Are infestations of Cymomelanodactylus killing Acropora cytherea in the Chagos archipelago?

Associations between branching corals and infaunal crabs are well known, mostly due to the beneficial effects of Trapezia and Tetralia crabs in protecting host corals from crown-of-thorns starfish (e.g., Pratchett et al. 2000) and/or sedimentation (Stewart et al. 2006). These crabs are obligate associates of live corals and highly prevalent across suitable coral hosts, with 1–2 individuals per colony (Patton 1994). Cymo melanodactylus (Fig. 1) are also prevalent in branching corals, mostly Acropora, and are known to feed on live coral tissue, but are generally found in low abundance (<3 per colony) and do not significantly affect their host corals (e.g., Patton 1994). In the Chagos archipelago, however, infestations of Cymo melanodactylus were found on recently dead and dying colonies of Acropora cytherea

A novel complexity-to-diversity strategy for the diversity-oriented synthesis of structurally diverse and complex macrocycles from quinine.

Recent years have witnessed a global decline in the productivity and advancement of the pharmaceutical industry. A major contributing factor to this is the downturn in drug discovery successes. This can be attributed to the lack of structural (particularly scaffold) diversity and structural complexity exhibited by current small molecule screening collections. Macrocycles have been shown to exhibit a diverse range of biological properties, with over 100 natural product-derived examples currently marketed as FDA-approved drugs. Despite this, synthetic macrocycles are widely considered to be a poorly explored structural class within drug discovery, which can be attributed to their synthetic intractability. Herein we describe a novel complexity-to-diversity strategy for the diversity-oriented synthesis of novel, structurally complex and diverse macrocyclic scaffolds from natural product starting materials. This approach exploits the inherent structural (including functional) and stereochemical complexity of natural products in order to rapidly generate diversity and complexity. Readily-accessible natural product-derived intermediates serve as structural templates which can be divergently functionalized with different building blocks to generate a diverse range of acyclic precursors. Subsequent macrocyclisation then furnishes compounds that are each based around a distinct molecular scaffold. Thus, high levels of library scaffold diversity can be rapidly achieved. In this proof-of-concept study, the natural product quinine was used as the foundation for library synthesis, and six novel structurally diverse, highly complex and functionalized macrocycles were generated.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council, Wellcome Trust and AstraZeneca

MicroRNA expression is altered in an ovalbumin-induced asthma model and targeting miR-155 with antagomirs reveals cellular specificity

©2015 Plank et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source arecredited. MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targets. We profiled miRNA expression in murine lungs from an ovalbumin-induced allergic airways disease model, and compared expression to animals receiving dexamethasone treatment and non-allergic controls. Our analysis identified 29 miRNAs that were significantly altered during allergic inflammation. Target prediction analysis revealed novel genes with altered expression in allergic airways disease and suggests synergistic miRNA regulation of target mRNAs. To assess the impacts of one induced miRNA on pathology, we targeted miR-155-5p using a specific antagomir. Antagomir administration successfully reduced miR-155-5p expression with high specificity, but failed to alter the disease phenotype. Interestingly, further investigation revealed that antagomir delivery has variable efficacy across different immune cell types, effectively targeting myeloid cell populations, but exhibiting poor uptake in lymphocytes. Our findings demonstrate that antagomir-based targeting of miRNA function in the lung is highly specific, but highlights cell-specificity as a key limitation to be considered for antagomir-based strategies as therapeutics

Using clinical audit to improve the quality of obstetric care at the Tibetan Delek Hospital in North India: a longitudinal study

BACKGROUND: The Tibetan Delek Hospital is a small general hospital providing primary and secondary care for the Tibetan refugee community and the local Indian population in Dharamsala, Himachal Pradesh, North India. In a baseline clinical audit of intrapartum care at the Tibetan Delek Hospital in 1996, high levels of postpartum haemorrhage associated with poor medical management of the third stage of labour, plus inappropriate transfer of women in labour were observed. These audit findings prompted the implementation of changes in the delivery of intrapartum care and follow-up audit cycles to monitor the ongoing effect of these changes. METHODS: The delivery of intrapartum care was modified in two ways. Firstly, nurses, midwives, and doctors were re-trained in the active management of the third stage of labour, which involved the administration of intramuscular syntocinon plus ergometrine with delivery of the anterior shoulder. Secondly partograms were introduced to help rationalise the management of labour, and in particular decisions about when to transfer women in labour. Follow up audits were conducted in 1997, 1998, and 2003 to quantify the effects of these changes. The key measures for improvement included the documented incidence of postpartum haemorrhage and the number of women transferred inappropriately for failure to progress in labour. RESULTS: A sustained reduction of approximately 50% in the incidence of postpartum haemorrhage was observed after the introduction of active management of the third stage of labour. The introduction of the routine use of partograms was associated with a more rational decision-making process regarding transfer during labour. CONCLUSION: Introducing and maintaining a clinical audit cycle can lead to improvements in the quality of obstetric care in a refugee population

What happens to clinical training fellows? A retrospective study of the 20 years outcome of a Medical Research Council UK cohort

Objectives: The Clinical Research Training Fellowship (CRTF) allows up to 3 years support for clinically qualified candidates to undertake specialised or further research training in biomedical sciences. CRTFs are perceived as a crucial step in the career development and progression of Clinical Academics but there are no published data to support this notion. We conducted an electronic survey of a large cohort of Medical Research Council (MRC) CRTFs followed for up to 20 years. Design: Retrospective analysis of CRTF outcome data held with the MRC, UK. Participants: Two cohorts comprising 40 CRFTs awarded by the MRC in the year 1991 and 299 MRC CRTFs who were awarded a fellowship between 1993 and 2003. Results: The MRC CRTF scheme built capacity in clinical academia across the UK with 40% of CRTFs progressing to a University professorship. Importantly, the CRTF scheme is also providing NHS consultants who remain research active. Conclusions: This is the first analysis of outcome of CRTFs in the UK and provides robust evidence of the importance of this capacity building mode of funding to underpin research excellence at the University-NHS interface

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Multiplexing of optical fiber gas sensors with a frequency-modulated continuous-wave technique

Author name used in this publication: W. JinAuthor name used in this publication: H. L. HoAuthor name used in this publicaiton: M. S. Demokan2000-2001 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Do personal stories make patient decision aids more effective? A critical review of theory and evidence

Background Patient decision aids support people to make informed decisions between healthcare options. Personal stories provide illustrative examples of others’ experiences and are seen as a useful way to communicate information about health and illness. Evidence indicates that providing information within personal stories affects the judgments and values people have, and the choices they make, differentially from facts presented in non-narrative prose. It is unclear if including narrative communications within patient decision aids enhances their effectiveness to support people to make informed decisions. Methods A survey of primary empirical research employing a systematic review method investigated the effect of patient decision aids with or without a personal story on people’s healthcare judgements and decisions. Searches were carried out between 2005-2012 of electronic databases (Medline, PsycINFO), and reference lists of identified articles, review articles, and key authors. A narrative analysis described and synthesised findings. Results Of 734 citations identified, 11 were included describing 13 studies. All studies found participants’ judgments and/or decisions differed depending on whether or not their decision aid included a patient story. Knowledge was equally facilitated when the decision aids with and without stories had similar information content. Story-enhanced aids may help people recall information over time and/or their motivation to engage with health information. Personal stories affected both “system 1” (e.g., less counterfactual reasoning, more emotional reactions and perceptions) and “system 2” (e.g., more perceived deliberative decision making, more stable evaluations over time) decision-making strategies. Findings exploring associations with narrative communications, decision quality measures, and different levels of literacy and numeracy were mixed. The pattern of findings was similar for both experimental and real-world studies. Conclusions There is insufficient evidence that adding personal stories to decision aids increases their effectiveness to support people’s informed decision making. More rigorous research is required to elicit evidence about the type of personal story that a) encourages people to make more reasoned decisions, b) discourages people from making choices based on another’s values, and c) motivates people equally to engage with healthcare resources