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Artificial intelligence (AI) is revolutionizing head and neck cancer (HNC) care by providing innovative tools that enhance diagnostic accuracy and personalize treatment strategies. This review highlights the advancements in AI technologies, including deep learning and natural language processing, and their applications in HNC. The integration of AI with imaging techniques, genomics, and electronic health records is explored, emphasizing its role in early detection, biomarker discovery, and treatment planning. Despite noticeable progress, challenges such as data quality, algorithmic bias, and the need for interdisciplinary collaboration remain. Emerging innovations like explainable AI, AI-powered robotics, and real-time monitoring systems are poised to further advance the field. Addressing these challenges and fostering collaboration among AI experts, clinicians, and researchers is crucial for developing equitable and effective AI applications. The future of AI in HNC holds significant promise, offering potential breakthroughs in diagnostics, personalized therapies, and improved patient outcomes.

Abstract Background Engagement and partnership with consumers and communities throughout research processes produces high quality research meeting community needs and promoting translation of research into improved policy and practice. Partnership is critical in research involving Aboriginal and/or Torres Strait Islander people (First Nations Peoples) to ensure cultural safety. We present lessons from the design, implementation and progress of the National Health and Medical Research Council funded INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on hemodialysis (INFERR) clinical trial. Main body The trial was designed to understand the benefits and harms of iron therapy in First Nations Australians on haemodialysis with anaemia and hyperferritinaemia. The lack of evidence for treatment was discussed with patients who were potential participants. A key element ensuring safe conduct of the INFERR trial was the establishment of the Indigenous Reference Groups (IRGs) comprising of dialysis patients based in the Top End of Australia and Central Australia. Two IRGs were needed based on advice from First Nations communities and researchers/academics on the project regarding local cultural differences and approaches to trial conduct. The IRGs underpin culturally safe trial conduct by providing input into study materials and translating study findings into effective messages and policies for First Nations dialysis patients. Throughout the trial conduct, the IRGs’ role has developed to provide key mechanisms for advice and guidance regarding research conduct both in this study and more broadly. Support provided to the IRGs by trial First Nations Research Officers and independent First Nations researchers/academics who simplify research concepts is critical. The IRGs have developed feedback documents and processes to participants, stakeholders, and the renal units. They guarantee culturally safe advice for embedding findings from the trial into clinical practice guidelines ensuring evidence-based approaches in managing anaemia in haemodialysis patients with hyperferritinaemia. Conclusion Active consumer and community partnership is critical in research conduct to ensure research impact. Strong partnership with consumers in the INFERR clinical trial has demonstrated that First Nations Consumers will engage in research they understand, that addresses health priorities for them and where they feel respected, listened to, and empowered to achieve change.

Estuarine compound flooding can happen when extreme sea level and river discharges occur concurrently, or in close succession, inundating low-lying coastal regions. Such events are hard to predict and amplify the hazard. Recent UK storms, including Storm Desmond (2015) and Ciara (2020), have highlighted the vulnerability of mountainous Atlantic-facing catchments to the impacts of compound flooding including risk to life and short- and long-term socio-economic damages. To improve prediction and early warning of compound flooding, combined sea and river thresholds need to be established. In this study, observational data and numerical modelling were used to reconstruct the historic flood record of an estuary particularly vulnerable to compound flooding (Conwy, North Wales). The record was used to develop a method for identifying combined sea level and river discharge thresholds for flooding using idealised simulations and joint-probability analyses. The results show how flooding extent responds to increasing total water level and river discharge, with notable amplification in flood extent due to the compounding drivers in some circumstances, and sensitivity (∼ 7 %) due to a 3 h time lag between the drivers. The influence of storm surge magnitude (as a component of total water level) on the flooding extent was only important for scenarios with minor flooding. There was variability as to when and where compound flooding occurred; it was most likely under moderate sea and river conditions (e.g. 60th–70th and 30th–50th percentiles) and only in the middle-estuary zone. For such cases, joint-probability analysis is important for establishing compound flood risk behaviour. Elsewhere in the estuary, either the sea state (lower estuary) or river flow (upper estuary) dominated the hazard, and single-value probability analysis is sufficient. These methods can be applied to estuaries worldwide to identify site-specific thresholds for flooding to support emergency response and long-term coastal management plans.

Abstract: Extreme summer temperatures are increasingly common across the Northern Hemisphere and inflict severe socioeconomic and biological consequences. In summer 2021, the Pacific Northwest region of North America (PNW) experienced a 2-week-long extreme heatwave, which contributed to record-breaking summer temperatures. Here, we use tree-ring records to show that summer temperatures in 2021, as well as the rate of summertime warming during the last several decades, are unprecedented within the context of the last millennium for the PNW. In the absence of committed efforts to curtail anthropogenic emissions below intermediate levels (SSP2–4.5), climate model projections indicate a rapidly increasing risk of the PNW regularly experiencing 2021-like extreme summer temperatures, with a 50% chance of yearly occurrence by 2050. The 2021 summer temperatures experienced across the PNW provide a benchmark and impetus for communities in historically temperate climates to account for extreme heat-related impacts in climate change adaptation strategies.

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer’s disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD.Methods and analysis ISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo. Up to 88 individuals aged ≥55 years with brain amyloid positivity as assessed by positron emission tomography (PET) or cerebrospinal fluid, and no or mild cognitive impairment, will be randomised. People with the low-affinity binding variant of the rs6971 allele of the Translocator Protein 18 kDa (TSPO) gene, which can interfere with interpreting TSPO PET scans (a measure of neuroinflammation), will be excluded.At baseline, participants undergo tau, TSPO PET and MRI scanning, and provide data on physical activity and cognition. Eligible individuals are randomised in a 1:1 ratio to once-daily oral semaglutide or placebo, starting at 3 mg and up-titrating to 14 mg over 8 weeks. They will attend safety visits and provide blood samples to measure AD biomarkers at weeks 4, 8, 26 and 39. All cognitive assessments are repeated at week 26. The last study visit will be at week 52, when all baseline measurements will be repeated. The primary end point is the 1-year change in tau PET signal.Ethics and dissemination The study was approved by the West Midlands—Edgbaston Research Ethics Committee (22/WM/0013). The results of the study will be disseminated through scientific presentations and peer-reviewed publications.Trial registration number ISRCTN71283871.

BackgroundSleep disturbances are a potentially modifiable risk factor for neurodegenerative dementia secondary to Alzheimer disease (AD) and Lewy body disease (LBD). Therefore, we need to identify the best methods to study sleep in this population. ObjectiveThis study will assess the feasibility and acceptability of various wearable devices, smart devices, and remote study tasks in sleep and cognition research for people with AD and LBD. MethodsWe will deliver a feasibility and acceptability study alongside a prospective observational cohort study assessing sleep and cognition longitudinally in the home environment. Adults aged older than 50 years who were diagnosed with mild to moderate dementia or mild cognitive impairment (MCI) due to probable AD or LBD and age-matched controls will be eligible. Exclusion criteria include lack of capacity to consent to research, other causes of MCI or dementia, and clinically significant sleep disorders. Participants will complete a cognitive assessment and questionnaires with a researcher and receive training and instructions for at-home study tasks across 8 weeks. At-home study tasks include remote sleep assessments using wearable devices (electroencephalography headband and actigraphy watch), app-based sleep diaries, online cognitive assessments, and saliva samples for melatonin- and cortisol-derived circadian markers. Feasibility outcomes will be assessed relating to recruitment and retention, data completeness, data quality, and support required. Feedback on acceptability and usability will be collected throughout the study period and end-of-study interviews will be analyzed using thematic analysis. ResultsRecruitment started in February 2022. Data collection is ongoing, with final data expected in February 2024 and data analysis and publication of findings scheduled for the summer of 2024. ConclusionsThis study will allow us to assess if remote testing using smart devices and wearable technology is a viable alternative to traditional sleep measurements, such as polysomnography and questionnaires, in older adults with and without MCI or dementia due to AD or LBD. Understanding participant experience and the barriers and facilitators to technology use for research purposes and remote research in this population will assist with the development of, recruitment to, and retention within future research projects studying sleep and cognition outside of the clinic or laboratory. International Registered Report Identifier (IRRID)DERR1-10.2196/52652

Abstract Background Sleep and circadian rhythm disorders are well recognised in both AD (Alzheimer’s Disease) dementia and MCI-AD (Mild Cognitive Impairment due to Alzheimer’s Disease). Such abnormalities include insomnia, excessive daytime sleepiness, decreased sleep efficiency, increased sleep fragmentation and sundowning. Enhancing understanding of sleep abnormalities may unveil targets for intervention in sleep, a promising approach given hypotheses that sleep disorders may exacerbate AD pathological progression and represent a contributory factor toward impaired cognitive performance and worse quality of life. This may also permit early diagnosis of AD pathology, widely acknowledged as a pre-requisite for future disease-modifying therapies. This study aims to bridge the divide between in-laboratory polysomnographic studies which allow for rich characterisation of sleep but in an unnatural setting, and naturalistic studies typically approximating sleep through use of non-EEG wearable devices. It is also designed to record sleep patterns over a 2 month duration sufficient to capture both infradian rhythm and compensatory responses following suboptimal sleep. Finally, it harnesses an extensively phenotyped population including with AD blood biomarkers. Its principal aims are to improve characterisation of sleep and biological rhythms in individuals with AD, particularly focusing on micro-architectural measures of sleep, compensatory responses to suboptimal sleep and the relationship between sleep parameters, biological rhythms and cognitive performance. Methods/design This observational cohort study has two arms (AD-MCI / mild AD dementia and aged-matched healthy adults). Each participant undergoes a baseline visit for collection of demographic, physiological and neuropsychological information utilising validated questionnaires. The main study period involves 7 nights of home-based multi-channel EEG sleep recording nested within an 8-week study period involving continuous wrist-worn actigraphy, sleep diaries and regular brief cognitive tests. Measurement of sleep parameters will be at home thereby obtaining a real-world, naturalistic dataset. Cognitive testing will be repeated at 6 months to stratify participants by longitudinal disease progression. Discussion This study will generate new insights particularly in micro-architectural measures of sleep, circadian patterns and compensatory sleep responses in a population with and without AD neurodegenerative change. It aims to enhance standards of remotely based sleep research through use of a well-phenotyped population and advanced sleep measurement technology.

Soft robotics is used in real-world clinical situations, including surgery, rehabilitation, and diagnosis. However, several challenges remain to make soft robots more viable, especially for clinical interventions such as improving sleep quality, which impacts physiological and mental health. This paper presents an autoethnographic account of the experience of sleeping with a companion robot (Somnox), which mimics breathing to promote better sleep. The study is motivated by the key author’s experience with insomnia and a desire to better understand how Somnox is used in different social contexts. Data were collected through diary entries for 16 weeks (8 weeks without, 8 weeks with) and analysed thematically. The findings indicate improved sleep and observations about the relationship developed with the companion robot, including emotional connection and empathy for the technology. Furthermore, Somnox is a multidimensional family companion robot that can ease stomach discomfort and stress, reduce anxiety, and provide holistic care.

Landscape evolution models (LEMs) are useful for understanding how large-scale processes and perturbations influence the development of the surface of the Earth and other planets. With their increasing sophistication and improvements in computational power, they are finding greater uptake in analyses at finer spatial and temporal scales. For many LEMs, the land surface is represented by a grid of regularly spaced and sized grid cells, or pixels, referred to as a digital elevation model (DEM), yet despite the importance of the DEM to LEM studies, there has been little work to understand the influence of grid cell size (i.e. resolution) on model behaviour. This is despite the choice of grid cell size being arbitrary for many studies, with users needing to balance detail with computational efficiency. Using the Morris method (MM) for global sensitivity analysis, the sensitivity of the CAESAR-Lisflood LEM to the grid cell size is evaluated relative to a set of influential user-defined parameters, showing that it had a similar level of influence as a key hydrological parameter and the choice of sediment transport law. Outputs relating to discharge and sediment yields remained stable across different grid cell sizes until the cells became so large that the representation of the hydrological network degraded. Although total sediment yields remained steady when changing the grid cell sizes, closer analysis revealed that using a coarser grid resulted in it being built up from fewer yet more geomorphically active events, risking outputs that are “the right answer but for the wrong reasons”. These results are important considerations for modellers using LEMs and the methodologies detailed provide solutions to understanding the impacts of modelling choices on outputs.

Abstract Background Domestic Violence and Abuse (DVA) is a persistent public health problem in the UK. Healthcare settings offer an opportunity to ask patients about DVA, either opportunistically or in response to the presence of injuries. However, it has been suggested that dental practices and dental teams have not been actively involved supporting adult patients when presenting with injuries that might have resulted from DVA. This qualitative study was conducted to satisfy the evaluative component of the Dentistry Responding in Domestic Violence and Abuse (DRiDVA) feasibility study. Methods In total, 30 participants took part in the study; nine associate dentists and practice principals/owners took part in one-to-one interviews and 21 auxiliary staff took part across two focus group discussion sessions. Data were analysed using the seven step Framework Analysis process. Result Three key themes were identified from the data, focusing on barriers to enquiring about domestic violence and abuse, Facilitators of identification and referral of DVA in dental settings, and recommendations for further adaptation of intervention to dental settings. Conclusion DVA training coupled with robust referral pathways to a named specialist DVA advocate increases knowledge and awareness of the signs of DVA and confidence in making onward referrals. Further research is needed to understand how to increase dental professional willingness to ask patients about DVA.

The mandible or lower jaw is the largest and hardest bone in the human facial skeleton. Fractures of the mandible are reported to be a common facial trauma in emergency medicine and gaining insights into mandibular morphology in different facial types can be helpful for trauma treatment. Furthermore, features of the mandible play an important role in forensics and anthropology for identifying gender and individuals. Thus, discovering hidden information of the mandible can benefit interdisciplinary research. Here, for the first time, a method of artificial intelligence-based nonlinear dynamics and network analysis are used for discovering dissimilar and similar radiographic features of mandibles between male and female subjects. Using a public dataset of 10 computed tomography scans of mandibles, the results suggest a difference in the distribution of spatial autocorrelation between genders, uniqueness in network topologies among individuals and shared values in recurrence quantification.

Abstract Background Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology. Objectives To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy. Design A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences. Setting Paediatric intensive care units in six UK hospitals. Participants Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance. Interventions Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration. Main outcome measures Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality. Data sources Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network. Results Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order. Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%). Harms No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency. Conclusions NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy. Future work Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Why do this study? Some children in intensive care are so poorly that their kidneys do not work well, and they need help, called dialysis, to get rid of fluid and chemicals from their blood. For babies, we currently use peritoneal dialysis, where fluid is cycled in and out of the tummy, or adapted machines designed for bigger children (continuous veno-venous haemofiltration). A new machine, the NIDUS® (Allmed, www.allmedgroup.com), was developed specifically for babies weighing under 8 kg with much smaller tubing. NIDUS worked well when studied in Newcastle but needed testing elsewhere. What was the question? How well does NIDUS work compared to other dialysis methods? What are the problems? What did we do? The study was done in six paediatric intensive care units who used their usual dialysis methods (=control) in the first part of the study and then later swapped to using the NIDUS (=intervention). What did we find? We recruited 97 participants, 62 to control (49 peritoneal dialysis, 13 continuous veno-venous haemofiltration) and 35 intervention (NIDUS). We found NIDUS provided much better control of fluid removal. The CVVH machines were more efficient at blood cleaning than NIDUS, which was better than peritoneal dialysis. What does this mean? We learnt a lot about babies needing kidney support in paediatric intensive care units and that all methods have advantages and disadvantages. We showed that NIDUS could be very useful for some participants because it cleans blood effectively and gives accurate, controllable fluid removal. We have gathered important information to help us improve NIDUS to make it easier to use and run. Many parents responded to our questionnaire and most told us they felt it was acceptable to be approached about taking part in research despite the circumstances. This is very important for future research studies. We are very grateful to families for their generosity in becoming involved in this study. Scientific summary Background Critically unwell babies in paediatric intensive care units (PICUs) may develop acute renal failure and require management with renal replacement therapy. Although mortality and morbidity vary and are related to the underlying diagnosis, survival of babies in paediatric intensive care is worse for those with fluid overload. Babies requiring renal replacement treatment present specific therapeutic challenges because of their small size and the current technology available. Difficulties with vascular access and blood flows, fluid balance, loss of circuits, filter clotting and hypotensive episodes at initiation are all described in the literature. The need for new solutions and improved technology is well recognised. Continuous veno-venous haemofiltration (CVVH) machines in use in the UK at the time of this study are not approved for use in babies weighing 80%) were similar. The median (IQR) age in controls 10.5 (7, 38) days was similar to that in the intervention group 11 (7, 61) days; the range of age of participants was between 1 and 477 days (approximately 15 months). The median (IQR) weights 3.2 (2.9, 3.9) and 3.7 (3.1, 5.6) kg were similar between control and intervention. Availability of primary outcome The primary outcome was available on all 62 control patients but only 21 of the 35 intervention patients. This was due to a range of reasons including difficulties in obtaining the information needed to compute the UF rate (accurate timing and weighing data) and technical difficulties using the NIDUS: full details are in the report. Precision of UF Analysis comparing the 62 control patients with the 21 intervention patients with a primary outcome showed that UF with the NIDUS was closer to that prescribed than with control: standard deviations (SDs) controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. For the NIDUS and CVVH devices, an important measure was to compare the difference between the actual fluid removal measured and that reported by the device. This had a mean closer to zero for the NIDUS than CVVH (means −0.44 vs. 11.6 ml/hour, respectively), with less variation in NIDUS than CVVH (SDs 3.2 vs. 28.4 ml/hour). Biochemical clearances The initial intention was to compare clearance rate on NIDUS with the control group. However, for these variables combining PD and CVVH in this way proved to be misleading because NIDUS clearances rates were intermediate between those of PD and CVVH. The clearance for creatinine on PD was smaller and less variable (mean 0.08, SD 0.03 ml/min/kg) than on the NIDUS (mean 0.46, SD 0.30 ml/min/kg), which was in turn smaller and less variable than for CVVH (mean 1.20, SD 0.72 ml/min/kg). The pattern was repeated for urea: PD (0.12, 0.06), NIDUS (0.48, 0.30) and CVVH (1.15, 0.67), all in ml/min/kg, and also for phosphate: PD (0.07, 0.04), NIDUS (0.44, 0.27) and CVVH (1.16, 0.71), all in ml/min/kg. All pairwise treatment comparisons of means and of SDs gave p

Patients with facial trauma may suffer from injuries such as broken bones, bleeding, swelling, bruising, lacerations, burns, and deformity in the face. Common causes of facial-bone fractures are the results of road accidents, violence, and sports injuries. Surgery is needed if the trauma patient would be deprived of normal functioning or subject to facial deformity based on findings from radiology. Although the image reading by radiologists is useful for evaluating suspected facial fractures, there are certain challenges in human-based diagnostics. Artificial intelligence (AI) is making a quantum leap in radiology, producing significant improvements of reports and workflows. Here, an updated literature review is presented on the impact of AI in facial trauma with a special reference to fracture detection in radiology. The purpose is to gain insights into the current development and demand for future research in facial trauma. This review also discusses limitations to be overcome and current important issues for investigation in order to make AI applications to the trauma more effective and realistic in practical settings. The publications selected for review were based on their clinical significance, journal metrics, and journal indexing.

We describe the formulation of a simple method of water source tracing for computational models of flood inundation and demonstrate its implementation within CAESAR-Lisflood. Water source tracing can provide additional insight into flood dynamics by accounting for flow pathways of each model boundary condition. The method developed is independent of the hydraulic formulation used, allowing it to be implemented in other model codes without affecting flow routing. In addition, we developed a method which allows up to three water sources to be visualised in the RGB colour space, while continuing to allow depth to be resolved. The number of water sources that may be traced is limited only by the computational resources. We show the application of the methods developed for example applications of a major flood event, a shallow estuary, and Amazonian wetland inundation. A key advantage is that the method is independent of the hydraulic formulation, meaning that it is relatively straightforward to add to existing finite-volume codes, including those based on or developed around the LISFLOOD-FP method. This method enables water tracing with a minimal computational overhead, allowing users of the LISFLOOD-FP method to address environmental issues relating to water sources and mixing, such as water quality and contamination problems.

Individuals with PhDs and postdoctoral experience in the life sciences can pursue a variety of career paths. Many PhD students and postdocs aspire to a permanent research position at a university or research institute, but competition for such positions has increased. Here, we report a time-resolved analysis of the career paths of 2284 researchers who completed a PhD or a postdoc at the European Molecular Biology Laboratory (EMBL) between 1997 and 2020. The most prevalent career outcome was Academia: Principal Investigator (636/2284=27.8% of alumni), followed by Academia: Other (16.8%), Science-related Non-research (15.3%), Industry Research (14.5%), Academia: Postdoc (10.7%) and Non-science-related (4%); we were unable to determine the career path of the remaining 10.9% of alumni. While positions in Academia (Principal Investigator, Postdoc and Other) remained the most common destination for more recent alumni, entry into Science-related Non-research, Industry Research and Non-science-related positions has increased over time, and entry into Academia: Principal Investigator positions has decreased. Our analysis also reveals information on a number of factors – including publication records – that correlate with the career paths followed by researchers.

Objectives To understand associations between the subjective experience of cognitive decline and objective cognition. This subjective experience is often conceptualised as an early step towards neurodegeneration, but this has not been scrutinised at the population level. An alternative explanation is poor meta-cognition, the extreme of which is seen in functional cognitive disorder (FCD).Design Prospective cohort (Caerphilly Prospective Study).Setting Population-based, South Wales, UK.Participants This men-only study began in 1979; 1225 men participated at an average age of 73 in 2002–2004, including assessments of simple subjective cognitive decline (sSCD, defined as a subjective report of worsening memory or concentration). Dementia outcomes were followed up to 2012–2014. Data on non-completers was additionally obtained from death certificates and local health records.Primary and secondary outcome measures The primary outcome measure was incident dementia over 10 years. Secondary outcome measures included prospective change in objective cognition and cross-sectional cognitive internal inconsistency (the existence of a cognitive ability at some times, and its absence at other times, with no intervening explanatory factors except for focus of attention).Results sSCD was common (30%) and only weakly associated with prior objective cognitive decline (sensitivity 36% (95% CI 30 to 42) and specificity 72% (95% CI 68 to 75)). Independent predictors of sSCD were older age, poor sleep quality and higher trait anxiety. Those with sSCD did not have excess cognitive internal inconsistency, but results suggested a mild attentional deficit. sSCD did not predict objective cognitive change (linear regression coefficient −0.01 (95% CI −0.13 to 0.15)) nor dementia (odds ratio 1.35 (0.61 to 2.99)) 10 years later.Conclusions sSCD is weakly associated with prior objective cognitive decline and does not predict future cognition. Prior sleep difficulties and anxiety were the most robust predictors of sSCD. sSCD in the absence of objective decline appears to be a highly prevalent example of poor meta-cognition (ie, poor self-awareness of cognitive performance), which could be a driver for later FCD.

Abstract: Cool- and warm-season precipitation totals have been reconstructed on a gridded basis for North America using 439 tree-ring chronologies correlated with December–April totals and 547 different chronologies correlated with May–July totals. These discrete seasonal chronologies are not significantly correlated with the alternate season; the December–April reconstructions are skillful over most of the southern and western United States and north-central Mexico, and the May–July estimates have skill over most of the United States, southwestern Canada, and northeastern Mexico. Both the strong continent-wide El Niño–Southern Oscillation (ENSO) signal embedded in the cool-season reconstructions and the Arctic Oscillation signal registered by the warm-season estimates faithfully reproduce the sign, intensity, and spatial patterns of these ocean–atmospheric influences on North American precipitation as recorded with instrumental data. The reconstructions are included in the North American Seasonal Precipitation Atlas (NASPA) and provide insight into decadal droughts and pluvials. They indicate that the sixteenth-century megadrought, the most severe and sustained North American drought of the past 500 years, was the combined result of three distinct seasonal droughts, each bearing unique spatial patterns potentially associated with seasonal forcing from ENSO, the Arctic Oscillation, and the Atlantic multidecadal oscillation. Significant 200–500-yr-long trends toward increased precipitation have been detected in the cool- and warm-season reconstructions for eastern North America. These seasonal precipitation changes appear to be part of the positive moisture trend measured in other paleoclimate proxies for the eastern area that began as a result of natural forcing before the industrial revolution and may have recently been enhanced by anthropogenic climate change.

Abstract Extreme summer temperatures are increasingly common across the Northern Hemisphere and inflict severe socioeconomic and biological consequences. In summer 2021, the Pacific Northwest region of North America (PNW) experienced a 2-week-long extreme heatwave, which contributed to record-breaking summer temperatures. Here, we use tree-ring records to show that summer temperatures in 2021, as well as the rate of summertime warming during the last several decades, are unprecedented within the context of the last millennium for the PNW. In the absence of committed efforts to curtail anthropogenic emissions below intermediate levels (SSP2–4.5), climate model projections indicate a rapidly increasing risk of the PNW regularly experiencing 2021-like extreme summer temperatures, with a 50% chance of yearly occurrence by 2050. The 2021 summer temperatures experienced across the PNW provide a benchmark and impetus for communities in historically temperate climates to account for extreme heat-related impacts in climate change adaptation strategies.

In Canada, there have been calls for increased research into and surveillance of wildlife trade and associated zoonotic disease risks. We provide the first comprehensive analysis of Canadian live wildlife imports over a 7-year period (2014–2020), based on data from federal government databases obtained via Access to Information requests. A total of 1 820 313 individual animals (including wild-caught and captive-bred animals but excluding fish, invertebrates, Columbiformes (pigeons), and Galliformes (game birds)), from 1028 documented import records, were imported into Canada during 2014–2020. Birds were the most imported taxonomic class (51%), followed by reptiles (28%), amphibians (19%), and mammals (2%). In total, 22 taxonomic orders from 79 countries were recorded as imported. Approximately half of the animals (49%) were imported for the exotic pet market. Based on existing literature and a review of the Canadian regulatory apparatus, we gesture to these importations' potential implications for zoonotic disease risk and discuss potential biosecurity challenges at the Canadian border. Finally, we identify data gaps that prevent an extensive assessment of the zoonotic disease risk of live wildlife imports. We recommend data collection for all wildlife importation and improved coordination between agencies to accurately assess zoonotic disease risk.

Ball pythons are traded as bushmeat, leather and belief-based medicine in West Africa, and specimens are exported in large numbers for the exotic pet trade. Here, we focused on understanding the purpose and socio-economic context of this trade in Benin through interviews with 44 actors involved in the trade of this species. We provided a snapshot of trade dynamics during a period when hunters are not predominantly actively involved in supplying eggs, neonates and gravid females for ranching and export as exotic pets. Our findings revealed that hunters and traders were largely focused on supplying the bushmeat and medicine markets in West Africa during this time. We estimated that the 21 collectors engaged in hunting in our study collectively hunt between 576 and 5,083 ball pythons from the wild each year. Collection rates reported by some suggests that they could earn more than 15,000 USD from ball python sales in bushmeat markets annually. Ball pythons hunted in Benin were mainly sold to local customers as “bushmeat” (53%) or for belief-based uses (39%) (including “fetish”, “medicinal products” and “voodoo”). However, cross-border trade with neighboring countries of Togo, Nigeria, and Ghana (or even further) also occurred. Although profitable for some, the scale of this practice, together with the widely reported decline in ball python populations in Benin, raises concern about the sustainability and long-term economic viability of this type of large-scale commercial wildlife trade in West Africa, especially as it occurs alongside extensive ranching practices to support the exotic pet trade.

IntroductionMillions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson’s disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson’s disease revealed that the timing of L-DOPA relative to sleep affects dopamine’s impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep.MethodsWe conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65–79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning.ResultsThe single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1–4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects.DiscussionOur results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications.Clinical trial registrationEudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.

Abstract Background Apolipoprotein E epsilon 4 (APOE-ε4) carrier status is an established risk factor for Alzheimer’s disease (AD) dementia. It has also been linked with sleep disturbance in healthy older adults and increased insomnia risk. This association may be driven by the effect of APOE-ε4 on AD pathological change, itself associated with sleep abnormalities. To assess this relationship, we have evaluated post-mortem neuropathological findings in patients with and without cognitive impairment and AD pathology, who had extensive clinical assessment within 12 months of death. Methods This retrospective cohort study used UK Brain Banks Network data. Eligible subjects were aged over 50, with pre-mortem neuropsychiatry inventory scores of sleep disturbance (NPI-K), neurocognitive testing and functional cognitive status assessment (Clinical Dementia Rating scale). Neuropathological data included Thal phase, Braak stage and CERAD scores (measures of Aβ plaque distribution, tangle distribution and neuritic plaque density, respectively) combined to form the National Institute on Aging Alzheimer’s Association (NIA-AA) ABC score reflecting AD neuropathology. Participants with other significant intracerebral pathology or pathological features of non-AD dementia were excluded. Multivariate linear regression was performed with NPIK Global Score (NPIK frequency score multiplied by severity score) as the dependent variable and APOE-ε4 heterozygosity or homozygosity as independent variables. Covariates included age, gender, APOE-ε2 status and ABC NPI measures reflecting depression and anxiety. Further models stratified by ABC score and functional cognitive status were also produced. Results Seven hundred twenty-eight records were identified. Two hundred two participants were included in the final analysis: mean (SD) age 84.0 (9.2) and MMSE 14.0 (11.8). Mean sleep disturbance scores were highest in ε4 homozygosity (n=11), 4.55 (5.4); intermediate in ε4 heterozygosity (n=95), 2.03 (4.0); and lowest in non-ε4 carriers (n=96), 1.36 (3.3). Within the full sample, controlling for pathological status, age, gender, depression, anxiety and CDR-SOB status, APOE-ε4 homozygosity was associated with sleep disturbance (β 2.53, p=0.034). APOE-ε4 heterozygosity was similarly associated in individuals without dementia (β 1.21, p=0.048). Conclusion These findings lend weight to the hypothesis that APOE-ε4 affects sleep by mechanisms independent of AD pathological change. Evaluation of those mechanisms would enhance understanding of sleep disturbance pathways and potentially provide treatment targets.

Methods: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. Results: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. Discussion: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slowwave sleep and long-term memory may have clinical implications. [ABSTRACT FROM AUTHOR]