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IMPORTANCE: An accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood. OBJECTIVE: To clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset. DESIGN, SETTING, AND PARTICIPANTS: Participant data came from 4 prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center. Data were collected between 1997 and 2024 and were analyzed from July 2023 to August 2024. The settings were retirement communities, national-level surveys, and a multiclinic-based cohort. Included individuals were 60 years or older and without cognitive impairment at baseline. Included individuals also had data on age, sex, education level, and ethnicity and a frailty index score calculated at baseline. EXPOSURE: Frailty was the main exposure, with participants’ degrees of frailty quantified using retrospectively calculated frailty index scores. MAIN OUTCOMES AND MEASURES: Incident all-cause dementia ascertained through physician-derived diagnoses, self- and informant-report, and estimated classifications based on combinations of cognitive tests. RESULTS: The participant number before exclusions was 87 737. After exclusions, data from 29 849 participants (mean [SD] age, 71.6 [7.7] years; 18 369 female [62%]; 257 963 person-years of follow-up; 3154 cases of incident dementia) were analyzed. Bayesian generalized linear mixed regression models revealed accelerations in frailty trajectories 4 to 9 years before incident dementia. Overall, frailty was positively associated with dementia risk (adjusted hazard ratios [aHRs] ranged from 1.18; 95% CI, 1.13-1.24 to 1.73; 95% CI, 1.57-1.92). This association held among participants whose time between frailty measurement and incident dementia exceeded the identified acceleration period (aHRs ranged from 1.18; 95% CI, 1.12-1.23 to 1.43; 95% CI, 1.14-1.80). CONCLUSIONS AND RELEVANCE: These findings suggest that frailty measurements may be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention.

IMPORTANCE: There is limited information on modifiable risk factors for young-onset dementia (YOD). OBJECTIVE: To examine factors that are associated with the incidence of YOD. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023. EXPOSURES: A total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic factors (apolipoprotein E), lifestyle factors (physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage), environmental factors (nitrogen oxide, particulate matter, pesticide, and diesel), blood marker factors (vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin), cardiometabolic factors (stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use), psychiatric factors (depression, anxiety, benzodiazepine use, delirium, and sleep problems), and other factors (traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength). MAIN OUTCOME AND MEASURES: Multivariable Cox proportional hazards regression was used to study the association between the risk factors and incidence of YOD. Factors were tested stepwise first within domains and then across domains. RESULTS: Of 356 052 included participants, 197 036 (55.3%) were women, and the mean (SD) age at baseline was 54.6 (7.0) years. During 2 891 409 person-years of follow-up, 485 incident YOD cases (251 of 485 men [51.8%]) were observed, yielding an incidence rate of 16.8 per 100 000 person-years (95% CI, 15.4-18.3). In the final model, 15 factors were significantly associated with a higher YOD risk, namely lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression. CONCLUSIONS AND RELEVANCE: In this study, several factors, mostly modifiable, were associated with a higher risk of YOD. These modifiable risk factors should be incorporated in future dementia prevention initiatives and raise new therapeutic possibilities for YOD.

IMPORTANCE: Several ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA). OBJECTIVE: To perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease. DATA SOURCES: MEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched. STUDY SELECTION: Systematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk Of Bias in Systematic reviews tool was used to assess review quality. MAIN OUTCOMES AND MEASURES: The prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference. RESULTS: From the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88). CONCLUSIONS AND RELEVANCE: This umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2009.02680.x Byline: Toru Okura (*[dagger]), Brenda L. Plassman ([double dagger]), David C. Steffens ([double dagger]s.), David J. Llewellyn ([parallel]), Guy G. Potter (#), Kenneth M. Langa (**[dagger][dagger]) Keywords: neuropsychiatric symptoms; cognitive impairment; prevalence; functional status Abstract: OBJECTIVES: To estimate the prevalence of neuropsychiatric symptoms and examine their association with functional limitations. DESIGN: Cross-sectional analysis. SETTING: The Aging, Demographics, and Memory Study (ADAMS). PARTICIPANTS: A sample of adults aged 71 and older (N=856) drawn from Health and Retirement Study (HRS), a nationally representative cohort of U.S. adults aged 51 and older. MEASUREMENTS: The presence of neuropsychiatric symptoms (delusions, hallucinations, agitation, depression, apathy, elation, anxiety, disinhibition, irritation, and aberrant motor behaviors) was identified using the Neuropsychiatric Inventory. A consensus panel in the ADAMS assigned a cognitive category (normal cognition; cognitive impairment, no dementia (CIND); mild, moderate, or severe dementia). Functional limitations, chronic medical conditions, and sociodemographic information were obtained from the HRS and ADAMS. RESULTS: Forty-three percent of individuals with CIND and 58% of those with dementia exhibited at least one neuropsychiatric symptom. Depression was the most common individual symptom in those with normal cognition (12%), CIND (30%), and mild dementia (25%), whereas apathy (42%) and agitation (41%) were most common in those with severe dementia. Individuals with three or more symptoms and one or more clinically significant symptoms had significantly higher odds of having functional limitations. Those with clinically significant depression had higher odds of activity of daily living limitations, and those with clinically significant depression, anxiety, or aberrant motor behaviors had significantly higher odds of instrumental activity of daily living limitations. CONCLUSION: Neuropsychiatric symptoms are highly prevalent in older adults with CIND and dementia. Of those with cognitive impairment, a greater number of total neuropsychiatric symptoms and some specific individual symptoms are strongly associated with functional limitations. Author Affiliation: (*)Geriatric Medicine (**)General Medicine, Department of Internal Medicine, University of Michigan Ann Arbor, Michigan ([dagger])Geriatric Research, Education and Clinical Center, Department of Veterans Affairs, Ann Arbor, Michigan ([double dagger])Department of Psychiatry and Behavioral Sciences and Divisions of (s.)Geriatric Psychiatry (#)Medical Psychology, Duke University Medical Center, Durham, North Carolina ([parallel])Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom ([dagger][dagger])Health Services Research and Development Center of Excellence, Department of Veterans Affairs, Ann Arbor, Michigan Article note: Address correspondence to Toru Okura, 300 North Ingalls, Room 932, Ann Arbor, MI 48109. E-mail: t-ohkura@t3.rim.or.jp

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2009.02480.x Byline: Iain A. Lang (*[dagger]), Ruth E. Hubbard ([double dagger]), Melissa K. Andrew ([double dagger]s.), David J. Llewellyn (*[parallel]), David Melzer (*), Kenneth Rockwood (s.[parallel]#) Keywords: frailty; socioeconomic status; neighborhood deprivation Abstract: OBJECTIVES: To assess how individual socioeconomic status and neighborhood deprivation affect frailty. DESIGN: Nationally representative population-based study, the English Longitudinal Study of Aging (ELSA), analyzed cross-sectionally. PARTICIPANTS: Four thousand eight hundred eighteen individuals aged 65 and older. MEASUREMENTS: Outcome was a frailty index (FI), based on 58 potential deficits, with a theoretical range from 0 to 1; exposures were individual wealth and neighborhood deprivation (lack of local resources, financial and otherwise), based on a set of standard indicators. RESULTS: The FI score varied independently according to wealth and neighborhood deprivation. The mean FI score for an individual in the highest 20% of wealth and least deprived 20% of neighborhoods was 0.09 (95% confidence interval (CI)=0.09-0.09) and for an individual in the lowest 20% of wealth and most deprived 20% of neighborhoods was 0.17 (95% CI=0.16-0.17). CONCLUSION: Frailty in older adults is independently associated with individual and neighborhood socioeconomic factors. Older adults who are poor and live in deprived neighborhoods are most vulnerable. Policies and interventions intended to prevent or reduce frailty must take into account individual circumstances and the broader social settings in which individuals are located. Author Affiliation: (*)Epidemiology and Public Health Group, Peninsula Medical School, Exeter, England ([dagger])Devon Primary Care Trust, Exeter, England ([double dagger])Geriatric Medicine Research Unit (s.)Division of Geriatric Medicine (#)Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada ([parallel])Institute of Public Health, University of Cambridge, Cambridge, England. Article note: Address correspondence to Iain A Lang, Epidemiology & Public Health Group, Peninsula Medical School, RD&E Hospital Site, Barrack Road, Exeter EX2 5DW, UK. E-mail: iain.lang@pms.ac.uk

ABSTRACTBackgroundCoffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant.ObjectivesWe examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke.MethodsWe conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37–73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression.ResultsThere were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (Pnon-linearity = 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055).ConclusionHigh coffee consumption was associated with smaller total brain volumes and increased odds of dementia.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2008.01813.x Byline: Iain A. Lang (*), David J. Llewellyn ([dagger]), Kirsty Alexander ([double dagger]), David Melzer (*) Keywords: elderly; obesity; physical function; mortality; disability Abstract: OBJECTIVES: To estimate the effects of excess body weight on objective and subjective physical function and mortality risks in noninstitutionalized older adults. DESIGN: Population-based cohort study. SETTING: The English Longitudinal Study of Ageing (ELSA). PARTICIPANTS: Three thousand seven hundred ninety-three participants in the ELSA aged 65 and older followed up for 5 years. MEASUREMENTS: Analyses compared the risks of impaired physical function and mortality for subjects who were at the recommended weight (body mass index (BMI)=20.0-24.9) with those who were overweight (BMI=25.0-29.9), obese (BMI=30.0-34.9) or severely obese (BMI[greater than or equal to]35.0). Outcome measures were difficulties with activities of daily living (ADLs), score on the Short Physical Performance Battery, and mortality. RESULTS: Participants in higher BMI categories had greater risk of impaired physical function at follow-up but little or no greater risk of mortality. For example, compared with men of recommended weight, obese men (BMI=30.0-34.9) had relative risk ratios of difficulties with ADLs of 1.99 (95% confidence interval (CI)=1.42-2.78), of measured functional impairment of 1.51 (95% CI=1.05-2.16), and of mortality of 0.99 (95% CI=0.60-1.61). Findings were robust when excluding those who lost weight, smoked, or had poor self-rated health. CONCLUSION: Excess body weight in people aged 65 and older is associated with greater risk of impaired physical function but not with greater mortality risk. Societies with growing numbers of overweight and obese older people are likely to face increasing burdens of disability-associated health and social care costs. Author Affiliation: (*)Epidemiology and Public Health Group, Peninsula Medical School, Exeter, United Kingdom ([dagger])Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom ([double dagger])South Gloucestershire Primary Care Trust, Bristol, United Kingdom. Article note: Address correspondence to Dr. Iain Lang, Epidemiology & Public Health Group, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK. E-mail: iain.lang@pms.ac.uk

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2007.01557.x Byline: Iain A. Lang (*), David J. Llewellyn ([dagger]), Kenneth M. Langa ([double dagger]), Robert B. Wallace (s.), Felicia A. Huppert ([parallel]), David Melzer (*) Keywords: deprivation; education; socioeconomic status; cognitive function; cognition Abstract: OBJECTIVES: To assess the relationship between cognitive function, socioeconomic status, and neighborhood deprivation (lack of local resources of all types, financial and otherwise). DESIGN: Nationally representative cross-section. SETTING: The English Longitudinal Study of Ageing (ELSA). PARTICIPANTS: Seven thousand one hundred twenty-six community-dwelling individuals aged 52 and older and resident in urban areas. MEASUREMENTS: Individual cognitive function score and index of multiple deprivation (IMD) at the Super Output Area level, adjusting for health, lifestyle, and sociodemographic confounders. Analyses were conducted separately according to sex and age group (52-69 and [greater than or equal to]70). RESULTS: IMD affected cognitive function independent of the effects of education and socioeconomic status. For example, in fully adjusted models, women aged 70 and older had a standardized cognitive function score (z-score) that was 0.20 points (95% confidence interval (CI)=0.01-0.39) lower in the bottom 20% of wealth than the top 20%, 0.44 points (95% CI=0.20-0.69) lower in the least-educated group than in the most educated, and 0.31 points (95% CI 0.15-0.48) lower if resident lived in an area in the bottom 20% of IMD than in the top 20%. CONCLUSION: In community-based older people in urban neighborhoods, neighborhood deprivation-living in a neighborhood with high levels of deprivation, compared with national levels-is associated with cognitive function independent of individual socioeconomic circumstances. The mechanisms underlying this relationship are unclear and warrant further investigation. Author Affiliation: (*)Epidemiology and Public Health Group, Peninsula Medical School, Exeter, United Kingdom ([dagger])Institute of Public Health, University of Cambridge, Cambridge, United Kingdom ([double dagger])University of Michigan and Veterans Affairs Center for Practice Management and Outcomes Research, Ann Arbor, Michigan (s.)College of Public Health, University of Iowa, Iowa City, Iowa ([parallel])Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom Article note: Address correspondence to Dr. Iain Lang, Epidemiology & Public Health Group, Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK. E-mail: iain.lang@pms.ac.uk

It is universally agreed that the UK needs to reduce its budget deficit and lower government debt to GDP ratio. Both are unsustainable and, unless corrected, will damage the economy [...]

ObjectiveTo optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.MethodsWe explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data.ResultsThe analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28).ConclusionFrailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

A study was conducted on alternative pricing strategies for bank payment services. Three alternatives are analyzed, namely, Disneyworld pricing, single transactions charges and two-part tariffs. They all support explicit pricing and have distributional implications. The UK in particular is not explicitly charging for payments services due to the lack of incentive for customers to economize current accounts use, the lack of incentive boosts bank costs and no particular incentive exists for consumers to use economical forms of payments medium.

A study extends J. Thornton's analysis of financial services regulation in line with imperfections in the market. Thornton believes that regulatory measures can distort a financial institution's behavior while neglecting the regulatory functions. Regulation differs widely between banking services and non-bank financial services due to the differences in the nature of market imperfections. In addition, the ideal financial regulation structure of other non-bank financial services depend on how the targets-instruments approach is applied.

Background: Telephone-based cognitive assessments may be preferable to in-person testing in terms of test burden, economic and opportunity cost. Objective: We sought to determine the accuracy of telephone-based screening for the identification of dementia or Mild Cognitive Impairment (MCI). Methods: Five multidisciplinary databases were searched. Two researchers independently screened articles and extracted data. Eligible studies compared any multi-domain telephone-based assessment of cognition to the face-to-face diagnostic evaluation. Where data allowed, we pooled test accuracy metrics using the bivariate approach. Results: From 11,732 titles, 34 papers were included, describing 15 different tests. There was variation in test scoring and quality of included studies. Pooled analyses of accuracy for dementia: Telephone Interview for Cognitive Status (TICS) (<31/41) sensitivity: 0.92, specificity: 0.66 (6 studies); TICSmodified (<28/50) sensitivity: 0.91, specificity: 0.91 (3 studies). For MCI: TICS-modified (<33/50) sensitivity: 0.82, specificity: 0.87 (3 studies); Telephone-Montreal Cognitive Assessment (<18/22) sensitivity: 0.98, specificity: 0.69 (2 studies). Conclusion: There is limited diagnostic accuracy evidence for the many telephonic cognitive screens that exist. The TICS and TICS-m have the greatest supporting evidence; their test accuracy profiles make them suitable as initial cognitive screens where face to face assessment is not possible.

SUMMARY. One principle for reducing undesirable stem extension in greenhouse production is to counteract the decrease in red-to-far red ratio that occurs naturally during twilight periods. This study evaluated three lighting treatments on the morphology of easter lily (Lilium longiflorum): 1) a 1-hour end-of-day treatment providing 20 mmolmL2sL1 of monochromatic red light (EOD R), 2) blackout curtains closed 45 to 75 minutes before sunset and kept closed until 0 to 60 minutes after sunrise (BO), and 3) a control with natural twilight (CTRL). Plants under the BOtreatment were 11% shorter than CTRL, while plants exposed toEODRdid not differ in height compared with BO or CTRL. There were no treatment effects on any other measured parameters, including aspects of flowering. [ABSTRACT FROM AUTHOR]

Progress in dementia research has been limited, with substantial gaps in our knowledge of targets for prevention, mechanisms for disease progression, and disease-modifying treatments. The growing availability of multimodal data sets opens possibilities for the application of machine learning and artificial intelligence (AI) to help answer key questions in the field. We provide an overview of the state of the science, highlighting current challenges and opportunities for utilisation of AI approaches to move the field forward in the areas of genetics, experimental medicine, drug discovery and trials optimisation, imaging, and prevention. Machine learning methods can enhance results of genetic studies, help determine biological effects and facilitate the identification of drug targets based on genetic and transcriptomic information. The use of unsupervised learning for understanding disease mechanisms for drug discovery is promising, while analysis of multimodal data sets to characterise and quantify disease severity and subtype are also beginning to contribute to optimisation of clinical trial recruitment. Data-driven experimental medicine is needed to analyse data across modalities and develop novel algorithms to translate insights from animal models to human disease biology. AI methods in neuroimaging outperform traditional approaches for diagnostic classification, and although challenges around validation and translation remain, there is optimism for their meaningful integration to clinical practice in the near future. AI-based models can also clarify our understanding of the causality and commonality of dementia risk factors, informing and improving risk prediction models along with the development of preventative interventions. The complexity and heterogeneity of dementia requires an alternative approach beyond traditional design and analytical approaches. Although not yet widely used in dementia research, machine learning and AI have the potential to unlock current challenges and advance precision dementia medicine.

I HOPE THERE AREN'T ANY READERS WHO take Ryan Dionne's stupid advice and strap a six-month-old onto their chest to even ski the bunny hill (On Skiing, 'My Kid. My [...]

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Make ads less "intrusive" and I might unblock them Dominic Reardon is right to worry that Microsoft will end up slapping adverts all over Windows (Letters, Issue 647), but you can hardly blame them. Some shops have stayed cashless since lockdowns I've campaigned locally to preserve cash as an option in shops, so I read Issue 647's "Question of the Fortnight" with interest ("Is the UK ready to become a cashless society?" But now almost every commercial website has an advert surrounding the entire content, and video ads that play automatically as you scroll down. [Extracted from the article]

Earlier diagnosis of dementia is increasingly being recognized as a public health priority. As screening is not generally recommended, case-finding in clinical practice is encouraged as an alternative dementia identification strategy. The approaches of screening and case-finding are often confused, with uncertainty about what case-finding should involve and under what circumstances it is appropriate. We propose a formal definition of dementia case-finding with a clear distinction from screening. We critically examine case-finding policy and practice and propose evidence requirements for implementation in clinical practice. Finally, we present a case-finding pathway and discuss the available evidence for best practice at each stage, with recommendations for research and practice. In conclusion, dementia case-finding is a promising strategy but currently not appropriate due to the substantial gaps in the evidence base for several components of this approach.

This paper explores the creative uses of stories and storytelling to engage groups and individuals with consideration of changes in energy systems across time and place. It summarises three story-based experiments that responded to the theme of ‘energy utopias’. These are drawn from the three core strands of a much wider body of work undertaken within the Stories of Change project. This took stories as a central motif and organising device to refresh public and political conversations about energy and decarbonisation. Our hypothesis was that stories could offer a popular and engaging route into thinking about the past and present of humanity’s lives with energy and a lively way of imagining possible futures. We also wanted to test the degree to which stories could offer a shared intellectual space that might support both interdisciplinary and co-productive working for a core team that includes social science, humanities, media, computing and design researchers as well as creative and community partners. The paper considers some of the practical, methodological and theoretical considerations and reflects on the strengths and limitations of stories as both motif and technique in supporting action on climate change.

Objectives:High-risk sports participants have typically been viewed as a homogeneous group despite variability in performance characteristics and the level of risk undertaken. Prolonged engagement high-risk sports such as winter climbing are relatively underserved within current literature. Elite winter climbers attempt climbs that are outside the scope of the current “known”, i.e. unclimbed routes. The majority of the current understanding of motivation in high-risk sports is based on quantitative research and the methodologies and instruments used. The purpose of this study was to explore the experiences of elite winter climbers and gain a richer understanding of their motivational orientation and risk-taking behaviour. Design:Qualitative–inductive. Method:Four elite male winter climbers (aged 42–49 years old) took part in semi-structured interviews and explore their motivational orientation and risk-taking behaviour. A thematic analysis was used. Results:Two superordinate themes of enactive mastery and engendered disinhibition emerged from the data. Enactive mastery was interpreted as a composite of two higher-order themes: Task mastery and self-mastery. Engendered disinhibition was interpreted as a composite of two higher-order themes: Social cognitive appraisal and self-perception. Conclusion:Enactive mastery and engendered disinhibition emerged as key behavioural and psychological determinants that influenced individuals to attempt more difficult and riskier forms of winter climbing. Goal achievement was their primary motive which was set within a confidence frame encapsulated within these superordinate themes.

Abstract

ABSTRACTSevere malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum. Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90; P= 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3, Plasmodium falciparumRh2 [PfRh2], MSP-119, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82; P= 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [rs] = 0.12; P= 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM.

To assess the effects of a history of alcohol use disorders (AUDs) on risk of severe cognitive and memory impairment in later life.

To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.

Malaria‐specific antibody‐dependent respiratory burst activity from neutrophils is acquired in mice following infection; however, vaccination with a leading vaccine antigen fails to induce this activity. New tools are required to expedite the development of an effective vaccine against the blood‐stage infection with the human malaria parasite Plasmodium falciparum. This work describes the assessment of the ADRB assay in a mouse model, characterizing the functional interaction between antimalarial serum antibodies and FcRs upon neutrophils. We describe a reproducible, antigen‐specific assay, dependent on functional FcR signaling, and show that ADRB activity is induced equally by IgG1 and IgG2a isotypes and is modulated by blocking FcR function. However, following immunization of mice with the blood‐stage vaccine candidate antigen MSP142, no measurable ADRB activity was induced against PEMS and neither was vaccine efficacy modulated against Plasmodium yoeliiblood‐stage challenge in γ−/−mice compared with WT mice. In contrast, following a primary, nonlethal P. yoeliiparasite challenge, serum from vaccinated mice and nonimmunized controls showed anti‐PEMS ADRB activity. Upon secondary challenge, nonimmunized γ−/−mice showed a reduced ability to control blood‐stage parasitemia compared with immunized γ−/−mice; however, WT mice, depleted of their neutrophils, did not lose their ability to control infection. Thus, whereas neutrophil‐induced ADRB against PEMS does not appear to play a role in protection against P. yoeliirodent malaria, induction of ADRB activity after challenge suggests that antigen targets of anti‐PEMS ADRB activity remain to be established, as well as further supporting the observation that ADRB activity to P. falciparumarises following repeated natural exposure.

Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia.

To examine the association between cognitive function and dementia with vitamin D concentration in adults.

Neuroimaging is increasingly important in psychology, yet psychologists can fall prey to misconceptions. We examined the presentation of key radiological techniques in 12 widely distributed contemporary psychology texts. Errors were common in descriptions of computed tomography (CT), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). For example, PET images are generated by detecting pairs of photons, not the direct measurement of positrons. Similarly, many authors omit the need for a radio frequency pulse in MRI, implying that the technique simply relies on the application of a magnetic field. Misconceptions should be addressed in an attempt to reduce levels of confusion and maximise the contribution of neuroimaging data to psychological theorising.

Perturbation of normal endoplasmic reticulum (ER) function induces a stress response found throughout eukaryotes, sometimes termed the unfolded protein response (UPR). In yeast, auxotrophic mutants have identified two genes, IRE1 and HAC1, whose products are key components. Normally HAC1 mRNA is not translated owing to a 252-nt “intron.” Disruption of ER function activates Ire1p to remove this intron through endogenous endoribonuclease activity. Together with tRNA ligase, cleavage and splicing produces a translatable HAC1 mRNA to give Hac1p, a transcription factor that upregulates the expression of genes responsive to ER stress. No Hac1p homologue has been identified in mammalian cells, but Ire1p homologues exist with endoribonuclease activity required for a fully functional UPR, raising the possibility that the key features of the yeast UPR might be conserved in higher eukaryotic cells. To address this, we expressed yeast HAC1 in HeLa and HEK 293T human cell lines, both on its own and as fusions with yellow fluorescent protein (YFP) to investigate its processing and translation. HAC1 mRNA was not processed, but efficiently translated irrespective of whether the cells were subjected to ER stress. Expression of exogenous HAC1 mRNA constructs in yeast showed UPR-induced splicing required the presence of its 3′ UTR. These results suggest that the mammalian ER stress response has diverged from the yeast UPR.

Recent bank crises in developed and developing countries have underlined the question of a good “regulatory regime,” which is a wider concept than the set of prudential principles and business rules established by external regulatory agencies. The role of external regulation in fostering a safe and sound banking system is limited. The incentive's structure for private banks and the efficiency of monitoring and supervision have to play a great role. Liberalization of markets can have bad effects in the transitional period, but advantages can be enormous after the system starts to work correctly. The main lesson of recent bank crises is that there needs to be more effective surveillance of financial institutions both by supervisory authorities and by markets. Effective regulation (internal and external) and supervision of banks and financial institutions have the potential to give a major contribution to the stability and robustness of financial system.

ERp57 is a lumenal protein of the endoplasmic reticulum (ER) and a member of the protein disulfide isomerase (PDI) family. In contrast to archetypal PDI, ERp57 interacts specifically with newly synthesized glycoproteins. In this study we demonstrate that ERp57 forms discrete complexes with the ER lectins, calnexin and calreticulin. Specific ERp57/calreticulin complexes exist in canine pancreatic microsomes, as demonstrated by SDS-PAGE after cross-linking, and by native electrophoresis in the absence of cross-linking. After in vitro translation and import into microsomes, radiolabeled ERp57 can be cross-linked to endogenous calreticulin and calnexin while radiolabeled PDI cannot. Likewise, radiolabeled calreticulin is cross-linked to endogenous ERp57 but not PDI. Similar results were obtained in Lec23 cells, which lack the glucosidase I necessary to produce glycoprotein substrates capable of binding to calnexin and calreticulin. This observation indicates that ERp57 interacts with both of the ER lectins in the absence of their glycoprotein substrate. This result was confirmed by a specific interaction between in vitro synthesized calreticulin and ERp57 prepared in solution in the absence of other ER components. We conclude that ERp57 forms complexes with both calnexin and calreticulin and propose that it is these complexes that can specifically modulate glycoprotein folding within the ER lumen.

Diffusion of alkali and low-atomic-number elements during the microbeam analysis of some silicates by analytical electron microscopy (AEM) has been known for some time. Our repeated analyses at 300 kV of kaolinite, halloysite, smectite, biotite, muscovite and pyrophyllite, however, showed differential loss (relative to Si) of not only alkali elements (such as K, Na, Mg) and low-atomic-number elements (such as Al) but also higher-atomic-number elements (such as Fe, Ti). For AEM of these phyllosilicates, a Philips EM430/EDAX facility with a tungsten filament was used to provide a current of 0.3 nA in a stationary beam of nominal diameter 90 nm. The loss of Al in kaolin minerals during analysis is particularly severe. Kaolin crystals can be damaged by the electron irradiation over several seconds, making it the most sensitive clay to the electron beam; in general, relative phyllosilicate stabilities are kaolin < smectite < pyrophyllite < mica. A clear dependence of element loss on crystallographic orientation has been observed for layer silicates in our study; a greater element loss occurred when the plane of the specimen foil was perpendicular to the basal planes of the phyllosilicate crystals than when the foil was parallel to the basal planes. Lower beam current, larger beam diameter and thicker specimens all reduce the loss of elements. The initial stage of irradiation produces highest rates of element loss and the rate of loss can be fitted by an exponential decay law. The analyses at low temperature of phyllosilicates showed that element loss remains serious in our analytical conditions. Since the element loss appears to be instrument- and method-dependent, one should use closely related, well-characterized phyllosilicates as compositional standards to calibrate any AEM instrument that is to be used to analyze unknown phyllosilicates, and the standards and unknowns should be analyzed under identical conditions.