From Domains to Sequences: A Protein-Level Machine-Learning Framework for Predicting Optimum Growth Temperature of Prokaryotes

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Simulation of the impacts of constructed wetlands on river flow using WSIMOD

Increased demands for land use in urban development have reduced the extent of open water bodies in recent decades, leading to more frequent extreme flows in urban rivers. Urban nature-based solutions, such as constructed wetlands, have the potential to provide significant water management benefits if implemented on a large scale, well-maintained, and used sustainably. However, their actual benefits in urban water systems have not been adequately evaluated, and the underlying mechanisms remain underexplored. These limitations hinder the effective planning of the integration methods for constructed wetlands. To assess the water management benefits of constructed wetlands at the catchment scale, this study analyses river flow data collected before and after wetland construction in Enfield, London. The Water Systems Integrated Modelling (WSIMOD) framework is used to simulate the integrated catchment water cycle, and the constructed wetlands module is conceptualised and included in the WSIMOD to evaluate their interactions within the urban catchment water cycle. Scenarios are designed to assess the impacts of varying configurations and sizes of the wetlands on the river flow. The findings indicate that constructed wetlands are observed to attenuate river flow peaks and increase low flows. Constructed wetlands reduce the frequency of river flow peaks at the catchment scale; results show that in the case of Enfield, converting 1% of the catchment area to wetlands can decrease high flows (10% exceedance probability) by 18–23% and increase low flows (90% exceedance probability) by 35–50%, reducing the flashiness of the urban water cycle. Incorporating wetlands arranged in parallel exhibits superior performance in attenuating flow peaks compared to wetlands arranged in series, as the wetlands placed in parallel can provide more space to store rapidly generated runoff. The results quantified the effects of constructed wetlands on high and low flows in the urban water system, using the WSIMOD to provide recommendations on wetland connection modes for decision-making

Building a molecular toolkit for gene editing and transgenesis in the farmed insect black soldier fly

Current agricultural methods are expected to fall short in addressing food security threats, with a pressing need for higher yields and greater resilience to climate variability. A promising solution for sustainable food security is the revalorization of food waste. Insect-based bioremediation is an innovative approach to tackling food waste, with several insect species demonstrating exceptional efficiency in converting low-value waste into valuable resources. The black soldier fly (BSF) stands out for its ability to effectively process waste into energy-dense larvae suitable for animal feed. Beyond this, BSF holds potential for producing fertilizers, biofuels, and many other valuable products, attracting interest from a burgeoning insect farming industry. While black soldier fly is already an efficient farmed insect, a need exists for enabling technologies that allow for genetic optimization towards desirable traits, such as larger weight and shorter development times. However, foundational research is necessary to develop more refined tools for genetic manipulation in BSF. The endogenous application of the CRISPR gene editing system could be particularly beneficial, streamlining the validation of advantageous mutant genotypes and accelerating the improvement of desirable traits. In this study, a molecular toolkit was developed for BSF to enable CRISPR production from an endogenous transgenic source, aimed at enhancing gene editing efficiency and accessibility for both the research and commercial sectors. This toolkit included the development and optimization of an efficient genetic transduction method, the embryo microinjection technique, which has yet to be thoroughly documented in the literature. Overall, this project aimed to build on the molecular toolkit currently available to BSF researchers, enabling more complex genetic investigation and manipulations to drive the development of novel, optimised BSF breeding lines. Enhancing the genetic potential of this insect could provide significant benefits as an innovative solution for managing food waste and strengthening sustainable food security.Open Acces

Non-invasive respiratory support in paediatric critical care: protocol for a cohort study emulating the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up randomised clinical trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database

Introduction The development of the target trial emulation (TTE) methodology has enhanced the conduct of non-randomised studies. By leveraging readily available routinely collected data, TTEs offer opportunities for complementing randomised controlled trials (RCTs), providing more precise estimates and improving the external validity of RCTs. To explore this potential, we selected a successfully completed RCT as a case study. In the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up RCT, high flow nasal cannula (HFNC) was found to be non-inferior to continuous positive airway pressure (CPAP) in terms of time to liberation from respiratory support in the paediatric critical care setting. We will emulate the FIRST-ABC step-up trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database. Methods and analysis This is a protocol for a TTE that will use longitudinally collected data from the PICANet database. The study aims to emulate the FIRST-ABC step-up RCT using an observational study design in a frequentist framework. We will benchmark the results against the published trial. The study will apply a new-user design by selecting children admitted to paediatric intensive care units that started HFNC or non-invasive ventilatory support (as a surrogate for CPAP). The eligibility criteria and selected outcomes will reflect those of FIRST-ABC within the constraints of the available routinely collected data. We will use advanced quantitative doubly robust methods to minimise the impact of confounding by indication and allow for heterogeneity according to child characteristics. The analysis will be repeated using a Bayesian approach for follow-up research. Ethics and dissemination The research received ethics approval from the London School of Hygiene & Tropical Medicine Research Ethics Committee. This study will expand the findings from the FIRST-ABC step-up RCT, providing additional insight from a large representative sample using real-world data. The frequentist and Bayesian approaches will enable a discussion about the advantages and drawbacks of the two strategies. The results will be disseminated to the research and clinical community and made accessible to the public. In addition, the study results will be used in future research, which aims to supplement RCTs with additional evidence from a TTE

Biological effects of rapid short pulses of focused ultrasound for drug delivery to the brain

Focused ultrasound in combination with intravenously injected microbubbles offers a non-invasive and localised method to deliver drugs across the blood-brain barrier, enabling targeted treatment of brain disorders. Recently, we have shown that applying sequences of Rapid Short-Pulses (RaSP; 5 μs pulses emitted at 1.25 kHz grouped into 10 ms bursts) of ultrasound can deliver drugs with an improved efficacy and safety profile compared with traditionally-used longer pulses (> 10 ms). In this study, we examined the extent to which RaSP sequences allowed the extravasation of endogenous blood proteins, including albumin and immunoglobulin, as well as T cells, into the brain parenchyma. We also investigated the effect of RaSP ultrasound treatments on synaptic connectivity, and the distribution and excretion of fluorescently-labelled 3 kDa dextran delivered to the brain with RaSP. The left hippocampus of mice was sonicated with either a RaSP sequence (5 μs at 1.25 kHz in groups of 10 ms at 0.5 Hz) or a long pulse sequence (10 ms at 0.5 Hz), at 0.35, 0.53 and 0.71 MPa with a 1-MHz center frequency. Significantly less albumin was detected in RaSP-treated brains immediately after treatment and was cleared within 10 min compared to those treated with long pulses, while immunoglobulin was hardly detected in RaSP-treated brains at 0, 10 or 20 min after treatment. No T cells were detected in RaSP-treated brains at 0.35, 0.53 or 0.71 MPa after 0 or 2 h. In long pulse samples, however, T cells did extravasate when using the two higher acoustic pressures, 0.53 and 0.71 MPa, immediately after treatment. Quantification of dendritic spine area revealed no differences between RaSP-treated hippocampi compared to untreated contralateral hippocampi and control mice following three weekly ultrasound treatments. Finally, fluorescently-labelled dextran increasingly moved towards blood vessels and away from the parenchyma once delivered to the brain with both RaSP and long pulse sequences. Uptake of dextran within cells decreased over time with both sequences, and long pulses lead to a larger number of vessels with dextran uptake. This study highlights that RaSP ultrasound sequences can deliver molecules across the blood-brain barrier with minimal extravasation of endogenous proteins and no T cell infiltration, while preserving dendritic spine integrity, thus offering an improved safety profile

Tactile, audio, and visual dataset during bare finger interaction with textured surfaces

This paper presents a comprehensive multi-modal dataset capturing concurrent haptic, audio, and visual signals recorded from ten participants as they interacted with ten different textured surfaces using their bare fingers. The dataset includes stereoscopic images of the textures, and fingertip position, speed, applied load, emitted sound, and friction-induced vibrations, providing an unprecedented insight into the complex dynamics underlying human tactile perception. Our approach utilizes a human finger (while most previous studies relied on rigid sensorized probes), enabling the naturalistic acquisition of haptic data and addressing a significant gap in resources for studies of human tactile exploration, perceptual mechanisms, and artificial tactile perception. Additionally, fifteen participants completed a questionnaire to evaluate their subjective perception of the surfaces. Through carefully designed data collection protocols, encompassing both controlled and free exploration scenarios, this dataset offers a rich resource for studying human multi-sensory integration and supports the development of algorithms for texture recognition based on multi-modal inputs. A preliminary analysis demonstrates the dataset’s potential, as classifiers trained on different combinations of data modalities show promising accuracy in surface identification, highlighting its value for advancing research in multi-sensory perception and the development of human-machine interfaces

Infinite-dimensional Mahalanobis distance with applications to kernelized novelty detection

The Mahalanobis distance is a classical tool used to measure the covariance-adjusted distance between points in Rd. In this work, we extend the concept of Mahalanobis distance to separable Banach spaces by reinterpreting it as a Cameron-Martin norm associated with a probability measure. This approach leads to a basis-free, data-driven notion of anomaly distance through the so-called variance norm, which can naturally be estimated using empirical measures of a sample. Our framework generalizes the classical Rd, functional (L2[0, 1])d, and kernelized settings; importantly, it incorporates non-injective covariance operators. We prove that the variance norm is invariant under invertible bounded linear transformations of the data, extending previous results which are limited to unitary operators. In the Hilbert space setting, we connect the variance norm to the RKHS of the covariance operator, and establish consistency and convergence results for estimation using empirical measures with Tikhonov regularization. Using the variance norm, we introduce the notion of a kernelized nearest-neighbour Mahalanobis distance, and study some of its finite-sample concentration properties. In an empirical study on 12 real-world data sets, we demonstrate that the kernelized nearest-neighbour Mahalanobis distance outperforms the traditional kernelized Mahalanobis distance for multivariate time series novelty detection, using state-of-the-art time series kernels such as the signature, global alignment, and Volterra reservoir kernels

Longitudinal study of care needs and behavioural changes in people living with dementia using in-home assessment data

Background: People living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability. Methods: We use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data. Results: Here we show, psychiatric behavioural symptoms and difficulties in activities of daily living, fluctuate alongside cognitive decline. 677 activities of daily living and 632 psychiatric behaviour questionnaires are available at intervals of 3 months. Clustering shows three severity-based groups. Mild cognitive decline associates with higher caregiver anxiety, while the most severe group interacts more with community services, but less with hospitals. Conclusions: We characterise behavioural symptoms and difficulties in activities of daily living in dementia, offering clinically relevant insights not commonly considered in current practice. We provide a holistic overview of participants’ health during their progression of dementia