Fenestrated Endovascular Aneurysm Repair – Validation of Current UK Practise

EVAR has revolutionised aneurysm management; level one evidence shows advantages of endovascular repair over open repair. However, analysis of the EUROSTAR database of >11,000 aneurysms shows that use of EVAR outside manufacturer’s instructions for use is associated with a significant risk of aneurysm related mortality and type 1 endoleak. Recent advances have seen the evolution of fenestrated endografts (FEVAR) to enable endovascular repair of aneurysms with a compromised proximal neck. However, these complex endografts are often technically difficult to insert and long term durability is unknown. In this thesis I hypothesise that all abdominal aortic aneurysms should be treated endovascularly and aim to determine the indications for fenestrated endografts. A meta-analysis found current evidence for FEVAR to be limited. A weakness in current evidence base is lack of concurrence between definition of juxta/para and supra-renal aneurysms leading to difficulty in comparison between series. A new classification system of aneurysm necks based on the endograft seal zone is proposed. Further adjuncts to complex endograft insertion are discussed including use of CO2 angiography to reduce incidence of contrast induced nephropathy and use of temporary axillo-bifemoral grafts to reduce reperfusion injury. Indications for FEVAR based on current evidence are unclear and a consensus statement to determine the indications was undertaken. An initial survey outlined current UK practise of aneurysm management. The consensus statement using RAND methodology determined the indications for FEVAR in approximately two thirds of all scenarios but outlined a grey area of equipoise in almost one third of scenarios. In conclusion, whilst most aneurysms are technically suitable for endovascular repair, it is not possible to conclude that FEVAR is superior to open repair in the long term. A grey area of equipoise was highlighted for the indications of EVAR; further evidence is required to determine guidelines for patient suitability

Biodiversity in a changing climate: a synthesis of current and projected trends in the US

This paper provides a synthesis of the recent literature describing how global biodiversity is being affected by climate change and is projected to respond in the future. Current studies reinforce earlier findings of major climate-change-related impacts on biological systems and document new, more subtle after-effects. For example, many species are shifting their distributions and phenologies at faster rates than were recorded just a few years ago; however, responses are not uniform across species. Shifts have been idiosyncratic and in some cases counterintuitive, promoting new community compositions and altering biotic interactions. Although genetic diversity enhances species\u27 potential to respond to variable conditions, climate change may outpace intrinsic adaptive capacities and increase the relative vulnerabilities of many organisms. Developing effective adaptation strategies for biodiversity conservation will not only require flexible decision-making and management approaches that account for uncertainties in climate projections and ecological responses but will also necessitate coordinated monitoring efforts

A review of tennis racket performance parameters

The application of advanced engineering to tennis racket design has influenced the nature of the sport. As a result, the International Tennis Federation has established rules to limit performance, with the aim of protecting the nature of the game. This paper illustrates how changes to the racket affect the player-racket system. The review integrates engineering and biomechanical issues related to tennis racket performance, covering the biomechanical characteristics of tennis strokes, tennis racket performance, the effect of racket parameters on ball rebound and biomechanical interactions. Racket properties influence the rebound of the ball. Ball rebound speed increases with frame stiffness and as string tension decreases. Reducing inter-string contacting forces increases rebound topspin. Historical trends and predictive modelling indicate swingweights of around 0.030–0.035 kg/m2 are best for high ball speed and accuracy. To fully understand the effect of their design changes, engineers should use impact conditions in their experiments, or models, which reflect those of actual tennis strokes. Sports engineers, therefore, benefit from working closely with biomechanists to ensure realistic impact conditions

Protein sequestration generates a flexible ultrasensitive response in a genetic network

Ultrasensitive responses are crucial for cellular regulation. Protein sequestration, where an active protein is bound in an inactive complex by an inhibitor, can potentially generate ultrasensitivity. Here, in a synthetic genetic circuit in budding yeast, we show that sequestration of a basic leucine zipper transcription factor by a dominant-negative inhibitor converts a graded transcriptional response into a sharply ultrasensitive response, with apparent Hill coefficients up to 12. A simple quantitative model for this genetic network shows that both the threshold and the degree of ultrasensitivity depend upon the abundance of the inhibitor, exactly as we observed experimentally. The abundance of the inhibitor can be altered by simple mutation; thus, ultrasensitive responses mediated by protein sequestration are easily tuneable. Gene duplication of regulatory homodimers and loss-of-function mutations can create dominant negatives that sequester and inactivate the original regulator. The generation of flexible ultrasensitive responses is an unappreciated adaptive advantage that could explain the frequent evolutionary emergence of dominant negatives

Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1

We investigate the evolution in the distribution of surface brightness, as a function of size, for elliptical and S0 galaxies in the two clusters RDCS J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging with the Advanced Camera for Surveys on the Hubble Space Telescope to determine these sizes and surface brightnesses. Using three different estimates of the surface brightnesses, we find that we reliably estimate the surface brightness for the galaxies in our sample with a scatter of < 0.2 mag and with systematic shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type morphologies in both clusters. For each cluster, we use a magnitude limit in a band which closely corresponds to the rest-frame B, to magnitude limit of M_B = -18.8 at z=0, and select only those galaxies within the color-magnitude sequence of the cluster or by using our spectroscopic redshifts. We measure evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15) z mag. Our statistical errors are dominated by the observed scatter in the size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no statistically significant evolution in this scatter, though an increase in the scatter could be expected. Overall, the pace of luminosity evolution we measure agrees with that of the Fundamental Plane of early-type galaxies, implying that the majority of massive early-type galaxies observed at z =~ 1 formed at high redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6 in colo

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Background: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children’s Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children’s general and cancer-related health-related quality of life (HRQoL) and parents’ emotional well-being. Methods: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1–213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children’s HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL

The Localizing and Lateralizing Value of Auras in Lesional Partial Epilepsy Patients

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Experts see it all: configural effects in action observation

Biological motion perception is influenced by observers’ familiarity with the observed action. Here we used classical dance as a means to investigate how visual and motor experience modulates perceptual mechanism for configural processing of actions. While some ballet moves are performed by only one gender, male and female dancers train together and acquire visual knowledge of all ballet moves. 24 expert ballet dancers (12 female) and matched non-expert participants viewed pairs of upright and inverted point light female and common dance movements. Visual discrimination between different exemplars of the same movement presented upright was significantly better in experts than controls, while no differences were found when the same stimuli were presented upside down. These results suggest expertise influences configural action processing. Within the expert group, effects were stronger for female participants than for males, while no differences were found between movement types. This observer gender effect could suggest an additional role for motor familiarity in action perception, over and above visual experience. Our results are consistent with a specific motor contribution to configural processing of action