Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake

Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time

ARIADNEplus Data Aggregation Pipeline:User Guide (2.4)

The purpose of this User Guide is to provide a short introduction to the ARIADNEplus data aggregation pipeline. It defines, for the archaeological data providers, the process by which their data should be uploaded to the ARIADNE Content Cloud, so that it appears in the ARIADNEplus Catalogue, and can be searched via the ARIADNEplus Portal

The Impact of Vitamin D Supplementation on Musculoskeletal Health Outcomes in Children, Adolescents, and Young Adults living with HIV:A Systematic Review

OBJECTIVE: HIV-positive children, adolescents, and young adults are at increased risk poor musculoskeletal outcomes. Increased incidence of vitamin D deficiency in youth living with HIV may further adversely affect musculoskeletal health. We investigated the impact of vitamin D supplementation on a range of musculoskeletal outcomes among individuals aged 0-25 years living with HIV. METHODS: A systematic review was conducted using databases: PubMed/Medline, CINAHL, Web of Knowledge, and EMBASE. Interventional randomised control trials, quasi-experimental trials, and previous systematic reviews/meta-analyses were included. Outcomes included: BMD, BMC, fracture incidence, muscle strength, linear growth (height-for-age Z-score [HAZ]), and biochemical/endocrine biomarkers including bone turnover markers. RESULTS: Of 497 records, 20 studies met inclusion criteria. Thirteen studies were conducted in North America, one in Asia, two in Europe, and four in Sub-Saharan Africa. High-dose vitamin D supplementation regimens (1,000-7,000 IU/day) were successful in achieving serum 25-hydroxyvitamin-D (25OHD) concentrations above study-defined thresholds. No improvements were observed in BMD, BMC, or in muscle power, force and strength; however, improvements in neuromuscular motor skills were demonstrated. HAZ was unaffected by low-dose (200-400 IU/day) supplementation. A single study found positive effects on HAZ with high-dose supplementation (7,000 vs 4,000IU/day). CONCLUSIONS: Measured bone outcomes were unaffected by high-dose vitamin D supplementation, even when target 25OHD measurements were achieved. This may be due to: insufficient sample size, follow-up, intermittent dosing, non-standardised definitions of vitamin D deficiency, or heterogeneity of enrolment criteria pertaining to baseline vitamin D concentration. High-dose vitamin D may improve HAZ and neuromuscular motor skills. Adequately powered trials are needed in settings where HIV burden is greatest. PROSPERO Number: CRD42016042938

Surgical ward rounds in England: a trainee-led multi-centre study of current practice

BACKGROUND: Recent guidance advocates daily consultant-led ward rounds, conducted in the morning with the presence of senior nursing staff and minimising patients on outlying wards. These recommendations aim to improve patient management through timely investigations, treatment and discharge. This study sought to evaluate the current surgical ward round practices in England. METHODS: Information regarding timing and staffing levels of surgical ward rounds was collected prospectively over a one-week period. The location of each patient was also documented. Two surgical trainee research collaboratives coordinated data collection from 19 hospitals and 13 surgical subspecialties. RESULTS: Data from 471 ward rounds involving 5622 patient encounters was obtained. 367 (77.9%) ward rounds commenced before 9am. Of 422 weekday rounds, 190 (45%) were consultant-led compared with 33 of the 49 (67%) weekend rounds. 2474 (44%) patients were seen with a nurse present. 1518 patients (27%) were classified as outliers, with 361 ward rounds (67%) reporting at least one outlying patient. CONCLUSION: Recommendations for daily consultant-led multi disciplinary ward rounds are poorly implemented in surgical practice, and patients continue to be managed on outlying wards. Although strategies may be employed to improve nursing attendance on ward rounds, substantial changes to workforce planning would be required to deliver daily consultant-led care. An increasing political focus on patient outcomes at weekends may prompt changes in these areas

Lessons from Love-Locks: The archaeology of a contemporary assemblage

This document is the Accepted Manuscript version. The final, definitive version of this paper has been published in Journal of Material Culture, November 2017, published by SAGE Publishing, All rights reserved.Loss of context is a challenge, if not the bane, of the ritual archaeologist’s craft. Those who research ritual frequently encounter difficulties in the interpretation of its often tantalisingly incomplete material record. Careful analysis of material remains may afford us glimpses into past ritual activity, but our often vast chronological separation from the ritual practitioners themselves prevent us from seeing the whole picture. The archaeologist engaging with structured deposits, for instance, is often forced to study ritual assemblages post-accumulation. Many nuances of its formation, therefore, may be lost in interpretation. This paper considers what insights an archaeologist could gain into the place, people, pace, and purpose of deposition by recording an accumulation of structured deposits during its formation, rather than after. To answer this, the paper will focus on a contemporary depositional practice: the love-lock. This custom involves the inscribing of names/initials onto a padlock, its attachment to a bridge or other public structure, and the deposition of the corresponding key into the water below; a ritual often enacted by a couple as a statement of their romantic commitment. Drawing on empirical data from a three-year diachronic site-specific investigation into a love-lock bridge in Manchester, UK, the author demonstrates the value of contemporary archaeology in engaging with the often enigmatic material culture of ritual accumulations.Peer reviewe

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised

Enabling European archaeological research: The ARIADNE E-infrastructure

Research e-infrastructures, digital archives and data services have become important pillars of scientific enterprise that in recent decades has become ever more collaborative, distributed and data-intensive. The archaeological research community has been an early adopter of digital tools for data acquisition, organisation, analysis and presentation of research results of individual projects. However, the provision of einfrastructure and services for data sharing, discovery, access and re-use has lagged behind. This situation is being addressed by ARIADNE: the Advanced Research Infrastructure for Archaeological Dataset Networking in Europe. This EUfunded network has developed an einfrastructure that enables data providers to register and provide access to their resources (datasets, collections) through the ARIADNE data portal, facilitating discovery, access and other services across the integrated resources. This article describes the current landscape of data repositories and services for archaeologists in Europe, and the issues that make interoperability between them difficult to realise. The results of the ARIADNE surveys on users' expectations and requirements are also presented. The main section of the article describes the architecture of the einfrastructure, core services (data registration, discovery and access) and various other extant or experimental services. The ongoing evaluation of the data integration and services is also discussed. Finally, the article summarises lessons learned, and outlines the prospects for the wider engagement of the archaeological research community in sharing data through ARIADNE

Feeling Healthy? A Survey of Physical and Psychological Wellbeing of Students from Seven Universities in the UK

University students’ physical and psychological health and wellbeing are important and comprise many variables. This study assessed perceived health status in addition to a range of physical and psychological wellbeing indicators of 3,706 undergraduate students from seven universities in England, Wales and Northern Ireland. We compared differences in these variables across males and females, and across the participating universities. The data was collected in 2007–2008. A self-administered questionnaire assessed socio-demographic information (e.g., gender, age), self-reported physical and psychological health data, as well as questions on health awareness, health service use, social support, burdens and stressors and university study related questions. While females generally reported more health problems and psychological burdens, male students felt that they received/had fewer persons to depend on for social support. The comparisons of health and wellbeing variables across the different universities suggested some evidence of ‘clustering’ of the variables under study, whereby favourable situations would be exhibited by a cluster of the variables that is encountered at some universities; and conversely, the clustering of less favourable variables as exhibited at other universities. We conclude that the level of health complaints and psychological problems/burdens is relatively high and calls for increased awareness of university administrators, leaders and policy makers to the health and well-being needs of their students. The observed clustering effects also indicated the need for local (university-specific) health and wellbeing profiles as basis and guidance for relevant health promotion programmes at universities

Engagement and Action for Health: The Contribution of Leaders’ Collaborative Skills to Partnership Success

A multi-site evaluation (survey) of five Kellogg-funded Community Partnerships (CPs) in South Africa was undertaken to explore the relationship between leadership skills and a range of 30 operational, functional and organisational factors deemed critical to successful CPs. The CPs were collaborative academic-health service-community efforts aimed at health professions education reforms. The level of agreement to eleven dichotomous (‘Yes/No’) leadership skills items was used to compute two measures of members’ appreciation of their CPs’ leadership. The associations between these measures and 30 CPs factors were explored, and the partnership factors that leadership skills explained were assessed after controlling. Respondents who perceived the leadership of their CPs favourably had more positive ratings across 30 other partnership factors than those who rated leadership skills less favourably, and were more likely to report a positive cost/ benefit ratio. In addition, respondents who viewed their CPs’ leadership positively also rated the operational understanding, the communication mechanisms, as well as the rules and procedures of the CPs more favourably. Leadership skills explained between 20% and 7% of the variance of 10 partnership factors. The influence of leaders’ skills in effective health-focussed partnerships is much broader than previously conceptualised

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types