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Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored. Discussion will focus on how changes in brain and bone signalling can underly associations between these conditions, and will consider the molecular and cellular drivers in the context of inflammation and the gut microbiome. There is a complex interplay between nutritional changes, which may precede or follow the onset of mild cognitive impairment (MCI) or dementia, and bone health. Polypharmacy is common in patients with MCI or dementia, and there are difficult prescribing decisions to be made due to the elevated risk of falls associated with many drugs used for associated problems, which can consequently increase fracture risk. Some medications prescribed for cognitive impairment may directly impact bone health. In addition, patients may have difficulty remembering medication without assistance, meaning that osteoporosis drugs may be prescribed but not taken. Cognitive impairment may be improved or delayed by physical activity and exercise, and there is evidence for the additional benefits of physical activity on falls and fractures. Research gaps and priorities with the aim of reducing the burden of osteoporosis and fractures in people with MCI or dementia will also be discussed., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Consents and ethical approval: This narrative article contains no original data and thus issues of ethics, informed consent and patient confidentiality do not apply., (© 2024. The Author(s).)

Electrical power sources used in outer planet missions are a key enabling technology for data acquisition and communications. State–of-the-art power sources generate electricity from alpha decay of 238Pu via thermoelectric conversion. However, production of 238Pu requires specialist facilities including a nuclear reactor, a source of 237Np for target irradiation and hotcells to chemically separate neptunium and plutonium within the irradiated targets. These specialist facilities are expensive to build and operate, so naturally, a more economical alternative is attractive to the industry. Within Europe 241Am is considered a promising alternative heat source for radioisotope thermoelectric generators (RTGs) and radioisotope heating units (RHUs). As a daughter product of 241Pu decay, 241Am exists in 1000 kgs quantities within the UK civil plutonium stockpile. A chemical separation process is required to extract the 241Am in a pure form and this paper describes the AMPPEX process (Americium and Plutonium Purification by Extraction), successfully developed over the past five years to isolate 241Am in high yield (> 99%) and to a high purity (> 99%). The process starts by dissolving plutonium dioxide in nitric acid with the aid of a silver(II) catalyst, which is generated electrochemically. The solution is then conditioned and fed to a PUREX type solvent extraction process, where the plutonium is separated from the americium and silver. The plutonium is converted back to plutonium dioxide and the americium is fed forward to a second solvent extraction step. Here the americium is selectively extracted leaving the silver in the aqueous phase. The americium is stripped from the solvent and recovered from solution as americium oxalate, which is calcined to give americium dioxide as the final product. This paper will describe the development of the separation process over a series of six solvent extraction separation trials using centrifugal contactors. The material produced (~ 4g 241Am) was used to make ceramic pellets to establish the behaviour of americium oxide material under high temperature (1450°C) sintering conditions. The chemical separation process is now demonstrated at concentrations expected on the full scale facility taking this process to TRL 4-5.

Introduction: The scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a range of morbidities due to chronic HIV infection and its treatment. Impaired linear growth (stunting) is a common manifestation, affecting up to 50% of children. However, the effect of HIV on bone and muscle development during adolescent growth is not well characterised. Given the close link between pubertal timing and musculoskeletal development, any impairments in adolescence are likely to impact on future adult musculoskeletal health. We hypothesise that bone and muscle mass accrual in CWH is reduced, putting them at risk of reduced bone mineral density (BMD) and muscle function and increasing fracture risk. This study aims to determine the impact of HIV on BMD and muscle function in peripubertal children on ART in Zimbabwe., Methods and Analysis: Children with (n=300) and without HIV (n=300), aged 8-16 years, established on ART, will be recruited into a frequency-matched prospective cohort study and compared. Musculoskeletal assessments including dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, grip strength and standing long jump will be conducted at baseline and after 1 year. Linear regression will be used to estimate mean size-adjusted bone density and Z-scores by HIV status (ie, total-body less-head bone mineral content for lean mass adjusted for height and lumbar spine bone mineral apparent density. The prevalence of low size-adjusted BMD (ie, Z-scores <-2) will also be determined., Ethics and Dissemination: Ethical approval for this study has been granted by the Medical Research Council of Zimbabwe and the London School of Hygiene and Tropical Medicine Ethics Committee. Baseline and longitudinal analyses will be published in peer-reviewed journals and disseminated to research communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Over 80 heat treatment experiments have been made on samples of chloride-contaminated plutonium dioxide retrieved from two packages in storage at Sellafield. These packages dated from 1974 and 1980 and were produced in a batch process by conversion of plutonium oxalate in a furnace at around 550 °C. The storage package contained a poly(vinyl chloride) (PVC) bag between the screw top inner and outer metal cans. Degradation of the PVC has led to adsorption of hydrogen chloride together with other atmospheric gases onto the PuO 2 surface. Analysis by caustic leaching and ion chromatography gave chloride contents of ∼2000 to >5000 ppm Cl (i.e., μgCl g -1 of the original sample). Although there are some subtle differences, in general, there is surprisingly good agreement in results from heat treatment experiments for all the samples from both cans. Mass loss on heating (LOH) plateaus at nearly 3 wt % above 700 °C, although samples that were long stored under an air atmosphere or preexposed to 95% relative humidity atmospheres, gave higher LOH up to ∼4 wt %. The majority of the mass loss is due to adsorbed water and other atmospheric gases rather than chloride. Heating volatilizes chloride only above ∼400 °C implying that simple physisorption of HCl is not the main cause of contamination. Interestingly, above 700 °C, >100% of the initial leachable chloride can be volatilized. Surface (leachable) chloride decreases quickly with heat treatment temperatures up to ∼600 °C but only slowly above this temperature. Storage in air atmosphere post-heat treatment apparently leads to a reequilibration as leachable chloride increases. The presence of a "nonleachable" form of chloride was thus inferred and subsequently confirmed in PuO 2 samples (pre- and post-heat treatment) that were fully dissolved and analyzed for the total chloride inventory. Reheating samples in either air or argon at temperatures up to the first heat treatment temperature did not volatilize significant amounts of additional chloride. With regard to a thermal stabilization process, heat treatment in flowing air at 800 °C with cooling and packaging under dry argon appears optimal, particularly, if thinner powder beds can be maintained. From electron microscopy, heat treatment appeared to have the most effect on degrading the square platelet particles compared to those with the trapezoidal morphology., Competing Interests: The authors declare no competing financial interest.

Introduction: To explore physiotherapists' perceptions of mechanisms to explain observed variation in early postoperative practice after hip fracture surgery demonstrated in a national audit. Methods: A qualitative semi-structured interview study of 21 physiotherapists working on orthopaedic wards at 7 hospitals with different durations of physiotherapy during a recent audit. Thematic analysis of interviews drawing on Normalisation Process Theory to aid interpretation of findings. Results: Four themes were identified: achieving protocolised and personalised care; patient and carer engagement; multidisciplinary team engagement across the care continuum; and strategies for service improvement. Most expressed variation from protocol was legitimate when driven by what is deemed clinically appropriate for a given patient. This tailored approach was deemed essential to optimise patient and carer engagement. Participants reported inconsistent degrees of engagement from the multidisciplinary team attributing this to competing workload priorities, interpreting 'postoperative physiotherapy' as a single professional activity rather than a care delivery approach, plus lack of integration between hospital and community care. All participants recognised changes needed at both structural and process levels to improve their services. Conclusion: Physiotherapists highlighted an inherent conflict between their intention to deliver protocolised care while allowing for an individual patient-tailored approach. This conflict has implications for how audit results should be interpreted, how future clinical guidelines are written, and how physiotherapists are trained. Physiotherapists also described additional factors explaining variation in practice which may be addressed through increased engagement of the multidisciplinary team and resources for additional staffing and advanced clinical roles. [ABSTRACT FROM AUTHOR]

Objective Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls. Design HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and body mass index (BMI). Results 530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs 13.6%), with adjusted odds ratio (OR) [95% CI] 1.52 [1.09, 2.11], P = 0.013. Osteophytes (OR 2.12 [1.61, 2.79], P < 0.001) and subchondral sclerosis (OR 2.78 [1.49, 5.18], P = 0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing (JSN) was seen (OR 0.97 [0.72, 1.33], P = 0.869). Conclusions An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype. [ABSTRACT FROM AUTHOR]

Introduction Older adults who sustain a hip fracture require complex multidisciplinary care, which can challenge organisational structures within hospitals. Despite standards and guidelines, substantial variation remains in hip fracture care delivery across the UK. We aimed to determine which hospital-level organisational factors predict adverse patient outcomes in the post injury period. Method A cohort of 178,757 patients aged 60+ years in England and Wales (2016–19) who sustained a hip fracture was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality data were linked to metrics from 18 hospital-level organisational audits/reports/series. Multilevel models determined the organisational factors, independent of patient case-mix, associated with three patient outcomes: length of hospital stay (LOS), 30-day all-cause mortality, and emergency 30-day readmission. Results Overall LOS was mean 21 days (standard deviation, 20); 13,126 (7.3%) died within 30-days; and 25,239 (15.3%) were readmitted. 25 organisational factors independently predicted LOS: for example, a hospital's ability to promptly mobilise ≥90% of patients was associated with a 2-day (95%CI:1.3–2.7) shorter LOS, and hospitals where all patients received orthogeriatric assessment within 72 hours of admission had mean 1.5-day (95%CI:0.6–2.3) shorter LOS. Ten organisational factors independently predicted 30-day mortality: providing prompt surgery (≤36 hours from admission) to >80% patients was associated with the same 10% reduction in mortality (95%CI:4–15%), as was discussion of 'patient experience' feedback at clinical governance meetings (95%CI:5–15%). Nine organisational factors independently predicted readmission: knowledge of time from discharge to start of community therapy was associated with 17% (95%CI:9–24%) lower readmission rates. Organisational delivery of clinical governance, surgery, and physiotherapy were associated with all outcomes. Conclusion Multiple, potentially modifiable, organisational factors are associated with important patient outcomes post-hip fracture. These factors, if causal, indicate auditable components of hospital care where interventions can be targeted to reduce variability in hip fracture care delivery, to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Non-communicable chronic disease is a major contributor to morbidity and mortality with potentially modifiable lifestyle factors. In women, the menopausal transition modifies women's risk of chronic disease, and pregnancy-related complications have been highlighted as female-specific risk factors. Later reproductive years, before onset of menopause, may represent a window of opportunity for promotion of lifestyle modifications. The aim of this scoping review is to investigate which interventions promoting lifestyle modifications in women of later reproductive years may influence cardiometabolic and bone disease. Methods: A search of three electronic databases (PubMed, Embase, CINAHL) in the English language was performed in January 2024. Eligible studies included women aged 40–55 participating in interventions focusing on lifestyle modification. Studies reporting outcomes related to cardiometabolic disease, bone disease or body composition were eligible for inclusion. Results: Improvements in body composition occurred following interventions focusing on aerobic physical activity. Interventions focusing on health promotion and education, incorporating both dietary and physical activity modifications, prevented weight gain and improved cardiometabolic outcomes. Interventions incorporating elements of behavioural theories enhanced patient-motivated lifestyle modifications, with effects on body composition and cardiometabolic outcomes. Conclusions: Lifestyle modifications in later reproductive years have the potential to influence cardiometabolic and bone disease. Our findings reinforce the benefits of regular aerobic physical activity, as well as health education, for improving body composition and lipid profile. This information could contribute to the development of clinical guidelines for the prevention of chronic disease. [ABSTRACT FROM AUTHOR]

Significant recent discoveries of a large group of high-pressure (HP) minerals are reviewed. These minerals can be classified into two genetic types: those formed in shocked meteorites and impact craters and those formed under static P-T conditions and found as inclusions in diamonds. Of particular interest are the HP-polymorphic modifications of minerals such as olivine, ilmenite, ulvöspinel, wollastonite, and feldspars. Some examples include asimowite, poirierite, ohtaniite, liuite, wangdaodeite, tschaunerite, breyite, davemaoite, lingunite, and liebermannite. Special attention is also devoted to new dense hydrous silicates, which show much better stability than other known hydrous minerals to act as water reservoirs in the early stage of Earth's geological history. The crystal structures and compositions of these new HP-minerals provide valuable insights into the complex petrology of deep geospheres, otherwise not obtainable in laboratory experiments. Using such a rich database, further steps became appropriate and possible toward the directions of a more advanced knowledge of evolution, composition, and structure of Earth. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is associated with substantially increased fracture risk, particularly hip fracture, which can occur relatively early in the course of PD. Despite this, current national clinical guidelines for PD fail to adequately address fracture risk assessment or the management of bone health. We appraise the evidence supporting bone health management in PD and propose a PD-specific algorithm for the fracture risk assessment and the management of bone health in patients with PD and related movement disorders. The algorithm considers (i) calcium and vitamin D replacement and maintenance, (ii) quantification of prior falls and fractures, (iii) calculation of 10-year major osteoporotic and hip fracture risks using Qfracture, (iv) application of fracture risk thresholds, which if fracture risk is high (v) prompts anti-resorptive treatment, with or without dual X-ray absorptiometry, and if low (vi) prompts re-assessment with FRAX and application of National Osteoporosis Guidelines Group (NOGG) guidance. A range of anti-resorptive agents are now available to treat osteoporosis; we review their use from the specific perspective of a clinician managing a patient population with PD. In conclusion, our current evidence base supports updating of guidelines globally concerning the management of PD, which presently fail to adequately address bone health., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Intravenous zolendronic acid is an established anti-resorptive treatment for post-menopausal osteoporosis and is usually well tolerated. Common side effects, including the classical 'acute phase response', are consented for prior to treatment. However, rare but serious adverse reactions to zolendronic acid have been described. We report the case of an older patient with osteoporosis and osteoarthritis who presented within 12 hours of her first zolendronic acid infusion with evidence of a severe acute polyarthritis affecting her peripheral appendicular skeleton, in joints affected by pre-existing osteoarthritis. Despite the prevalence of osteoarthritis, this is the most severe case of polyarthritis following intravenous zolendronic acid to date and only the second reported case. We remind prescribing physicians treating patients with intravenous bisphosphonates, to bear in mind possible rare serious adverse reactions as well as common benign side effects. We postulate age-associated frailty may reduce tolerability to even milder acute phase reactions.

Transforming growth factor-βs (TGF-βs) and bone morphometric proteins (BMPs) belong to the TGF-β superfamily and perform essential functions during osteoblast and chondrocyte lineage commitment and differentiation, skeletal development, and homeostasis. TGF-βs and BMPs transduce signals through SMAD-dependent and -independent pathways; specifically, they recruit different receptor heterotetramers and R-Smad complexes, resulting in unique biological readouts. BMPs promote osteogenesis, osteoclastogenesis, and chondrogenesis at all differentiation stages, while TGF-βs play different roles in a stage-dependent manner. BMPs and TGF-β have opposite functions in articular cartilage homeostasis. Moreover, TGF-β has a specific role in maintaining the osteocyte network. The precise activation of BMP and TGF-β signaling requires regulatory machinery at multiple levels, including latency control in the matrix, extracellular antagonists, ubiquitination and phosphorylation in the cytoplasm, nucleus-cytoplasm transportation, and transcriptional co-regulation in the nuclei. This review weaves the background information with the latest advances in the signaling facilitated by TGF-βs and BMPs, and the advanced understanding of their diverse physiological functions and regulations. This review also summarizes the human diseases and mouse models associated with disordered TGF-β and BMP signaling. A more precise understanding of the BMP and TGF-β signaling could facilitate the development of bona fide clinical applications in treating bone and cartilage disorders., (© 2024. The Author(s).)