Melatonin as a potential therapy for sepsis : a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis

This article is protected by copyright. All rights reserved. This study was funded by the Chief Scientist Office, NHS Scotland. We would like to thank all the volunteers who gave up their time and blood to take part in the study and the data monitoring committee and staff of the intensive care unit for their support. In addition, thanks to Dr Malachy Columb for performing Page's trend test for us and to Annette Fearnley at Nu-Pharm Ltd for her advice.Peer reviewedPublisher PD

Techniques for analysing pattern formation in populations of stem cells and their progeny

<p>Abstract</p> <p>Background</p> <p>To investigate how patterns of cell differentiation are related to underlying intra- and inter-cellular signalling pathways, we use a stochastic individual-based model to simulate pattern formation when stem cells and their progeny are cultured as a monolayer. We assume that the fate of an individual cell is regulated by the signals it receives from neighbouring cells via either diffusive or juxtacrine signalling. We analyse simulated patterns using two different spatial statistical measures that are suited to planar multicellular systems: pair correlation functions (PCFs) and quadrat histograms (QHs).</p> <p>Results</p> <p>With a diffusive signalling mechanism, pattern size (revealed by PCFs) is determined by both morphogen decay rate and a sensitivity parameter that determines the degree to which morphogen biases differentiation; high sensitivity and slow decay give rise to large-scale patterns. In contrast, with juxtacrine signalling, high sensitivity produces well-defined patterns over shorter lengthscales. QHs are simpler to compute than PCFs and allow us to distinguish between random differentiation at low sensitivities and patterned states generated at higher sensitivities.</p> <p>Conclusions</p> <p>PCFs and QHs together provide an effective means of characterising emergent patterns of differentiation in planar multicellular aggregates.</p

Melatonin is a feasible, safe and acceptable intervention in doctors and nurses working nightshifts : the MIDNIGHT trial

Funding: The study was funded by the British Journal of Anaesthesia and the Royal College of Anaesthetists, funding partners of the National Institute of Academic Anaesthesia (grant number WKR0-2015-0027). Acknowledgments: We are extremely grateful to Flynn Pharma for the gift of Circadin and placebo tablets for this trial, to Gary Cameron for the assay of melatonin, and to Sally Galt for helping with recruitment. We also thank Drs Lorna Aucott and David McClernon of the medical statistics team for help with randomization. We acknowledge the members of the Trial Steering Group and the Data and Safety Monitoring Committee. Finally we thank all the doctors and nurses who took part in this trial.Peer reviewedPublisher PD

Correlation of Clinical Trachoma and Infection in Aboriginal Communities

Repeated episodes of C. trachomatis infection lead to active trachoma clinically characterised by an often intense inflammatory response to chlamydial antigens with later scarring and distortion of the eyelid leading to blindness. However, the clinical signs of trachoma do not correlate well with laboratory tests to detect the presence of Chlamydia. The WHO simplified clinical grading scheme currently used for assessment of trachoma has a poor correlation with C. trachomatis genomic test findings, even though the detection of bacterial genome is strongly correlated with the prevalence and severity of active trachoma. A detailed assessment of the clinical signs using a finer grading system was studied in a population-based survey in five Australian Aboriginal communities. Much clinical activity and infection was found in those with clinical signs below the threshold used in the current WHO grading scheme. Future studies of the distribution of infection and pathogenesis should use finer grading methods than the current WHO scheme. The prevalence of trachoma in these communities confirms that trachoma remains of public health importance and sustained interventions to control trachoma are warranted

Role of many-body entanglement in decoherence processes

A pure state decoheres into a mixed state as it entangles with an environment. When an entangled two-mode system is embedded in a thermal environment, however, each mode may not be entangled with its environment by their simple linear interaction. We consider an exactly solvable model to study the dynamics of a total system, which is composed of an entangled two-mode system and a thermal environment, and also an array of infinite beam splitters. It is shown that many-body entanglement of the system and the environment plays a crucial role in the process of disentangling the system.Comment: 4 pages, 1 figur

Help in Time: An Evaluation of Philadelphia\u27s Community-Based Homelessness Prevention Program

This report provides an evaluation of Philadelphia\u27s neighborhood-based homelessness prevention initiative. Results indicate that nearly all households served do not become homeless. But it is unclear if households would have become homeless had they not been served. Recommendations are made for targeting prevention interventions to families requesting shelter

Concerted reductive coupling of an alkyl chloride at Pt(IV)

Oxidation of a doubly cyclometallated platinum(II) complex results in two isomeric platinum(IV) complexes. Whereas the trans isomer is robust, being manipulable in air at room temperature, the cis isomer decomposes at −20 °C and above. Reductive coupling of an alkyl chloride at the cis isomer gives a new species which can be reoxidised. The independence of this coupling on additional halide rules out the reverse of an SN2 reaction, leaving a concerted process as the only sensible reaction pathway

Tuberculosis in Dr Granville's mummy: a molecular re-examination of the earliest known Egyptian mummy to be scientifically examined and given a medical diagnosis

‘Dr Granville's mummy’ was described to the Royal Society of London in 1825 and was the first ancient Egyptian mummy to be subjected to a scientific autopsy. The remains are those of a woman, Irtyersenu, aged about 50, from the necropolis of Thebes and dated to about 600 BC. Augustus Bozzi Granville (1783–1872), an eminent physician and obstetrician, described many organs still in situ and attributed the cause of death to a tumour of the ovary. However, subsequent histological investigations indicate that the tumour is a benign cystadenoma. Histology of the lungs demonstrated a potentially fatal pulmonary exudate and earlier studies attempted to associate this with particular disease conditions. Palaeopathology and ancient DNA analyses show that tuberculosis was widespread in ancient Egypt, so a systematic search for tuberculosis was made, using specific DNA and lipid biomarker analyses. Clear evidence for Mycobacterium tuberculosis complex DNA was obtained in lung tissue and gall bladder samples, based on nested PCR of the IS6110 locus. Lung and femurs were positive for specific M. tuberculosis complex cell-wall mycolic acids, demonstrated by high-performance liquid chromatography of pyrenebutyric acid–pentafluorobenzyl mycolates. Therefore, tuberculosis is likely to have been the major cause of death of Irtyersenu

Acceptability of Treatments and Services for Individuals with Hoarding Behaviors

Objective To explore the acceptability of currently available treatments and services for individuals who self-report hoarding behaviors. Method Between 10/2013 and 8/2014, participants were invited to complete an online survey that provided them descriptions of eleven treatments and services for hoarding behaviors and asked them to evaluate their acceptability using quantitative (0 [not at all acceptable]−10 [completely acceptable]) Likert scale ratings. The a priori definition of acceptability for a given resource was an average Likert scale score of six or greater. Two well-validated self-report measures assessed hoarding symptom severity: the Saving Inventory-Revised and the Clutter Image Rating Scale. Results Two hundred and seventy two participants who self-reported having hoarding behaviors completed the questionnaire. Analyses focused on the 73% of responders (n=203) who reported clinically significant hoarding behaviors (i.e., Saving Inventory-Revised scores of ≥40). The three most acceptable treatments were individual cognitive behavioral therapy (6.2±3.1 on the Likert scale), professional organizing service (6.1±3.2), and use of a self-help book (6.0±3.0). Conclusion In this sample of individuals with self-reported clinically significant hoarding behaviors (n=203), only 3 out of 11 treatments and services for hoarding were deemed acceptable using an a priori score. While needing replication, these findings indicate the need to design more acceptable treatments and services to engage clients and maximize treatment outcomes for hoarding disorder