Functionality of primary hepatic non-parenchymal cells in a 3D spheroid model and contribution to acetaminophen hepatotoxicity.

In addition to hepatocytes, the liver comprises a host of specialised non-parenchymal cells which are important to consider in the development of in vitro models which are both physiologically and toxicologically relevant. We have characterized a 3D co-culture system comprising primary human hepatocytes (PHH) and non-parenchymal cells (NPC) and applied it to the investigation of acetaminophen-induced toxicity. Firstly, we titrated ratios of PHH:NPC and confirmed the presence of functional NPCs via both immunohistochemistry and activation with both LPS and TGF-β. Based on these data we selected a ratio of 2:1 PHH:NPC for further studies. We observed that spheroids supplemented with NPCs were protected against acetaminophen (APAP) toxicity as determined by ATP (up to threefold difference in EC50 at day 14 compared to hepatocytes alone) and glutathione depletion, as well as miR-122 release. APAP metabolism was also altered in the presence of NPCs, with significantly lower levels of APAP-GSH detected. Expression of several CYP450 enzymes involved in the bioactivation of APAP was also lower in NPC-containing spheroids. Spheroids containing NPCs also expressed higher levels of miRNAs which have been implicated in APAP-induced hepatotoxicity, including miR-382 and miR-155 which have potential roles in liver regeneration and inflammation, respectively. These data indicate that the interaction between hepatocytes and NPCs can have significant metabolic and toxicological consequences important for the correct elucidation of hepatic safety mechanisms

Change in level of physical activity during pregnancy in obese women: findings from the UPBEAT pilot trial

Background: Maternal obesity is associated with an increased risk of pregnancy complications, including gestational diabetes. Physical activity (PA) might improve glucose metabolism and reduce the incidence of gestational diabetes. The purpose of this study was to explore patterns of PA and factors associated with change in PA in obese pregnant women. Methods: PA was assessed objectively by accelerometer at 16 – 18 weeks’ (T0), 27 – 28 weeks’ (T1) and 35 – 36 weeks’ gestation (T2) in 183 obese pregnant women recruited to a pilot randomised trial of a combined diet and PA intervention (the UPBEAT study). Results: Valid PA data were available for 140 (77%), 76 (42%) and 54 (30%) women at T0, T1 and T2 respectively. Moderate and vigorous physical activity as a proportion of accelerometer wear time declined with gestation from a median of 4.8% at T0 to 3% at T2 (p < 0.05). Total activity as a proportion of accelerometer wear time did not change. Being more active in early pregnancy was associated with a higher level of PA later in pregnancy. The intervention had no effect on PA. Conclusions: PA in early pregnancy was the factor most strongly associated with PA at later gestations. Women should be encouraged to participate in PA before becoming pregnant and to maintain their activity levels during pregnancy. There is a need for effective interventions, tailored to the needs of individuals and delivered early in pregnancy to support obese women to be sufficiently active during pregnancy. Trial registration: Current Controlled Trials ISRCTN89971375 (Registered 28/11/2008)

Partnering with Patients and Families to Improve Diagnostic Safety through the OurDX Tool: Effects of Race, Ethnicity, and Language Preference

BACKGROUND: Patients and families at risk for health disparities may also be at higher risk for diagnostic errors but less likely to report them. OBJECTIVES: This study aimed to explore differences in race, ethnicity, and language preference associated with patient and family contributions and concerns using an electronic previsit tool designed to engage patients and families in the diagnostic process (DxP). METHODS: Cross-sectional study of 5,731 patients and families presenting to three subspecialty clinics at an urban pediatric hospital May to December 2021 who completed a previsit tool, codeveloped and tested with patients and families. Prior to each visit, patients/families were invited to share visit priorities, recent histories, and potential diagnostic concerns. We used logistic regression to determine factors associated with patient-reported diagnostic concerns. We conducted chart review on a random subset of visits to review concerns and determine whether patient/family contributions were included in the visit note. RESULTS: Participants provided a similar mean number of contributions regardless of patient race, ethnicity, or language preference. Compared with patients self-identifying as White, those self-identifying as Black (odds ratio [OR]: 1.70; 95% confidence interval [CI]: [1.18, 2.43]) or other race (OR: 1.48; 95% CI: [1.08, 2.03]) were more likely to report a diagnostic concern. Participants who preferred a language other than English were more likely to report a diagnostic concern than English-preferring patients (OR: 2.53; 95% CI: [1.78, 3.59]. There were no significant differences in physician-verified diagnostic concerns or in integration of patient contributions into the note based on race, ethnicity, or language preference. CONCLUSION: Participants self-identifying as Black or other race, or those who prefer a language other than English were 1.5 to 2.5 times more likely than their counterparts to report potential diagnostic concerns when proactively asked to provide this information prior to a visit. Actively engaging patients and families in the DxP may uncover opportunities to reduce the risk of diagnostic errors and potential safety disparities

Understanding young people's transitions in university halls through space and time

This article contributes to the theoretical discussion about young people's transitions through space and time. Space and time are complex overarching concepts that have creative potential in deepening understanding of transition. The focus of this research is young people's experiences of communal living in university halls. It is argued that particular space-time concepts draw attention to different facets of experience and in combination deepen the understanding of young people's individual and collective transitions. The focus of the article is the uses of the space-time concepts 'routine', 'representation', 'rhythm' and 'ritual' to research young people's experiences. The article draws on research findings from two studies in the North of England. © 2010 SAGE Publications

The dark matter environment of the Abell 901/902 supercluster: a weak lensing analysis of the HST STAGES survey

We present a high resolution dark matter reconstruction of the z=0.165 Abell 901/902 supercluster from a weak lensing analysis of the HST STAGES survey. We detect the four main structures of the supercluster at high significance, resolving substructure within and between the clusters. We find that the distribution of dark matter is well traced by the cluster galaxies, with the brightest cluster galaxies marking out the strongest peaks in the dark matter distribution. We also find a significant extension of the dark matter distribution of Abell 901a in the direction of an infalling X-ray group Abell 901alpha. We present mass, mass-to-light and mass-to-stellar mass ratio measurements of the structures and substructures that we detect. We find no evidence for variation of the mass-to-light and mass-to-stellar mass ratio between the different clusters. We compare our space-based lensing analysis with an earlier ground-based lensing analysis of the supercluster to demonstrate the importance of space-based imaging for future weak lensing dark matter 'observations'.Comment: 13 pages, 6 figures and 4 tables. Accepted for publication in MNRA

Why is it difficult to implement e-health initiatives? A qualitative study

&lt;b&gt;Background&lt;/b&gt; The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&#38;B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Use of abstraction and discharge data to improve the performance of a national‐scale hydrological model

Across the UK, water abstracted from ground, surface, and tidal stores is regulated through a system of licenses to protect both the sources and the environment. Similar permits are required for discharging wastewater to rivers or onto the ground. These abstractions and discharges can have a significant impact on UK Rivers, but measurements are not readily available, which discourages their use in hydrological models of river flows. However, these very unique data sets provide a means to improve the performance of spatially distributed hydrological models, particularly during periods when abstraction regulations change and at ungauged river locations. To demonstrate this, point source abstraction and discharge measurements across England have been transformed into 1 × 1 km resolution gridded data and used with an enhanced formulation of the Grid-to-Grid (G2G) hydrological model where these processes are mathematically represented. A comparison of G2G-simulated and gauged river flows for 605 catchments across England between 1999 and 2014 indicates that model simulation of river flows is generally improved at gauged locations downstream of abstraction/discharge sites. The main improvement is in the simulation of low flows, for which the median performance is improved by 10.7%, however, the impact on simulation of high river flows is more modest (1.5% improvement). These results demonstrate the potential gains available to the international hydrological and land-surface modeling community from using records of actual water use (where available) in models, in place of more widely used national statistics

Inflammation and acute traffic-related air pollution exposures among a cohort of youth with type 1 diabetes

Background: Evidence remains equivocal regarding the association of inflammation, a precursor to cardiovascular disease, and acute exposures to ambient air pollution from traffic-related particulate matter. Though youth with type 1 diabetes are at higher risk for cardiovascular disease, the relationship of inflammation and ambient air pollution exposures in this population has received little attention. Objectives: Using five geographically diverse US sites from the racially- and ethnically-diverse SEARCH for Diabetes in Youth Cohort, we examined the relationship of acute exposures to PM2.5 mass, Atmospheric Dispersion Modeling System (ADMS)-Roads traffic-related PM concentrations near roadways, and elemental carbon (EC) with biomarkers of inflammation including interleukin-6 (IL-6), c-reactive protein (hs-CRP) and fibrinogen. Methods: Baseline questionnaires and blood were obtained at a study visit. Using a spatio-temporal modeling approach, pollutant exposures for 7 days prior to blood draw were assigned to residential addresses. Linear mixed models for each outcome and exposure were adjusted for demographic and lifestyle factors identified a priori. Results: Among the 2566 participants with complete data, fully-adjusted models showed positive associations of EC average week exposures with IL-6 and hs-CRP, and PM2.5 mass exposures on lag day 3 with IL-6 levels. Comparing the 25th and 75th percentiles of average week EC exposures resulted in 8.3% higher IL-6 (95%CI: 2.7%,14.3%) and 9.8% higher hs-CRP (95%CI: 2.4%,17.7%). We observed some evidence of effect modification for the relationships of PM2.5 mass exposures with hs-CRP by gender and with IL-6 by race/ethnicity. Conclusions: Indicators of inflammation were associated with estimated traffic-related air pollutant exposures in this study population of youth with type 1 diabetes. Thus youth with type 1 diabetes may be at increased risk of air pollution-related inflammation. These findings and the racial/ethnic and gender differences observed deserve further exploration

Objectively measured physical activity during pregnancy: a study in obese and overweight women.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Obese and overweight women may benefit from increased physical activity (PA) during pregnancy. There is limited published data describing objectively measured PA in such women. METHODS: A longitudinal observational study of PA intensity, type and duration using objective and subjective measurement methods. Fifty five pregnant women with booking body mass index (BMI) ≥ 25 kg/m2 were recruited from a hospital ultrasound clinic in North East England. 26 (47%) were nulliparous and 22 (40%) were obese (BMI ≥ 30 kg/m2). PA was measured by accelerometry and self report questionnaire at 13 weeks, 26 weeks and/or 36 weeks gestation. Outcome measures were daily duration of light, moderate or vigorous activity assessed by accelerometry; calculated overall PA energy expenditure, (PAEE), and PAEE within four domains of activity based on self report. RESULTS: At median 13 weeks gestation, women recorded a median 125 mins/day light activity and 35 mins/day moderate or vigorous activity (MVPA). 65% achieved the minimum recommended 30 mins/day MVPA. This proportion was maintained at 26 weeks (62%) and 36 weeks (71%). Women achieving more than 30 mins/day MVPA in the first trimester showed a significant reduction in duration of MVPA by the third trimester (11 mins/day, p = 0.003). Walking, swimming and floor exercises were the most commonly reported recreational activities but their contribution to estimated energy expenditure was small. CONCLUSION: Overweight and obese pregnant women can achieve and maintain recommended levels of PA throughout pregnancy. Interventions to promote PA should target changes in habitual activities at work and at home, and in particular walking.Published versio