Book Review

Title: Catch and Kill: Lies, Spies and Conspiracy to Protect Predators Author: Ronan Farrow Publisher: Fleet/Little, Brown & Company, London Date of Publication: 2019 Hard Back, pp 448 (including endnotes) Title: She Said: Breaking the Sexual Harassment Story that Helped Ignite a Movement Authors: Jodi Kantor and Megan Twohey Publisher: Bloomsbury Circus/Bloomsbury, London Date of Publication: 2019 Hardback, pp 310 (including index) Title: Brave – A revealing and empowering memoir Author: Rose McGowan Publisher: HarperCollins Date of Publication: 2018 Hardback, pp. 245 (plus Author’s Note & Preface ix-xvi

Religious Freedom and the Australian Constitution – Origins and Future

The most recent Australian Census, conducted by the Australian Bureau of Statistics (ABS) in 2016 (with a 95.1 per cent response rate), confirms that Australia is ‘increasingly a story of religious diversity, with Hinduism, Sikhism, Islam, and Buddhism all increasingly common religious beliefs’.1 Of these, between 2006 and 2016 Hinduism shows the ‘most significant growth’, attributed to immigration from South East Asia, whilst Islam (2.6 per cent of the population) and Buddhism (2.4 per cent) were the most common religions reported next to Christianity, the latter ‘remaining the most common religion’ (52 per cent stating this as their belief). Nevertheless, Christianity is declining, dropping from 88 per cent in 1966 to 74 per cent in 1991, and thence to the 2016 figure. At the same time, nearly one-third of Australians (30 per cent) state they have no religion, this group reflecting ‘a trend for decades’ which, says the ABS, is ‘accelerating

The US Constitution – A Very Short Introduction

The Oxford University Press began its very short introduction series in 1995 and now, two decades into the 2000s, comprises some 500 volumes translated into more than forty-five different languages, covering ‘everything from Psychology and Philosophy of Science to American History and Relativity’. The aim of the series, says Oxford University Press, is to provide ‘a stimulating and accessible way into a new subject’ for readers unfamiliar with the topic. David Bodenhamer’s The US Constitution – A Very Short Introduction fulfils this aim, yet does far more than this and its title may imply

Tissue-specific ageing of rat tendon-derived progenitor cells

Although ageing predisposes tendons for various pathologies, the effect of ageing on tendon stem/progenitor cells has received little attention. In this study, we compared tendon progenitor cells from patellar, Achilles and tail tendons derived from young (8-12 weeks old) and mature (52 weeks old) rats. The mean number of progenitor cells/ mg was reduced with age in all three tendons and this reduction reached statistical significance in both Achilles and tail tendons. As determined by colony-forming-unit-fibroblasts assays, mean colony number and size were both statistically unchanged with age in patellar and Achilles tendons. In contrast, both colony number and size were significantly reduced in cultures derived from mature tail tendons relative to those derived from young tail tendons. While colonies per mg tissue were reduced with age in all three tendons, this reduction was only statistically significant for tail tendon. Lipofuscin and ROS content in cell progenitors were unchanged with age in all 3 tendons. Conversely, carbonyl content was significantly increased and telomerase activity significantly decreased in mature tail tendon cells relative to young tendon cells. These data suggest that, in the first year of life, rat Achilles and patellar tendons suffer relatively little oxidative damage. In contrast, tail tendons experience an increase protein oxidation, a decrease in telomerase activity and a substantial reduction in progenitor cell numbers. That the source and age of tendon progenitors used influences the quality and density of the progenitor cells isolated from it has important implications for clinical strategies aimed at tendon repair

Effect of Age and Diabetes on the Response of Mesenchymal Progenitor Cells to Fibrin Matrices

Mesenchymal stem cells are showing increasing promise in applications such as tissue engineering and cell therapy. MSC are low in number in bone marrow, and therefore in vitro expansion is often necessary. In vivo, stem cells often reside within a niche acting to protect the cells. These niches are composed of niche cells, stem cells, and extracellular matrix. When blood vessels are damaged, a fibrin clot forms as part of the wound healing response. The clot constitutes a form of stem cell niche as it appears to maintain the stem cell phenotype while supporting MSC proliferation and differentiation during healing. This is particularly appropriate as fibrin is increasingly being suggested as a scaffold meaning that fibrin-based tissue engineering may to some extent recapitulate wound healing. Here, we describe how fibrin modulates the clonogenic capacity of MSC derived from young/old human donors and normal/diabetic rats. Fibrin was prepared using different concentrations to modulate the stiffness of the substrate. MSC were expanded on these scaffolds and analysed. MSC showed an increased self-renewal on soft surfaces. Old and diabetic cells lost the ability to react to these signals and can no longer adapt to the changed environment

Passage and concentration-dependent effects of Indomethacin on tendon derived cells

<p>Abstract</p> <p>Background</p> <p>Non-steroidal anti-inflammatory drugs (NSAID) are commonly used in the treatment of tendinopathies such as tendonitis and tendinosis. Despite this, little is known of their direct actions on tendon-derived cells. As NSAIDs have been shown to delay healing in a number of mesenchymal tissues we have investigated the direct effects of indomethacin on the proliferation of tendon-derived cells.</p> <p>Results and Discussion</p> <p>The results obtained were dependent on both the type of cells used and the method of measurement. When measured using the Alamar blue assay, a common method for the measurement of cell proliferation and viability, no effect of indomethacin was seen regardless of cell source. It is likely that this lack of effect was due to a paucity of mitochondrial enzymes in tendon cells.</p> <p>However, when cell number was assessed using the methylene blue assay, which is a simple nuclear staining technique, an Indomethacin-induced inhibition of proliferation was seen in primary cells but not in secondary subcultures.</p> <p>Conclusion</p> <p>These results suggest that firstly, care must be taken when deciding on methodology used to investigate tendon-derived cells as these cells have a quite different metabolism to other mesenchymal derive cells. Secondly, Indomethacin can inhibit the proliferation of primary tendon derived cells and that secondary subculture selects for a population of cells that is unresponsive to this drug.</p

Tissue specific characteristics of cells isolated from human and rat tendons and ligaments

<p>Abstract</p> <p>Background</p> <p>Tendon and ligament injuries are common and costly in terms of surgery and rehabilitation. This might be improved by using tissue engineered constructs to accelerate the repair process; a method used successfully for skin wound healing and cartilage repair. Progress in this field has however been limited; possibly due to an over-simplistic choice of donor cell. For tissue engineering purposes it is often assumed that all tendon and ligament cells are similar despite their differing roles and biomechanics. To clarify this, we have characterised cells from various tendons and ligaments of human and rat origin in terms of proliferation, response to dexamethasone and cell surface marker expression.</p> <p>Methods</p> <p>Cells isolated from tendons by collagenase digestion were plated out in DMEM containing 10% fetal calf serum, penicillin/streptomycin and ultraglutamine. Cell number and collagen accumulation were by determined methylene blue and Sirius red staining respectively. Expression of cell surface markers was established by flow cytometry.</p> <p>Results</p> <p>In the CFU-f assay, human PT-derived cells produced more and bigger colonies suggesting the presence of more progenitor cells with a higher proliferative capacity. Dexamethasone had no effect on colony number in ACL or PT cells but 10 nM dexamethasone increased colony size in ACL cultures whereas higher concentrations decreased colony size in both ACL and PT cultures. In secondary subcultures, dexamethasone had no significant effect on PT cultures whereas a stimulation was seen at low concentrations in the ACL cultures and an inhibition at higher concentrations. Collagen accumulation was inhibited with increasing doses in both ACL and PT cultures. This differential response was also seen in rat-derived cells with similar differences being seen between Achilles, Patellar and tail tendon cells. Cell surface marker expression was also source dependent; CD90 was expressed at higher levels by PT cells and in both humans and rats whereas D7fib was expressed at lower levels by PT cells in humans.</p> <p>Conclusion</p> <p>These data show that tendon & ligament cells from different sources possess intrinsic differences in terms of their growth, dexamethasone responsiveness and cell surface marker expression. This suggests that for tissue engineering purposes the cell source must be carefully considered to maximise their efficacy.</p

Data sharing: experience of accessing individual patient data from completed randomised controlled trials in vascular and cognitive medicine

ObjectivesMeta-analysis based on individual patient data (IPD) from randomised trials is superior to using published summary data since it facilitates subgroup and multiple variable analyses. Guidelines and funders expect that researchers share IPD for bona fide analyses, but in practice, this is done variably. Here we report the experience of obtaining IPD for two collaborative analysis studies.SettingTwo linked studies required IPD from published randomised trials. The leading researchers for eligible trials were approached and asked to share IPD including trial characteristics, patient demographics, baseline clinical data and outcome measures. ParticipantsParticipants in eligible randomised controlled trials included patients with or at risk of cognitive decline/vascular events.Primary and secondary outcome measuresNumbers (%) of trials where the leading researcher responded favourably/negatively or did not respond. If negative, reasons behind the response were collected. If positive, methods used to share IPD were recorded.ResultsAcross the two studies, 391 completed trials were identified. Email addresses for researchers were found for 313 (80%) of the trials. 148 (47%) researchers did not respond despite being sent multiple emails. Following contact, positive initial responses were received from 92 researchers, resulting in IPD being shared for 78 trials. 87 (28%) researchers declined to share data; justifications were recorded. The median time from first request to accessing data in one study was 241 [IQR 383.3] days. IPD sources included: direct from researcher, via academic trial funders repository and a website requiring remote analysis of commercial data. Where data were shared, a variety of methods were used to transfer data.ConclusionSharing of IPD from trials is desirable and a requirement of many funding bodies. However, accessing IPD faces multiple challenges including refusals to share, delays in access to data, and having to perform analyses on a remote website

Superheated Microdrops as Cold Dark Matter Detectors

It is shown that under realistic background considerations, an improvement in Cold Dark Matter sensitivity of several orders of magnitude is expected from a detector based on superheated liquid droplets. Such devices are totally insensitive to minimum ionizing radiation while responsive to nuclear recoils of energies ~ few keV. They operate on the same principle as the bubble chamber, but offer unattended, continuous, and safe operation at room temperature and atmospheric pressure.Comment: 15 pgs, 4 figures include