Making the Case for “Whole System” Approaches Integrating Public Health and Housing

This is the final version. Available on open from MDPI via the DOI in this recordHousing conditions have been an enduring focus for public health activity throughout the modern public health era. However, the nature of the housing and health challenge has changed in response to an evolution in the understanding of the diverse factors influencing public health. Today, the traditional public health emphasis on the type and quality of housing merges with other wider determinants of health. These include the neighbourhood, community, and “place” where a house is located, but also the policies which make access to a healthy house possible and affordable for everyone. Encouragingly, these approaches to policy and action on housing have the potential to contribute to the “triple win” of health and well-being, equity, and environmental sustainability. However, more effective housing policies (and in public health in general) that adopt more systemic approaches to addressing the complex interactions between health, housing, and wider environment are needed. This paper illustrates some of the key components of the housing and health challenge in developed countries, and presents a conceptual model to co-ordinate activities that can deliver the “triple win.” This is achieved by offering a perspective on how to navigate more effectively, inclusively and across sectors when identifying sustainable housing interventions.This research was supported in part by funding provided by: (1) the South West Academic Health Science Network (grant number SW AHSN G005) and the European Regional Development Fund (grant number SZ07660) for the SMARTLINE Project; (2) the Eaga Charitable Trust; (3) the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England, and in collaboration with the University of Exeter, University College London, and the Met Office; and (4) the European Commission Horizon 2020 funded INHERIT project, coordinated by EuroHealthNet (grant number 667364)

The Accelerations of Stars Orbiting the Milky Way's Central Black Hole

Recent measurements, of the velocities of stars near the center of the Milky Way have provided the strongest evidence for the presence of a supermassive black hole in a galaxy, but the observational uncertainties poorly constrain many of the properties of the black hole. Determining the accelerations of stars in their orbits around the center provides much more precise information about the position and mass of the black hole. Here we report measurements of the accelerations for three stars located ~0.005 pc from the central radio source Sgr A*; these accelerations are comparable to those experienced by the Earth as it orbits the Sun. These data increase the inferred minimum mass density in the central region of the Galaxy by an order of magnitude relative to previous results and localized the dark mass to within 0.05 +- 0.04 arcsec of the nominal position of Sgr A*. In addition, the orbital period of one of the observed stars could be as short as 15 years, allowing us the opportunity in the near future to observe an entire period.Comment: To appear in September 21 2000 issue of Natur

The formation and function of the neutrophil phagosome.

Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate

CAR-Net: Clairvoyant Attentive Recurrent Network

We present an interpretable framework for path prediction that leverages dependencies between agents' behaviors and their spatial navigation environment. We exploit two sources of information: the past motion trajectory of the agent of interest and a wide top-view image of the navigation scene. We propose a Clairvoyant Attentive Recurrent Network (CAR-Net) that learns where to look in a large image of the scene when solving the path prediction task. Our method can attend to any area, or combination of areas, within the raw image (e.g., road intersections) when predicting the trajectory of the agent. This allows us to visualize fine-grained semantic elements of navigation scenes that influence the prediction of trajectories. To study the impact of space on agents' trajectories, we build a new dataset made of top-view images of hundreds of scenes (Formula One racing tracks) where agents' behaviors are heavily influenced by known areas in the images (e.g., upcoming turns). CAR-Net successfully attends to these salient regions. Additionally, CAR-Net reaches state-of-the-art accuracy on the standard trajectory forecasting benchmark, Stanford Drone Dataset (SDD). Finally, we show CAR-Net's ability to generalize to unseen scenes.Comment: The 2nd and 3rd authors contributed equall

Mapping the shoreface of coastal sediment compartments to improve shoreline change forecasts in New South Wales, Australia

The potential response of shoreface depositional environments to sea level rise over the present century and beyond remains poorly understood. The shoreface is shaped by wave action across a sedimentary seabed and may aggrade or deflate depending on the balance between time-averaged wave energy and the availability and character of sediment, within the context of the inherited geological control. For embayed and accommodation-dominated coastal settings, where shoreline change is particularly sensitive to cross-shore sediment transport, whether the shoreface is a source or sink for coastal sediment during rising sea level may be a crucial determinant of future shoreline change. While simple equilibrium-based models (e.g. the Bruun Rule) are widely used in coastal risk planning practice to predict shoreline change due to sea level rise, the relevance of fundamental model assumptions to the shoreface depositional setting is often overlooked due to limited knowledge about the geomorphology of the nearshore seabed. We present high-resolution mapping of the shoreface-inner shelf in southeastern Australia from airborne lidar and vessel-based multibeam echosounder surveys, which reveals a more complex seabed than was previously known. The mapping data are used to interpret the extent, depositional character and morphodynamic state of the shoreface, by comparing the observed geomorphology to theoretical predictions from wave-driven sediment transport theory. The benefits of high-resolution seabed mapping for improving shoreline change predictions in practice are explored by comparing idealised shoreline change modelling based on our understanding of shoreface geomorphology and morphodynamics before and after the mapping exercise

Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246

TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes. Uptake of these exosomes by neighboring macrophages triggers their miR-1246-dependent reprogramming into a cancerpromoting state. Mutp53-reprogammed TAMs favor anti-inflammatory immunosuppression with increased activity of TGF-β. These findings, associated with poor survival in colon cancer patients, strongly support a microenvironmental GOF role for mutp53 in actively engaging the immune system to promote cancer progression and metastasis

A Digital Health Solution for Child Growth Monitoring at Home: Testing the Accuracy of a Novel “GrowthMonitor” Smartphone Application to Detect Abnormal Height and Body Mass Indices

Objective: To develop and evaluate a smartphone application that accurately measures height and provides notifications when abnormalities are detected. Patients and Methods: A total of 145 (75 boys) participants with a mean age ± SD of 8.7±4.5 years (range, 1.0-17.0 years), from the Children’s Hospital at Barts Health Trust, London, United Kingdom, were enrolled in the study. “GrowthMonitor” (UCL Creatives) iPhone application (GMA) measures height using augmented reality. Using population-based (UK-WHO) references, algorithms calculated height SD score (HSDS), distance from target height (THSDSDEV), and HSDS change over time (ΔHSDS). Pre-established thresholds discriminated normal/abnormal growth. The GMA and a stadiometer (Harpenden; gold standard) measured standing heights of children at routine clinic visits. A subset of parents used GMA to measure their child’s height at home. Outcome targets were 95% of GMA measurements within ±0.5 SDS of the stadiometer and the correct identification of abnormal HSDS, THSDSDEV, and ΔHSDS. Results: Bland-Altman plots revealed no appreciable bias in differences between paired study team GMA and stadiometer height measurements, with a mean of the differences of 0.11 cm with 95% limits of agreement of −2.21 to 2.42 cm. There was no evidence of greater bias occurring for either shorter/younger children or taller/older children. The 2 methods of measurements were highly correlated (R=0.999). GrowthMonitor iPhone application measurements performed by parents in clinic and at home were slightly less accurate. The κ coefficient indicated reliable and consistent agreement of flag alerts for HSDS (κ=0.74) and THSDSDEV (κ=0.88) between 83 paired GMA and stadiometer measurements. GrowthMonitor iPhone application yielded a detection rate of 96% and 97% for HSDS-based and THSDSDEV-based red flags, respectively. Forty-two (18 boys) participants had GMA calculated ΔHSDS using an additional height measurement 6-16 months later, and no abnormal flag alerts were triggered for ΔHSDS values. Conclusion: GrowthMonitor iPhone application provides the potential for parents/carers and health care professionals to capture serial height measurements at home and without specialized equipment. Reliable interpretation and flagging of abnormal measurements indicate the potential of this technology to transform childhood growth monitoring

Impact of e-cigarette retail displays on attitudes to smoking and vaping in children: an online experimental study

OBJECTIVES: To estimate the impact of electronic cigarette (e-cigarette) retail display exposure on attitudes to smoking and vaping (susceptibility to tobacco smoking and using e-cigarettes, and perceptions of the harms of smoking and e-cigarette use). DESIGN: Between-subjects randomised experiment using a 2 (e-cigarette retail display visibility: high vs low)×2 (proportion of e-cigarette images: 75% vs 25%) factorial design. SETTING: Online via the Qualtrics survey platform. PARTICIPANTS: UK children aged 13-17 years (n=1034), recruited through a research agency. INTERVENTION: Participants viewed 12 images of retail displays that contained e-cigarette display images or unrelated product images. E-cigarette display images were either high or low visibility, based on a conspicuousness score. Participants were randomised to one of four groups, with e-cigarette display visibility and proportion of e-cigarette images, compared with images of unrelated products, manipulated: (1) 75% e-cigarettes, high visibility; (2) 25% e-cigarettes, high visibility; (3) 75% e-cigarettes, low visibility; (4) 25% e-cigarettes, low visibility. MAIN OUTCOME MEASURES: The primary outcome was susceptibility to smoking (among never smokers only). Secondary outcomes were susceptibility to using e-cigarettes (among never vapers only), and perceptions of smoking and e-cigarette harm (all participants). RESULTS: Neither e-cigarette retail display visibility, nor the proportion of e-cigarette images displayed, appeared to influence susceptibility to smoking (visibility: OR=0.84, 95% CI 0.62 to 1.13, p=0.24; proportion: OR=1.34, 95% CI 1.00 to 1.82, p=0.054 (reference: low visibility, not susceptible)).Planned subgroup analyses indicated that exposure to a higher proportion of e-cigarette images increased susceptibility to smoking among children who visited retail stores more regularly (n=524, OR=1.59, 95% CI 1.04 to 2.43, p=0.034), and those who passed the attention check (n=880, OR=1.43, 95% CI 1.03 to 1.98, p=0.031).In addition, neither e-cigarette retail display visibility nor the proportion of e-cigarette images displayed, appeared to influence susceptibility to using e-cigarettes (visibility: OR=1.07, 95% CI 0.80 to 1.43, p=0.65; proportion: OR=1.22, 95% CI 0.91 to 1.64, p=0.18).Greater visibility of e-cigarette retail displays reduced perceived harm of smoking (mean difference (MD)=-0.19, 95% CI -0.34 to -0.04, p=0.016). There was no evidence that the proportion of e-cigarette images displayed had an effect (MD=-0.07, 95% CI -0.22 to 0.09, p=0.40).Perceived harm of e-cigarette use did not appear to be affected by e-cigarette retail display visibility (MD=-0.12, 95% CI -0.28 to 0.05, p=0.16) or by the proportion of e-cigarette images displayed (MD=-0.10, 95% CI -0.26 to 0.07, p=0.24). CONCLUSIONS: There is no evidence in the full sample to suggest that children's susceptibility to smoking is increased by exposure to higher visibility e-cigarette retail displays, or to a higher proportion of e-cigarette images. However, for regular store visitors or those paying more attention, viewing a higher proportion of e-cigarette images increased susceptibility to smoking. In addition, viewing higher visibility e-cigarette images reduced perceived harm of smoking. A review of the current regulatory discrepancy between tobacco and e-cigarette point-of-sale marketing is warranted. TRIAL REGISTRATION NUMBER: ISRCTN18215632

Management of pain in Fabry disease in the UK clinical setting: consensus findings from an expert Delphi panel

Background: Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting. Methods: Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel’s responses were conducted between September 2021 and December 2021. All questions required an answer. Results: The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain. Conclusions: The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines