Ageing Biomarkers and their role in the development of an aged skin model in vitro

Ageing describes the decreased functionality and inability to resist physiological stress exhibited by all tissues as they get older. The skin is no exception to this rule; experiencing both intrinsic and extrinsic ageing which results in the remodelling of the entire tissue through degradation of extracellular matrix (ECM) proteins. In recent years, advancements in 2D cell culture and 3D bioengineered skin models have begun to help us better understand the workings of human skin. However, there is a need for the development of an ‘aged’ skin model, which would offer an innovative opportunity to further explore the ageing process, in a realistic, reproducible and readily available format. A key aspect of any ageing model, is that it must exhibit changes in biomarkers that have been linked to in vivo skin ageing. With this in mind, this project aims to identify key biomarkers of ageing through analysis of both mRNA and protein levels; specifically focusing on the dermal compartment

Investigating the impact of the 2D mechanical environment on skin cells cultured in vitro

Mechanotransduction describes a cell’s ability to sense mechanical stimuli imparted by its surroundings and translate them into biochemical signals. These signals subsequently influence cell behaviour by promoting remodelling of the cytoskeleton, changes to gene expression and tumour suppression. This is particularly important for tissues with a high cell turnover like the skin. Fibroblasts and keratinocytes, the skin’s predominant cell populations, have been shown to respond to physical stimuli such as stretch, compression and shear forces, leading to changes in collagen deposition, and proliferation and migration. During in vitro cell culture it is conventional to use extremely stiff substrates that do not reflect the physiological microenvironment (e.g., plastic and glass). Whilst there have been attempts to limit this issue with the development of 3D tissue models, cells are still first being cultured, or “primed”, on a highly stiff surface. The aim of this project was to investigate keratinocyte and fibroblast behaviour, phenotype, and genotype expression when cultured on biomimetic hydrogel-coated dishes with similar mechanical properties to their in vivo environment. It was hypothesised that optimisation of this 2D culture environment would facilitate the development of 3D skin equivalents that better reflected in vivo tissue than current models grown from cells primed on plastic. This study showed that primary keratinocytes and fibroblasts cultured on biomimetic substrates were more reminiscent of cells in quiescent skin rather than the activated phenotype observed on plastic. Keratinocytes exhibited reduced nuclear and cytoplasmic stiffness in response to a 4 kPa culture substrate, and changes were observed in the expression of proliferation and differentiation markers, and proteins involved in mechanosensing. Epidermal 3D models produced using keratinocytes primed on 50 kPa dishes were thicker and better organised. Fibroblasts cultured on soft 2D substrates of 1 kPa and 4 kPa were observed to have fewer reactive oxygen species and expressed fewer DNA damage markers following irradiation to induce senescence

The Energetic Gamma-Ray Experiment Telescope (EGRET) Science Symposium

The principle purpose of this symposium is to provide the EGRET (Energetic Gamma-Ray Experiment Telescope) scientists with an opportunity to study and improve their understanding of high energy gamma ray astronomy. The Symposium began with the galactic diffusion radiation both because of its importance in studying galactic cosmic rays, galactic structure, and dynamic balance, and because an understanding of its characteristics is important in the study of galactic sources. The galactic objects to be reviewed included pulsars, bursts, solar flares, and other galactic sources of several types. The symposium papers then proceeded outward from the Milky Way to normal galaxies, active galaxies, and the extragalactic diffuse radiation

Development of a telescope for medium-energy gamma-ray astronomy

The Advanced Energetic Pair Telescope (AdEPT) is being developed at GSFC as a future NASA MIDEX mission to explore the medium-energy (5–200 MeV) gamma-ray range. The enabling technology for AdEPT is the Three- Dimensional Track Imager (3-DTI), a gaseous time projection chamber. The high spatial resolution 3-D electron tracking of 3-DTI enables AdEPT to achieve high angular resolution gamma-ray imaging via pair production and triplet production (pair production on electrons) in the medium-energy range. The low density and high spatial resolution of 3-DTI allows the electron positron track directions to be measured before they are dominated by Coulomb scattering. Further, the significant reduction of Coulomb scattering allows AdEPT to be the first medium-energy gamma-ray telescope to have high gamma-ray polarization sensitivity. We review the science goals that can be addressed with a medium-energy pair telescope, how these goals drive the telescope design, and the realization of this design with AdEPT. The AdEPT telescope for a future MIDEX mission is envisioned as a 8 m3 active volume filled with argon at 2 atm. The design and performance of the 3-DTI detectors for the AdEPT telescope are described as well as the outstanding instrument challenges that need to be met for the AdEPT mission

Neutron Imaging Camera

The Neutron Imaging Camera (NIC) is based on the Three-dimensional Track Imager (3DTI) technology developed at GSFC for gamma-ray astrophysics applications. The 3-DTI, a large volume time-projection chamber, provides accurate, approximately 0.4 mm resolution, 3-D tracking of charged particles. The incident direction of fast neutrons, En > 0.5 MeV, are reconstructed from the momenta and energies of the proton and triton fragments resulting from (sup 3)He(n,p) (sup 3)H interactions in the 3-DTI volume. The performance of the NIC from laboratory and accelerator tests is presented

Place of Birth and Concepts of Wellbeing: An Analysis from Two Ethnographic Studies of Midwifery Units in England

This article is based on analysis of a series of ethnographic case studies of midwifery Units in England. Midwifery units are spaces that were developed to provide more home-like and less medically oriented care for birth that would support physiological processes of labour, women’s comfort and a positive experience of birth for women and their families. They are run by midwives, either on a hospital site alongside an obstetric unit (Alongside Midwifery Unit – AMU) or a freestanding unit away from an obstetric unit (Freestanding Midwifery Unit – FMU). Midwifery units have been designed and intended specifically as locations of wellbeing and although the meaning of the term is used very loosely in public discourse, this claim is supported by a large epidemiological study, which found that they provide safe care for babies while reducing use of medical interventions and with better health outcomes for the women. Our research indicated that midwifery units function as a protected space, one which uses domestic features as metaphors of home in order to promote a sense of wellbeing and to re-normalise concepts of birth, which had become inhabited by medical models and a preoccupation with risk. However, we argue that this protected space has a function for midwives as well as for birthing women. Midwifery units are intended to support midwives’ wellbeing following decades of professional struggles to maintain autonomy, midwife-led care and a professional identity founded on supporting normal, healthy birth. This development, which is focused on place of birth rather than other aspects of maternity care such as continuity, shows potential for restoring wellbeing on individual, professional and community levels, through improving rates of normal physiological birth and improving experiences of providing and receiving care. Nevertheless, this very focus also poses challenges for health service providers attempting to provide a ‘social model of care’ within an institutional context

Gamma-Ray Imaging for Explosives Detection

We describe a gamma-ray imaging camera (GIC) for active interrogation of explosives being developed by NASA/GSFC and NSWCICarderock. The GIC is based on the Three-dimensional Track Imager (3-DTI) technology developed at GSFC for gamma-ray astrophysics. The 3-DTI, a large volume time-projection chamber, provides accurate, approx.0.4 mm resolution, 3-D tracking of charged particles. The incident direction of gamma rays, E, > 6 MeV, are reconstructed from the momenta and energies of the electron-positron pair resulting from interactions in the 3-DTI volume. The optimization of the 3-DTI technology for this specific application and the performance of the GIC from laboratory tests is presented

An ethnographic organisational study of alongside midwifery units: a follow-on study from the Birthplace in England programme - Full Report

Background: Alongside midwifery units (AMUs) were identified as a novel hybrid organisational form in the Birthplace in England Research Programme, to which this is a follow-on study. The number of such units (also known as hospital birth centres) has increased greatly in the UK since 2007. They provide midwife-led care to low-risk women adjacent to maternity units run by obstetricians, aiming to provide a homely environment to support normal childbirth. Women are transferred to the obstetric unit (OU) if they want an epidural or if complications occur. Aims: This study aimed to investigate the ways that AMUs in England are organised, staffed and managed. It also aimed to look at the experiences of women receiving maternity care in an AMU and the views and experiences of maternity staff, including both those who work in an AMU and those in the adjacent OU. Methods: An organisational ethnography approach was used, incorporating case studies of four AMUs, selected for maximum variation on the basis of geographical context, length of establishment of an AMU, size of unit, management, leadership and physical design. Interviews were conducted between December 2011 and October 2012 with service managers and key stakeholders (n = 35), with professionals working within and in relation to AMUs (n = 54) and with postnatal women and birth partners (n = 47). Observations were conducted of key decision-making points in the service (n = 20) and relevant service documents and guidelines were collected and reviewed. Findings: Women and their families valued AMU care highly for its relaxed and comfortable environment, in which they felt cared for and valued, and for its support for normal birth. However, key points of transition for women could pose threats to equity of access and quality of their care, such as information and preparation for AMU care, and gaining admission in labour and transfer out of the unit. Midwives working in AMUs highly valued the environment, approach and the opportunity to exercise greater professional autonomy, but relations between units could also be experienced as problematic and as threats to professional autonomy as well as to quality and safety of care. We identified key themes that pose potential challenges for the quality, safety and sustainability of AMU care: boundary work and management, professional issues, staffing models and relationships, skills and confidence, and information and access for women. Conclusions: AMUs have a role to play in contributing to service quality and safety. They provide care that is satisfying for women, their partners and families and for health professionals, and they facilitate appropriate care pathways and professional roles and skills. There is a potential for AMUs to provide equitable access to midwife-led care when midwifery unit care is the default option (opt-out) for all healthy women. The Birthplace in England study indicated that AMUs provide safe and cost-effective care. However, the opportunity to plan to birth in an AMU is not yet available to all eligible women, and is often an opt-in service, which may limit access. The alignment of physical, philosophical and professional boundaries is inherent in the rationale for AMU provision, but poses challenges for managing the service to ensure key safety features of quality and safety are maintained. We discuss some key issues that may be relevant to managers in seeking to respond to such challenges, including professional education, inter- and intraprofessional communication, relationships and teamwork, integrated models of midwifery and women’s care pathways. Further work is recommended to examine approaches to scaling up of midwifery unit provision, including staffing and support models. Research is also recommended on how to support women effectively in early labour and on provision of evidence-based and supportive information for women. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Components of the Extragalactic Gamma Ray Background

We present new theoretical estimates of the relative contributions of unresolved blazars and star-forming galaxies to the extragalactic gamma-ray background (EGB) and discuss constraints on the contributions from alternative mechanisms such as dark matter annihilation and truly diffuse gamma-ray production. We find that the Fermi source count data do not rule out a scenario in which the EGB is dominated by emission from unresolved blazars, though unresolved star-forming galaxies may also contribute significantly to the background, within order-of-magnitude uncertainties. In addition, we find that the spectrum of the unresolved star-forming galaxy contribution cannot explain the EGB spectrum found by EGRET at energies between 50 and 200 MeV, whereas the spectrum of unresolved FSRQs, when accounting for the energy-dependent effects of source confusion, could be consistent with the combined spectrum of the low-energy EGRET EGB measurements and the Fermi-LAT EGB measurements.Comment: version accepted for publication in the Astrophysical Journa