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HYPERSCALING HOUSING:Venture Capital, Real Estate Start-Ups and the Race to Build a Global Residential Brand
No full textWhat happens when venture capitalists try to reinvent housing in their own image? Synonymous with the rise of Big Tech, venture capitalists (VCs) are asset managers that invest in early-stage companies, pursuing aggressive growth and market domination. Since the 2008 financial crisis, VCs have poured huge sums into real estate start-ups. Yet these actors are largely overlooked in the housing financialization and platform real estate literature. Attending to this gap, this article traces VC-fuelled attempts to build a globally scaled residential operator. It closely follows investment, acquisition and consolidation activity in the co-living sector over the past decade, where companies seek expansion via parasitic landlordism: exploiting urban rent-gaps as intermediaries between landlords and tenants. I show how venture capitalists have pushed these start-ups to rapidly increase the number of beds under operation and cities covered. But, faced with the complex, costly and variegated reality of housing systems, they invariably incur spiraling losses. It is tenants who pay the price, suffering emotionally and financially from the hazards of hyperscaling—from negligence to dispossession. In all, the article interrogates a key set of actors underlying the housing-tech-finance nexus, and the consequences of their experimentation for households and cities. It calls for closer attention to how investors are reshaping housing markets beyond asset ownership, and to who is financing ʻproptech’ and why this matters.</p
COVID-19, economic downturn, and long-term trajectories of population mental health:Evidence from two nationally representative British birth cohorts at the intersection of gender and socioeconomic position
Get PDFBackgroundWe examined long-term trajectories of mental (ill-)health in two British generations (‘Baby Boomers’ and ‘Generation X’) across the life-course, including the COVID-19 lockdowns and the following cost-of-living increases. We analysed inequalities by generation, gender, socioeconomic position (SEP), and their intersections, and explored the relationship between inflation and mental (ill-)health post-lockdown.Methods and findingsWe used data from the National Child Development Study (NCDS/1958, n = 8215) and the 1970 British Cohort Study (BCS/1970, n = 7789), with repeated measures of psychological distress (Malaise Inventory) between ages 23–64.5 (NCDS/58) and 26–52.5 (BCS/70). We used multilevel growth curve models to study long-term trajectories, and negative binomial regression models to analyse associations with inflation/cost-of-living in the 2021–2023 period. Distress increased during the pandemic but declined post-lockdown (second quadratic spline: BNCDS/58 = −0.12 [-0.17, −0.08], p < 0.001; BBCS/70 = −0.16 [-0.21, −0.11], p < 0.001). Women and individuals from disadvantaged childhood SEPs started their trajectories with significantly (p < 0.001) higher distress levels in both cohorts (women: BNCDS/58 = 0.72 [0.62, 0.82], BBCS/70 = 0.73 [0.62, 0.83]; manual-class background: BNCDS/58 = 0.24 [0.14, 0.35], BBCS/70 = 0.23 [0.12, 0.35]; rented housing: BNCDS/58 = 0.34 [0.22, 0.46], BBCS/70 = 0.30 [0.15, 0.45]). Inequalities were larger for women from disadvantaged SEPs born in 1958, indicating intersectional effects. None of these inequalities significantly reduced in the long term. Inflation/cost-of-living was significantly associated with distress, but effects did not vary by gender, concurrent SEP, or their intersection.ConclusionsDespite post-pandemic improvements, persistent inequalities by gender and childhood SEP remain. Considering the high levels of socioeconomic adversity in the UK, action is needed to reduce these inequalities and prevent their transmission across generations
Epigenome-wide analysis identifies DNA methylation signatures associated with the infant pupillary light reflex, a candidate intermediate phenotype for autism
No full textThe pupillary light reflex (PLR), the automatic constriction of the pupil in response to increased luminance, is a candidate early intermediate phenotype associated with autism, with potential to help understand early neurodevelopmental differences because it is controlled by relatively simple neural circuitry. We conducted epigenome-wide association analyses of PLR onset latency and constriction amplitude at 9, 14, and 24 months, with 51 male infants enriched for familial autism likelihood (~ 80% with a first-degree autistic relative), using buccal DNA collected at 9 months. We identified four epigenome-wide differentially methylated probes (p < 2.4 × 10⁻⁷) significantly associated with PLR latency at 14 and 24 months, and 14- to 24-month developmental change in latency. Probes linked to PLR amplitude were identified at a discovery threshold (p < 5 × 10⁻⁵). Regional analyses revealed multiple differentially methylated regions associated with both latency and amplitude. Associated probes were enriched for neurodevelopmental processes and autism-associated genes, including NR4A2, HNRNPU, and NAV2. While the findings are most directly relevant to male infants in whom PLR variability may be associated with familial autism likelihood, they provide novel evidence that DNAm contributes to early variation in PLR. These insights into the biological underpinnings of this reflex support PLR as an early intermediate phenotype associated with autism.</p
<i>Candida albicans</i>-induced ubiquitination of EGFR reveals novel host-fungal interaction pathways
No full textCandida albicans causes severe mucosal and systemic infections, with hypha formation playing a key role in its virulence. Hyphal invasion via endocytosis is mediated predominantly through interactions between Als3p and the epidermal growth factor receptor (EGFR). Subsequent EGFR activation by candidalysin, a hyphal-secreted cytolytic peptide toxin encoded by the ECE1 gene, induces receptor signaling and immune responses. While EGFR ubiquitination critically regulates receptor trafficking and signaling, its involvement during C. albicans infection has remained unexplored. Here, we demonstrate that C. albicans induces EGFR ubiquitination, leading to altered trafficking and lysosomal degradation in an ECE1- and ALS3-dependent manner. This correlates with changes in EGFR ligand expression, adaptor recruitment, and protein ubiquitination in oral epithelial cells. In a mouse model of oropharyngeal candidiasis, wild-type C. albicans and ece1Δ/Δ and als3Δ/Δ mutant strains were found to differentially regulate Egfr expression, ubiquitin pathway-associated genes, and protein ubiquitination. Furthermore, conditional EGFR knockout was protective during infection. Together, our findings reveal that C. albicans infection modulates the host ubiquitin system, including direct effects on EGFR, highlighting a novel aspect of host–fungal interactions. IMPORTANCE Candida albicans is a common fungal pathogen that causes both mucosal infections, such as thrush, and life-threatening systemic diseases. A key step in infection is the fungus invading epithelial tissues and activating the host epidermal growth factor receptor (EGFR). We discovered that C. albicans alters how EGFR is regulated by inducing its ubiquitination, a modification that leads to receptor degradation. This process depends on two major fungal virulence factors: the adhesin Als3p and Ece1p, the polypeptide that contains the candidalysin toxin. The fungus also broadly increases protein ubiquitination in oral epithelial cells. In a mouse model of oral infection, loss of EGFR in epithelial tissues reduced disease severity, suggesting that the receptor helps the fungus establish infection. These findings reveal a previously unrecognized strategy by which C. albicans manipulates protein ubiquitination and regulation in epithelial cells, offering new insights into fungal pathogenesis and potential therapeutic approaches that target host pathways.</p
Social connection and living with severe chronic obstructive pulmonary disease:A qualitative analysis
Get PDFGrand Challenges for Skin Health Revisited:the International League of Dermatological Societies skin disease atlases
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Temporal trends in pregnancy outcomes during a health system shock
No full textBackground: To better understand reported COVID-19 pandemic effects on pregnancy, we examined temporal trends in pregnancy outcomes in a diverse population from South London, United Kingdom.Methods: We included 31,411 singleton pregnancies with complete registration and birth outcomes across pre-pandemic (May 1/2019–March 22/2020, 24.5%), pandemic lockdowns (March 23/2020–July 17/2021, 32.3%), and pandemic without lockdown epochs (July 18/2021–April 22/2023, 43.2%). Multivariable regression was employed to evaluate outcomes by study epoch, adjusting for potential confounders (e.g., ethnicity, deprivation, site), followed by generalized additive modelling to visualise monthly trends.Results: Here we show that of 17 outcomes: six have stable trends (e.g., preterm birth, stillbirth); eight show linear trends, either decreasing (e.g., gestational age at birth, vaginal tears) or increasing (e.g., Caesareans, postpartum haemorrhage); and three show quadratic (complex) trends (e.g., secondary mental health services, labour induction).Conclusions: Overall, most outcomes during the pandemic mirror pre-pandemic trends, with fluctuations observed likely due to site-specific responses. Our findings highlight the need for temporal analysis of pregnancy outcomes
Development of a 4Pi national involvement standards-based questionnaire to evaluate patient and public involvement
No full textBackgroundEvaluation of patient and public involvement (PPI) is crucial to ensuring it is conducted with quality. However, determining how best to evaluate the experience of those doing involvement activities remains challenging, particularly given the complex landscape of diverse terminology and wide range of methods. There is a need for robust and accessible tools, grounded in established standards, that reflect the perspectives of patients and public contributors involved in PPI activities. To address this, we developed a questionnaire (4Pi Questionnaire) based on the 4Pi National Involvement Standards, a project that developed a framework around good practice and measurement, monitoring and evaluation of involvement activities.MethodsThe questionnaire was developed through an iterative process involving literature review, experts’ input and extensive consultation with PPI contributors. Initial items were generated deductively from the five domains of the 4Pi National Involvement Standards framework (i.e., Principle, Purpose, Presence, Process and Impact). Subsequent versions of the questionnaire were refined using a face validity workshop, a Questionnaire Appraisal System, and focus group-based cognitive interviewing (CI) with PPI contributors. Feedback focussed on clarity, relevance, accessibility and questionnaire structure. There was a final round of testing to assess accessibility and usability.ResultsThe 4Pi Questionnaire is a structured measure designed to capture experiences of involvement in diverse contexts across healthcare and research. The questionnaire consists of an introduction followed by 31 items grouped into two sections A and B. Section A (“Your experience of involvement”) includes 22 items relating to a single recent involvement activity and cover the five domains of the 4Pi National Involvement Standards framework. Respondents rate their agreement with 19 statements using a five-point Likert scale, and answer two open-ended questions. Section B (“About you”) collects demographic information. Completion time is approximately 15–30 min. Involvement of subject-matter experts and PPI contributors ensured clarity of language, relevance of each question, and usability of the questionnaire.ConclusionsGrounded in the 4Pi National Involvement Standards, the 4Pi Questionnaire provides an accessible and acceptable tool to measure the experiences and perceptions of patients and public contributors doing involvement activities. Systematically developed with and for people with lived experience, the 4Pi Questionnaire addresses a gap in the availability of standardised, meaningful measures and supports efforts to embed inclusive involvement practices across healthcare and research settings
Biallelic <i>PAX7 </i>variants cause a novel Satellite Cell-opathy with progressive muscle involvement resembling facioscapulohumeral muscular dystrophy
No full textInherited myopathies are genetic disorders characterised by declining motor function due to progressive muscle weakening and wasting. Recently, pathogenic variants in PAX7, the master transcriptional regulator of muscle stem cells, have been associated with myopathies of variable severity, arguing for impaired satellite cell function as the main pathogenic driver. Here, we report the characterisation of two missense PAX7 variants in a patient with asymmetric, progressive muscle weakness affecting facial, upper and lower body muscles, and myopathic changes on muscle pathology. Despite this disorder closely phenocopying the clinical presentation of Facioscapulohumeral muscular dystrophy (FSHD), genetic, epigenetic and transcriptomic profiling indicated that FSHD was unlikely. However, exome sequencing revealed two heterozygous variants in PAX7: c.335 C > T, (p.Pro112Leu) and c.1328 G > A (p.Cys443Tyr). Modelling these PAX7 variants in human myoblasts resembled the transcriptomic findings found in the muscle biopsy from the patient. Specifically, these PAX7 variants caused upregulation of splicing factors, an increase in mitochondrial reactive oxygen species levels and reduced cell proliferation. The phenotypic cell changes caused by the PAX7 variants support a pathomechanism whereby diminished satellite cell function impairs muscle homoeostasis. Together, multimodal investigation suggests that these variants in PAX7 are likely causative of an FSHD-like autosomal recessive myopathy and expand the spectrum of neuromuscular disorders originating from impaired satellite cell function.</p