Understanding the complexity of living with, and managing, secretions in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS): protocol for a complex intervention systematic review

Introduction Motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS) is an incurable disease which leads to muscle weakness that worsens over time. MND/ALS is highly heterogeneous in its presentation, with many people experiencing a rapidly progressive trajectory of symptoms. Many people living with MND/ALS (plwMND/ALS) experience a combination of flaccidity and spasticity of the muscles involved in speech, swallowing, breathing and coughing. This makes it challenging to deal with the saliva and mucous (‘secretions”) produced by the body. Failure to manage these problems effectively can lead to accumulation and aspiration of secretions, which may cause pneumonia and respiratory insufficiency. Knowing the best way to treat this problem is a challenge. Systematic reviews report substantive ongoing uncertainty regarding secretions management (SM). Little is known about the comparative effectiveness of secretion management interventions, their impact on quality of life and acceptability for plwMND/ALS and their unpaid/family. Methods and analysis A complex intervention systematic review of SM for plwMND/ALS and/or their carers will be conducted using an iterative logic model approach, designed in accordance with the principles and guidance laid out in a series of articles published by the Agency for Healthcare Research and Quality on complex intervention reviews . Eight electronic databases will be searched for publications between 1996 and present: Ovid Embase, EBSCO CINAHL, EBSCO Academic Search Ultimate, Scopus, EBSCO PsycInfo, Ovid MEDLINE and the Social Sciences Citation Index. This will be supplemented by hand searching of reference lists of included studies. Two reviewers will independently screen the results for potentially eligible studies using AS Review Lab (a semi-automated machine learning tool). Study selection, data extraction and risk of bias assessment, using Gough’s Weight of Evidence Framework, will be independently performed by two reviewers. A framework thematic synthesis approach will be employed to analyse and report quantitative and qualitative data. The reporting will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Intervention Extension Statement and Checklist

Computational fluid dynamics of polymer flow-induced crystallization using the polySTRAND model

A computational model for predicting regions of flow-induced crystallization (FIC) during processing of a polydisperse polymer melt is presented. Flow produces local alignment of polymer segments that reduces the energy barrier for nucleation, which can lead to a dramatic increase in the rate of formation of crystal nuclei. However, simulating FIC in a complex flow geometry is challenging due to the need to couple a molecular-level description of chain configuration to the macroscale flow dynamics. This is compounded in polydisperse melts as the most marked flow-induced effects occur from the long-chain species at low undercooling. In this work, we use the Rolie-Double-Poly (RDP) model [Boudara et al., J. Rheol. 63, 71–91 (2019)] in combination with the polySTRAND model [Read et al., Phys. Rev. Lett. 124, 147802 (2020)] to create a computationally viable method for modeling FIC. This model is used to examine flow-induced crystallization in a contraction-expansion geometry, where previous experiments [Scelsi et al., J. Rheol. 53, 859–876 (2009)] found a highly localized region of crystal formation at and downstream of the wall of the constriction

Current strategies and future directions to enhance recovery following critical illness

Improvements in critical care treatments have led to an increased number of survivors of critical illness and an enhanced recognition of the problems which these patients encounter. Despite this, the ideal strategies to both prevent and manage the problems which people face are yet to be fully elucidated. This review explores the current methods employed to help mitigate problems encountered by survivors of critical illnesses and current barriers that limit their implementation. We will explore the effect of these issues on under-represented communities and the feasibility of delivering these strategies globally, as well as recent advances in mechanistic research and methodological innovation as promising areas for further work. In doing so, it summarises the potential avenues for future research with a view to advancing clinical care and outcomes in survivors of critical illness

Warm proglacial lake temperatures and thermal undercutting enhances rapid retreat of an Arctic glacier

Determining the characteristics of Arctic proglacial lakes is essential for understanding their current and future influence on glacier mass loss, capacity as a carbon sink and the associated impacts for downstream hydrology and ecology. Field observations of how proglacial lake properties influence rates of glacier mass loss remain sparse yet are increasingly critical for accurate projection of lake-terminating glacier responses to warming air and lake temperatures, particularly in high-latitude Scandinavia under the influence of Arctic amplification. Here we combine satellite and field observations of Kaskasapakte Glacier (KG) (a lake-terminating glacier in Arctic Sweden) to reveal the interplay between lake parameters and glacier mass loss from 2008 to 2019. We present the first field evidence of warmer-than-expected water temperatures (>4 °C at the ice front) at a Scandinavian proglacial lake and illustrate how these drove rapid thermo-erosional undercutting and calving at the terminus, with width-averaged retreat rates of up to 25m/yr and frontal ablation accounting for ~30% of glacier volume loss between 2015 and 2019

Health impact and cost-effectiveness of COVID-19 booster vaccination strategies in the early post-Omicron era: a dynamic modelling study

Introduction Following widespread exposure to Omicron variants, SARS-CoV-2 has transitioned to endemic circulation. Populations now have diverse infection and vaccination histories, resulting in heterogeneous immune landscapes. Careful consideration of the value of ongoing vaccination is required through the post-Omicron phase of COVID-19 management to minimise disease burden. We demonstrate the utility of a modelling approach to address this question, supporting recommendations for targeted vaccine use across different country settings. Methods We integrated immunological, transmission, clinical and cost-effectiveness models and simulated populations with different characteristics and immune landscapes over the early post-Omicron period. We calculated the expected number of infections, hospitalisations and deaths for different vaccine scenarios. Costs (from a healthcare perspective) were estimated for exemplar country income-level groupings in the Western Pacific Region using pandemic-era vaccine prices and healthcare-seeking behaviour assumptions. We assessed the impact and cost-effectiveness of targeted vaccination strategies. Results are reported as incremental costs and disability-adjusted life years averted compared with no additional vaccination. Parameter and stochastic uncertainty were captured through scenario and sensitivity analysis. Results Across different population demographics and income levels, we consistently found that annual elder-targeted boosting strategies are most likely to be cost-effective or cost-saving (>75% probability of being cost-effective among older, high-income settings; >50% probability of being cost-effective in younger, middle-income settings), while paediatric programmes are unlikely to be cost-effective. Results remained broadly consistent while accounting for uncertainties in the epidemiological and economic models, although they were sensitive to the cost of home-based care and vaccination. Use of pandemic-era vaccine prices may underestimate current vaccine prices available in upper-middle-income and high-income settings, potentially overestimating the cost-effectiveness of boosting in these settings. Half-yearly boosting may only be cost-effective in higher income settings with older population demographics and higher cost-effectiveness thresholds. Conclusion Competing health priorities and resource constraints mean COVID-19 vaccine allocation needs to be carefully considered in context. These results, reflecting modelling conducted on the early post-Omicron period, demonstrate the value of continued booster vaccinations to protect against severe COVID-19 disease outcomes across high-income and middle-income settings and show that the biggest health gains relative to vaccine costs are achieved by targeting older age groups

Warm proglacial lake temperatures and thermal undercutting enhance rapid retreat of an Arctic glacier

Determining the characteristics of Arctic proglacial lakes is essential for understanding their current and future influence on glacier mass loss, capacity as a carbon sink and the associated impacts for downstream hydrology and ecology. Field observations of how proglacial lake properties influence rates of glacier mass loss remain sparse yet are increasingly critical for accurate projection of lake-terminating glacier responses to warming air and lake temperatures, particularly in high-latitude Scandinavia under the influence of Arctic amplification. Here we combine satellite and field observations of Kaskasapakte Glacier (KG) (a lake-terminating glacier in Arctic Sweden) to reveal the interplay between lake parameters and glacier mass loss from 2008 to 2019. We present the first field evidence of warmer-than-expected water temperatures (> 4 °C at the ice front) at a Scandinavian proglacial lake and illustrate how these drove rapid thermo-erosional undercutting and calving at the terminus, with width-averaged retreat rates of up to 25 m yr−1 and frontal ablation accounting for ∼ 30 % of glacier volume loss between 2015 and 2019

Thousand cuts: a realistic route to decarbonise the UK cement and concrete sector by 2050

To meet net-zero CO2 targets by 2050, the United Kingdom (UK)’s cement and concrete sector must implement decarbonisation strategies of different readiness levels and effectiveness. These strategies have been presented thoroughly in UK and European Union decarbonisation roadmaps. However, it is challenging to predict, with confidence, whether the UK's 2050 net-zero targets are achievable. This study aims to balance the expectations placed on low-maturity (LM) and high-maturity (HM) strategies such as utilising a lower clinker factor and the use of carbon capture technologies respectively to determine a realistic route in which the UK can reach net-zero targets through a decomposition analysis of each strategy. The sector's carbon emissions were determined by performing a material flow analysis and life cycle assessment. The results showed that by 2050, 11 MtCO2eq/yr is expected to be emitted in 2050 under the business-as-usual scenario. HM strategies have an abatement potential of 4.2 MtCO2eq/yr, while LM strategies are expected to abate 3.4 MtCO2eq/yr. However, LM strategies are limited by industry's willingness to shift from current practices, while the implementation of HM strategies are impeded by financial and resource constraints. Accordingly, it is improbable for the sector to meet UK net-zero carbon targets with confidence unless the yearly concrete demand is reduced by 40 %. To enable the maximum potential of reusing the UK's building stock, direct public incentives, shifts in economic models and policy frameworks are needed