Systematic review of the efficacy and safety of biological therapy for inflammatory conditions in HIV-infected individuals

Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies

Sub-luminous type Ia supernovae from the mergers of equal-mass white dwarfs with M~0.9 M_sun

Type Ia supernovae (SNe Ia) are thought to result from thermonuclear explosions of carbon-oxygen white dwarf stars. Existing models generally explain the observed properties, with the exception of the sub-luminous 1991-bg-like supernovae. It has long been suspected that the merger of two white dwarfs could give rise to a type Ia event, but hitherto simulations have failed to produce an explosion. Here we report a simulation of the merger of two equal-mass white dwarfs that leads to an underluminous explosion, though at the expense of requiring a single common-envelope phase, and component masses of ~0.9 M_sun. The light curve is too broad, but the synthesized spectra, red colour and low expansion velocities are all close to what is observed for sub-luminous 1991bg-like events. While mass ratios can be slightly less than one and still produce an underluminous event, the masses have to be in the range 0.83-0.9 M_sun.Comment: Accepted to Natur

Statistical and visual differentiation of subcellular imaging

<p>Abstract</p> <p>Background</p> <p>Automated microscopy technologies have led to a rapid growth in imaging data on a scale comparable to that of the genomic revolution. High throughput screens are now being performed to determine the localisation of all of proteins in a proteome. Closer to the bench, large image sets of proteins in treated and untreated cells are being captured on a daily basis to determine function and interactions. Hence there is a need for new methodologies and protocols to test for difference in subcellular imaging both to remove bias and enable throughput. Here we introduce a novel method of statistical testing, and supporting software, to give a rigorous test for difference in imaging. We also outline the key questions and steps in establishing an analysis pipeline.</p> <p>Results</p> <p>The methodology is tested on a high throughput set of images of 10 subcellular localisations, and it is shown that the localisations may be distinguished to a statistically significant degree with as few as 12 images of each. Further, subtle changes in a protein's distribution between nocodazole treated and control experiments are shown to be detectable. The effect of outlier images is also examined and it is shown that while the significance of the test may be reduced by outliers this may be compensated for by utilising more images. Finally, the test is compared to previous work and shown to be more sensitive in detecting difference. The methodology has been implemented within the iCluster system for visualising and clustering bio-image sets.</p> <p>Conclusion</p> <p>The aim here is to establish a methodology and protocol for testing for difference in subcellular imaging, and to provide tools to do so. While iCluster is applicable to moderate (<1000) size image sets, the statistical test is simple to implement and will readily be adapted to high throughput pipelines to provide more sensitive discrimination of difference.</p

Women’s self-rated attraction to male faces does not correspond with physiological arousal

Data Availability Statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.Peer reviewedPublisher PD

A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable tumours (MSS). The primary tumours also had MSI in the residual tumours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest that tumour MSI changes during CDDP-based chemotherapy, and that the loss of hMLH1 expression is one of the factors that has the greatest effect on this transformation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Spitting Performance Parameters and Their Biomechanical Implications in the Spitting Spider, Scytodes thoracica

Spitting spiders Scytodes spp. subdue prey by entangling them at a distance with a mixture of silk, glue, and venom. Using high-speed videography and differential interference contrast microscopy, the performance parameters involved in spit ejection by Scytodes thoracica (Araneae, Scytodidae) were measured. These will ultimately need to be explained in biomechanical and fluid dynamic terms. It was found that the ejection of “spit” from the opening of the venom duct (near the proximal end of the fang) was orderly. It resulted in a pattern that scanned along a lateral-medial axis (due to fang oscillations) while traversing from ventral to dorsal (due to cheliceral elevation). Each lateral-to-medial sweep of a fang produced silk-borne beads of glue that were not present during each subsequent medial-to-lateral sweep. The ejection of “spit” was very rapid. A full scan (5–57 fang cycles, one upsweep of a chelicera) typically occupied less than 30 ms and involved fang oscillations at 278–1781 Hz. Ejection velocities were measured as high as 28.8 m/s. The “spit” was contractile. During the 0.2 s following ejection, silk shortened by 40–60% and the product of a full scan by both of the chelicerae could exert an aggregate contractile force of 0.1 – 0.3 mN. Based on these parameters, hypotheses are described concerning the biomechanical and fluid dynamic processes that could enable this kind of material ejection

Fast automated cell phenotype image classification

BACKGROUND: The genomic revolution has led to rapid growth in sequencing of genes and proteins, and attention is now turning to the function of the encoded proteins. In this respect, microscope imaging of a protein's sub-cellular localisation is proving invaluable, and recent advances in automated fluorescent microscopy allow protein localisations to be imaged in high throughput. Hence there is a need for large scale automated computational techniques to efficiently quantify, distinguish and classify sub-cellular images. While image statistics have proved highly successful in distinguishing localisation, commonly used measures suffer from being relatively slow to compute, and often require cells to be individually selected from experimental images, thus limiting both throughput and the range of potential applications. Here we introduce threshold adjacency statistics, the essence which is to threshold the image and to count the number of above threshold pixels with a given number of above threshold pixels adjacent. These novel measures are shown to distinguish and classify images of distinct sub-cellular localization with high speed and accuracy without image cropping. RESULTS: Threshold adjacency statistics are applied to classification of protein sub-cellular localization images. They are tested on two image sets (available for download), one for which fluorescently tagged proteins are endogenously expressed in 10 sub-cellular locations, and another for which proteins are transfected into 11 locations. For each image set, a support vector machine was trained and tested. Classification accuracies of 94.4% and 86.6% are obtained on the endogenous and transfected sets, respectively. Threshold adjacency statistics are found to provide comparable or higher accuracy than other commonly used statistics while being an order of magnitude faster to calculate. Further, threshold adjacency statistics in combination with Haralick measures give accuracies of 98.2% and 93.2% on the endogenous and transfected sets, respectively. CONCLUSION: Threshold adjacency statistics have the potential to greatly extend the scale and range of applications of image statistics in computational image analysis. They remove the need for cropping of individual cells from images, and are an order of magnitude faster to calculate than other commonly used statistics while providing comparable or better classification accuracy, both essential requirements for application to large-scale approaches

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Ptychographic electron microscopy using high-angle dark-field scattering for sub-nanometre resolution imaging

Diffractive imaging, in which image-forming optics are replaced by an inverse computation using scattered intensity data, could, in principle, realize wavelength-scale resolution in a transmission electron microscope. However, to date all implementations of this approach have suffered from various experimental restrictions. Here we demonstrate a form of diffractive imaging that unshackles the image formation process from the constraints of electron optics, improving resolution over that of the lens used by a factor of five and showing for the first time that it is possible to recover the complex exit wave (in modulus and phase) at atomic resolution, over an unlimited field of view, using low-energy (30 keV) electrons. Our method, called electron ptychography, has no fundamental experimental boundaries: further development of this proof-of-principle could revolutionize sub-atomic scale transmission imaging