Cardiovascular toxicities after anthracycline and VEGF-targeted therapies in adolescent and young adult cancer survivors

BACKGROUND: Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood. OBJECTIVE: This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy. METHODS: Data were extracted from electronic medical records over a fourteen-year period at a single institution. Cox proportional hazards regression modeling was used to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk. RESULTS: Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04-1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up). CONCLUSIONS: CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy

Robust methodology for fractal analysis of the retinal vasculature

We have developed a robust method to perform retinal vascular fractal analysis from digital retina images. The technique preprocesses the green channel retina images with Gabor wavelet transforms to enhance the retinal images. Fourier Fractal dimension is computed on these preprocessed images and does not require any segmentation of the vessels. This novel technique requires human input only at a single step; the allocation of the optic disk center. We have tested this technique on 380 retina images from healthy individuals aged 50+ years, randomly selected from the Blue Mountains Eye Study population. To assess its reliability in assessing retinal vascular fractals from different allocation of optic center, we performed pair-wise Pearson correlation between the fractal dimension estimates with 100 simulated region of interest for each of the 380 images. There was Gaussian distribution variation in the optic center allocation in each simulation. The resulting mean correlation coefficient (standard deviation) was 0.93 (0.005). The repeatability of this method was found to be better than the earlier box-counting method. Using this method to assess retinal vascular fractals, we have also confirmed a reduction in the retinal vasculature complexity with aging, consistent with observations from other human organ systems

Discovery of Eurytrema Eggs in Sediment from a Colonial Period Latrine in Taiwan.

In this study we take a closer look at the diseases that afflicted Japanese police officers who were stationed in a remote mountainous region of Taiwan from 1921 to 1944. Samples were taken from the latrine at the Huabanuo police outpost, and analyzed for the eggs of intestinal parasites, using microscopy and ELISA. The eggs of Eurytrema sp., (possibly E. pancreaticum), whipworm and roundworm were shown to be present. True infection with Eurytrema would indicate that the policemen ate uncooked grasshoppers and crickets infected with the parasite. However, false parasitism might also occur if the policemen ate the uncooked intestines of infected cattle, and the Eurytrema eggs passed through the human intestines. These findings provide an insight into the diet and health of the Japanese colonists in Taiwan nearly a century ago

How Easy is it to Read the Minds of People with Autism Spectrum Disorder?

yesHow well can neurotypical adults’ interpret mental states in people with ASD? ‘Targets’ (ASD and neurotypical) reactions to four events were video-recorded then shown to neurotypical participants whose task was to identify which event the target had experienced. In study 1 participants were more successful for neurotypical than ASD targets. In study 2, participants rated ASD targets equally expressive as neurotypical targets for three of the events, while in study 3 participants gave different verbal descriptions of the reactions of ASD and neurotypical targets. It thus seems people with ASD react differently but not less expressively to events. Because neurotypicals are ineffective in interpreting the behaviour of those with ASD, this could contribute to the social difficulties in ASD

Optimisation problems and replica symmetry breaking in finite connectivity spin-glasses

A formalism capable of handling the first step of hierarchical replica symmetry breaking in finite-connectivity models is introduced. The emerging order parameter is claimed to be a probability distribution over the space of field distributions (or, equivalently magnetisation distributions) inside the cluster of states. The approach is shown to coincide with the previous works in the replica symmetric case and in the two limit cases m=0,1 where m is Parisi's break-point. As an application to the study of optimization problems, the ground-state properties of the random 3-Satisfiability problem are investigated and we present a first RSB solution improving replica symmetric results.Comment: 16 pages Revtex file, 1 figure; amended version with two new appendices; to be published in J.Phys.

The Mariner 6 and 7 flight paths and their determination from tracking data

Determination of orbit estimates for Mariner 6 and 7 space probe flight

An impact assessment methodology for urban surface runoff quality following best practice treatment

The paper develops an easy to apply desk-based semi-quantitative approach for the assessment of residual receiving water quality risks associated with urban surface runoff following its conveyance through best practice sustainable drainage systems (SUDS). The innovative procedure utilises an integrated geographical information system (GIS)-based pollution index approach based on surface area impermeability, runoff concentrations/loadings and individual SUDS treatment performance potential to evaluate the level of risk mitigation achievable by SUDS drainage infrastructure. The residual impact is assessed through comparison of the determined pollution index with regulatory receiving water quality standards and objectives. The methodology provides an original theoretically based procedure which complements the current acute risk assessment approaches being widely applied within pluvial flood risk management

Epigenetic and transcriptome profiling identifies a population of visceral adipose-derived progenitor cells with potential to differentiate into an endocrine pancreatic lineage

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing β-cells in the pancreas. T1D can be treated using cadaveric islet transplantation, but this therapy is severely limited by a lack of pancreas donors. To develop an alternative cell source for transplantation therapy, we carried out the epigenetic characterization in nine different adult mouse tissues and identified visceral adipose-derived progenitors as a candidate cell population. Chromatin conformation, assessed using chromatin immunoprecipitation (ChIP) sequencing and validated by ChIP-polymerase chain reaction (PCR) at key endocrine pancreatic gene promoters, revealed similarities between visceral fat and endocrine pancreas. Multiple techniques involving quantitative PCR, in-situ PCR, confocal microscopy, and flow cytometry confirmed the presence of measurable (2–1000-fold over detectable limits) pancreatic gene transcripts and mesenchymal progenitor cell markers (CD73, CD90 and CD105; >98%) in visceral adipose tissue-derived mesenchymal cells (AMCs). The differentiation potential of AMCs was explored in transgenic reporter mice expressing green fluorescent protein (GFP) under the regulation of the Pdx1 (pancreatic and duodenal homeobox-1) gene promoter. GFP expression was measured as an index of Pdx1 promoter activity to optimize culture conditions for endocrine pancreatic differentiation. Differentiated AMCs demonstrated their capacity to induce pancreatic endocrine genes as evidenced by increased GFP expression and validated using TaqMan real-time PCR (at least 2–200-fold relative to undifferentiated AMCs). Human AMCs differentiated using optimized protocols continued to produce insulin following transplantation in NOD/SCID mice. Our studies provide a systematic analysis of potential islet progenitor populations using genome-wide profiling studies and characterize visceral adipose-derived cells for replacement therapy in diabetes