Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

From passionate labour to compassionate work: Cultural co-ops, do what you love and social change

This article focuses on the relation between work and pleasure in the cultural sector. I first unpack the concept of passionate work, situating it within four possible ways of relating work and pleasure. I argue that the work ethic of do what you love, contrary to what it promises, limits the prospects of loveable work. As part of a neoliberal work culture, do what you love transfers the battleground from society onto the self. It favours self-management over politics. Drawing on findings from interview research with members of worker co-operatives in the UK cultural industries, I then go on to explore the relation between work and pleasure within cultural co-ops. I discuss how cultural co-ops might inspire and contribute to a movement for transforming the future of work by turning the desire for loveable work from a matter of individual transformation and competition into a practice of co-operation and social change

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships

Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p<0 center dot 0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2 center dot 60, 2 center dot 30-2 center dot 94) than in older individuals (aged 70-89 years: 2 center dot 01, 1 center dot 85-2 center dot 19; p=0 center dot 0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5 center dot 55, 4 center dot 15-7 center dot 44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0 center dot 05% (95% CI 0 center dot 03-0 center dot 07) per year in women compared with 0 center dot 08% (0 center dot 05-0 center dot 10) per year in men; the corresponding excess at ages 70-89 years was 1 center dot 08% (0 center dot 84-1 center dot 3 2) per year in women and 0 center dot 91% (0 center dot 77-1 center dot 05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study.

BACKGROUND: Low-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice. METHODS: This was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases. RESULTS: Overall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations. CONCLUSIONS: Methoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics. TRIAL REGISTRATION: Study registered in the EU PAS Register (ENCEPP/SDPP/13040)

Carcinoma developing in ectopic pancreatic tissue in the stomach: a case report

The development of pancreatic tissue outside the confines of the main gland, without anatomic or vascular connections between them, is a congenital abnormality referred to as heterotopic pancreas. A heterotopic pancreas in the gastrointestinal tract is usually discovered incidentally and the risk of its malignant transformation is extremely low. In this study, we describe the first case of endoepithelial carcinoma arising in a gastric heterotopic pancreas of a 56-year old woman in Greece. She presented with epigastric pain, periodic nausea and vomiting. Esophagogastroduodenoscopy revealed an ulcerated lesion in the gastric antrum, biopsies of which showed intense epithelial dysplasia with incipient malignant degeneration. The pathology report of the distal gastrectomy specimen demonstrated a 2 cm in diameter ulcerative mass in the gastric antrum. Microscopically, an endoepithelial (in situ) carcinoma of the gastric antrum was determined, which in places turned into an microinvasive endomucosal adenocarcinoma. It also incidentally demonstrated heterotopic pancreatic ducts, detected within the mucosa to the muscularis propria of the same region of the stomach, in which an endoepithelial (in situ) carcinoma was evolving. The follow-up course was uneventful 6 months postoperatively

Examining if being overweight really confers protection against dementia: Sixty-four year follow-up of participants in the Glasgow University alumni cohort study

BACKGROUND: Recent large-scale studies suggest that obesity and overweight may confer protection against future dementia. This observation could, however, be generated by reverse causality. That is, weight loss in the incipient phase of dementia ascribed to diminished self-care, including sub-optimal nutrition, would have the effect of generating such an inverse association. One approach to circumventing this problem would be to measure weight in a population which is young enough to be free of the symptoms of dementia which is then followed up for dementia occurrence over many decades. METHODS: In a prospective cohort study, body mass index, and other potential risk factors, were measured in 9547 male university undergraduates (mean age 20.5 years) in 1948-68 who were then linked to national mortality registers. RESULTS: Of 2537 deaths over a mean of 50.6 years follow up, 140 were ascribed to dementia. There was no association between overweight and future dementia deaths (age-adjusted hazard ratio; 95 % confidence interval: 0.93; 0.49, 1.79). CONCLUSION: In this cohort study of former university students, being overweight in youth did not confer protection against later dementia death

Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice

Background: Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings: Focal cerebral ischemia was induced in Vasp2/2 mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan’s Blue tracer was applied to visualize the extent of blood-brainbarrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p,0.05) and edema volumes (1.7 mm360.5 mm3 versus 0.8 mm360.4 mm3; p,0.0001) were significantly enhanced in Vasp2/2 mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3617.3 mm3 versus 39.3 mm3610.7 mm3, respectively; p,0.01) and a non significant trend (p.0.05) towards worse neurological outcomes. Conclusion: Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage

Association of anthropometry and weight change with risk of dementia and its major subtypes : A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m(2)), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2)) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.Peer reviewe