Evaporation of microdroplets of azeotropic liquids

This work reports data showing the evolution of contact angle with time for mixtures of water and 1-propanol at room temperature on poly(methyl methacrylate) (PMMA). The composition range investigated spans the azeotropic composition, thus encompassing systems containing excess water and excess 1-propanol. A discontinuity in the contact angle behavior is observed and it is suggested that this enables the identification of the azeotropic composition as 0.39 mole fraction of 1-propanol. This suggestion is supported by boiling point measurements made at around 20 mmHg. The discontinuity is associated with the presence of an instability, which causes a distortion around the droplet perimeter. It is suggested that the distortion is caused by competing effects of local surface tension maxima and minima

Nonuniform sampling of urodynamic signals: a comparison of different methods

Several different techniques for urodynamic signal compression have been proposed in the last few years. Using these techniques it is possible to reduce the requirements for digital storage or transmission. There are a number of applications where it is essential to use such techniques in diagnostic and ambulatory urodynamics. The purpose of this study is to compare different techniques of urodynamic data compression. The so-called FAN, voltage triggered, two point projection and second difference methods. The comparison between the methods is based on 65 pressure, 46 uroflow and 18 surface electromyogram signals. The reduction ratio achieved for different allowable errors between the original and compressed signals is calculated and compared for the different techniques. Results show that it is possible to store urodynamic signals accurately at a low sampling rate, where FAN and voltage triggered methods seem to be superior to the rest

Expansion of airway basal epithelial cells from primary human non-small cell lung cancer tumors

Pre-clinical non-small cell lung cancer (NSCLC) models are poorly representative of the considerable inter- and intra-tumor heterogeneity of the disease in patients. Primary cell-based in vitro models of NSCLC are therefore desirable for novel therapy development and personalized cancer medicine. Methods have been described to generate rapidly proliferating epithelial cell cultures from multiple human epithelia using 3T3-J2 feeder cell culture in the presence of Y-27632, a RHO-associated protein kinase (ROCK) inhibitor, in what are known as "conditional reprograming conditions" (CRC) or 3T3+Y. In some cancer studies, variations of this methodology have allowed primary tumor cell expansion across a number of cancer types but other studies have demonstrated the preferential expansion of normal epithelial cells from tumors in such conditions. Here, we report our experience regarding the derivation of primary NSCLC cell cultures from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution through Therapy (TRACERx) clinical study and discuss these in the context of improving the success rate for in vitro cultivation of cells from NSCLC tumors. This article is protected by copyright. All rights reserved

Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial): a mixed methods study

OBJECTIVE: To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. DESIGN: Mixed methods study with data collected at three time points: (1) before, (2) during and (3) after a pilot trial. SETTING: English, Paediatric Intensive Care Units (PICUs). PARTICIPANTS: (1) Pre-pilot trial focus groups with pilot site staff (n=56) and interviews with parents (n=25) whose child had been admitted to PICU in the last 3 years with a fever and suspected infection, (2) Questionnaires with parents of randomised children following pilot trial recruitment (n=48 from 47 families) and (3) post-pilot trial interviews with parents (n=19), focus groups (n=50) and a survey (n=48) with site staff. Analysis drew on Sekhon et al's theoretical framework of acceptability. RESULTS: There was initial support for the trial, yet some held concerns regarding the proposed temperature thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed protocol changes and training, which influenced views on trial acceptability. Staff trained by the FEVER team found the trial more acceptable than those trained by colleagues. Parents and staff found the trial acceptable. Some concerns about pain or discomfort during weaning from ventilation remained. CONCLUSIONS: Pre-trial findings and pilot trial experience influenced acceptability, providing insight into how challenges may be overcome. We present an adapted theoretical framework of acceptability to inform future trial feasibility studies. TRIAL REGISTRATION NUMBERS: ISRCTN16022198 and NCT03028818

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (turdus merula)

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems

The association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study

IntroductionBullous pemphigoid (BP) is a serious skin disease that results in large painful blisters developing over the body and occurs most commonly in older people (over 70 years). Despite several comorbidities such as stroke and a threefold increase in mortality, BP remains under-researched. The cause of BP is unclear. The auto-immune process may be triggered by medicines such as diuretics, but current evidence mainly comprises case-reports and small hospital-based studies. Electronic healthcare records from the Clinical Practice Research Datalink (CPRD) provide an opportunity to conduct a large population-based study, representative of people with BP in the UK, to assess exposure to prescribed medicines. Early identification of BP and prompt withdrawal of suspect medicines may lead to BP remission and improve long-term patient outcomes, including quality of life. We aim to determine whether medicines/vaccines, prescribed for common conditions in older people, are associated with BP in the UK population. The objectives are:i.To determine the adjusted odds ratio of developing BP per therapeutic group and class, and for multiple exposure (i.e. the use of more than one therapeutic group of medicine/vaccine during the observation period), for medicines/vaccines commonly prescribed to older people in the UK.ii.To identify which of the above are less associated with risk of BP, giving clinicians/prescribers alternative treatment options.iii.To identify additional medicines associated with BP using machine learning.iv.To identify associations between combinations of medicines prescribed to BP patients using machine learning.v.To describe patient characteristics of those at risk of BP, following medicine use, using machine learning.MethodsA UK population-based nested case-control study using the CPRD to determine associations between identified medicines/vaccines and BP. BP cases will be matched to up to 4 controls (age, sex, GP practice) using incidence density sampling. Exposure: medicines/vaccines commonly prescribed for older people; antibacterial, medicine for the cardiovascular system, stroke, diabetes, dementia, and influenza vaccination in the year leading up to diagnosis. Outcome measures: the odds of BP per therapeutic group, per class, and individual medicine; (reference=no exposure). Analysis: multivariable conditional logistic regression adjusted for a priori confounders. Confounding by indication will be considered and different exposure criteria assessed. We will undertake exploratory association rule mining to identify individual and combinations of medicines prescribed prior to BP. We will conduct unsupervised machine learning cluster analysis to identify groups of patients with demographic and clinical characteristics and their associations with prescribed medicines linked to BP.DiscussionThis study will (i) provide greater awareness of the risk of drug-associated BP amongst specialist and non-specialist healthcare professionals and therefore may facilitate earlier diagnosis of BP; (ii) support withdrawal of suspect medicines and switching to alternatives, where available, to achieve earlier remission of BP

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial) : a mixed methods study

Objective: To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. Design: Mixed methods study with data collected at three time points: (1) before, (2) during and (3) after a pilot trial. Setting: English, Paediatric Intensive Care Units (PICUs). Participants: (1) Pre-pilot trial focus groups with pilot site staff (n=56) and interviews with parents (n=25) whose child had been admitted to PICU in the last 3 years with a fever and suspected infection, (2) Questionnaires with parents of randomised children following pilot trial recruitment (n=48 from 47 families) and (3) post-pilot trial interviews with parents (n=19), focus groups (n=50) and a survey (n=48) with site staff. Analysis drew on Sekhon et al’s theoretical framework of acceptability. Results: There was initial support for the trial, yet some held concerns regarding the proposed temperature thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed protocol changes and training, which influenced views on trial acceptability. Staff trained by the FEVER team found the trial more acceptable than those trained by colleagues. Parents and staff found the trial acceptable. Some concerns about pain or discomfort during weaning from ventilation remained. Conclusions: Pre-trial findings and pilot trial experience influenced acceptability, providing insight into how challenges may be overcome. We present an adapted theoretical framework of acceptability to inform future trial feasibility studies. Trial registration numbers: ISRCTN16022198 and NCT03028818