A novel classifier of radiographic knee osteoarthritis for use on knee DXA images is predictive of joint replacement in UK Biobank

ObjectivesDXA scans may offer a novel means of evaluating radiographic knee OA (rKOA) in large population studies and through opportunistic screening. We aimed to develop and apply a semi-automated method for assessing rKOA using ≈20 000 knee DXA images from UK Biobank (UKB) and assess its face validity by checking for expected relationships with clinical outcomes.MethodsRight knee DXA scans were manually annotated for osteophytes to derive corresponding grades. Joint space narrowing (JSN) grades in the medial joint compartment were determined from automatically measured minimum joint space width. Overall rKOA grade (0–4) was determined by combining osteophyte and JSN grades. Logistic regression was employed to investigate the associations of osteophyte, JSN and rKOA grades with knee pain and hospital-diagnosed KOA. Cox proportional hazards modelling was used to examine the associations of these variables with risk of subsequent total knee replacement (TKR).ResultsOf the 19 595 participants included (mean age 63.7 years), 19.5% had rKOA grade ≥1 (26.1% female, 12.5% male). Grade ≥1 osteophytes and grade ≥1 JSN were associated with knee pain, hospital-diagnosed KOA and TKR. Higher rKOA grades were linked to stronger associations with these clinical outcomes, with the most pronounced effects observed for TKR. Hazard ratios for the association of rKOA grades with TKR were 3.28, 8.75 and 28.63 for grades 1, 2 and 3–4, respectively.ConclusionsOur DXA-derived measure of rKOA demonstrated a progressive relationship with clinical outcomes. These findings support the use of DXA for classifying rKOA in large epidemiological studies and in future population-based screening

¹⁰Be evidence for extensive, low-elevation Late Pleistocene glaciation in far eastern (Arunachal) Himalayas - timing and palaeoclimate reconstruction

The glacial history of the eastern Himalayas has remained undocumented compared to its western and central regions. In this study, we present 63 Be-10 exposure ages from glacial deposits in the Dri Valley, situated at the eastern extremity of the Himalayas, to reconstruct the first Pleistocene glaciation history of the ~900 km long Arunachal Himalayas. The most extensive glaciation occurred before ~48 ka (and possibly earlier than ~58 ka), when the (inferred) trunk glacier reached 100 km in length and descended to around 1500 to 1300 m above sea level (a.s.l) – among the lowest elevations recorded for glaciers in the Himalayan-Tibetan Orogen. The main valley glacier remained substantial during the Last (Global) Glacial Maximum (LGM) and had a length of ~76 km and terminated around 1680 m a.s.l. Despite dense forest cover, paraglacial and postglacial erosion obscuring (prominent) glacial landforms in the Dri Valley, an integrated approach combining geomorphological evidence and high-resolution satellite imagery with cosmogenic-based geochronological data has enabled a detailed reconstruction of its Pleistocene glaciation. Glacial deposits covering elevations from 3700 to 1600 m a.s.l were subdivided based on morphostratigraphy, revealing four periods of postglacial exposure dating to ≥58 ka, ~48 ka, ~19 ka and ~13 ka. The results indicate that the Dri Valley cirques (elevations ~3700 to ~3800 m a.s.l) became ice free between ~14 – 13 ka. Reconstruction of the cirque glacier yields an equilibrium line altitude (ELA) of approximately 3750 m, corresponding to a ∆ELA of ~900 m compared to today which is among the largest ELA depressions in the Himalayas for this period (~14 ka to present). Our findings reveal that Late Quaternary glaciation in the Dri Valley was primarily temperature-driven, influenced by long-term orbital forcing. With approximately 90% of the region’s abundant annual precipitation today occurring in summer, a positive mass balance for the Dri glacier is maintained up to a temperature-sensitive threshold. Beyond this threshold, even minimal warming would have caused glacier retreat (or collapse) due to a larger percentage of the summer precipitation falling as rain rather than snow, reducing the glacier’s accumulation. This is reflected in the termination of Dri Valley glacial phases correlating with known regional warm periods. This study offers critical insights into the climate-glacier interactions in the understudied eastern Himalayas and enhances our understanding of broader Himalayan-Tibetan palaeoclimate

Hearing loss as a risk factor for dementia: A systematic review and meta-analysis from a global perspective

Background: Hearing loss is a risk factor for dementia with estimated hazard ratios (HRs) of 1.28-2.39. However, potential intercontinental variability in this HR remains unexplored. This meta-analysis examined whether intercontinental variability exists in the relation between hearing loss and dementia.Methods: MEDLINE, PsychInfo, Academic Search Ultimate, Web of Science, and EMBASE were searched, from inception to 2024, for cohort studies of dementia-free individuals with hearing assessments at baseline, minimum 2-year follow-up, and incident dementia outcomes. Random-effect and multilevel models with subgroup difference tests were conducted.Results: Forty-nine studies analysed cohorts from North America (n =20), Europe (n = 20), Asia (n = 7), and Oceania (n = 2). Hearing loss (yes vs. no) was associated with increased risk of incident dementia (HR = 1.32 [95% CI: 1.23–1.41]) with HRs varying across continents (p &lt;.001). HRs were largest for Oceania and smallest for Asia. In a sensitivity analysis where the one study from Oceania was removed, HRs did not differ significantly by continent. Imprecise estimates create uncertainty around whether mild (HR = 1.35 [95% CI: 0.86 – 2.11]), moderate (HR = 1.39 [95% CI: 0.57–3.35]) or severe (HR = 1.66 [95% CI: 0.59–4.64]) hearing loss are associated with increased dementia risk, with little evidence that HRs by severity differ by continent (p = .059).Conclusions: Findings indicate that the association between hearing loss and incidence of dementia is consistent globally. However, HRs may vary slightly by continent. <br/

Brexit voters: Who has changed their mind?

We analyse which demographic groups in the UK were more likely to change their views on Brexit following the 2016 referendum on EU membership. Drawing on a large individual-level dataset of over 12,000 respondents, we find that women and middle-aged individuals were significantly more likely to shift towards a negative view of Brexit during the UK–EU negotiation period (2017 to 2019). Our analysis reveals that women and middle-age individuals were more likely to develop increasingly negative views of Brexit over time, while older individuals were more likely to report more favourable views. We also find that individuals with higher level of education were less likely to alter their views, maintaining consistent opinions over time. Importantly, we find no evidence that pre-referendum exposure to austerity policies influenced the likelihood of opinion change

The efficacy, mechanisms and implementation of physical activity as an adjunctive treatment in mental disorders:a meta-review of outcomes, neurobiology and key determinants

Research examining physical activity interventions for mental disorders has grown exponentially in the past decade. At this critical juncture, there is a need to synthesize the best evidence to guide researchers, clinicians and people with lived experience. This meta-review aimed to systematically identify and comprehensively evaluate the current evidence about: a) the efficacy of physical activity interventions on mental, cognitive and physical outcomes for individuals with mental disorders; b) the potential neurobiological, psychosocial and behavioral mechanisms underlying the observed effects; and c) the barriers and facilitators for individuals to successfully engage in these interventions. Our systematic search identified 13 meta-analyses of high methodological quality (i.e., A Measurement Tool to Assess Systematic Reviews, AMSTAR score ≥8) assessing outcomes of physical activity as an adjunctive treatment, which included 256 randomized clinical trials (RCTs) and 12,233 individuals. Large effect sizes were found for adjunctive physical activity interventions in improving attention in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); reducing depressive symptoms in children, adolescents and adults with depressive disorders; and reducing body mass index in adults with schizophrenia. Moderate effect sizes were found for reductions of hyperactivity, impulsivity and anxiety, and improvements of executive and social functioning in children and adolescents with ADHD; reduction of anxiety symptoms in adults with anxiety disorders; improved physical and psychological quality of life and cardiovascular fitness in adults with depressive disorders; improved daily living skills, overall quality of life and cardiorespiratory fitness in adults with schizophrenia; reduction of depressive symptoms in older people with depressive disorders; and improvements in cognition and functional mobility in older people with dementia. There is, to date, no meta-analytic evidence for physical activity as a first-line treatment for people with a mental disorder. Five meta-analyses, including 89 RCTs and 4,575 individuals, investigated potential underlying mechanisms. There is a very preliminary evidence for an effect of physical activity on circulating levels of kynurenine, growth hormone, tumor necrosis factor-alpha and brain-derived neurotrophic factor in people with major depressive disorder. No meta-analytic evidence could be found for psychosocial or behavioral mechanisms. Based on 15 umbrella or systematic reviews, covering 432 studies and 48 guidelines, six implementation strategies, along with the most evidence-based behavioral change techniques to support them, were identified. Recommendations to support implementation research in this area were finally formulated.</p