Does arts and cultural engagement vary geographically? Evidence from the UK household longitudinal study.

OBJECTIVES: Previous studies have shown the beneficial impacts of arts participation and cultural engagement on health outcomes. However, this engagement is socially patterned and is also possibly influenced by geographical factors. STUDY DESIGN: The aim of this study was to examine the association between geographical factors (spatial setting and neighbourhood characteristics) and arts and cultural engagement amongst adults in the UK. METHODS: Data analysed were from Understanding Society Wave 2 (2010/12) with a total sample size of 26,215. Logistic and ordinal regression was used to identify geographical predictors for the patterns of the engagement. RESULTS: Our results show that there are geographical differences in participation independent of individual demographic and socio-economic backgrounds. In particular, there was more evidence for differences in the participation based on neighbourhood characteristics (e.g. level of area deprivation). We also found some interactions between individual and geographical factors for cultural engagement but not for arts participation. CONCLUSIONS: This study reveals a geographical and individual socio-economic gradient in arts and cultural engagement. Given the health benefits of arts engagement, improving access to arts and cultural programmes geographically may potentially help to reduce health inequalities.

Is social capital higher in areas with a higher density of historic assets? Analyses of 11,112 adults living in England.

AIMS: Previous evidence suggests that engagement with heritage such as visiting heritage sites provides benefits for people's mental and social wellbeing, and helps to establish social capital. However, far less is known about whether living in areas of historic built environment also helps build social capital. Furthermore, it remains unclear how the association between historic built environment and social capital may vary across heritage engagement frequency and areas of deprivation levels. This study was therefore designed to explore the cross-sectional relationship between historic built environment and social capital. METHODS: Analysis was based on three datasets: Understanding Society: The UK Household Longitudinal Study Waves 5 (2013/2015) and 6 (2014/2016), 2019 National Heritage List for England, and 2015 English Index of Multiple Deprivation (IMD). Ordinary least squares (OLS) regressions were applied to estimate the relationships between historic built environment (listed buildings, scheduled monuments, and registered parks and gardens) and social capital (personal relationships, social network support, civic engagement, and trust and cooperative norms). RESULTS: We found that people living in places with greater historic built environment experienced higher levels of personal relationships, social network support, and civic engagement. However, these associations were attenuated once rurality was adjusted. Individuals living in areas of greater levels of historic built environment displayed higher levels of trust and cooperative norms, even after adjusting for all relevant covariates. Heritage engagement frequency was found to moderate the association between historic built environment and personal relationships. Similarly, IMD was also found to moderate the association between historic built environment and trust and cooperative norms. CONCLUSION: These findings highlight the importance of neighbourhood environment in building social capital in communities. Particularly, areas with heritage assets may provide both socially inviting and aesthetically pleasing environments that could help strengthen community and restore pride in place.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Predictors of engaging in voluntary work during the COVID-19 pandemic: analyses of data from 31,890 adults in the UK.

AIMS: As the COVID-19 pandemic has grown internationally, there has been an increased need for volunteers. This study aimed to identify the predictors of volunteering including demographic backgrounds, socio-economic characteristics, personality, and psychosocial factors. METHODS: Data were analysed from 31,890 adults in the UK COVID-19 Social Study run by the University College London - a longitudinal study focusing on the psychological and social experiences of adults living in the UK during the COVID-19 pandemic. Tetrachoric factor analysis was applied to identify latent categories of voluntary work. Multivariate logistic regression was used to identity predictors for volunteering and change in volunteering behaviours since before the COVID-19 pandemic. RESULTS: Three types of volunteering during the pandemic were identified as follows: formal volunteering, social action volunteering, and neighbourhood volunteering. Regression analysis showed that the pattern of voluntary work was structured by demographic backgrounds, socio-economic factors, personality, and psychosocial factors. CONCLUSION: The predictors of volunteering during the pandemic may be slightly different from other non-emergency period.

Longitudinal changes in home-based arts engagement during and following the first national lockdown due to the COVID-19 pandemic in the UK.

AIMS: This study aimed to examine potential heterogeneity in longitudinal changes in home-based arts engagement during the first national lockdown and following gradual easing of restrictions in the UK. Furthermore, it sought to explore factors that were associated with patterns of longitudinal changes in home-based arts engagement. METHOD: Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 29,147 adults in the UK who were followed up for 22 weeks from 21 March to 21 August 2020. Data were analysed using growth mixture models. RESULTS: Our analyses identified five classes of growth trajectories. There were two stable classes showing little change in arts engagement over time (64.4% in total), two classes showing initial increases in arts engagement followed by declines as restrictions were eased (29.8%), and one class showing slight declines during strict lockdown followed by an increase in arts engagement after the easing of restrictions (5.9%). A range of factors were found to be associated with class membership of these arts engagement trajectories, such as age, gender, education, income, employment status, and health. CONCLUSION: There is substantial heterogeneity in longitudinal changes in home-based arts engagement. For participants whose engagement changed over time, growth trajectories of arts engagement were related to changes in lockdown measures. These findings suggest that some individuals may have drawn on the arts when they needed them the most, such as during the strict lockdown period, even if they usually had lower levels of arts engagement before the pandemic. Overall, our results indicate the importance of promoting arts engagement during pandemics and periods of lockdown as part of public health campaigns.

Reversible cerebral vasoconstriction syndrome with posterior leucoencephalopathy after oral contraceptive pills.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset recurrent 'thunderclap' headaches with reversible multifocal narrowing of the cerebral arteries, often associated with focal neurological deficits from ischaemic or haemorrhagic stroke. It has been associated with exposure to vasoconstrictive drugs, pregnancy, migraine, and a variety of other conditions. Whereas the pathophysiology of RCVS remains unclear, changes in the levels of female hormones are considered important because RCVS predominantly affects women and is frequently associated with pregnancy. We report a patient with angiographically confirmed RCVS whose MRI showed reversible brain oedema, suggesting an overlap between RCVS and the reversible posterior leucoencephalopathy syndrome. The only identified risk factor was oral contraceptive pills started 1 month prior to onset, supporting a role for female reproductive hormones in precipitating this overlap syndrome.

Coronary atherosclerosis using computed tomography coronary angiography in patients with systemic sclerosis.

BACKGROUND: Impaired coronary artery reserve has previously been demonstrated in patients with systemic sclerosis (SSc). Both micro- and macrovascular factors are probably contributory to the underlying pathogenesis. OBJECTIVES: To examine the frequency of coronary atherosclerosis in a series of SSc patients by computed tomography coronary angiography (CTCA), a less invasive method than conventional coronary angiography, the current gold standard in the detection of coronary atherosclerosis, and to explore its clinical associations. METHODS: Nineteen consecutive SSc patients [six with diffuse (dSSc) and 13 with limited disease (lSSc)] with disease duration of >or= 3 years were recruited. Coronary calcium score and contrast angiography were examined by CT scan. Conventional cardiovascular factors and inflammatory markers were measured and correlated with CT findings. RESULTS: The mean+/-SD age of these patients was 52.5+/-12.5 years with median disease duration of 12.5 years. Six (31.6%) patients were found to have coronary artery calcification (calcium score 13-2008). Coronary calcium was detected in one dSSc patient but contrast angiography was not performed because of interference from an in situ implantable cardiac device. Some parts of the coronary arteries were not assessable in two patients who had ectopic cardiac rhythm. Five lSSc patients had calcified plaques causing variable coronary luminal stenosis. All patients were asymptomatic. Patients with abnormal CTCA findings were more likely to be older (p < 0.001) and were less likely to have serum anti-Scl70 antibodies (p = 0.003) than those without, after Bonferroni correction. CONCLUSIONS: Coronary atherosclerosis is not uncommon in asymptomatic SSc patients. CTCA is a convenient and non-invasive method for studying coronary atherosclerosis.

CellCircuits: a database of protein network models.

CellCircuits (http://www.cellcircuits.org) is an open-access database of molecular network models, designed to bridge the gap between databases of individual pairwise molecular interactions and databases of validated pathways. CellCircuits captures the output from an increasing number of approaches that screen molecular interaction networks to identify functional subnetworks, based on their correspondence with expression or phenotypic data, their internal structure or their conservation across species. This initial release catalogs 2019 computationally derived models drawn from 11 journal articles and spanning five organisms (yeast, worm, fly, Plasmodium falciparum and human). Models are available either as images or in machine-readable formats and can be queried by the names of proteins they contain or by their enriched biological functions. We envision CellCircuits as a clearinghouse in which theorists may distribute or revise models in need of validation and experimentalists may search for models or specific hypotheses relevant to their interests. We demonstrate how such a repository of network models is a novel systems biology resource by performing several meta-analyses not currently possible with existing databases.

Adolescent Emotion Network Dynamics in Daily Life and Implications for Depression.

Emotion network density describes the degree of interdependence among emotion states across time. Higher density is theorized to reflect rigidity in emotion functioning and has been associated with depression in adult samples. This paper extended research on emotion networks to adolescents and examined associations between emotion network density and: 1) emotion regulation and 2) symptoms of depression. Data from a daily diary study (t = 21 days) of adolescents (N = 151; 61.59% female; mean age = 14.60 years) were used to construct emotion network density scores. Emotion regulation was measured using The Difficulties in Emotion Regulation Scale Short Form (DERS-SF). Depression was measured using the Revised Child Anxiety and Depression Scale-Short Version (RCADS-SV). Associations between emotion network density and DERS-SF were examined through Pearson correlations. Multiple regression analyses examined associations between emotion network density and depression. Emotion network density was not associated with the DERS-SF. Follow-up analyses showed that it was positively associated with non-acceptance of emotions (a subscale of the DERS-SF). Emotion network density was positively associated with RCADS-SV depression. Non-acceptance of emotions may encourage the spread of emotion across time and states given that a feature of non-acceptance is to have secondary emotional responses to one's emotions. Emotion networks that are self-predictive may be a risk factor for adolescent depression.

Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway.

Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are observed in human cancers. In addition to gain-of-function, loss of negative regulation also contributes to oncogenic activation of RTKs. Negative regulation of many RTKs involves their internalization and degradation in the lysosome, a process regulated through ubiquitination. RTK oncoproteins activated following chromosomal translocation, are no longer transmembrane proteins, and are predicted to escape lysosomal degradation. To test this, we used the Tpr-Met oncogene, generated following chromosomal translocation of the hepatocyte growth factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also lacks the binding site for Cbl ubiquitin ligases. We determined whether subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is important for oncogenic activity. Presence of a Cbl-binding site and ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to enter the endocytic pathway, and Tpr-Met transforming activity as well as protein stability are decreased in a Cbl-dependent manner. We show that transformation by Tpr-Met is in part dependent on its ability to escape normal downregulatory mechanisms. This provides a paradigm for many RTK oncoproteins activated following chromosomal translocation.

Use of suppressor mutants to probe the function of estrogen receptor-p160 coactivator interactions.

Estrogen-dependent recruitment of coactivators by estrogen receptor alpha (ERalpha) represents a crucial step in the transcriptional activation of target genes. However, studies of the function of individual coactivators has been hindered by the presence of endogenous coactivators, many of which are potentially recruited in the presence of agonist via a common mechanism. To circumvent this problem, we have generated second-site suppressor mutations in the nuclear receptor interaction domain of p160 coactivators which rescue their binding to a transcriptionally defective ERalpha that is refractory to wild-type coactivators. Analysis of these altered-specificity receptor-coactivator combinations, in the absence of interference from endogenous coregulators, indicated that estrogen-dependent transcription from reporter genes is critically dependent on direct recruitment of a p160 coactivator in mammalian cells and that the three p160 family members serve functionally redundant roles. Furthermore, our results suggest that such a change-of-specificity mutation may act as a transposable protein-protein interaction module which provides a novel tool with which to dissect the functional roles of other nuclear receptor coregulators at the cellular level.

Molecular determinants of the estrogen receptor-coactivator interface.

Transcriptional activation by the estrogen receptor is mediated through its interaction with coactivator proteins upon ligand binding. By systematic mutagenesis, we have identified a group of conserved hydrophobic residues in the ligand binding domain that are required for binding the p160 family of coactivators. Together with helix 12 and lysine 366 at the C-terminal end of helix 3, they form a hydrophobic groove that accommodates an LXXLL motif, which is essential for mediating coactivator binding to the receptor. Furthermore, we demonstrated that the high-affinity binding of motif 2, conserved in the p160 family, is due to the presence of three basic residues N terminal to the core LXXLL motif. The recruitment of p160 coactivators to the estrogen receptor is therefore likely to depend not only on the LXXLL motif making hydrophobic interactions with the docking surface on the receptor, but also on adjacent basic residues, which may be involved in the recognition of charged residues on the receptor to allow the initial docking of the motif.

Structural Brain Network Reorganization in Patients with Neuropsychiatric Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Patients with neuropsychiatric systemic lupus erythematosus have worse outcomes compared with those with systemic lupus erythematosus. A better understanding of the mechanisms of neuropsychiatric systemic lupus erythematosus could potentially improve diagnosis and management. The goal of this study was to investigate the differences in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus compared with patients with systemic lupus erythematosus by using brain connectivity analysis. MATERIALS AND METHODS: We recruited 20 subjects for each patient cohort and age-matched healthy controls. The topology and efficiency of the network and the characteristics of various brain hubs were investigated by using brain connectivity analysis of diffusion MR imaging data. RESULTS: There were more extensive reorganizations in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus than in patients with systemic lupus erythematosus. For example, the network of the former had significantly decreased clustering coefficient and local efficiency. They also had significantly lower nodal efficiency in the superior temporal gyrus (P = .046) and middle temporal gyrus (P = .041). CONCLUSIONS: Our results hint at a plausible relationship between the neuropsychiatric symptoms and reorganization of the structural brain network of patients with systemic lupus erythematosus. Brain connectivity analysis may be a potential tool to subtype these patients.

The State of Systems Genetics in 2017.

Cell Systems invited 16 experts to share their views on the field of systems genetics. In questions repeated in the headings, we asked them to define systems genetics, highlight its relevance to researchers outside the field, discuss what makes a strong systems genetics paper, and paint a picture of where the field is heading in the coming years. Their responses, ordered by the journal but otherwise unedited, make it clear that deciphering genotype to phenotype relationships is a central challenge of systems genetics and will require understanding how networks and higher-order properties of biological systems underlie complex traits. In addition, our experts illuminate the applications and relevance of systems genetics to human disease, the gut microbiome, development of tools that connect the global research community, sustainability, drug discovery, patient-specific disease and network models, and personalized treatments. Finally, a table of suggested reading provides a sample of influential work in the field.

Uterine fibroid embolisation in Chinese women: medium-term results.

OBJECTIVE: To evaluate the medium-term results of uterine fibroid embolisation in Chinese women with symptomatic uterine fibroids. DESIGN: Prospective case series study. SETTING: Gynaecology and Interventional Radiology units in a public hospital, Hong Kong. PATIENTS: Patients with symptomatic fibroids who underwent uterine fibroid embolisation in Queen Elizabeth Hospital from October 1998 to June 2004. RESULTS: Fifty women (mean age, 42.9 years; median follow-up period, 27.5 months) were recruited. Most (82%) had menorrhagia as the chief presenting symptom. Embolisation was successful in 49 (98%) women. Complications occurred in 12 (24%) patients, but were all self-limiting. Significant decrease in the median clinical uterine size (14 weeks vs 10 weeks) and median volume of the largest fibroid on magnetic resonance imaging (157.9 mL vs 45 mL) were observed during the first year. The reduction seemed to be maintained till the last follow-up. Menorrhagia improved in 34 (84%) patients, dysmenorrhoea in 28 (88%), pelvic pain in 18 (82%) and abdominal mass in 15 (83%). Poor response was found for urinary symptoms (29% improvement). Eight (16%) patients underwent hysterectomies after uterine fibroid embolisation. On logistic regression analysis, the only significant predictive factor for symptomatic improvement was fibroid volume reduction at 6 months (P=0.03). CONCLUSION: Uterine fibroid embolisation is an effective uterine-preserving therapy in patients with symptomatic fibroids; overall symptomatic improvement was estimated as 80%. Uterine or fibroid size reduction correlated well with clinical outcome. The impact of uterine fibroid embolisation on young women wishing to conceive is yet to be determined.

Trends in Precision Medicine: An Interview with UCSF's Atul Butte.

Atul Butte discusses large patient cohorts, non-genomic factors in precision medicine, mobile devices, and the outsourcing of experimental work.

Nocturnal oxygen saturation in normal and asthmatic children.

At sea level, it appears that oxygen desaturation does not occur in normal children at night and that the desaturation that occurs in moderately severe asthmatic children with therapeutic levels of theophylline does not approach dangerously low levels.

Usual interstitial pneumonitis in infancy. Clinical and pathologic evaluation.

Interstitial lung disease is uncommon in infancy and childhood, and the long-term clinical and pathologic evolution of this entity in infants has not been published previously. We describe an infant with a steroid-sensitive chronic interstitial pneumonitis for which the clinical and histopathologic progression of the disease are presented. A family history of interstitial pneumonitis consistent with an autosomal dominant trait was present, and Pneumocystis carinii were found in the lung biopsy specimen.