Dementia Screening Accuracy is Robust to Premorbid IQ Variation: Evidence from the Addenbrooke's Cognitive Examination-III and the Test of Premorbid Function

BACKGROUND: Scores on cognitive screening tools for dementia are associated with premorbid IQ. It has been suggested that screening scores should be adjusted accordingly. However, no study has examined whether premorbid IQ variation affects screening accuracy. OBJECTIVE: To investigate whether the screening accuracy of a widely used cognitive screening tool for dementia, the Addenbrooke's cognitive examination-III (ACE-III), is improved by adjusting for premorbid IQ. METHODS: 171 UK based adults (96 memory service attendees diagnosed with dementia and 75 healthy volunteers over the age of 65 without subjective memory impairments) completed the ACE-III and the Test of Premorbid Function (TOPF). The difference in screening performance between the ACE-III alone and the ACE-III adjusted for TOPF was assessed against a reference standard; the presence or absence of a diagnosis of dementia (Alzheimer's disease, vascular dementia, or others). RESULTS: Logistic regression and receiver operating curve analyses indicated that the ACE-III has excellent screening accuracy (93% sensitivity, 94% specificity) in distinguishing those with and without a dementia diagnosis. Although ACE-III scores were associated with TOPF scores, TOPF scores may be affected by having dementia and screening accuracy was not improved by accounting for premorbid IQ, age, or years of education. CONCLUSION: ACE-III screening accuracy is high and screening performance is robust to variation in premorbid IQ, age, and years of education. Adjustment of ACE-III cut-offs for premorbid IQ is not recommended in clinical practice. The analytic strategy used here may be useful to assess the impact of premorbid IQ on other screening tools

Barriers to social participation among lonely older adults: the influence of social fears and identity

INTRODUCTION: Loneliness among older adults is a major public health problem that may be associated with processes of social participation and identity. This study therefore sought to examine the relationship between social participation and identity in a sample of lonely older adults living independently in London, England. METHOD: An inductive qualitative approach, based on semi-structured interviews and thematic analysis, was employed. RESULTS: Participants commonly spoke of barriers to social participation that have been reported elsewhere, including illness/disability, loss of contact with friends/relatives, lack of a supportive community, and lack of acceptable social opportunities. However, novel findings were also derived. In particular, participants commonly minimised the difficulties they faced alone, and described attempts to avoid social opportunities. These behaviours were linked to fears about engaging in social participation opportunities, including fears of social rejection and/or exploitation, and fears of losing valued aspects of identity. DISCUSSION: It is concluded that social participation amongst lonely older people will not improve through the removal of previously reported barriers alone; instead, older peoples’ beliefs, fears and identities must be addressed. Suggestions for implementing these findings within community organisations are provided

Peer support and reminiscence therapy for people with dementia and their family carers: a factorial pragmatic randomised trial

Objective The objective of this study was to evaluate peer support and reminiscence therapy, separately and together, in comparison with usual care for people with dementia and their family carers. Design Factorial pragmatic randomised trial, analysed by treatment allocated, was used for this study. Setting The trial ran in Community settings in England. Participants People with dementia and their family carers were the participants. Interventions Treatment as usual (TAU) plus one of the following: one-to-one peer support to family carers from experienced carers (Carer Supporter Programme; CSP), group reminiscence therapy (Remembering Yesterday, Caring Today; RYCT) for people with dementia and carers, both or neither. Main outcome measures Primary outcomes included health-related quality of life (SF-12) for carers and quality of life (QoL-AD) for people with dementia; secondary outcomes included quality of relationship for carers and people with dementia; both were collected by blinded assessors at baseline, 5 and 12 months (primary end point). Results Of 291 pairs recruited, we randomised 145 (50%) to CSP (71% uptake) and 194 (67%) to RYCT (61% uptake). CSP and RYCT, separately or together, were not effective in improving primary outcomes or most secondary outcomes. For CSP versus ‘no CSP’, adjusted difference in means was 0.52 points on the SF-12 (95% CI −1.28 to 2.32) and −0.08 points on the QoL-AD (95% CI −1.70 to 1.56). For RYCT versus ‘no RYCT’, the difference was 0.10 points on the SF-12 (95% CI −1.72 to 1.93) and 0.51 points on the QoL-AD (95% CI −1.17 to 2.08). However, carers reported better relationships with the people with dementia (difference 1.11, 95% CI 0.00 to 2.21, p=0.05). Comparison of combined intervention with TAU, and of intervention received, suggested differential impacts for carers and persons with dementia. Conclusions There is no evidence from the trial that either peer support or reminiscence is effective in improving the quality of life. Trial registration number ISRCTN37956201

An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference

Acceptance Checklist for Clinical Effectiveness Pilot Trials: a systematic approach.

Conducting a pilot trial is important in preparing for, and justifying investment in, the ensuing larger trial. Pilot trials using the same design and methods as the subsequent main trial are ethically and financially advantageous especially when pilot and main trial data can be pooled. For explanatory trials in which internal validity is paramount, there is little room for variation of methods between the pilot and main trial. For pragmatic trials, where generalisability or external validity is key, greater flexibility is written into trial protocols to allow for 'real life' variation in procedures. We describe the development of a checklist for use in decision-making on whether pilot data can be carried forward to the main trial dataset without compromising trial integrity. We illustrate the use of the checklist using a pragmatic trial of psychosocial interventions for family carers of people with dementia as a case study

Blood ties: ABO is a trans-species polymorphism in primates

The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World Monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multi-allelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the ABO polymorphism is a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years, to date, the only such example in Hominoids and Old World Monkeys outside of the Major Histocompatibility Complex.Comment: 45 pages, 4 Figures, 4 Supplementary Figures, 5 Supplementary Table

Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

Impact of Lagrangian transport on lower-stratospheric transport timescales in a climate model

We investigate the impact of model trace gas transport schemes on the representation of transport processes in the upper troposphere and lower stratosphere. Towards this end, the Chemical Lagrangian Model of the Stratosphere (CLaMS) was coupled to the ECHAM/MESSy Atmospheric Chemistry (EMAC) model and results from the two transport schemes (Lagrangian critical Lyapunov scheme and flux-form semi-Lagrangian, respectively) were compared. Advection in CLaMS was driven by the EMAC simulation winds, and thereby the only differences in transport between the two sets of results were caused by differences in the transport schemes. To analyze the timescales of large-scale transport, multiple tropical-surface-emitted tracer pulses were performed to calculate age of air spectra, while smaller-scale transport was analyzed via idealized, radioactively decaying tracers emitted in smaller regions (nine grid cells) within the stratosphere. The results show that stratospheric transport barriers are significantly stronger for Lagrangian EMAC-CLaMS transport due to reduced numerical diffusion. In particular, stronger tracer gradients emerge around the polar vortex, at the subtropical jets, and at the edge of the tropical pipe. Inside the polar vortex, the more diffusive EMAC flux-form semi-Lagrangian transport scheme results in a substantially higher amount of air with ages from 0 to 2 years (up to a factor of 5 higher). In the lowermost stratosphere, mean age of air is much smaller in EMAC, owing to stronger diffusive cross-tropopause transport. Conversely, EMAC-CLaMS shows a summertime lowermost stratosphere age inversion – a layer of older air residing below younger air (an “eave”). This pattern is caused by strong poleward transport above the subtropical jet and is entirely blurred by diffusive cross-tropopause transport in EMAC. Potential consequences from the choice of the transport scheme on chemistry–climate and geoengineering simulations are discussed

Expression and trans-specific polymorphism of self-incompatibility RNases in Coffea (Rubiaceae)

Self-incompatibility (SI) is widespread in the angiosperms, but identifying the biochemical components of SI mechanisms has proven to be difficult in most lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory trees in which the vast majority of diploid species utilize a mechanism of gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the first SI mechanisms to be biochemically characterized, and likely represents the ancestral Eudicot condition as evidenced by its functional characterization in both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S-RNase GSI mechanism employs the activity of class III RNase T2 proteins to terminate the growth of "self" pollen tubes. Here, we investigate the mechanism of Coffea GSI and specifically examine the potential for homology to S-RNase GSI by sequencing class III RNase T2 genes in populations of 14 African and Madagascan Coffea species and the closely related self-compatible species Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a diverse sample of plant RNase T2 genes show that the Coffea genome contains at least three class III RNase T2 genes. Patterns of tissue-specific gene expression identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show that populations of SI Coffea are remarkably polymorphic for putative S-RNase alleles, and exhibit a persistent pattern of trans-specific polymorphism characteristic of all S-RNase genes previously isolated from GSI Eudicot lineages. We thus conclude that Coffea GSI is most likely homologous to the classic Eudicot S-RNase system, which was retained since the divergence of the Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years ago.United States National Science Foundation [0849186]; Society of Systematic Biologists; American Society of Plant Taxonomists; Duke University Graduate Schoolinfo:eu-repo/semantics/publishedVersio

An examination of the association between seeing smoking in films and tobacco use in young adults in the west of Scotland: cross-sectional study

The objective is to examine the association between the amount of smoking seen in films and current smoking in young adults living in the west of Scotland in the UK. Cross-sectional analyses (using multivariable logistic regression) of data collected at age 19 (2002–04) from a longitudinal cohort originally surveyed at age 11 (1994–95) were conducted. The main outcome measure is smoking at age 19. No association was found between the number of occurrences of smoking estimated to have been seen in films (film smoking exposure) and current (or ever) smoking in young adults. This lack of association was unaffected by adjustment for predictors of smoking, including education, risk-taking orientation and smoking among peers. There was no association between film smoking exposure and smoking behaviour for any covariate-defined subgroup. Associations have been found between film smoking exposure and smoking initiation in younger adolescents in the United States. In this study, conducted in Scotland, no similar association was seen, suggesting that there may be age or cultural limitations on the effects of film smoking exposure on smoking. The lack of association could be due to methodological issues or greater sophistication of older adolescents and young adults in interpreting media images or the greater ubiquity of real-life smoking instances in Scotland. If the latter, film smoking exposure could become a more important risk factor for smoking uptake and maintenants in older adolescents following the recent ban on smoking in public places in Scotland