Severe acute respiratory syndrome (SARS) mathematical models and disease parameters: a systematic review

We conducted a systematic review (PROSPERO CRD42023393345) of severe acute respiratory syndrome (SARS) transmission models and parameters characterising its transmission, evolution, natural history, severity, risk factors and seroprevalence. Information was extracted using a custom database and quality assessment tool. We extracted 519 parameters, 243 risk factors, and 112 models from 289 papers. Our analyses show SARS is characterised by high lethality (case fatality ratio 10.9%), transmissibility (R0 range 1.1-4.59), and is prone to superspreading (20% top infectors causing up to 91% of infections). Infection risk was highest among healthcare workers and close contacts of infected individuals. Severe disease and death were associated with age and existing comorbidities. SARS's natural history is poorly characterised, except for the incubation period and mean onset-to-hospitalisation. Our associated R package, epireview, contains this database, which can continue to be updated to maintain a living review of SARS epidemiology and models, thus providing a key resource for informing response to future coronavirus outbreaks

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

Time encoding via unlimited sampling: theory, algorithms and hardware validation

An alternative to conventional uniform sampling is that of time encoding, which converts continuous-time signals into streams of trigger times. This gives rise to Event-Driven Sampling (EDS) models. The data-driven nature of EDS acquisition is advantageous in terms of power consumption and time resolution and is inspired by the information representation in biological nervous systems. If an analog signal is outside a predefined dynamic range, then EDS generates a low density of trigger times, which in turn leads to recovery distortion due to aliasing. In this paper, inspired by the Unlimited Sensing Framework (USF), we propose a new EDS architecture that incorporates a modulo nonlinearity prior to acquisition that we refer to as the modulo EDS or MEDS. In MEDS, the modulo nonlinearity folds high dynamic range inputs into low dynamic range amplitudes, thus avoiding recovery distortion. In particular, we consider the asynchronous sigma-delta modulator (ASDM), previously used for low power analog-to-digital conversion. This novel MEDS based acquisition is enabled by a recent generalization of the modulo nonlinearity called modulo-hysteresis. We design a mathematically guaranteed recovery algorithm for bandlimited inputs based on a sampling rate criterion and provide reconstruction error bounds. We go beyond numerical experiments and also provide a first hardware validation of our approach, thus bridging the gap between theory and practice, while corroborating the conceptual underpinnings of our work

Marangoni-driven patterns, ridges and hills in surfactant-covered parametric surface waves

Parametric oscillations of an interface separating two fluid phases create nonlinear surface waves, called Faraday waves, which organise into simple patterns, such as squares and hexagons, as well as complex structures, such as double hexagonal and superlattice patterns. In this work, we study the influence of surfactant-induced Marangoni stresses on the formation and transition of Faraday-wave patterns. We use a control parameter, B, that assesses the relative importance of Marangoni stresses as compared with the surface-wave dynamics. Our results show that the threshold acceleration required to destabilise a surfactant-covered interface through vibration increases with increasing B. For a surfactant-free interface, a square-wave pattern is observed. As B is incremented, we report transitions from squares to asymmetric squares, weakly wavy stripes and ultimately to ridges and hills. These hills are a consequence of the bidirectional Marangoni stresses at the neck of the ridges. The mechanisms underlying the pattern transitions and the formation of exotic ridges and hills are discussed

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

Are food taxes for healthy eating acceptable? A survey of public attitudes in the UK

Introduction Appropriately designed food taxes can improve diet quality and health. Fiscal levers are used in several countries to combat the rise in obesity and diet-related diseases. This study aims to investigate public attitudes, knowledge and policy preferences regarding food taxes for promoting healthy eating in the UK. Methods A survey was administered through YouGov Plc to a nationally representative sample of 2125 adults, gathering information on: acceptability and support for different types of food taxes, awareness and knowledge of existing taxes and preferences for the characteristics of possible new taxes. Results Overall, 48% of respondents support higher taxes on unhealthy foods, rising to 72% if taxes made healthy foods more affordable. Respondents with high socioeconomic status and those living in London showed the highest support. Respondents had limited awareness of existing food and beverage taxes and prioritised discretionary items such as cakes and crisps for possible increased taxation. Conclusions The survey shows a high level of support for taxing unhealthy foods, as well as concern for the affordability of healthy foods. A carefully designed holistic approach to food taxation can be part of a wider public health strategy and can be favourably met by the general population in the UK

SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB in <i>Staphylococcus aureus<i>

Staphylococcus aureus is a Gram-positive pathogen that causes life threatening infections. Its cell envelope contains anionic polymers called teichoic acids that are required for cell viability. Teichoic acids come in two forms and are made by different biosynthetic pathways. One form, lipoteichoic acid (LTA), is anchored in the cell membrane; the other form, wall teichoic acid (WTA), is covalently linked to the peptidoglycan cell wall. Although the LTA and WTA biosynthetic pathways have been characterized, regulation of teichoic acid production is not well understood. Here, we identified SpbR (SAOUHSC_00965), a polytopic membrane protein similar to a eukaryotic CAAX protease, as a new factor that controls LTA levels in S. aureus cells. We show that loss of SpbR results in short LTAs and a synthetically sick phenotype when WTA biosynthesis is prevented, whereas overexpressing SpbR results in elongated LTAs. Mechanistically, we find that SpbR physically associates with the type I signal peptidase SpsB, which cleaves LtaS, the polymerase that assembles LTA on the extracellular side of the membrane, and we show that this physical interaction inhibits SpsB cleavage of LtaS both in vivo and in vitro. Although the phenotypes investigated here are dominated by SpbR’s effects on LtaS, it also inhibits cleavage of other SpsB substrates. Based on its role in regulating the activity of SpsB, we named this factor SpbR (Signal peptidase b Regulator). To the best of our knowledge, SpbR is the first known factor that directly modulates the activity of a type I signal peptidase in bacteria

Association of distal adenomas and hyperplastic polyp characteristics with long-term proximal colon cancer risk: a secondary, observational analysis of data from the UK Flexible Sigmoidoscopy Screening Trial

Objectives Colorectal cancer screening with flexible sigmoidoscopy focuses on the distal colorectum but it is unclear which distal polyps characteristics are associated with future proximal colon cancer incidence. We examined associations between distal adenoma or hyperplastic polyp characteristics and long-term incident proximal colon cancer. Methods In secondary, observational analyses of UK Flexible Sigmoidoscopy Screening Trial data, we obtained data on number and size of distal hyperplastic polyps (n=4,872) and adenomas (n=4,581), adenoma histology and dysplasia from endoscopy and pathology reports for screened asymptomatic participants. Adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for the association between distal polyp characteristics and proximal colon cancer incidence were estimated using multivariable Cox proportional hazard models. Results Over a median of 20.7 years of follow-up (IQR 16.5–21.7), 110 proximal colon cancers were diagnosed among participants with distal adenomas and 96 were diagnosed among those with only distal hyperplastic polyps detected at baseline. Larger adenoma size (6-9mm vs. ≤5mm: HR 1.67 [95%CI: 1.07–2.59] and ≥10mm vs. ≤5mm: HR 2.08 [95%CI: 0.98–4.43]; p=0.037) and high-grade (vs. low-grade) adenoma dysplasia (HR 2.82, 95%CI: 1.34-5.93; p=0.012) at baseline were positively associated with proximal colon cancer incidence. No associations were observed for the number or histology of distal adenomas or the number or size of hyperplastic polyps and proximal colon cancer incidence. Conclusions We found some evidence that larger distal adenomas and those with high-grade dysplasia at baseline were positively associated with proximal colon cancer incidence. Larger studies are needed to confirm these findings

The relationship of baseline high-sensitivity C-reactive protein with incident cardiovascular events and all-cause mortality over 20 years

Background: The prediction of future cardiovascular events in those with risk factors is important for the appropriate optimisation of preventative therapies for those at greatest risk. The value of high sensitivity C-reactive Protein (hsCRP) has been questioned in this regard. The objectives of this post-hoc analysis of a randomised controlled trial were to investigate the usefulness of baseline serum hsCRP for predicting very long-term cardiovascular events in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study. Methods: The ASCOT Legacy Study reports events up to 20 years of follow-up of the UK participants in the Lipid Lowering Arm of the original ASCOT trial. We examined outcomes related to serum hsCRP levels measured using a commercial ELISA, in tertiles or continuously, adjusting for classical cardiovascular risk factors as well as treatment allocation within ASCOT. The primary outcome was non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD); whilst secondary outcomes were all-cause mortality, total coronary events and procedures, total cardiovascular events and stroke. Findings: After excluding 3286 participants without hsCRP data, 5294 participants were included in the final cohort. The highest tertile of hsCRP was associated with the following outcomes compared to the lowest tertile: non-fatal myocardial infarction (MI) and fatal CHD (HR 1.32 [1.05–1.67]); total coronary events and procedures (HR 1.27 [1.09–1.47]); total cardiovascular events (HR 1.22 [1.08–1.37]); and all-cause mortality (HR 1.25 [1.10–1.42]). However, there was insufficient evidence regarding the association between hsCRP levels and stroke events. Addition of hsCRP in tertiles resulted in an improved net reclassification index for the prediction of non-fatal MI and fatal CHD at 20 years (9.68%, p < 0.0001). Interpretation: Higher baseline serum hsCRP levels can independently predict cardiovascular events and all-cause mortality at long-term follow-up in stable patients with hypertension. Funding: British Heart Foundation Clinical Research Fellowship (FS/17/16/32560), Wellcome Trust Clinical Research Fellowship (220572/Z/20/Z), and Sansour Fund at Imperial Healthcare Charity. The substudy of ASCOT Biomarker Programme was supported by Pfizer, New York, NY, USA. Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre as well as the Imperial British Heart Foundation Research Excellence Award (4) (RE/24/130023)

Rate-induced phenomena in dynamical systems with attracting limit cycles

We study the behaviour of dynamical systems under a time-dependent change of an external parameter. We are interested in phenomena induced by the parameter changing sufficiently quickly, and we refer to these as rate-induced phenomena. We investigate such rate-induced phenomena in continuous-time planar dynamical systems, where the underlying fixed-parameter autonomous dynamics have limit cycles attractors, extending the work of Alkhayuon and Ashwin [1]. We discover a new phenomena of rate-induced phase sensitivity, where the rate at which the parameter changes can trigger finite-time unpredictability in the dynamics. We also find that this new phenomenon interacts in an interesting way with the established notion of rate-induced tipping