Promoting Resilience in the Face of Fundamental Uncertainty

Complex systems at different levels (states, organisations, individuals) undergo phase transitions when faced with a sudden shock. The phase transitions are unpredictable and can lead to unstable states and also introduce a source of fundamental uncertainty about the future. In the face of this type of fundamental uncertainty, we know from pioneering work on population health that social determinants (e.g. education, employment, housing, etc.) will have a substantial influence on the ability of individuals and society to be resilient and recover from these shocks. This chapter will start with an overview of complex systems, phase transitions and the nature of fundamental uncertainty. These concepts will then be discussed in light of the COVID-19 pandemic. The importance of social determinants in promoting both mental and physical health, and thus resilience at individual and population levels, will be described and the chapter will finish with an exploration of historical and contemporary examples of means that can be used to support individual and collective resilience in the face of fundamental uncertainty

Car harm:A global review of automobility’s harm to people and the environment

Despite the widespread harm caused by cars and automobility, governments, corporations, and individuals continue to facilitate it by expanding roads, manufacturing larger vehicles, and subsidising parking, electric cars, and resource extraction. This literature review synthesises the negative consequences of automobility, or car harm, which we have grouped into four categories: violence, ill health, social injustice, and environmental damage. We find that, since their invention, cars and automobility have killed 60–80 million people and injured at least 2 billion. Currently, 1 in 34 deaths are caused by automobility. Cars have exacerbated social inequities and damaged ecosystems in every global region, including in remote car-free places. While some people benefit from automobility, nearly everyone—whether or not they drive—is harmed by it. Slowing automobility’s violence and pollution will be impracticable without the replacement of policies that encourage car harm with policies that reduce it. To that end, the paper briefly summarises interventions that are ready for implementation

Chromatin remodeling complex in Treg function

Regulatory T cells (Treg), formerly known as suppressor T cells, are essential for maintaining self-tolerance as well as immune homeostasis. Lack of Treg or normal function of Treg often leads to lymphoproliferative syndrome and autoimmunity in human and mouse. The chromatin remodeling BAF complex regulates gene expression through the activity of Brg. Genetic ablation of Brg gene in mouse resulted in early embryonic lethality. T cell failed to develop in the thymus when Brg is deleted at DN stage. Using a Brg conditional KO mouse model, we deleted Brg at the DP stage in the thymus. Unexpectedly, T cells developed and matured normally. However, these mice displayed lympho-proliferative syndrome 2–4 months of age with enlarged peripheral lymphoid organs and leukocyte infiltration in non-lymphoid organs. T cells from these mice turned into effector cells producing increased amounts of effector cytokines as early as 4 weeks after birth. Further analysis revealed that the Treg population was specifically affected by Brg deletion. In this mini-review, we will discuss in detail the properties of Tregs controlled by Brg and the potential underlying mechanisms for an unanticipated, specific role of the Brg-containing BAF complex in controlling Treg functions

Use of lifestyle interventions in primary care for individuals with newly diagnosed hypertension, hyperlipidaemia or obesity: a retrospective cohort study

Abstract Summary Objective Lifestyle interventions can be efficacious in reducing cardiovascular disease risk factors and are recommended as first-line interventions in England. However, recent information on the use of these interventions in primary care is lacking. We investigated for how many patients with newly diagnosed hypertension, hyperlipidaemia or obesity, lifestyle interventions were recorded in their primary care electronic health record. Design A retrospective cohort study. Setting English primary care, using UK Clinical Practice Research Datalink. Participants A total of 770,711 patients who were aged 18 years or older and received a new diagnosis of hypertension, hyperlipidaemia or obesity between 2010 and 2019. Main outcome measures Record of lifestyle intervention and/or medication in 12 months before to 12 months after initial diagnosis (2-year timeframe). Results Analyses show varying results across conditions: While 55.6% (95% CI 54.9–56.4) of individuals with an initial diagnosis of hypertension were recorded as having lifestyle support (lifestyle intervention or signposting) within the 2-year timeframe, this number was reduced to 45.2% (95% CI 43.8–46.6) for hyperlipidaemia and 52.6% (95% CI 51.1–54.1) for obesity. For substantial proportions of individuals neither lifestyle support nor medication (hypertension: 12.2%, 95% CI 11.9–12.5; hyperlipidaemia: 32.2%, 95% CI 31.2–33.3; obesity: 43.9%, 95% CI 42.3–45.4) were recorded. Sensitivity analyses confirm that limited proportions of patients had lifestyle support recorded in their electronic health record before they were first prescribed medication (diagnosed and undiagnosed), ranging from 12.1% for hypertension to 19.7% for hyperlipidaemia, and 19.5% for obesity (23.4% if restricted to Orlistat). Conclusions Limited evidence of lifestyle support for individuals with cardiovascular risk factors (hypertension, hyperlipidaemia, obesity) recommended by national guidelines in England may stem from poor recording in electronic health records but may also represent missed opportunities. Given the link between progression to cardiovascular disease and modifiable lifestyle factors, early support for patients to manage their conditions through non-pharmaceutical interventions by establishing lifestyle modification as first-line treatment is crucial

Better value primary care is needed now more than ever

Healthcare systems globally are facing multiple challenges, with ageing populations, increasing chronic disease, rising multimorbidity, and innovative treatments and technologies all leading to rising costs. With finite resources, and an increasing recognition of the potential harms to patients of overdiagnosis and overtreatment, it is essential that resources are used optimally. We explore how the value based healthcare framework can help decisions about how to allocate resources, and the importance of good evidence not only for patient treatment but for the organisation of health service

Overcoming the incumbency and barriers to sustainable cooling

This article examines cooling in the built environment, an area of rapidly rising energy demand and greenhouse gas emissions. Specifically, the status quo of cooling is assessed and proposals are made for how to advance towards sustainable cooling through five levers of change: social interactions, technology innovations, business models, governance and infrastructure design. Achieving sustainable cooling requires navigating the opportunities and barriers presented by the incumbent technology that currently dominates the way in which cooling is provided—the vapour-compression refrigerant technology (or air-conditioners). Air-conditioners remain the go-to solution for growing cooling demand, with other alternatives often overlooked. This incumbent technology has contributed to five barriers hindering the transition to sustainable cooling: (1) building policies based exclusively on energy efficiency; (2) a focus on temperature rather than other thermal comfort variables; (3) building-centric design of cooling systems instead of occupant-centric design; (4) businesses guided by product-only sales; and (5) lack of innovation beyond the standard operational phase of the incumbent technology. Opportunities and priority actions are identified for policymakers, cooling professionals, technicians and citizens to promote a transition towards sustainable cooling. Policy relevance The priority actions that can overcome key barriers to a sustainable cooling pathway are as follows. (1) Moving building policies beyond energy efficiency to address climate mitigation and adaptation for improving the heat resilience of the built environment. Building indicators are needed to measure the passive survivability to heat. (2) Conventional cooling control and related regulations based exclusively on air temperature require expansion in scope to consider a wider range of thermal comfort variables, thus stimulating technological innovation. (3) Shifting building-centric cooling control to an occupant-centric design, downsizing centralised cooling requirements and enabling adaptive environments integrating personalised environmental control systems. (4) Business models moving from product-oriented to service-based businesses. (5) Environmental cooling considerations that address the humidity influence, the role of energy storage to support renewables through energy flexibility in cooling, and the impact of F-gases. Regulation and citizen empowerment through better environmental labelling can play an important role

A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation

A tissue-specific transcriptional enhancer, Eμ, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core Eμ results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define Eμ-independent and Eμ-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression