Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms

Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. We explored risk factors for CSF discordance and escape in patients presenting with diverse neurological problems. Methods: HIV-infected adult patients undergoing diagnostic lumbar puncture (LP) at a single center between 2011 and 2015 were included in the analysis. Clinical and neuroimaging variables associated with CSF discordance/escape were identified using multivariate logistic regression. Results: One hundred forty-six patients with a median age of 45.3 (interquartile range [IQR], 39.6–51.5) years underwent 163 LPs. Median CD4 count was 430 (IQR, 190–620) cells/µL. Twenty-four (14.7%) LPs in 22 patients showed CSF discordance, of which 10 (6.1%) LPs in 9 patients represented CSF escape. In multivariate analysis, both CSF discordance and escape were associated with diffuse white matter signal abnormalities (DWMSAs) on cranial magnetic resonance imaging (adjusted odds ratio, 10.3 [95% confidence interval {CI}, 2.3–45.0], P = .007 and 56.9 [95% CI, 4.0–882.8], P = .01, respectively). All 7 patients with CSF escape (10 LPs) had been diagnosed with HIV >7 years prior to LP, and 6 of 6 patients with resistance data had documented evidence of drug-resistant virus in plasma. Conclusions: Among patients presenting with diverse neurological problems, CSF discordance or escape was observed in 15%, with treatment-experienced patients dominating the escape group. DWMSAs in HIV-infected individuals presenting with neurological problems should raise suspicion of possible CSF discordance/escape

Seagrass Canopy Photosynthetic Response Is a Function of Canopy Density and Light Environment: A Model for Amphibolis griffithii

A three-dimensional computer model of canopies of the seagrass Amphibolis griffithii was used to investigate the consequences of variations in canopy structure and benthic light environment on leaf-level photosynthetic saturation state. The model was constructed using empirical data of plant morphometrics from a previously conducted shading experiment and validated well to in-situ data on light attenuation in canopies of different densities. Using published values of the leaf-level saturating irradiance for photosynthesis, results show that the interaction of canopy density and canopy-scale photosynthetic response is complex and non-linear, due to the combination of self-shading and the non-linearity of photosynthesis versus irradiance (P-I) curves near saturating irradiance. Therefore studies of light limitation in seagrasses should consider variation in canopy structure and density. Based on empirical work, we propose a number of possible measures for canopy scale photosynthetic response that can be plotted to yield isoclines in the space of canopy density and light environment. These plots can be used to interpret the significance of canopy changes induced as a response to decreases in the benthic light environment: in some cases canopy thinning can lead to an equivalent leaf level light environment, in others physiological changes may also be required but these alone may be inadequate for canopy survival. By providing insight to these processes the methods developed here could be a valuable management tool for seagrass conservation during dredging or other coastal developments

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

SCN1A variants from bench to bedside-improved clinical prediction from functional characterization

Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch‐clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole‐cell current, whereas those without any whole‐cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses

SPECULOOS exoplanet search and its prototype on TRAPPIST

One of the most significant goals of modern science is establishing whether life exists around other suns. The most direct path towards its achievement is the detection and atmospheric characterization of terrestrial exoplanets with potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs), i.e. very-low-mass stars and brown dwarfs with effective temperatures lower than 2700 K, represent a unique opportunity to reach this goal within the next decade. The potential of the transit method for detecting potentially habitable Earth-sized planets around these objects is drastically increased compared to Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby UCD would be amenable for a thorough atmospheric characterization, including the search for possible biosignatures, with near-future facilities such as the James Webb Space Telescope. In this chapter, we first describe the physical properties of UCDs as well as the unique potential they offer for the detection of potentially habitable Earth-sized planets suitable for atmospheric characterization. Then, we present the SPECULOOS ground-based transit survey, that will search for Earth-sized planets transiting the nearest UCDs, as well as its prototype survey on the TRAPPIST telescopes. We conclude by discussing the prospects offered by the recent detection by this prototype survey of a system of seven temperate Earth-sized planets transiting a nearby UCD, TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H. Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure

Induction of fish biomarkers by synthetic-based drilling muds

The study investigated the effects of chronic exposure of pink snapper (Pagrus auratus Forster), to synthetic based drilling muds (SBMs). Fish were exposed to three mud systems comprised of three different types of synthetic based fluids (SBFs): an ester (E), an isomerized olefin (IO) and linear alpha olefin (LAO). Condition factor (CF), liver somatic index (LSI), hepatic detoxification (EROD activity), biliary metabolites, DNA damage and stress proteins (HSP-70) were determined. Exposure to E caused biologically significant effects by increasing CF and LSI, and triggered biliary metabolite accumulation. While ester-based SBFs have a rapid biodegradation rate in the environment, they caused the most pronounced effects on fish health. IO induced EROD activity and biliary metabolites and LAO induced EROD activity and stress protein levels. The results demonstrate that while acute toxicity of SBMs is generally low, chronic exposure to weathering cutting piles has the potential to affect fish health. The study illustrates the advantages of the Western Australian government case-by-case approach to drilling fluid management, and highlights the importance of considering the receiving environment in the selection of SBMs

"I am your mother and your father!": In vitro derived gametes and the ethics of solo reproduction

In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes

Метафизическое значение категорий предмета и непредмета в логике, поясняемое примерами решения антиномии Рассела в теории типов и аксиоматической системе NBG

Метафизическое значение категорий предмета и непредмета в логике, поясняемое примерами решения антиномии Рассела в теории типов и аксиоматической системе NB