The genetics of neurodegenerative diseases is the genetics of age-related damage clearance failure.

In this perspective we draw together the data from the genome wide association studies for Alzheimer's disease, Parkinson's disease and the tauopathies and reach the conclusion that in each case, most of the risk loci are involved in the clearance of the deposited proteins: in Alzheimer's disease, the microglial removal of Aβ, in the synucleinopathies, the lysosomal clearance of synuclein and in the tauopathies, the removal of tau protein by the ubiquitin proteasome. We make the point that most loci identified through genome wide association studies are not strictly pathogenic but rather relate to failures to remove age related damage. We discuss these issues in the context of copathologies in elderly individuals and the prediction of disease through polygenic risk score analysis at different ages.

Neural signatures of risk-taking adaptions across health, bipolar disorder, and lithium treatment.

Cognitive and neural mechanisms underlying bipolar disorder (BD) and its treatment are still poorly understood. Here we examined the role of adaptations in risk-taking using a reward-guided decision-making task. We recruited volunteers with high (n = 40) scores on the Mood Disorder Questionnaire, MDQ, suspected of high risk for bipolar disorder and those with low-risk scores (n = 37).

Progress in personalized immunotherapy for patients with brain metastasis.

Brain metastasis leads to poor outcomes and CNS injury, significantly reducing quality of life and survival rates. Advances in understanding the tumor immune microenvironment have revealed the promise of immunotherapies, which, alongside surgery, chemotherapy, and radiation, offer improved survival for some patients. However, resistance to immunotherapy remains a critical challenge.

Examining the physical and psychological effects of combining multimodal feedback with continuous control in prosthetic hands.

Myoelectric prosthetic hands are typically controlled to move between discrete positions and do not provide sensory feedback to the user. In this work, we present and evaluate a closed-loop, continuous myoelectric prosthetic hand controller, that can continuously control the position of multiple degrees of freedom of a prosthesis while rendering proprioceptive feedback to the user via a haptic feedback armband. Twenty-eight participants without and ten participants with upper limb difference (ULD) were recruited to holistically evaluate the physical and psychological effects of the controller via isolated control and sensory tasks, dexterity assessments, embodiment and task load questionnaires, and post-study interviews.

Emergence of opposing arrows of time in open quantum systems.

Deriving an arrow of time from time-reversal symmetric microscopic dynamics is a fundamental open problem in many areas of physics, ranging from cosmology, to particle physics, to thermodynamics and statistical mechanics. Here we focus on the derivation of the arrow of time in open quantum systems and study precisely how time-reversal symmetry is broken. This derivation involves the Markov approximation applied to a system interacting with an infinite heat bath.

Investigate physiological and psychological responses to environment scenes, elements and components in different urban settings.

Research has proved a close relationship between environments and physiological as well as psychological responses. However, existing research based on neuroscience experiments demonstrated a clear dichotomy between natural and built environments in the selection of exposure settings. There is very limited research analyzing and comparing the effects of different urban environments on individual psychological health.

Convergent evidence for the temperature-dependent emergence of silicification in terrestrial plants.

Research on silicon (Si) biogeochemistry and its beneficial effects for plants has received significant attention over several decades, but the reasons for the emergence of high-Si plants remain unclear. Here, we combine experimentation, field studies and analysis of existing databases to test the role of temperature on the expression and emergence of silicification in terrestrial plants. We first show that Si is beneficial for rice under high temperature (40 °C), but harmful under low temperature (0 °C), whilst a 2 °C increase results in a 37% increase in leaf Si concentrations.

Is there a mental health diagnostic crisis in primary care? Current research practices in global mental health cannot answer that question.

In low- and middle-income countries, fewer than 1 in 10 people with mental health conditions are estimated to be accurately diagnosed in primary care. This is despite more than 90 countries providing mental health training for primary healthcare workers in the past two decades. The lack of accurate diagnoses is a major bottleneck to reducing the global mental health treatment gap.

CODE-ACCORD: A Corpus of building regulatory data for rule generation towards automatic compliance checking.

Automatic Compliance Checking (ACC) within the Architecture, Engineering, and Construction (AEC) sector necessitates automating the interpretation of building regulations to achieve its full potential. Converting textual rules into machine-readable formats is challenging due to the complexities of natural language and the scarcity of resources for advanced Machine Learning (ML). Addressing these challenges, we introduce CODE-ACCORD, a dataset of 862 sentences from the building regulations of England and Finland.

Diffusion-driven transient hydrogenation in metal superhydrides at extreme conditions.

In recent years, metal hydride research has become one of the driving forces of the high-pressure community, as it is believed to hold the key to superconductivity close to ambient temperature. While numerous novel metal hydride compounds have been reported and extensively investigated for their superconducting properties, little attention has been focused on the atomic and electronic states of hydrogen, the main ingredient in these novel compounds. Here, we present combined H- and La-NMR data on lanthanum superhydrides, LaH, (x = 10.

Predicting falls with ultrasound, physical parameters or fall-risk questions among older adults: A prospective cohort study.

Background: Falls are a significant issue among older adults, leading to morbidity and mortality. Screening for fall risk in the ED is crucial but challenging due to time limitations and patient conditions. Sarcopenia, characterized by muscle loss, is associated with increased fall risk, and ultrasound has been proposed as a non-invasive tool to measure muscle mass in this context.

A Systematic Review and Meta-analysis of the Clinical Impact of Prophylactic Quinolones with Adjuvant Bacillus Calmette-Guérin Instillation for Non-muscle-invasive Bladder Cancer.

Background And Objective: Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events.

Cancer evolution: from Darwin to the Extended Evolutionary Synthesis.

The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well as preclinical models, continue to unravel the evolution of premalignant cells, and progression to metastatic stages and to drug-resistant end-stage disease. Here, we summarize recent advances and distil evolutionary principles and their relevance for the clinic.

Advances in systematic conservation planning to meet global biodiversity goals.

Systematic conservation planning (SCP) involves the cost-effective placement and application of management actions to achieve biodiversity conservation objectives. Given the political momentum for greater global nature protection, restoration, and improved management of natural resources articulated in the targets of the Global Biodiversity Framework, assessing the state-of-the-art of SCP is timely. Recent advances in SCP include faster and more exact algorithms and software, inclusion of ecosystem services and multiple facets of biodiversity (e.

Advancing gastrointestinal endoscopy in Sub-Saharan Africa: Leveraging Sudan's example and the potential role of the British Society of Gastroenterology (BSG).

Access to advanced medical procedures, such as gastrointestinal (GI) endoscopy, is critical for effective healthcare. In Sub-Saharan Africa, including Sudan, GI endoscopy services remain limited, posing significant barriers to early diagnosis and treatment of GI diseases. Expanding GI endoscopy services in Sudan and other regions of Sub-Saharan Africa is crucial to improve early detection, reduce mortality, and increase the cost-effectiveness of healthcare delivery.

MemScreen: A smartphone application for detection of mild cognitive impairment: A validation study: Smartphone App for MCI Detection.

Background And Objectives: Primary care is often the first point of contact for patients with cognitive complaints, making initial cognitive screening an essential step to avoid delays in diagnosing Alzheimer's disease (AD) at an early stage. We developed MemScreen, a self-administered smartphone application that assesses overall cognition and verbal memory, and evaluated its ability to detect mild cognitive impairment (MCI) in both general and clinical populations.

Methods: We conducted two validation cohort studies: (1) UK-based Whitehall II cohort study (13th wave, 2018-2022) involving a general population (MCI defined by poor performance on a global cognitive score), and (2) five French memory clinics involving patients without dementia (amnestic MCI defined by the Free and Cued Selective Reminding Test).

Neuropathic corneal pain following refractive surgery: risk factors, clinical manifestations, imaging and proteomic characteristics.

Background/aims: To identify the risk factors for neuropathic corneal pain (NCP) following corneal refractive surgery and to report its clinical manifestations, imaging and proteomic characteristics.

Methods: This 1 year prospective cohort study included 100 eyes that underwent small incision lenticule extraction (SMILE) or laser-assisted in situ keratomileusis (LASIK). Ocular surface assessments, in-vivo confocal microscopy scans, tear neuromediators and proteomics analyses were performed.

Long-term visual outcomes and side effects of ruthenium plaque brachytherapy in 310 eyes with small choroidal melanoma.

Background/aims: To report the long-term visual outcomes and side effects in patients with small choroidal melanoma (CM) undergoing ruthenium-106 (Ru-106) plaque brachytherapy.

Methods: Retrospective, interventional, consecutive series of small CM ≤2.5 mm in height and ≤16 mm in largest basal diameter treated with Ru-106 plaque with a median radiation dose of 100 Gy prescribed to tumour apical height.

Change in subjective well-being and the associated costs of a woman-targeted presbyopia correction programme among older craftswomen in Zanzibar: a cost-outcome and scenario analysis.

Background: A pilot eyecare programme aimed to address the urgent eye health needs of older Zanzibari craftswomen. We investigated the impact of correcting presbyopia on their subjective well-being (SWB) 6 months post-correction and assessed the cost-effectiveness of a women-targeted presbyopia correction programme.

Methods: This study involved Zanzibari craftswomen aged 40 and older with presenting and corrected distance visual acuity better than 6/12 in both eyes and were presbyopic.

Doing 'detective work' to find a cancer: how are non-specific symptom pathways for cancer investigation organised, and what are the implications for safety and quality of care? A multisite qualitative approach.

Background: Over the past two decades, the UK has actively developed policies to enhance early cancer diagnosis, particularly for individuals with non-specific cancer symptoms. Non-specific symptom (NSS) pathways were piloted and then implemented in 2015 to address delays in referral and diagnosis. The aim of this study was to outline the functions that enable NSS teams to investigate cancer and other diagnoses for patients with NSSs.

'What Matters to Staff Programme': eight steps to improve staff well-being at work.

Background And Aim: The What Matters to Staff programme was designed at the Royal Free Hospital to address a key priority of improving workforce well-being. The initial aim was to set up a programme that responded to what mattered to staff and could be spread to 70 teams across the hospital within 2 years.

Methods: The programme was developed by adding a set of simple, yet important steps around the 'what matters to you' conversation from the Joy in Work Framework.