340 research outputs found
Communication tools in the COVID-19 era and beyond which can optimise professional practice and patient care
Following the outbreak of the novel SARS-CoV-2 (COVID-19), the World Health Organization made a number of recommendations regarding the utilisation of healthcare services. In general, there has been a reduction in elective healthcare services including outpatient clinics, diagnostic services and elective surgery. Inevitably these reductions for all but the most urgent clinical work will have a detrimental impact on patients, and alternative ways of working including the use of telemedicine may help to mitigate this. Similarly, electronic solutions may enable clinicians to maintain inter and intra-professional working in both clinical and academic settings. Implementation of electronic solutions to minimise direct patient contact will be new to many clinicians, and the sheer number of software solutions available and varying functionality may be overwhelming to anyone unfamiliar with ‘virtual communication’. In this article, we will aim to summarise the variety of electronic communication platforms and tools available for clinicians and patients, detailing their utility, pros and cons, and some 'tips and tricks' from our experience through our work as an international research collaborative
Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis
CONTEXT: Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. OBJECTIVE: To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. EVIDENCE ACQUISITION: We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. EVIDENCE SYNTHESIS: We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. CONCLUSIONS: Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. PATIENT SUMMARY: Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility
Postpartum mental health after Hurricane Katrina: A cohort study
<p>Abstract</p> <p>Background</p> <p>Natural disaster is often a cause of psychopathology, and women are vulnerable to post-traumatic stress disorder (PTSD) and depression. Depression is also common after a woman gives birth. However, no research has addressed postpartum women's mental health after natural disaster.</p> <p>Methods</p> <p>Interviews were conducted in 2006–2007 with women who had been pregnant during or shortly after Hurricane Katrina. 292 New Orleans and Baton Rouge women were interviewed at delivery and 2 months postpartum. Depression was assessed using the Edinburgh Depression Scale and PTSD using the Post-Traumatic Stress Checklist. Women were asked about their experience of the hurricane with questions addressing threat, illness, loss, and damage. Chi-square tests and log-binomial/Poisson models were used to calculate associations and relative risks (RR).</p> <p>Results</p> <p>Black women and women with less education were more likely to have had a serious experience of the hurricane. 18% of the sample met the criteria for depression and 13% for PTSD at two months postpartum. Feeling that one's life was in danger was associated with depression and PTSD, as were injury to a family member and severe impact on property. Overall, two or more severe experiences of the storm was associated with an increased risk for both depression (relative risk (RR) 1.77, 95% confidence interval (CI) 1.08–2.89) and PTSD (RR 3.68, 95% CI 1.80–7.52).</p> <p>Conclusion</p> <p>Postpartum women who experience natural disaster severely are at increased risk for mental health problems, but overall rates of depression and PTSD do not seem to be higher than in studies of the general population.</p
LNCS
Discrete-time Markov Chains (MCs) and Markov Decision Processes (MDPs) are two standard formalisms in system analysis. Their main associated quantitative objectives are hitting probabilities, discounted sum, and mean payoff. Although there are many techniques for computing these objectives in general MCs/MDPs, they have not been thoroughly studied in terms of parameterized algorithms, particularly when treewidth is used as the parameter. This is in sharp contrast to qualitative objectives for MCs, MDPs and graph games, for which treewidth-based algorithms yield significant complexity improvements. In this work, we show that treewidth can also be used to obtain faster algorithms for the quantitative problems. For an MC with n states and m transitions, we show that each of the classical quantitative objectives can be computed in O((n+m)⋅t2) time, given a tree decomposition of the MC with width t. Our results also imply a bound of O(κ⋅(n+m)⋅t2) for each objective on MDPs, where κ is the number of strategy-iteration refinements required for the given input and objective. Finally, we make an experimental evaluation of our new algorithms on low-treewidth MCs and MDPs obtained from the DaCapo benchmark suite. Our experiments show that on low-treewidth MCs and MDPs, our algorithms outperform existing well-established methods by one or more orders of magnitude
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters
Recent progress in studies of globular clusters has shown that they are not
simple stellar populations, being rather made of multiple generations. Evidence
stems both from photometry and spectroscopy. A new paradigm is then arising for
the formation of massive star clusters, which includes several episodes of star
formation. While this provides an explanation for several features of globular
clusters, including the second parameter problem, it also opens new
perspectives about the relation between globular clusters and the halo of our
Galaxy, and by extension of all populations with a high specific frequency of
globular clusters, such as, e.g., giant elliptical galaxies. We review progress
in this area, focusing on the most recent studies. Several points remain to be
properly understood, in particular those concerning the nature of the polluters
producing the abundance pattern in the clusters and the typical timescale, the
range of cluster masses where this phenomenon is active, and the relation
between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review
Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy
Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tumour radioresistance; therefore, it is recognised as an excellent target during radiation therapy. However, the inhibition of HIF-1 in unsuitable timing can suppress rather than enhance the effect of radiation therapy because its anti-angiogenic effect increases the radioresistant hypoxic fraction. In this study, we imaged changes of HIF-1 activity after treatment with radiation and/or an HIF-1 inhibitor, YC-1, and optimised their combination. Hypoxic tumour cells were reoxygenated 6 h postirradiation, leading to von Hippel-Lindau (VHL)-dependent proteolysis of HIF-1α and a resultant decrease in HIF-1 activity. The activity then increased as HIF-1α accumulated in the reoxygenated regions 24 h postirradiation. Meanwhile, YC-1 temporarily but significantly suppressed HIF-1 activity, leading to a decrease in microvessel density and an increase in tumour hypoxia. On treatment with YC-1 and then radiation, the YC-1-mediated increase in tumour hypoxia suppressed the effect of radiation therapy, whereas on treatment in the reverse order, YC-1 suppressed the postirradiation upregulation of HIF-1 activity and consequently delayed tumour growth. These results indicate that treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the therapeutic effect of radiation, and the suppression of the postirradiation upregulation of HIF-1 activity is important for the best therapeutic benefit
Migratory Pathways and Connectivity in Asian Houbara Bustards: Evidence from 15 Years of Satellite Tracking
Information on migratory pathways and connectivity is essential to understanding population dynamics and structure of migrant species. Our manuscript uses a unique dataset, the fruit of 103 individual Asian houbara bustards captured on their breeding grounds in Central Asia over 15 years and equipped with satellite transmitters, to provide a better understanding of migratory pathways and connectivity; such information is critical to the implementation of biologically sound conservation measures in migrant species. At the scale of the distribution range we find substantial migratory connectivity, with a clear separation of migration pathways and wintering areas between western and eastern migrants. Within eastern migrants, we also describe a pattern of segregation on the wintering grounds. But at the local level connectivity is weak: birds breeding within the limits of our study areas were often found several hundreds of kilometres apart during winter. Although houbara wintering in Arabia are known to originate from Central Asia, out of all the birds captured and tracked here not one wintered on the Arabian Peninsula. This is very likely the result of decades of unregulated off-take and severe habitat degradation in this area. At a time when conservation measures are being implemented to safeguard the long-term future of this species, this study provides critical data on the spatial structuring of populations
Metal-Poor Stars and the Chemical Enrichment of the Universe
Metal-poor stars hold the key to our understanding of the origin of the
elements and the chemical evolution of the Universe. This chapter describes the
process of discovery of these rare stars, the manner in which their surface
abundances (produced in supernovae and other evolved stars) are determined from
the analysis of their spectra, and the interpretation of their abundance
patterns to elucidate questions of origin and evolution. More generally,
studies of these stars contribute to other fundamental areas that include
nuclear astrophysics, conditions at the earliest times, the nature of the first
stars, and the formation and evolution of galaxies -- including our own Milky
Way. We illustrate this with results from studies of lithium formed during the
Big Bang; of stars dated to within ~1 Gyr of that event; of the most metal-poor
stars, with abundance signatures very different from all other stars; and of
the build-up of the elements over the first several Gyr. The combination of
abundance and kinematic signatures constrains how the Milky Way formed, while
recent discoveries of extremely metal-poor stars in the Milky Way's dwarf
galaxy satellites constrain the hierarchical build-up of its stellar halo from
small dark-matter dominated systems. [abridged]Comment: Book chapter, emulated version, 34 pages; number of references are
limited by publisher; to appear in Vol. 5 of textbook "Planets, Stars and
Stellar Systems", by Springer, in 201
Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells
The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30 hours. The above system and resource provide tools to study morphogen function in development
- …