Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy

Investigating the Effects of Finite Resolution on Observed Transverse Jet Profiles

Both the emission properties and evolution of Active Galactic Nuclei (AGN) radio jets are dependent on the magnetic fields that thread them. Faraday Rotation gradients are a very important way of investigating these magnetic fields, and can provide information on the orientation and structure of the magnetic field in the immediate vicinity of the jet; for example, a toroidal or helical field component should give rise to a systematic gradient in the observed Faraday rotation across the jet, as well as characteristic intensity and polarization profiles. However, real observed radio images have finite resolution, usually expressed via convolution with a Gaussian beam whose size corresponds to the central lobe of the point source response function. This will tend to blur transverse structure in the jet profile, raising the question of how well resolved a jet must be in the transverse direction in order to reliably detect transverse structure associated with a helical jet magnetic field. We present results of simulated intensity, polarization and Faraday rotation images designed to directly and empirically investigate the effect of finite resolution on observed transverse jet structures

Tough nanoparticle-modified polymers

A crosslinked epoxy polymer has been modified by the addition of nano-silica particles. The particles were introduced via a sol-gel technique which gave a very well dispersed phase of nano-silica particles which were about 20 nm in diameter. The glass transition temperature was unchanged by the addition of the nanoparticles, but both the modulus and toughness were increased. The fracture energy, GIc, increased from 100 J/m 2 for the unmodified epoxy to 460 J/m2 for the epoxy with 20 wt. % of nano-silica. The microscopy studies showed evidence of debonding of the nanoparticles and subsequent plastic void growth of the epoxy polymer. A theoretical model of plastic void growth was used to confirm this mechanism. The cyclic-fatigue behaviour of the epoxy polymers has also been studied and the fatigue properties were clearly enhanced by the presence of the nano-silica particles. Indeed, it was found that the values of the strain-energy release rate at threshold, Gth, from the cyclic-fatigue tests increased steadily as the toughness, GIc, also increased, i.e. as the concentration of nano-silica particles was increased

A Case Study of Eukaryogenesis: The Evolution of Photoreception by Photolyase/Cryptochrome Proteins

Eukaryogenesis, the origin of the eukaryotes, is still poorly understood. Herein, we show how a detailed all-kingdom phylogenetic analysis overlaid with a map of key biochemical features can provide valuable clues. The photolyase/cryptochrome family of proteins are well known to repair DNA in response to potentially harmful effects of sunlight and to entrain circadian rhythms. Phylogenetic analysis of photolyase/cryptochrome protein sequences from a wide range of prokaryotes and eukaryotes points to a number of horizontal gene transfer events between ancestral bacteria and ancestral eukaryotes. Previous experimental research has characterised patterns of tryptophan residues in these proteins that are important for photoreception, specifically a tryptophan dyad, a canonical tryptophan triad, an alternative tryptophan triad, a tryptophan tetrad and an alternative tetrad. Our results suggest that the spread of the different triad and tetrad motifs across the kingdoms of life accompanied the putative horizontal gene transfers and is consistent with multiple bacterial contributions to eukaryogenesis

Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predomi- nantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase ‘paradigm shift’ in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and col- leagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the man- agement of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples’ dogma makes his contribution truly a genuine paradigm shift

Additive opportunistic capture explains group hunting benefits in African wild dogs

African wild dogs (Lycaon pictus) are described as highly collaborative endurance pursuit hunters based on observations derived primarily from the grass plains of East Africa. However, the remaining population of this endangered species mainly occupies mixed woodland savannah where hunting strategies appear to differ from those previously described. We used high-resolution GPS and inertial technology to record fine-scale movement of all members of a single pack of six adult African wild dogs in northern Botswana. The dogs used multiple short-distance hunting attempts with a low individual kill rate (15.5%), but high group feeding rate due to the sharing of prey. Use of high-level cooperative chase strategies (coordination and collaboration) was not recorded. In the mixed woodland habitats typical of their current range, simultaneous, opportunistic, short-distance chasing by dogs pursuing multiple prey (rather than long collaborative pursuits of single prey by multiple individuals) could be the key to their relative success in these habitats

Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection

HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection