The effect of ageing on in vivo human ciliary muscle morphology and contractility

Purpose. To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Methods. Seventy-nine subjects, aged 19–70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Results. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 µm/year nasally (R = 0.54, P < 0.001) and 3.0 µm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. Conclusions. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.

The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens

The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.

An evaluation of the epidemiology of medication discrepancies and clinical significance of medicines reconciliation in children admitted to hospital

Aims: To determine the incidence of unintended medication discrepancies in paediatric patients at the time of hospital admission; evaluate the process of medicines reconciliation; assess the benefit of medicines reconciliation in preventing clinical harm. Method: A 5 month prospective multisite study. Pharmacists at four English hospitals conducted admission medicines reconciliation in children using a standardised data collection form. A discrepancy was defined as a difference between the patient's preadmission medication (PAM), compared with the initial admission medication orders written by the hospital doctor. The discrepancies were classified into intentional and unintentional discrepancies. The unintentional discrepancies were assessed for potential clinical harm by a team of healthcare professionals, which included doctors, pharmacists and nurses. Results: Medicines reconciliation was conducted in 244 children admitted to hospital. 45% (109/244) of the children had at least one unintentional medication discrepancy between the PAM and admission medication order. The overall results indicated that 32% (78/244) of patients had at least one clinically significant unintentional medication discrepancy with potential to cause moderate 20% (50/244) or severe 11% (28/244) harm. No single source of information provided all the relevant details of a patient's medication history. Parents/carers provided the most accurate details of a patient's medication history in 81% of cases. Conclusions: This study demonstrates that in the absence of medicines reconciliation, children admitted to hospitals across England are at risk of harm from unintended medication discrepancies at the transition of care from the community to hospital. No single source of information provided a reliable medication history.

The impact of ageing on the barriers to drug delivery

Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery. © 2012 Elsevier B.V. All rights reserved.

Epidemiology of myopia in a United Kingdom urban child population

The Aston Eye Study (AES) was instigated in October 2005 to determine the distribution of refractive error and associated ocular biometry in a sample of UK urban school children. The AES is the first study to compare outcome measures separately in White, South Asian and Black children. Children were selected from two age groups (Year 2 children aged 6/7 years, Year8 children aged 12/13 years of age) using random cluster sampling of schools in Birmingham, West Midlands UK. To date, the AES has examined 598 children (302 Year 2,296 Year 8). Using open-field cycloplegic autorefraction, the overall prevalence of myopia (=-0.50D SER in either eye) determined was 19.6%, with a higher prevalence in older (29.4%) compared to younger (9.9%) children (p<0.001). Using multiple logistic regression models, the risk of myopia was higher in Year 8 South Asian compared to White children and higher in children attending grammar schools relative to comprehensive schools. In addition, the prevalence of uncorrected ametropia was found to be high (Year 8: 12.84%, Year 2: 15.23%), which will be of concern to bodies responsible for the implementation of school vision screening strategies. Biometric data using non-contact partial coherence interferometry revealed a contributory effect of axial length (AL) and central corneal radius (CR) on myopic refraction, resulting in a strong coefficient of determination of the AL/CR ratio on refractive error. Ocular biometric measures did not vary significantly as a function of ethnicity, suggesting a greater miscorrelation of components in susceptible ethnic groups to account for their higher myopia prevalence. Corneal radius was found to be steeper in myopes in both age groups, but was found to flatten with increasing axial length. Due to the inextricable link between myopia and axial elongation, the paradoxical finding of the cornea demands further longitudinal investigation, particularly in relation to myopia onset. Questionnaire analysis revealed a history of myopia in parents and siblings to be significantly associated with myopia in Year 8 children, with a dose-dependent rise in the odds ratio of myopia evident with increasing number of myopic parents. By classifying socioeconomic status (SES) using Index of Multiple Deprivation values, it was found that Year 8 children from moderately deprived backgrounds were more at risk of myopia compared with children located at both extremities of the deprivation spectrum. However, the main effect of SES weakened following multivariate analysis, with South Asian ethnicity and grammar schooling remaining associated with Year 8 myopia after adjustment.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.

The influence of ageing on fatigue crack growth in SiC-particulate reinforced 8090

A study of the influence of SiC-particulate reinforcement on ageing and subsequent fatigue crack growth resistance in a powder metallurgy 8090 aluminium alloy-SiC composite has been made. Macroscopic hardness measurements revealed that ageing at 170°C in the composite is accelerated with respect to the unreinforced alloy, though TEM studies indicate that this is not due to the enhanced precipitation of S′. Fatigue crack growth rates in the naturally aged condition of the composite and unreinforced matrix are similar at low to medium values of ΔK, but diverge above ≈ 8 MPa√m owing to the lower fracture toughness of the composite. As a result of the presence of the reinforcement, planar slip in the composite is suppressed and facetted crack growth is not observed. Ageing at or above 170°C has a deleterious effect on fatigue crack growth. Increased ageing time decreases the roughness of the fracture path at higher growth rates. These effect are though to be due to microstructural changes occurring at or near to the SiC/matrix interfaces, providing sites for static mode failure mechanisms to operate. This suggestion is supported by the observation that as ΔK increases, crack growth rates become Kmax dependent, implying the crack growth rate is strongly influenced by static modes.

‘Death talk’, ‘loss talk’ and identification in the process of ageing

In this paper, we examine the injunction issued by the prominent politician, broadcaster and older people's advocate, Baroness Joan Bakewell, to engage in ‘death talk’. We see positive ethical potential in this injunction, insofar as it serves as a call to confront more directly the prospects of death and dying, thereby releasing creative energies with which to change our outlook on life and ageing more generally. However, when set against a culture that valorises choice, independence and control, the positive ethical potential of such injunctions is invariably thwarted. We illustrate this with reference to one of Bakewell's interventions in a debate on scientific innovation and population ageing. In examining the context of her intervention, we affirm her intuition about its positive ethical potential, but we also point to an ambivalence that accompanies the formulation of the injunction – one that ultimately blunts the force and significance of her intuition. We suggest that Gilleard and Higgs' idea of the third age/fourth age dialectic, combined with the psycho-analytic concepts of fantasy and mourning, allow us to express this intuition better. In particular, we argue that the expression ‘loss talk’ (rather than ‘death talk’) better captures the ethical negotiations that should ultimately underpin the transformation processes associated with ageing, and that our theoretical contextualisation of her remarks can help us see this more clearly. In this view, deteriorations in our physical and mental capacities are best understood as involving changes in how we see ourselves, i.e. in our identifications, and so what is at stake are losses of identity and the conditions under which we can engage in new processes of identification.

The interconnectedness of ageing:does the convoy principal apply?

This is an excerpt from the content: The convoy principal states that any system is only as functional as its ‘slowest’ unit. As organisms are made up of interconnected networks of physiological systems, it is possible that this principle applies to the biology of ageing. Often biogerontology will focus either on organismal ageing (mechanisms associated with increased longevity of a lower model organism for example), ageing of an individual organ system (such as the cardiovascular/musculoskeletal/immune) or ageing at the cellular level (from telomere length to cellular senescence, with many different cell types being studied) without considering the interconnectedness between the three and importantly, between the separate units of the convoy; the different organ systems. Conceptually, research that aims to identify ‘anti-ageing’ therapies is often deemed to be reaching for a panacea that will arrest or slow down the ageing process as a whole, whereas a more realistic aim is to first identify how we can improve the perfor ...

MARK-AGE biomarkers of ageing

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation.

The impact of ageing and gender on visual mental imagery processes:a study of performance on tasks from the Complete Visual Mental Imagery Battery (CVMIB)

In this study we aim to evaluate the impact of ageing and gender on different visual mental imagery processes. Two hundred and fifty-one participants (130 women and 121 men; age range = 18–77 years) were given an extensive neuropsychological battery including tasks probing the generation, maintenance, inspection, and transformation of visual mental images (Complete Visual Mental Imagery Battery, CVMIB). Our results show that all mental imagery processes with the exception of the maintenance are affected by ageing, suggesting that other deficits, such as working memory deficits, could account for this effect. However, the analysis of the transformation process, investigated in terms of mental rotation and mental folding skills, shows a steeper decline in mental rotation, suggesting that age could affect rigid transformations of objects and spare non-rigid transformations. Our study also adds to previous ones in showing gender differences favoring men across the lifespan in the transformation process, and, interestingly, it shows a steeper decline in men than in women in inspecting mental images, which could partially account for the mixed results about the effect of ageing on this specific process. We also discuss the possibility to introduce the CVMIB in clinical assessment in the context of theoretical models of mental imagery.

Epidemiology of medication discrepancies upon hospital admission in children - a systematic review

Objectives: NICE/NPSA excluded children under 16 from their guidance concerning medicines reconciliation (MR) upon admission.1 Our aims and objectives of conducting the literature review was to identify the epidemiology of medication discrepancies upon admission, transfer and discharge in children, and if they require MR. Method: Six bibliographical databases (Medline, Embase, CINAHL, International Pharmaceutical Abstracts, Web of Science and Biosis Previews) and selected key words were used to find epidemiological studies on medication discrepancies in children upon hospital admission, transfer and discharge (key words included ‘medication discrepancy’; ‘medication reconciliation’; ‘hospital admission’; ‘hospital discharge’; ‘hospital transfer’); studies where the data for children could be extracted were included. Results: From the 1239 articles found (in May 2011), eight of the articles had extractable paediatric information, (five from Canada, two from USA, one from UK). Five of the studies involved discrepancies on admission, one involved discrepancies on admission and transfer, one involved discrepancies at transfer and one considered discharge. The reference point used to compare against the admission, transfer and the discharge order differed in each of the studies. Four studies used a rating scale to assess the clinical significance of the discrepancies to demonstrate the potential adverse clinical outcome of patients in the absence of clinical intervention. Two studies2 3 used a rating scale that was used in adults.4 A study of paediatric neurosurgical patients found that initial hospital prescriptions for children differed from the preadmission prescriptions in 39% of occasions and 50% of all prescribing variations had the potential to cause moderate or severe discomfort or clinical deterioration.2 A study by Coffey et al in general paediatric admissions in Canada showed 22% of patients experienced at least one discrepancy and 29% of the discrepancies had the potential to cause moderate or severe discomfort or clinical deterioration.3 By comparison an epidemiological study in discrepancies in adults on admission had 38.6% of the discrepancies identified with a potential to cause moderate or severe discomfort or clinical deterioration.4 All the studies involved small samples or specific patient groups such as medically complex patients. However all of the studies demonstrated that discrepancies occurred among paediatric populations during transitions in care settings and mentioned MR as an intervention. Conclusion: The results have shown that discrepancies of medication upon hospital admission, transfer and discharge occur regularly in children. With only one published study in the UK looking at hospital admission in children, and no published articles on the incidence and epidemiology of medication discrepancies upon hospital transfer or discharge further research is required in a wider paediatric population. Further work is also required to define the required interventions to improve practice.

Exploring psychologies of ageing

Three universities, Worcester, Keele and Aston, came together between May 2015 and February 2016 to explore psychologies of ageing: the range of social, critical, cognitive, biological and community psychology perspectives adopted when researchers and practitioners focus on the topic.