Breathlessness and opioid prescribing in COPD in general practice: a cross-sectional, observational study.

Chronic breathlessness is a disabling syndrome, prevalent in people with advanced chronic obstructive pulmonary disease (COPD). Regular, low-dose, oral sustained-release morphine is approved in Australia to reduce symptomatic chronic breathlessness. We aimed to determine the current prescribing patterns of opioids for chronic breathlessness in COPD in Australian general practice and to define any associated patient and practitioner characteristics. Five years (2011 to 2016) of the Bettering the Evaluation and Care of Health database, an Australian national, continual, cross-sectional study of clinical care in general practice were used. The database included 100 consecutive clinical encounters from almost 1000 general practitioners annually (n=488 100 encounters). Descriptive analyses with subsequent regression models were generated. Breathlessness as a patient-defined reason for encounter was identified in 621 of 4522 encounters where COPD was managed. Opioids were prescribed in 309 of 4522 encounters where COPD was managed (6.8%; (95% CI) 6.1-7.6), of which only 17 were prescribed for breathlessness, and the rest for other conditions almost entirely related to pain. Patient age (45-64 years versus age 80+ years, OR 1.68; 1.19-2.36), Commonwealth Concession Card holders (OR 1.70; 1.23-2.34) and socioeconomic disadvantage (OR 1.30; 1.01-1.68) were associated with increased likelihood of opioid prescription at COPD encounters. The rate of opioid prescriptions rose over the 5 years of study. In primary care encounters for COPD, opioids were prescribed in 6.8% of cases, but almost never for breathlessness. These data create a baseline against which to compare changes in prescribing as the treatment of chronic breathlessness evolves

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse

A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments

The volatile compound dimethylsulphide (DMS) is important in climate regulation, the sulphur cycle and signalling to higher organisms. Microbial catabolism of the marine osmolyte dimethylsulphoniopropionate (DMSP) is thought to be the major biological process generating DMS. Here we report the discovery and characterisation of the first gene for DMSP-independent DMS production in any bacterium. This gene, mddA, encodes a methyltransferase that methylates methanethiol (MeSH) and generates DMS. MddA functions in many taxonomically diverse bacteria including sediment-dwelling pseudomonads, nitrogen-fixing bradyrhizobia and cyanobacteria, and mycobacteria, including the pathogen Mycobacterium tuberculosis. The mddA gene is present in metagenomes from varied environments, being particularly abundant in soil environments, where it is predicted to occur in up to 76% of bacteria. This novel pathway may significantly contribute to global DMS emissions, especially in terrestrial environments, and could represent a shift from the notion that DMSP is the only significant precursor of DMS

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Climate change and the global pattern of moraine-dammed glacial lake outburst floods

This is the author accepted manuscript. The final version is available from EGU via the DOI in this recordThe published version, as published in The Cryosphere, is in ORE: http://hdl.handle.net/10871/32433Despite recent research identifying a clear anthropogenic impact on glacier recession, the effect of recent climate change on glacier-related hazards is at present unclear. Here we present the first global spatio-temporal assessment of glacial lake outburst floods (GLOFs) focusing explicitly on lake drainage following moraine dam failure. These floods occur as mountain glaciers recede and downwaste and many have an enormous impact on downstream communities and infrastructure. Our assessment of GLOFs associated with the collapse of moraine-dammed lakes provides insights into the historical trends of GLOFs and their distributions under current and future global climate change. We observe a clear global increase in GLOF frequency and their regularity around 1930, which likely represents a lagged response to post-Little Ice Age warming. Notably, we also show that GLOF frequency and their regularity – rather unexpectedly – has declined in recent decades even during a time of rapid glacier recession. Although previous studies have suggested that GLOFs will increase in response to climate warming and glacier recession, our global results demonstrate that this has not yet clearly happened. From assessment of the timing of climate forcing, lag times in glacier recession, lake formation and moraine dam failure, we predict increased GLOF frequencies during the next decades and into the 22nd century.SH was funded by a Leverhulme Research Fellowship. SH, RAB and AW acknowledge funding under the HELIX (European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n° 603864). AW and RAB acknowledge funding from the Joint UK DECC/Defra Met Office Hadley Centre Climate Programme (GA01101)

Meta-analysis of Prevalence and Risk Factors for Delirium After Transcatheter Aortic Valve Implantation

Delirium is a severe and common complication following transcatheter aortic valve implantation (TAVI). We sought to identify the prevalence and risk factors associated with the development of postprocedural delirium in patients aged over 60 years who underwent elective TAVI for aortic stenosis. Overall, 1,051 articles were searched, from which 9 studies were included. The prevalence of delirium following TAVI was higher in studies that assessed delirium for a minimum of 3 consecutive days (24.9%) compared with the studies that did not (2%). There were large effect sizes (d > 0.8) for 3 risk factors: acute kidney injury (odds ratio [OR] 5, p < 0.001), transapical approach (OR 4, p < 0.001) and carotid artery disease (OR 4, p < 0.001), whilst small effect sizes were found for a history of atrial fibrillation, prior stroke/transient ischemic attack, peripheral artery disease, hypertension, and prior cognitive impairment. In conclusion, 23% of patients 60 years and over who underwent TAVI experience delirium, a preventative cause of cognitive impairment and dementia. Recognition of risk factors for delirium after TAVI, such as a history of carotid artery disease, development of acute kidney injury, or use of a transapical approach, provides an opportunity to implement proven delirium preventative measures