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CRISPR–Cas9 potential for identifying novel therapeutic targets in muscle-invasive bladder cancer
Get PDFGene editing technologies help identify the genetic perturbations driving tumour initiation, growth, metastasis and resistance to therapeutics. This wealth of information highlights tumour complexity and is driving cancer research towards precision medicine approaches based on an individual's tumour genetics. Bladder cancer is the 11th most common cancer in the UK, with high rates of relapse and low survival rates in patients with muscle-invasive bladder cancer (MIBC). MIBC is highly heterogeneous and encompasses multiple molecular subtypes, each with different responses to therapeutics. This evidence highlights the need to identify innovative therapeutic targets to address the challenges posed by this heterogeneity. CRISPR-Cas9 technologies have been used to advance our understanding of MIBC and determine novel drug targets through the identification of drug resistance mechanisms, targetable cell-cycle regulators, and novel tumour suppressor and oncogenes. However, the use of these technologies in the clinic remains a substantial challenge and will require careful consideration of dosage, safety and ethics. CRISPR-Cas9 offers considerable potential for revolutionizing bladder cancer therapies, but substantial research is required for validation before these technologies can be used in the clinical setting. [Abstract copyright: © 2024. Springer Nature Limited.
Intraspecific functional traits and stable isotope signatures of ground-dwelling ants across an elevational gradient
Get PDFImmune effects of α and β radionuclides in metastatic prostate cancer
Get PDFExternal beam radiotherapy is used for radical treatment of organ-confined prostate cancer and to treat lesions in metastatic disease whereas molecular radiotherapy with labelled prostate-specific membrane antigen ligands and radium-223 ( Ra) is indicated for metastatic prostate cancer and has demonstrated substantial improvements in symptom control and overall survival compared with standard-of-care treatment. Prostate cancer is considered an immunologically cold tumour, so limited studies investigating the treatment-induced effects on the immune response have been completed. However, emerging data support the idea that radiotherapy induces an immune response in prostate cancer, but whether the response is an antitumour or pro-tumour response is dependent on the radiotherapy regime and is also cell-line dependent. In vitro data demonstrate that single-dose radiotherapy regimes induce a greater immune-suppressive profile than fractionated regimes; less is known about the immune response induced by molecular radiotherapy agents, but evidence suggests that these agents might induce an immune-suppressive systemic immune response, indicated by increased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could be associated with clinical response. Different radiotherapy modalities can induce distinct immune profiles, which can either activate or suppress immune-mediated tumour killing and the current preclinical models used for prostate cancer research are not yet optimal for studying the complexity of the radiotherapy-induced immune response. [Abstract copyright: © 2024. Springer Nature Limited.
Widespread societal and ecological impacts from projected Tibetan Plateau lake expansion
No full textLakes on the Tibetan Plateau are expanding rapidly in response to climate change. The potential impact on the local environment if lake expansion continues remains uncertain. Here we integrate field surveys, remote sensing observations and numerical modelling to assess future changes in lake surface area, water level and water volume. We also assess the ensuing risks to critical infrastructure, human settlements and key ecosystem components. Our results suggest that by 2100, even under a low-emissions scenario, the surface area of endorheic lakes on the Tibetan Plateau will increase by over 50% (~20,000 km2) and water levels will rise by around 10 m relative to 2020. This expansion represents approximately a fourfold increase in water storage compared with the period from the 1970s to 2020. A shift from lake shrinkage to expansion was projected in the southern plateau around 2021. The expansion is primarily fuelled by amplified lake water inputs from increased precipitation and glacier meltwater, profoundly reshaping the hydrological connectivity of the lake basins. In the absence of hazard mitigation measures, lake expansion is projected to submerge critical human infrastructure, including more than 1,000 km of roads, approximately 500 settlements and around 10,000 km2 of ecological components such as grasslands, wetlands and croplands. Our study highlights the urgent need for water hazard mitigation and management across the Tibetan Plateau
The effects of the EBA's stress testing framework on banks' lending
Get PDFThis paper investigates the impact of the European Banking Authority (EBA)'s supervisory stress tests on bank lending. Using a sample of 282 European banks over the period 2006–2018, we find that stress-tested banks experience higher credit risk and reduce lending for specific loan types. In particular, due to country heterogeneities, we find that the contraction in lending is more pronounced for stress-tested banks in the GIIPS region. Our results also suggest that the elevated credit risk of highly-exposed stress-tested banks can be a driving factor of a reduction in bank lending. Consequently, prudential measures requiring banks to hold higher capital buffers are justified to contain credit risk shocks
Effects of Home-Based EEG Neurofeedback Training as a Non-Pharmacological Intervention for Parkinson’s Disease
Get PDFObjectives. Aberrant movement-related cortical activity has been linked to impaired motor function in Parkinson’s disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. Effective non-pharmacological treatments could help reduce reliance on drugs. This experiment reports the first study of home-based electroencephalographic (EEG) neurofeedback training as a non-pharmacological candidate treatment for PD. Our primary aim was to test the feasibility of our EEG neurofeedback intervention in a home setting.Methods. Sixteen people with PD received six home visits comprising symptomology self-reports, a standardised motor assessment, and a precision handgrip force production task while EEG was recorded (visits 1, 2 and 6); and 3 × 1-hr EEG neurofeedback training sessions to supress the EEG mu rhythm before initiating handgrip movements (visits 3 to 5). Results. Participants successfully learned to self-regulate mu activity, and this appeared to expedite the initiation of precision movements (i.e., time to reach target handgrip force off-medication pre-intervention = 628ms, off-medication post-intervention = 564ms). There was no evidence of wider symptomology reduction (e.g., Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III Motor Examination, off-medication pre-intervention = 29.00, off-medication post intervention = 30.07). Interviews indicated that the intervention was well-received. Conclusion. Based on the significant effect of neurofeedback on movement-related cortical activity, positive qualitative reports from participants, and a suggestive benefit to movement initiation, we conclude that home-based neurofeedback for people with PD is a feasible and promising non-pharmacological treatment that warrants further research.<br/
Fine sediment in mixed sand-silt environments impact bedform geometry by altering sediment mobility
Get PDFGeometric characteristics of subaqueous bedforms, such as height, length and leeside angle, are crucial for determining hydraulic form roughness and interpreting sedimentary records. Traditionally, bedform existence and geometry predictors are primarily based on uniform, cohesionless sediments. However, mixtures of sand, silt and clay are common in deltaic, estuarine, and lowland river environments, where bedforms are ubiquitous. Therefore, we investigate the impact of fine sand and silt in sand-silt mixtures on bedform geometry, based on laboratory experiments conducted in a recirculating flume.We systematically varied the fraction of sand and silt for different discharges, and utlized an acoustic Doppler velocimeter to measure flow velocity profiles. The final bed geometry was captured using a line laser scanner. Our findings reveal that the response of bedforms to an altered fine sediment percentage is ambiguous, and likely depends on, among others, bimodality-driven bed mobility and sediment cohesiveness. When fine, non-cohesive material (fine sand or coarse silt) is mixed with the base material (medium sand), an increased dune height and length is observed, possibly caused by the hiding exposure effect, resulting in enhanced mobility of the coarser material. However, weakly cohesive fine silt suppresses dune height and length, possibly caused by reduced sedimentmobility. Finally, in the transition from dunes to upper stage plane bed, there are indications that the bed becomes unstable and dune heights vary over time. The composition of the bed material does not significantly impact the hydraulic roughness, but mainly affects roughness via the bed morphology, especially the leeside angle
SuperNANO: Enabling Nanoscale Laser Anti-Counterfeiting Marking and Precision Cutting with Super-Resolution Imaging
Get PDFIn this paper, we present a unique multi-functional super-resolution instrument, the Super- NANO system, which integrates real-time super-resolution imaging with direct laser nanofabrication capabilities. Central to the functionality of the SuperNANO system is its capacity for simultaneous nanoimaging and nanopatterning, enabling the creation of anti-counterfeiting markings and precision cutting with exceptional accuracy. The SuperNANO system, featuring a unibody superlens objective, achieves a resolution ranging from 50 to 320 nm. We showcase the instrument’s versatility through its application in generating high-security anti-counterfeiting features on an aluminum film. These ‘invisible’ security features, which are nanoscale in dimension, can be crafted with arbitrary shapes at designated locations. Moreover, the system’s precision is further evidenced by its ability to cut silver nanowires to a minimum width of 50 nm. The integrated imaging and fabricating functions of the SuperNANO make it a pivotal tool for a variety of applications, including nanotrapping, sensing, cutting, welding, drilling, signal enhancement, detection, and nanoscale laser treatment.<br/
Recent Developments about Lay Judges in the European Union
Get PDFLay participation adds to the quality of the administration of justice. Few people, though, have an idea about the extent to which EU member states draw on lay judges. This article for the first time provides an overview on lay participation in civil and criminal justice in EU countries. Of the EU member states, the majority has some form of lay participation in criminal courts, mostly mixed courts (18 countries), in which lay and professional judges deliberate on cases together. Also in civil courts, a majority employ lay decision-makers, where 16 states have mixed courts. Juries, single lay judges, or panels exclusively consisting of lay people have become rare. Only four EU countries – Latvia, Lithuania, Romania, and The Netherlands – have no lay participation in criminal and civil trials. In some countries, lay participation is widespread, including for example, Austria, Finland, France, Germany, and Sweden. The article also identifies factors influencing the extent of lay participation in the courts. In conclusion: Lay judges are part of European legal culture
Methodological approaches to measuring mental health in a cost-of-living crisis: A rapid review
Get PDFBackgroundCost-of-living crises are damaging to population mental health and require a public health response. It is important to assess whether public health interventions are effective. We aimed to identify population-level methods and measures and the appropriateness of the measures for vulnerable populations.MethodsA rapid evidence review was undertaken. Nineteen databases, including grey literature, were searched for evidence published between 1970 and April 2023.ResultsSeven reviews, nine primary studies and two reports from grey literature were identified. Methods consisted of analyses of existing data from national or regional cohort studies, household panel surveys, repeated cross-sectional surveys, routine medical data, or data on suicide death rates. Twelve brief validated mental health measurement tools, embedded in population-level surveys, were identified. Two quasi-experimental studies used data from a UK household panel survey to examine the impact of the introduction of specific welfare policies on mental health. Studies identified socio-economic vulnerabilities, but it was not possible to determine whether data were effectively captured from people from minority ethnic groups.ConclusionPopulation-level surveys can be used in quasi-experimental studies to measure the effects of a public health initiative with specific roll out dates to tackle cost-of-living impacts. It is unclear as to whether the identified methods and tools are suitable for use with people from minority ethnic groups.<br/