Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality

Background: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. Aim: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. Methods: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. Findings: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2–7) vs 3 (2–5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. Conclusion: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

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

CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion

Background: In order to understand how biological systems function it is necessary to determine the interactions and associations between proteins. Gene fusion prediction is one approach to detection of such functional relationships. Its use is however known to be problematic in higher eukaryotic genomes due to the presence of large homologous domain families. Here we introduce CODA (Co-Occurrence of Domains Analysis), a method to predict functional associations based on the gene fusion idiom.Methodology/Principal Findings: We apply a novel scoring scheme which takes account of the genome-specific size of homologous domain families involved in fusion to improve accuracy in predicting functional associations. We show that CODA is able to accurately predict functional similarities in human with comparison to state-of-the-art methods and show that different methods can be complementary. CODA is used to produce evidence that a currently uncharacterised human protein may be involved in pathways related to depression and that another is involved in DNA replication.Conclusions/Significance: The relative performance of different gene fusion methodologies has not previously been explored. We find that they are largely complementary, with different methods being more or less appropriate in different genomes. Our method is the only one currently available for download and can be run on an arbitrary dataset by the user. The CODA software and datasets are freely available from ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/. Predictions are also available via web services from http://funcnet.eu/

The Role of Zinc in the Modulation of Neuronal Proliferation and Apoptosis

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis

Simulating crowd evacuation with socio-cultural, cognitive, and emotional elements

In this research, the effects of culture, cognitions, and emotions on crisis management and prevention are analysed. An agent-based crowd evacuation simulation model was created, named IMPACT, to study the evacuation process from a transport hub. To extend previous research, various socio-cultural, cognitive, and emotional factors were modelled, including: language, gender, familiarity with the environment, emotional contagion, prosocial behaviour, falls, group decision making, and compliance. The IMPACT model was validated against data from an evacuation drill using the existing EXODUS evacuation model. Results show that on all measures, the IMPACT model is within or close to the prescribed boundaries, thereby establishing its validity. Structured simulations with the validated model revealed important findings, including: the effect of doors as bottlenecks, social contagion speeding up evacuation time, falling behaviour not affecting evacuation time significantly, and travelling in groups being more beneficial for evacuation time than travelling alone. This research has important practical applications for crowd management professionals, including transport hub operators, first responders, and risk assessors

Trends in Depression and Antidepressant Prescribing in Children and Adolescents: A Cohort Study in The Health Improvement Network (THIN)

In 2003, the Committee on Safety of Medicines (CSM) advised against treatment with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine in children, due to a possible increased risk of suicidal behaviour. This study examined the effects of this safety warning on general practitioners' depression diagnosing and prescription behaviour in children

Invasive Predators Deplete Genetic Diversity of Island Lizards

Invasive species can dramatically impact natural populations, especially those living on islands. Though numerous examples illustrate the ecological impact of invasive predators, no study has examined the genetic consequences for native populations subject to invasion. Here we capitalize on a natural experiment in which a long-term study of the brown anole lizard (Anolis sagrei) was interrupted by rat invasion. An island population that was devastated by rats recovered numerically following rat extermination. However, population genetic analyses at six microsatellite loci suggested a possible loss of genetic diversity due to invasion when compared to an uninvaded island studied over the same time frame. Our results provide partial support for the hypothesis that invasive predators can impact the genetic diversity of resident island populations

The ISO LWS grating spectrum of NGC 7027

We present a high signal-to-noise ISO Long Wavelength Spectrometer (LWS) grating spectrum of the planetary nebula NGC 7027 from 43-194μm. In total 40 emission lines have been detected, with 30 identified. From the ionized region, we observe fine-structure lines from [N II], [N III] and [O III]. The [O I] and [C II] fine-structure lines from the photodissociation region are the strongest features observed in this spectral region. Amongst the molecular lines, 11 pure rotation CO lines from J=14-13 up to J=24-23 have been detected. The most striking result, however, is the detection in this carbon-rich nebula of the o-H_2_O 179.53μm and the OH 119.3μm fundamental lines. Astrophysical implications are briefly discussed

Explaining oscillations and variability in the p53-Mdm2 system

<p>Abstract</p> <p>Background</p> <p>In individual living cells p53 has been found to be expressed in a series of discrete pulses after DNA damage. Its negative regulator Mdm2 also demonstrates oscillatory behaviour. Attempts have been made recently to explain this behaviour by mathematical models but these have not addressed explicit molecular mechanisms. We describe two stochastic mechanistic models of the p53/Mdm2 circuit and show that sustained oscillations result directly from the key biological features, without assuming complicated mathematical functions or requiring more than one feedback loop. Each model examines a different mechanism for providing a negative feedback loop which results in p53 activation after DNA damage. The first model (ARF model) looks at the mechanism of p14^ARFwhich sequesters Mdm2 and leads to stabilisation of p53. The second model (ATM model) examines the mechanism of ATM activation which leads to phosphorylation of both p53 and Mdm2 and increased degradation of Mdm2, which again results in p53 stabilisation. The models can readily be modified as further information becomes available, and linked to other models of cellular ageing.</p> <p>Results</p> <p>The ARF model is robust to changes in its parameters and predicts undamped oscillations after DNA damage so long as the signal persists. It also predicts that if there is a gradual accumulation of DNA damage, such as may occur in ageing, oscillations break out once a threshold level of damage is acquired. The ATM model requires an additional step for p53 synthesis for sustained oscillations to develop. The ATM model shows much more variability in the oscillatory behaviour and this variability is observed over a wide range of parameter values. This may account for the large variability seen in the experimental data which so far has examined ARF negative cells.</p> <p>Conclusion</p> <p>The models predict more regular oscillations if ARF is present and suggest the need for further experiments in ARF positive cells to test these predictions. Our work illustrates the importance of systems biology approaches to understanding the complex role of p53 in both ageing and cancer.</p