatric (including "depression", "overdose", "confusion") > cardiac (including "chest pain" and "palpitations") > self neglect > repeat attendance.Conclusions: Ongoing audit with feedback improves both PAT use and detection of alcohol misuse. The PAT is now simpler including only 10 conditions, which should further aid its use. [ABSTRACT FROM AUTHOR]

Culled dry dairy goats, which differed in their level of production in previous lactations, received a single infection with Trichostrongylus colubriformis. The objectives of the study were twofold. First, the study aimed at examining the ability of dairy goats to develop an immune response to trichostrongyle infection and the associated cellular changes developing within the intestinal mucosa. Second, a comparison between animals differing in their level of production was assessed, in order to determine whether these differed in their susceptibility to infection. No difference occurred in egg excretion, worm burden and local inflammatory cell responses between high (HP) and low (LP) producer dairy goats, in contrast to observations in previous studies. Because their nutrition was controlled and milk production absent in the goats employed in the present study, these results suggest that any genetic component associated with the selection of HP and LP goats had little influence on the development of acquired resistance to T. colubriformis. The analysis of the relationship between different cell types in the mucosa and some characteristics of the worm population show that eosinophils are negatively related to worm burden. Also, a role is suggested for mast cells and globule leukocytes in the modulation of egg excretion. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the development and the duration of immunity achieved with drug-abbreviated infections of Trichostrongylus colubriformis in jirds ( Meriones unguiculatus). Jirds were primarily infected either by trickle infection with 6 × 100 infective larvae (L3) of T. colubriformis at 3-day intervals or by a single infection with 600 L3. On day 35 post-infection, one batch of jirds from each group was autopsied; the others were treated with oxfendazole at a dose of 5 mg/kg and were challenged with 1,000 L3 on either day 7 or day 42 post-treatment. All jirds were autopsied at 17 days post-challenge. Trickle infection resulted in lower levels of egg production during the primary infection period. The systemic IgM and IgG antibody response was significantly stronger in trickle- and single-infected groups as compared with the negative control group ( P < 0.01– P < 0.05). Significantly higher levels of intestinal IgA were demonstrated in trickle- and single-infected groups than in the negative control group ( P < 0.01). Numbers of mucosal mast cells increased following infection, but this was not dependent on the type of immunisation. After challenge the extent of worm reduction was greater in trickle-infected than in single-infected subgroups. The IgM and IgG response was significantly stronger in challenged subgroups as compared with negative control subgroups ( P < 0.01). However, the IgG response was weaker in control challenged subgroups than in challenged subgroups ( P < 0.01). There was a negative correlation between the IgG response and the worm burden after the second challenge ( r=−0.73). The acquired immunity to T. colubriformis infection in jirds developed within 5 weeks of primary infection. The level of immunity was higher after trickle infection than after single infection. Furthermore, the immunity persisted for at least 6 weeks after oxfendazole treatment in the absence of a worm burden and larval intake, which is very similar to the situation in domestic ruminant hosts. [ABSTRACT FROM AUTHOR]