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Adaptive fluorescence lifetime imaging with per-pixel signal optimization and flexible scanning
Get PDFAdvances in time-resolved fluorescence lifetime imaging microscopy (FLIM) havesignificantly enhanced biological imaging compared to steady-state techniques alone. The primary goal of modern FLIM is to acquire high-resolution fluorescence lifetime profiles with a high signal-to-noise ratio (SNR) from heterogeneous samples at high speeds, posing challenges in balancing imaging speed, signal strength, and sample integrity. In this study, we present Fluorescence Lifetime Intensity-Inverted Imaging Microscopy (FLI3M), an daptive imaging technique based on confocal laser scanning microscopy (CLSM) that dynamically adjusts pixel dwell times using a priori intensity information from a pre-scan and supports flexible scanning patterns. This approach achieves uniform SNR imaging by either providing up to an eightfold signal enhancement without increasing imaging time, or reducing imaging time without compromising SNR. We demonstrate the potential of this technique through imaging studies of biological samples, including Convallaria majalis and human lung tissue. The results show a 56% average improvement in fluorescence lifetime estimation reliability in low-SNR regions and an increase in imaging speed ranging from 27% to 53% across various samples. This enablesdetailed resolution of optical fingerprints in complex biological environments that are challenging for conventional imaging. Collectively, these results establish our adaptive FLIM system as a powerful tool for high-performance cellular imaging, FLIM-guided diagnostics, and a wide range of biomedical applications
Coupled, decoupled, and abrupt responses of vegetation to climate across timescales
Get PDFClimate and ecosystem dynamics vary across timescales, but research into climate-driven vegetation dynamics usually focuses on singular timescales. We developed a spectral analysis–based approach that provides detailed estimates of the timescales at which vegetation tracks climate change, from 101 to 105 years. We report dynamic similarity of vegetation and climate even at centennial frequencies (149−1 to 18,012−1 year−1, that is, one cycle per 149 to 18,012 years). A breakpoint in vegetation turnover (797−1 year−1) matches a breakpoint between stochastic and autocorrelated climate processes, suggesting that ecological dynamics are governed by climate across these frequencies. Heightened vegetation turnover at millennial frequencies (4650−1 year−1) highlights the risk of abrupt responses to climate change, whereas vegetation-climate decoupling at frequencies >149−1 year−1 may indicate long-lasting consequences of anthropogenic climate change for ecosystem function and biodiversity
Neuroimmunology beyond the CNS: Nerve-macrophage interactions in peripheral tissues
Get PDFMacrophages are now recognised to be highly heterogeneous, with diverse ontogenies, anatomical locations and characteristics, all of which inform their function. Nerve-associated macrophage subpopulations have been found to exist across tissues, and whilst they appear to have roles in neuronal maintenance and repair, their function is still being elucidated. Although nerve-associated macrophage functions in the Central Nervous System have taken centre-stage, nerve-associated macrophages also interact with peripheral nerves and this field remains relatively understudied. This review discusses recent studies into nerve-associated macrophages across peripheral tissues. These studies identify populations of nerve-associated macrophages in many peripheral tissues, and reveal elegant neuroimmune communication pathways which coordinate functions from infection defence and anti-inflammatory actions to neuronal maintenance for homeostatic tissue function and nerve repair. We highlight nerve-associated macrophage interactions with nerves in peripheral tissues as a rapidly evolving field which could revolutionise our understanding of macrophage function in both homeostasis and disease
Barriers to acceptance of vasectomy among married males in India:A systematic review
Get PDFVasectomy was introduced under the National Family Planning Programme in 1954 to enhance male participation in family planning in India. Despite adopting the non-scalpel technique in 1992 to popularise vasectomy, its acceptance among married couples has declined from 3.31% to 0.3% over the past 3 decades. This study aims to identify the barriers among the married male population in India for adopting vasectomy as a method of family planning. This systematic review was conducted following PRISMA guidelines after PROSPERO registration (CRD42023434518). Six electronic databases (MEDLINE, Embase, Global Health, Allied and Complementary Medicine, APA PsycInfo, and CAB Abstracts Archive) were searched using terms including "vasectomy", "barriers", and "India" for studies reporting the barriers to accepting vasectomy as a family planning method. Qualitative, quantitative, and mixed-method studies on Indian male populations, reported in English and published up to May 2023, were included. Quality assessments were conducted using the JBI Critical Appraisal Tools. Extracted data were analysed using a thematic synthesis. Twenty-four studies conducted across India were included in the systematic review (18 cross-sectional, 2 interview-based, 2 mixed-method, 1 case-control and 1 focus group discussion-based). Five themes of barriers were identified: fear, social issues, cultural issues, knowledge, and health system issues. Men feared undergoing a surgical procedure for sterilisation. They presumed the procedure would lead to loss of libido, physical weakness leading to income loss, and social stigma from community members. Health education and financial incentives are likely to increase vasectomy acceptance in India.</p
Dementia education and training for in-patient health care support workers in acute care contexts:A mixed-methods pilot evaluation
Get PDFAim: To understand dementia care knowledge, attitudes, and confidence among acute-care support staff following a dementia education intervention titled Dementia Workforce Excellence in Acute Care. Design: A convergent parallel mixed-methods pilot study. Methods: Data were collected from 30 participants using an online survey and three individual interviews between January and March 2024. Survey data were analysed using descriptive statistics, and a thematic analysis underpinned by Kirkpatrick’s framework was used to analyse the qualitative data from interviews. Results: The online survey established good levels of dementia knowledge, attitudes, and confidence among support staff with enhanced attitudes among staff who completed the training. Analysis of interviews resulted in three themes: dementia in the acute care setting; motivation for learning; and evaluation of the intervention on four levels [satisfaction, learning gains, behaviours, and results]. Conclusion: Findings suggest that the dementia education intervention used in this study is a comprehensive dementia training resource that promotes person-centred and compassionate dementia care across all stages of the dementia journey. Dementia is a public health priority with workforce education identified as a key response for capacity building. This pilot evaluation offers insight and new learning on the pedagogical approaches that are inclusive of peer-supported reflective learning in small groups that remain untapped for dementia workforce development. Dementia inclusive and enabling environments with a knowledgeable and skilled workforce are crucial to mitigate stigma and discrimination. This can be best achieved by raising awareness through targeted staff education and training to make hospital environments more dementia inclusive. Patient or Public Contributions: Dementia care scenarios used in this study were co-designed by experts with lived experience of dementia. Additionally, these experts along with family carers of people living with dementia were involved in the delivery of the training where appropriate.</p
Deep learning can be used to classify the disease status of the canine middle ear from computed tomographic images.
Get PDFMiddle ear disease occurs frequently in dogs. CT has proven to be an excellent diagnostic tool for detecting middle ear structures, helping to achieve rapid and accurate diagnoses. Deep learning techniques are now widely used in CT scan-based human medical image analysis, providing decision support and diagnostics. However, such techniques are currently underutilized in veterinary radiology. The focus of this study was to develop a deep learning model capable of diagnosing middle ear disease in dogs using CT images. To achieve this with a relatively small dataset, transfer learning and data augmentation techniques were applied. During the experimental phase of the study, we tested 10 binary classification models based on the ResNet architecture, combined with data augmentation and transfer learning, on a dataset consisting of a total of 535 canine CT images. We achieved a classification accuracy of up to 84.7%. The developed classifier, trained on relatively few CT images, can detect normal middle ears and middle ear disease in dogs with over 80% accuracy.</p
Computed tomographic and clinical findings in domestic rabbits (Oryctolagus cuniculus domesticus) with pulmonary emphysema
Get PDFPulmonary emphysema (PE) is a poorly understood condition in rabbits. This retrospective case-control study investigated the CT and clinical findings of rabbits with PE. Institutional archive review identified 724 thoracic CT studies of 529 rabbits, including 76 PE-positive studies of 59/529 rabbits. Twenty-five PE-negative cases were selected randomly as a control group. The mean age of affected rabbits was 9 years (range 5-13 years). Cranial lung lobes were more commonly affected (p < .01). The X-ray attenuation in Hounsfield units (HU) of the emphysematous lung areas (median -905 HU) was significantly lower than in nonemphysematous lung lobes of the case (median -667 HU) and control group (median -652 HU). There was significantly lower X-ray attenuation in peripheral and bullous emphysema than in diffuse emphysema. There was no statistical correlation between clinical lower respiratory signs and PE presence. However, the small portion (n = 6, 10.2%) of affected rabbits with severe respiratory signs, such as open-mouth breathing and cyanotic mucous membranes, all had advanced PE and poor outcome. Secondary changes attributable to PE included pathologic rib fractures in 3 (5.1%) and bulla rupture leading to pneumothorax in 2 (3.4%) rabbits. Of the 15 rabbits with repeat examinations, PE was progressive in 12 (80%) and static in 3 (20%). PE is a common condition in rabbits that is readily detectable with CT. The progressive nature of PE should be considered when detected in asymptomatic rabbits. In rabbits with severe lower respiratory signs, PE should be considered as a potential cause.</p
ARTIC RSV amplicon sequencing reveals global RSV genotype dynamics: [version 1; peer review: awaiting peer review]
Get PDFBackgroundRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LTRIs) in young children and adults over 65, contributing significantly to global healthcare burdens. With the recent approval of multiple pharmacological interventions for RSV, there is an increased demand for efficient, high-throughput sequencing methods to monitor RSV genetic diversity and any potential impact these interventions may have.MethodTo address this, we introduce two novel amplicon-based sequencing schemes designed for RSV A and B, optimised for integration with widespread existing ARTIC sequencing workflows. To examine their effectiveness at sequencing RSV samples from across the globe, eight external laboratories used these primers in their sequencing workflows, using both Illumina and Nanopore sequencing technologies.ResultsWe demonstrate that these primer schemes can produce high quality genomes from a diverse range of RSV samples, with eight laboratories in five countries generating complete genomes on both Nanopore and Illumina sequencing platforms. The ability to effectively multiplex these RSV A and B primer schemes, enables streamlined, high-throughput sequencing without prior subtyping. Furthermore, these results provide a snapshot of the circulating diversity of RSV. Phylogenetic analysis of the 882 samples sequenced for this study suggests only minimal geographic clustering of RSV sequences, underscoring the global nature of RSV spread. It also highlights the distinct lineage dynamics seen between RSV A and B.ConclusionsThis study represents an advancement in RSV genomics, providing robust tools for global sequencing efforts aimed at tracking RSV evolution and assessing the efficacy of new therapeutic interventions both rapidly and at scale
A Lagrangian view of flame-vortex interaction during turbulent side-wall quenching using high-speed OH-LIF and PIV
Get PDFFlame-vortex interactions have been suggested to play an important role in flame-wall interactions (FWI). This study presents an experimental investigation of flame-vortex interactions and their influence on flame quenching. Experiments are conducted in a side-wall quenching (SWQ) burner with V-flame configuration. Simultaneous high-resolution particle image velocimetry and OH laser induced fluorescence are conducted to study the flame-flow-wall dynamics under turbulent FWI conditions. Reynolds decomposition is used to provide a Lagrangian reference frame relative to the ensemble-mean velocity field to visualize the evolution of coherent turbulent vortical structures. These vortical flow structures are correlated with regions of elevated swirling strength in the instantaneous velocity field. Three classifications of flame-vortex interaction are identified. One of these classifications emulates a flame-vortex interaction mechanism recently proposed in the literature. This particular flame-vortex interaction reveals a vortex that emanates from the burnt gas and moves quickly towards the wall. The vortex impacts the wall, where local flame quenching occurs and the flame transitions from a head-on quenching (HOQ) to a SWQ flame topology. After quenching, the vortex remains next to the wall and directly above the flame tip as the flame progresses downstream. Each flame quenching event observed in the data exhibits this flame-vortex interaction. This work evaluates the kinematic attributes of the vortex and reveals the tendency of the vortex to push the flame closer to the wall, where the flame experiences flame quenching. Alongside previous DNS studies, this work shows that flame-vortex interactions are phenomenological features that influence flame quenching, as well as heat and mass transport near the wall
Stopping Versus Continuing Metformin in Patients With Advanced CKD:A Nationwide Scottish Target Trial Emulation Study
Get PDFRATIONALE & OBJECTIVE: Despite a lack of supporting evidence, current guidance recommends against the use of metformin in people with advanced kidney impairment. This observational study compared the outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR]<30mL/min/1.73m 2). STUDY DESIGN: Nationwide observational cohort study.SETTING & PARTICIPANTS: All adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019.EXPOSURE: Stopping versus continuing metformin within 6 months following incident stage 4 CKD.OUTCOME: Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE).ANALYTICAL APPROACH: Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.RESULTS: In a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before April 30, 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within 6 months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]), and the incidence of MACE was similar between both strategies (HR, 1.05 [95% CI, 0.88-1.26]). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR, 1.34 [95% CI, 1.08-1.67]; MACE: HR, 1.04 [95% CI, 0.81-1.33]).LIMITATIONS: Residual confounding.CONCLUSIONS: The continued use of metformin may be appropriate when eGFR falls below 30mL/min/1.73m 2. Randomized controlled trials are needed to confirm these findings. PLAIN-LANGUAGE SUMMARY: Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of evidence. It is therefore currently unclear how the decision to stop versus continue metformin in patients who reach stage 4 CKD impacts their risk of mortality and cardiovascular events. This study showed that stopping metformin after reaching stage 4 CKD was associated with reduced survival that did not appear to be mediated by an increase in adverse cardiovascular outcomes. These findings may support the continued use of metformin in patients with advanced kidney impairment, but further research is needed to confirm these observations.</p
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