Does the housing market reflect cultural heritage? A case study of Greater Dublin

Does the housing market reflect cultural heritage? We estimate several specifications of a hedonic price equation to establish whether distance to cultural heritage site is capitalised into housing prices in Greater Dublin, Ireland. The results show that distance to the nearest historic building has a significant and robust effect on housing prices. To our knowledge this is the first application of the hedonic price method to cultural heritage

Physical and mental quality of life in patients with end-stage liver disease and their informal caregivers

Background & Aims Management of end-stage liver disease (ESLD) has implications for not only patients’ quality of life (QOL), but also their caregivers’. We aimed to identify characteristics of patients with ESLD and their caregivers that are associated with QOL. Methods We obtained cross-sectional baseline data from patients and their caregivers (132 dyads; 62% were married or partners), recruited from outpatient hepatology clinics within 2 healthcare centers. Patients were included if their model for end-stage liver disease score was 15 or more; caregivers were identified by the patient as the primary informal caregiver. QOL was measured by the SF-36 and relationship quality using the mutuality scale. We measured uncertainty using the uncertainty in illness scales for patients and caregivers. Multilevel modeling was used to analyze the data. Results Refractory ascites was associated with worse physical QOL for patients (unstandardized beta [B], –9.19; standard error [SE], 2.28) and caregivers (B, –5.41; SE, 2.33); history of hepatic encephalopathy was associated with worse patient physical QOL (B, –3.86; SE, 1.65). High levels of uncertainty were associated with worse physical and mental QOL for both members of the dyads; relationship quality was significantly associated with patient mental QOL (B, 2.73; SE, 1.19). Conclusions Clinicians and researchers should consider the effects of ESLD on caregivers as well as their patients to optimize the QOL for both

Determinants of Heart Failure Self-Care Maintenance and Management in Patients and Caregivers: A Dyadic Analysis

Disease self-management is a critical component of maintaining clinical stability for patients with chronic illness. This is particularly evident in the context of heart failure (HF), which is the leading cause of hospitalization for older adults. HF self-management, commonly known as HF self-care, is often performed with the support of informal caregivers. However, little is known about how a HF dyad manages the patient\u27s care together. The purpose of this study was to identify determinants of patient and caregiver contributions to HF self-care maintenance (daily adherence and symptom monitoring) and management (appropriate recognition and response to symptoms), utilizing an approach that controls for dyadic interdependence. This was a secondary analysis of cross-sectional data from 364 dyads of Italian HF patients and caregivers. Multilevel modeling was used to identify determinants of HF self-care within patient-caregiver dyads. Patients averaged 76.2 (SD = 10.7) years old, and a slight majority (56.9%) was male, whereas caregivers averaged 57.4 (SD = 14.6) years old, and about half (48.1%) were male. Most caregivers were adult children (48.4%) or spouses (32.7%) of patients. Both patients and caregivers reported low levels of HF maintenance and management behaviors. Significant individual and dyadic determinants of self-care maintenance and self-care management included gender, quality of life, comorbid burden, impaired ADLs, cognition, hospitalizations, HF duration, relationship type, relationship quality, and social support. These comprehensive dyadic models assist in elucidating the complex nature of patient-caregiver relationships and their influence on HF self-care, leading to more effective ways to intervene and optimize outcomes

A Dyadic Approach to Managing Heart Failure with Confidence

Background: The majority of heart failure (HF) self-care research remains focused on patients, despite the important involvement of family caregivers. Although self-care confidence has been found to play an important role in the effectiveness of HF self-care management on patient outcomes, no known research has examined self-care confidence within a dyadic context. Objective: The purpose of this study was to identify individual and dyadic determinants of self-care confidence in HF care dyads. Methods: Multilevel modeling, which controls for the interdependent nature of dyadic data, was used to examine 329 Italian HF dyads (caregivers were either spouses or adult children). Results: Both patients and caregivers reported lower-than-adequate levels of confidence, with caregivers reporting slightly higher confidence than patients. Patient and caregiver levels of confidence were significantly associated with greater patient-reported relationship quality and better caregiver mental health. Patient confidence in self-care was significantly associated with patient female gender, nonspousal care dyads, poor caregiver physical health, and low care strain. Caregiver confidence to contribute to self-care was significantly associated with poor emotional quality of life in patients and greater perceived social support by caregivers. Conclusions: Findings are supportive of the need for a dyadic perspective of HF self-care in practice and research as well as the importance of addressing the needs of both members of the dyad to maximize optimal outcomes for both

Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.Fil: Wu, Ling. University of California at Los Angeles; Estados UnidosFil: Bluguermann, Carolina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados UnidosFil: Kyupelyan, Levon. University of California at Los Angeles; Estados UnidosFil: Latour, Brooke. University of California at Los Angeles; Estados UnidosFil: Gonzalez, Stephanie. University of California at Los Angeles; Estados UnidosFil: Shah, Saumya. University of California at Los Angeles; Estados UnidosFil: Galic, Zoran. University of California at Los Angeles; Estados UnidosFil: Ge, Sundi. University of California at Los Angeles; Estados UnidosFil: Zhu, Yuhua. University of California at Los Angeles; Estados UnidosFil: Petrigliano, Frank A.. University of California at Los Angeles; Estados UnidosFil: Nsair, Ali. University of California at Los Angeles; Estados UnidosFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Li, Xinmin. University of California at Los Angeles; Estados UnidosFil: Lyons, Karen M.. University of California at Los Angeles; Estados UnidosFil: Crooks, Gay M.. University of California at Los Angeles; Estados UnidosFil: McAllister, David R.. University of California at Los Angeles; Estados UnidosFil: Van Handel, Ben. Novogenix Laboratories; Estados UnidosFil: Adams, John S.. University of California at Los Angeles; Estados UnidosFil: Evseenko, Denis. University of California at Los Angeles; Estados Unido

Heart Failure Symptom Biology in Response to Ventricular Assist Device Implantation.

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF. METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], depression [Patient Health Questionnaire], and anxiety [Brief Symptom Inventory]) and peripheral biomarkers of myocardial stretch, systemic inflammation, and hypervolumetric mechanical stress were measured before implantation with a commercially available LVAD and again at 30, 90, and 180 days after LVAD implantation. Latent growth curve and parallel process modeling were used to describe changes in symptoms and biomarkers and the degree to which they change in parallel in response to LVAD implantation. RESULTS: In response to LVAD implantation, changes in myocardial stretch were closely associated with changes in early and subtle physical symptoms as well as depression, and changes in hypervolumetric stress were closely associated with changes in pain severity and wake disturbances. Changes in systemic inflammation were not closely associated with changes in physical or affective symptoms in response to LVAD implantation. CONCLUSIONS: These findings provide new insights into the many ways in which symptoms and biomarkers provide concordant or discordant information about LVAD response

Childhood asthma prevalence: cross-sectional record linkage study comparing parent-reported wheeze with general practitioner-recorded asthma diagnoses from primary care electronic health records in Wales

Introduction Electronic health records (EHRs) are increasingly used to estimate the prevalence of childhood asthma. The relation of these estimates to those obtained from parent-reported wheezing suggestive of asthma is unclear. We hypothesised that parent-reported wheezing would be more prevalent than general practitioner (GP)-recorded asthma diagnoses in preschool-aged children. Methods 1529 of 1840 (83%) Millennium Cohort Study children registered with GPs in the Welsh Secure Anonymised Information Linkage databank were linked. Prevalences of parent-reported wheezing and GP-recorded asthma diagnoses in the previous 12 months were estimated, respectively, from parent report at ages 3, 5, 7 and 11 years, and from Read codes for asthma diagnoses and prescriptions based on GP EHRs over the same time period. Prevalences were weighted to account for clustered survey design and non-response. Cohen’s kappa statistics were used to assess agreement. Results Parent-reported wheezing was more prevalent than GP-recorded asthma diagnoses at 3 and 5 years. Both diminished with age: by age 11, prevalences of parent-reported wheezing and GP-recorded asthma diagnosis were 12.9% (95% CI 10.6 to 15.4) and 10.9% (8.8 to 13.3), respectively (difference: 2% (−0.5 to 4.5)). Other GP-recorded respiratory diagnoses accounted for 45.7% (95% CI 37.7 to 53.9) and 44.8% (33.9 to 56.2) of the excess in parent-reported wheezing at ages 3 and 5 years, respectively. Conclusion Parent-reported wheezing is more prevalent than GP-recorded asthma diagnoses in the preschool years, and this difference diminishes in primary school aged children. Further research is needed to evaluate the implications of these differences for the characterisation of longitudinal childhood asthma phenotypes from EHRs

Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life

BACKGROUND: Low-dose-rate permanent prostate brachytherapy (PPB) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes. As standard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity, this exploratory (proof of concept) study was conducted to investigate correlations between radiation − induced DNA damage biomarker levels, and acute and late bowel, urinary, and sexual toxicity. METHODS: Twelve patients treated with (125)I PPB monotherapy (145Gy) for prostate cancer were included in this prospective study. Post-implant CT based dosimetry assessed the minimum dose encompassing 90% (D(90%)) of the whole prostate volume (global), sub-regions of the prostate (12 sectors) and the near maximum doses (D(0.1cc), D(2cc)) for the rectum and bladder. Six blood samples were collected from each patient; pre-treatment, 1 h (h), 4 h, 24 h post-implant, at 4 weeks (w) and at 3 months (m). DNA double strand breaks were investigated by staining the blood samples with immunofluorescence antibodies to γH2AX and 53BP1 proteins (γH2AX/53BP1). Patient self-scored quality of life from the Expanded Prostate Cancer Index Composite (EPIC) were obtained at baseline, 1 m, 3 m, 6 m, 9 m, 1 year (y), 2y and 3y post-treatment. Spearman’s correlation coefficients were used to evaluate correlations between temporal changes in γH2AX/53BP1, dose and toxicity. RESULTS: The minimum follow up was 2 years. Population mean prostate D(90%) was 144.6 ± 12.1 Gy and rectal near maximum dose D(0.1cc) = 153.0 ± 30.8 Gy and D(2cc) = 62.7 ± 12.1 Gy and for the bladder D(0.1cc) = 123.1 ± 27.0 Gy and D(2cc) = 70.9 ± 11.9 Gy. Changes in EPIC scores from baseline showed high positive correlation between acute toxicity and late toxicity for both urinary and bowel symptoms. Increased production of γH2AX/53BP1 at 24 h relative to baseline positively correlated with late bowel symptoms. Overall, no correlations were observed between dose metrics (prostate global or sector doses) and γH2AX/53BP1 foci counts. CONCLUSIONS: Our results show that a prompt increase in γH2AX/53BP1foci at 24 h post-implant relative to baseline may be a useful measure to assess elevated risk of late RT − related toxicities for PPB patients. A subsequent investigation recruiting a larger cohort of patients is warranted to verify our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13014-017-0792-1) contains supplementary material, which is available to authorized users

Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.

BACKGROUND:ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methylation patterns that could be used in the molecular diagnosis of ADNP syndrome. RESULTS: We identified two distinct and partially opposing genomic DNA methylation episignatures in the peripheral blood samples from 22 patients with ADNP syndrome. The epi-ADNP-1 episignature included ~ 6000 mostly hypomethylated CpGs, and the epi-ADNP-2 episignature included ~ 1000 predominantly hypermethylated CpGs. The two signatures correlated with the locations of the ADNP mutations. Epi-ADNP-1 mutations occupy the N- and C-terminus, and epi-ADNP-2 mutations are centered on the nuclear localization signal. The episignatures were enriched for genes involved in neuronal system development and function. A classifier trained on these profiles yielded full sensitivity and specificity in detecting patients with either of the two episignatures. Applying this model to seven patients with uncertain clinical diagnosis enabled reclassification of genetic variants of uncertain significance and assigned new diagnosis when the primary clinical suspicion was not correct. When applied to a large cohort of unresolved patients with developmental delay (N = 1150), the model predicted three additional previously undiagnosed patients to have ADNP syndrome. DNA sequencing of these subjects, wherever available, identified pathogenic mutations within the gene domains predicted by the model. CONCLUSIONS: We describe the first Mendelian condition with two distinct episignatures caused by mutations in a single gene. These highly sensitive and specific DNA methylation episignatures enable diagnosis, screening, and genetic variant classifications in ADNP syndrome

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations