Cardiovascular magnetic resonance reference ranges for the heart and aorta in Chinese at 3T.

Cardiovascular magnetic resonance (CMR) reference ranges have not been well established in Chinese. Here we determined normal cardiac and aortic reference ranges in healthy Singaporean Chinese and investigated how these data might affect clinical interpretation of CMR scans.In 180 healthy Singaporean Chinese (20 to 69 years old; males, n = 91), comprehensive cardiac assessment was performed using the steady state free precision technique (3T Ingenia, Philips) and images were analysed by two independent observers (CMR42, Circle Cardiovascular Imaging). Measurements were internally validated using standardized approaches: left ventricular mass (LVM) was measured in diastole and systole (with and without papillary muscles) and stroke volumes were compared in both ventricles. All reference ranges were stratified by sex and age; and indeterminate/borderline regions were defined statistically at the limits of the normal reference ranges. Results were compared with clinical measurements reported in the same individuals.LVM was equivalent in both phases (mean difference 3.0 ± 2.5 g; P = 0.22) and stroke volumes were not significantly different in the left and right ventricles (P = 0.91). Compared to females, males had larger left and right ventricular volumes (P  0.05 for all measures). In both sexes, age correlated negatively with left and right ventricular volumes; and positively with aortic sinus and sinotubular junction diameters (P < 0.0001 for all). There was excellent agreement in indexed stroke volumes in the left and right ventricles (0.1±5.7 mL/m2, 0.7±6.2 mL/m2, respectively), LVM (0.6±6.4 g/m2), atrial sizes and aortic root dimensions between values reported in clinical reports and our measured reference ranges.Comprehensive sex and age-corrected CMR reference ranges at 3T have been established in Singaporean Chinese. This is an important step for clinical practice and research studies of the heart and aorta in Asia

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Intrinsic and Extrinsic Performance Limits of Graphene Devices on SiO2

The linear dispersion relation in graphene[1,2] gives rise to a surprising prediction: the resistivity due to isotropic scatterers (e.g. white-noise disorder[3] or phonons[4-8]) is independent of carrier density n. Here we show that acoustic phonon scattering[4-6] is indeed independent of n, and places an intrinsic limit on the resistivity in graphene of only 30 Ohm at room temperature (RT). At a technologically-relevant carrier density of 10^12 cm^-2, the mean free path for electron-acoustic phonon scattering is >2 microns, and the intrinsic mobility limit is 2x10^5 cm^2/Vs, exceeding the highest known inorganic semiconductor (InSb, ~7.7x10^4 cm^2/Vs[9]) and semiconducting carbon nanotubes (~1x10^5 cm^2/Vs[10]). We also show that extrinsic scattering by surface phonons of the SiO2 substrate[11,12] adds a strong temperature dependent resistivity above ~200 K[8], limiting the RT mobility to ~4x10^4 cm^2/Vs, pointing out the importance of substrate choice for graphene devices[13].Comment: 16 pages, 3 figure

Life and consciousness – The Vedāntic view

In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter — and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself – omne vivum ex vivo – life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all sentient and insentient nature. In contrast to the idea of objective evolution of bodies, as envisioned by Darwin and followers, Vedānta advocates the idea of subjective evolution of consciousness as the developing principle of the world. In this paper, an attempt has been made to highlight a few relevant developments supporting a sentient view of life in scientific research, which has caused a paradigm shift in our understanding of life and its origin

Characterizing phase change materials using the T-History method: On the factors influencing the accuracy and precision of the enthalpy-temperature curve

While research on using the latent heat of so called phase change materials (PCMs) for thermal energy storage has gained increasing interest in the last decade, the measurement of its thermal properties are still subject to research. The T-History method has been frequently used by researchers to measure the enthalpy–temperature curve of PCMs but the factors influencing its accuracy and precision have rarely been discussed. This work provides a systematic experimental study of an organic PCM based on different insulated sample holders. It is first shown that the data evaluation method has to be adjusted against noise to improve both accuracy and precision for all experimental setups. The results moreover show that neglecting the insulation thermal mass in the experimental setup leads to systematic errors in the enthalpy results due to oversimplification of the mathematical model. This confirms a previous numerical study by the authors. It is recommended that either the mathematical model or the experimental setup are adjusted in future work to decrease this error. Until then it is generally recommended to use sample holders with a high ratio between the thermal mass of the PCM to the insulated sample holder. This is further supported by a measurement uncertainty analysis via Monte Carlo simulations

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial

OBJECTIVE: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). METHODS: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. RESULTS: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints. CONCLUSION: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™ this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium