The APPLE Tree programme: Active Prevention in People at risk of dementia through Lifestyle, bEhaviour change and Technology to build REsiliEnce-randomised controlled trial.

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.

Undular bores generated by fracture.

Undular bores, or dispersive shock waves, are nonstationary waves propagating as oscillatory transitions between two basic states, in which the oscillatory structure gradually expands and grows in amplitude with distance traveled. In this work we report an important mechanism of generation of nonlinear dispersive shock waves in solids. We demonstrate, using high-speed pointwise photoelasticity, the generation of undular bores in solid (polymethylmethacrylate) prestrained bars by natural and induced tensile fracture. For the distances relevant to our experiments, the viscoelastic extended Korteweg-de Vries equation is shown to provide very good agreement with the key observed experimental features for suitable choice of material parameters, while some local features at the front of the bore are also captured reasonably well by the linearization near the nonzero prestrain level. The experimental and theoretical approaches presented open avenues and analytical tools for the study and applications of dispersive shock waves in solids.

The effects of climate change on the Pleistocene rock art of Sulawesi.

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.

Molecular systematics and biogeographic history of the African climbing-mouse complex (Dendromus).

Climbing mice in the genus Dendromus (sensu lato) are widely distributed in Africa, south of the Saharan Desert. The 17 currently recognized species in the genus range from widespread taxa to single-mountain endemics, and there is considerable variation across species with respect to habitats occupied. These habitats range from arid grasslands and savannahs to sub-alpine and alpine vegetation. Using the most comprehensive geographic and genetic survey to date and after reviewing many type specimens, we assess the systematics and biogeography of Dendromus. Given the structure of our molecular phylogenetic hypotheses, in which we recover six major clades, we propose the recognition of three genera within the Dendromus group (sensu lato): in addition to Dendromus (26 lineages), we suggest the retention of Megadendromus (monotypic) and the resurrection of the genus Poemys (six lineages). From our model-based molecular phylogenetic results and morphological comparisons, we suggest that six formerly synonymized taxa should be resurrected, and we highlight 14 previously undescribed lineages. We also constructed time-calibrations on our phylogeny, and performed ancestral area reconstructions using BioGeoBEARS. Based on fossil evidence, Dendromus appears to have had a widespread African distribution dating back to the Late Miocene (8-10 Ma), and our basal ancestral area reconstruction (Ethiopians Highlands + Eastern African Mountains + Zambezian region) supports this. Divergence of the six major clades we recover (Poemys, Megadendromus and four within Dendromus) occurred prior to or at the Miocene-Pliocene boundary 5.3 Ma. Biogeographically, Megadendromus is restricted to the Ethiopian Highlands. The ancestral area for Poemys is reconstructed as the Zambezian region, with species distributions ranging from South Africa to Western Africa. The ancestral area for Dendromus is reconstructed as the Ethiopian Highlands, with the ancestral areas of the four major clades being reconstructed as Ethiopian Highlands, Albertine Rift, South Africa or Western Africa. None of the four Dendromus clades are reciprocally monophyletic with respect to distributional area.

Awareness in severe Alzheimer's disease: a systematic review.

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.

Professional caregivers' knowledge, beliefs and attitudes about awareness in advanced dementia: a systematic review of qualitative studies.

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.

Palaeolithic cave art in Borneo.

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.

The Top 20 Most Prolific Authors in the American Journal of Neuroradiology: What Is Their Impact?

BACKGROUND AND PURPOSE: Many articles that are relevant to patient care but published in radiology journals may escape notice by clinicians. We sought to determine how often the 20 most prolific American Journal of Neuroradiology (AJNR) authors from 2013 to 2017 published in clinical journals and the extent to which their articles were disseminated into the clinical literature. MATERIALS AND METHODS: We counted all authors' first- or senior-authored articles in the AJNR from 2013 to 2017 to identify the 20 most prolific authors in AJNR. We searched for these 20 authors' total articles from 2013 to 2017 to determine which were published in radiology or clinical journals and the number of citations received from radiology and clinical journals. Authors were sorted into quartiles according to these metrics, and other descriptive statistics were performed. RESULTS: The top 20 AJNR authors contributed to 1463 articles during 5 years, including 711 (48.6%) in radiology and 752 (51.4%) in clinical journals. These articles were cited 15,857 times, including 4659 (29.3%) by articles in radiology journals. The more prolific authors published in clinical journals more often (Spearman ρ = 0.65, P = .002) and were cited more (ρ = 0.42, P = .07). Articles published in clinical journals were cited more often (mean, 12.3 clinical, 9.3 radiology general versus 8.7 in AJNR), and whether published in radiology or clinical journals, they were cited more frequently by clinical journals. CONCLUSIONS: Regardless of where it is published, radiology research is disseminating into the clinical realm. Radiology articles published in clinical journals are cited more often than those published in radiology journals.

Survivorship care for early-stage colorectal cancer: a national survey of general surgeons and colorectal surgeons.

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.

Immune development and performance characteristics of Romney sheep selected for either resistance or resilience to gastrointestinal nematodes.

Immunological and performance characteristics were explored in Romney sheep from lines selected for either resistance or resilience to parasite infection. At a mean 78 days-of-age, twin lambs from a line selected for resistance (RT) and lambs from a line selected for resilience (RL) were infected with the intestinal nematode Trichostrongylus colubriformis for 100 days (I) while their twin remained as an uninfected control (C). Compared with RL, RT animals had lower levels of circulating CD4+ T-cells (P = 0.003) but a greater proportion of these were activated (CD4+CD25+) in response to infection (P = 0.007). Differences between the lines in humoral immune responses to nematode infection varied with higher levels of T. colubriformis specific immunoglobulin (Ig) E in RT-I than RL-I (P = 0.002) but similar levels of both IgG (P = 0.926) and IgA (P = 0.321) responses. Temporal differences in the immune response also existed between the lines with RT-I animals displaying an earlier peak and more rapid reduction in FEC and an earlier peak in T. colubriformis specific IgA. In addition, compared with their RT-C and RL-C counterparts, infection caused a 22% reduction in feed intake from day 56 (P = 0.001) with total feed intake reduced by 15% and 9% for RT-I and RL-I, respectively. Cumulative liveweight gain was greatest for RL animals (P = 0.026) and relative to RT-C and RL-C was reduced by 5.8 kg and 4.9 kg for RT-I and RL-I, respectively. Overall, the selection lines appear to have differences in immunological characteristics that are both dependent on, and independent of parasite infection. Further, the difference in growth in the uninfected animals coupled with the similar cost of infection suggests the lower liveweight gain of RT-I compared with RL-I may be due to inherent differences between the lines in their growth potential, rather than a greater cost of infection in animals selected for resistance.

Online assessment of risk factors for dementia and cognitive function in healthy adults.

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.

Adaptive working memory strategy training in early Alzheimer's disease: randomised controlled trial.

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.

Obtaining the Transfer Function of optical instruments using large calibrated reference objects.

It has been suggested recently that the Transfer Function of instruments such as Coherence Scanning Interferometers could be measured via a single measurement of a large spherical artefact [Appl. Opt.53(8), 1554-1563 (2014)]. In the current paper we present analytical solutions for the Fourier transform of the 'foil' model used in this technique, which thus avoids the artefacts resulting from the numerical approach used earlier. The Fourier transform of a partial spherical shell is found to contain points of zero amplitude for spatial frequencies that lie within the Transfer Function. This implies that the Transfer Function is unmeasurable at these points when a single spherical artefact is used, in situations where the foil model is a valid representation of the physical system. We propose extensions to the method to address this issue.

Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression.

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 0.35 to 0.66; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.64; 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.

The osteotome: a design by Sir William Macewen.

The osteotome is ostensibly a simple surgical instrument. In fact it was carefully designed to allow accurate aseptic osteotomy for deformities around the knee. Here we outline William Macewen's classic work on the design of this tool and set this work in the context of his life.

Nuclear magnetic resonance measurements of velocity distributions in an ultrasonically vibrated granular bed.

We report the results of nuclear magnetic resonance imaging experiments on granular beds of mustard grains fluidized by vertical vibration at ultrasonic frequencies. The variation of both granular temperature and packing fraction with height was measured within the three-dimensional cell for a range of vibration frequencies, amplitudes and numbers of grains. Small increases in vibration frequency were found--contrary to the predictions of classical 'hard-sphere' expressions for the energy flux through a vibrating boundary--to result in dramatic reductions in granular temperature. Numerical simulations of the grain-wall interactions, using experimentally determined Hertzian contact stiffness coefficients, showed that energy flux drops significantly as the vibration period approaches the grain-wall contact time. The experiments thus demonstrate the need for new models for 'soft-sphere' boundary conditions at ultrasonic frequencies.

Neonatal hip septic arthritis: ultrasound should not influence decision to aspirate.

An 18-week-old boy presented to the emergency department with 24-h history of fever and irritability with a painful left hip held in flexion. Blood tests showed an elevated ESR of 65 mm/h, but white cell count and C-reactive protein were in the reference range. Admission hip ultrasound identified a small effusion (<2 mm at the recess), not large enough to determine turbidity. Joint aspiration under general anaesthesia yielded frank pus and mandated open arthrotomy. Physicians must maintain a high index of suspicion of hip septic arthritis irrespective of ultrasound findings and have a low threshold for joint aspiration. Aspiration 'to dryness' would have left substantial pus within the joint and is consistent with advocating arthrotomy and washout in this age group, when the diagnosis of septic arthritis has been made.

Acute distal radial epiphyseal osteomyelitis: a case report.

A child developed acute epiphyseal osteomyelitis of the distal radius following a fall. Despite a delay in diagnosis the patient was successfully treated by surgery and antibiotics. Magnetic resonance imaging was the key to the diagnosis and surgical planning.