Functional assessment of cognitively impaired older adults : are we asking the right questions?

Background: Recent attention has turned to the development of preventative treatments for Alzheimer’s disease (AD) by targeting the early stages of impairment. However, current neuropsychological and functional assessments are not ideally suited to identify early deviations from healthy ageing (HA). The Details of Functions of Everyday Life (DoFEL; Parra & Kaplan, 2019) is a theory-driven scale that incorporates cognitive constructs sensitive to the preclinical stages of dementia (memory binding). DoFEL can help assess the extent to which instrumental functions of daily living are supported by such cognitive abilities and if so, whether by asking the right questions through such a scale we could unveil subtle and still undetected impairments. We predict this would increase the sensitivity of scales to detect older adults with cognitive impairment who are at a high risk of dementia.   Methods: Twenty-five MCI and 21 HA controls (ACE-R score ≥ 88) (Mioshi et al., 2006) underwent an extensive baseline neuropsychological assessment followed by yearly follow-up assessments. The DoFEL is an informant-based neuropsychological assessment that measures a range of functional abilities which rely on different forms of binding functions. This measure includes 82 statements subdivided into 7 functional domains that comprehensively assess different aspects of daily living. Higher DoFEL score indicate greater impairment.   Results: Five key findings from this study were: (1) The total DoFEL score differentiates MCI from HA U=406.00, p=0.002. Higher scores were detected in individuals with MCI (Mdn= 0.41, Mean rank= 29.24) than in the HA (Mdn= 0.35, Mean rank= 16.67). (2) Individuals with MCI showed domain-specific impairments on DoFEL such as Objects and People, Technology and Communication, Work and Social Life. (3) Relative to HA, MCI patients presented with impaired functional abilities that rely on relational (i.e., forming associations, p=0.001) and conjunctive (i.e., forming object identity, p=0.004). (4) DoFEL scores correlate with (r= -0.62, p=0.000), and predicts cognitive performance on the ACE-R (β= -128.68, t(44)= -6.97, p=0.000).   Conclusion: DoFEL can detect differences between individuals with MCI and HA in overall and specific functional abilities seemingly supported by binding functions and therefore may be a useful tool to identify individuals at risk of developing AD

Accuracy of non-physician health workers in respiratory rate measurement to identify paediatric pneumonia in low- and middle-income countries: a systematic review and meta-analysis

BACKGROUND: Non-physician health workers play an important role in identifying and treating pneumonia in children in low- and middle-income countries (LMICs). In this systematic review, we summarized the evidence on whether health workers can accurately measure respiratory rate (RR) and identify fast breathing to diagnose pneumonia in children under five years of age. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Scopus from January 1990 to August 2020 without any language restrictions. Reference lists of included studies were also screened for additional records. Studies evaluating the performance of health workers in measuring RR and/or identifying fast breathing compared to a reference standard were included. The methodological quality of the included studies was assessed using the QUADAS-2 tool. A meta-analysis was conducted to report pooled estimates of sensitivity and specificity. Hierarchical summary receiver operating characteristic curve (HSROC) models were fitted, and subgroup and sensitivity analyses were performed to examine the effects of study variables. RESULTS: We included 16 studies, eight of which reported the agreement in RR count between health workers and a reference standard. The median agreements were 39%, 47%, and 67% within ±2, ±3, and ±5 breaths per minute, respectively. Among the 16 included studies, we identified 15 studies that reported the accuracy of a health worker classifying breathing into either fast or normal categories compared to a reference standard. The median sensitivity, specificity, accuracy, and kappa value were 77%, 86%, 81%, and 0.75, respectively. Seven studies reporting the accuracy of identifying fast breathing were included in the meta-analysis. The pooled estimates of sensitivity and specificity were 78% (95% CI = 72-82) and 86% (95% CI = 78-91), respectively. CONCLUSIONS: Despite the problematic nature of reference standards and their variability across studies, our review suggests that the health worker performance in accurately counting RR is relatively poor. However, their performance shows reasonable specificity and moderate sensitivity in identifying fast breathing. Improving the detection of fast breathing in children with suspected pneumonia among health workers is an important child health programme objective and should be given appropriate priority

The classical case of character release: Darwin's finches ( Geospiza ) on Isla Daphne Major, GalÁpagos

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75575/1/j.1095-8312.1984.tb01679.x.pd

A Model for Damage Load and Its Implications for the Evolution of Bacterial Aging

Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry

The contrasting role of male relatedness in different mechanisms of sexual selection in red junglefowl

In structured populations, competition for reproductive opportunities should be relaxed among related males. The few tests of this prediction often neglect the fact that sexual selection acts through multiple mechanisms, both before and after mating. We performed experiments to study the role of within-group male relatedness across pre- and postcopulatory mechanisms of sexual selection in social groups of red junglefowl, Gallus gallus, in which two related males and one unrelated male competed over females unrelated to all the males. We confirm theoretical expectations that, after controlling for male social status, competition over mating was reduced among related males. However, this effect was contrasted by other sexual selection mechanisms. First, females biased male mating in favor of the unrelated male, and might also favor his inseminations after mating. Second, males invested more—rather than fewer—sperm in postcopulatory competition with relatives. A number of factors may contribute to explain this counterintuitive pattern of sperm allocation, including trade-offs between male investment in pre- versus postcopulatory competition, differences in the relative relatedness of pre- versus postcopulatory competitors, and female bias in sperm utilization in response to male relatedness. Collectively, these results reveal that within-group male relatedness may have contrasting effects in different mechanisms of sexual selection

Evolution of Assortative Mating in a Population Expressing Dominance

In this article, we study the influence of dominance on the evolution of assortative mating. We perform a population-genetic analysis of a two-locus two-allele model. We consider a quantitative trait that is under a mixture of frequency-independent stabilizing selection and density- and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The trait is determined by a single (ecological) locus and expresses intermediate dominance. The second (modifier) locus determines the degree of assortative mating, which is expressed in females only. Assortative mating is based on similarities in the quantitative trait (‘magic trait’ model). Analytical conditions for the invasion of assortment modifiers are derived in the limit of weak selection and weak assortment. For the full model, extensive numerical iterations are performed to study the global dynamics. This allows us to gain a better understanding of the interaction of the different selective forces. Remarkably, depending on the size of modifier effects, dominance can have different effects on the evolution of assortment. We show that dominance hinders the evolution of assortment if modifier effects are small, but promotes it if modifier effects are large. These findings differ from those in previous work based on adaptive dynamics