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This article presents empirical findings about the distinctiveness of smaller voluntary sector organisations (VSOs) involved in welfare service provision, based on in-depth, qualitative case study research. We identify a series of organisational features and practices which can mean that smaller VSOs are distinctive from larger organisations. These include how they are governed and managed, their approach to their work, and their position relative to other providers. To explain our findings, we draw on the concept of stakeholder ambiguity. This idea was posited by Billis and Glennerster (1998) and is commonly cited in relation to distinctiveness. We identified several manifestations of stakeholder ambiguity and confirm the concept’s explanatory importance, although we argue that our understanding of distinctiveness is enhanced when stakeholder ambiguity is considered alongside other closely related features, such as being embedded in a local geographic community and informal familial care-based organisational cultures. Our findings also highlight the fragility of smaller VSOs. We argue that this combination of distinctiveness and fragility creates a tension for social policy makers, many of whom recognise the value of smaller VSOs and the risks that they face but must weigh this against a requirement to allocate resources for statutory services as effectively as possible.

(1) Background. There is interest in the role community organisations can play to support healthy ageing and the integration of health and social care. This study explored the contribution community organisations can make to this goal through the Leeds (UK) Neighbourhood Networks (LNNs), a novel example of community-based support. (2) Methods. An observational study of 148 LNN beneficiaries compared to the Leeds population aged 64 and over (n = 143,418) using the Leeds Data Model, and an analytical resource developed to support care planning. Measures included demographic characteristics, Electronic Frailty Index (EFI), the number of long-term health conditions (LTCs), and public health management cohort categorisation. (3) Results. LNN’s are primarily focussed on older people who are fit (44 percent) or experiencing the onset of LTCs (27 percent) and/or mild frailty (41 percent). However, they also support smaller numbers of people with moderate/severe frailty (15 percent) and five or more long-term conditions (19 percent). (4) Conclusions. Community organisations are well placed to support the ambitions of integrated care by providing support for older people with mild to moderate health and care needs. They also have the capacity to support older people with more severe needs if resourced to do so.

In August 2018, the UK government published its Civil society strategy for England, aiming to establish a policy agenda for creating social value. This paper reviews the strategy, critically assessing its contribution to the creation of social value, the civil society-state relationship, public sector commissioning and youth participation. By concluding with an analysis of the strategy's language, we argue that there are risks in the strategy's narrative positioning of voluntary action and wider civil society.

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

Blood biomarkers of multiple sclerosis (MS) can provide a better understanding of pathophysiology and enable disease monitoring. Here, we performed quantitative shotgun lipidomics on the plasma of a unique cohort of 73 monozygotic twins discordant for MS. We analyzed 243 lipid species, evaluated lipid features such as fatty acyl chain length and number of acyl chain double bonds, and detected phospholipids that were significantly altered in the plasma of co‐twins with MS compared to their non‐affected siblings. Strikingly, changes were most prominent in ether phosphatidylethanolamines and ether phosphatidylcholines, suggesting a role for altered lipid signaling in the disease.

The Hobby-Eberly Telescope (HET) Dark Energy Experiment (HETDEX) is undertaking a blind wide-field low-resolution spectroscopic survey of 540 square degrees of sky to identify and derive redshifts for a million Lyman-alpha emitting galaxies (LAEs) in the redshift range 1.9 < z < 3.5. The ultimate goal is to measure the expansion rate of the Universe at this epoch, to sharply constrain cosmological parameters and thus the nature of dark energy. A major multi-year wide field upgrade (WFU) of the HET was completed in 2016 that substantially increased the field of view to 22 arcminutes diameter and the pupil to 10 meters, by replacing the optical corrector, tracker, and prime focus instrument package and by developing a new telescope control system. The new, wide-field HET now feeds the Visible Integral-field Replicable Unit Spectrograph (VIRUS), a new low-resolution integral field spectrograph (LRS2), and the Habitable Zone Planet Finder (HPF), a precision near-infrared radial velocity spectrograph. VIRUS consists of 156 identical spectrographs fed by almost 35,000 fibers in 78 integral field units arrayed at the focus of the upgraded HET. VIRUS operates in a bandpass of 3500-5500 Angstroms with resolving power R~800. VIRUS is the first example of large scale replication applied to instrumentation in optical astronomy to achieve spectroscopic surveys of very large areas of sky. This paper presents technical details of the HET WFU and VIRUS, as flowed-down from the HETDEX science requirements, along with experience from commissioning this major telescope upgrade and the innovative instrumentation suite for HETDEX.