Ultra-Filtration of Human Serum for Improved Quantitative Analysis of Low Molecular Weight Biomarkers using ATR-IR Spectroscopy

Infrared spectroscopy is a reliable, rapid and cost effective characterisation technique, delivering a molecular finger print of the sample. It is expected that its sensitivity would enable detection of small chemical variations in biological samples associated with disease. ATR-IR is particularly suitable for liquid sample analysis and, although air drying is commonly performed before data collection, just a drop of human serum is enough for screening and early diagnosis. However, the dynamic range of constituent biochemical concentrations in the serum composition remains a limiting factor to the reliability of the technique. Using glucose as a model spike in human serum, it has been demonstrated in the present study that fractionating the serum prior to spectroscopic analysis can considerably improve the precision and accuracy of quantitative models based on the Partial Least Squares Regression algorithm. By depleting the abundant high molecular weight proteins, which otherwise dominate the spectral signatures collected, the ability to monitor changes in the concentrations of the low molecular weight constituents is enhanced. The Root Mean Square Error for the Validation set (RMSEV) has been improved by a factor of 5 following human serum processing with an average relative error in the predictive values below 1% is achieved. Moreover, the approach is easily transferable to different bodily fluids, which would support the development of more efficient and suitable clinical protocols for exploration of vibrational spectroscopy based ex-vivo diagnostic tools

Diffusion in hot subdwarf progenitors from the common envelope channel

© 2017 C. M. Byrne et al. Diffusion of elements in the atmosphere of a star can drastically affect its surface composition, sometimes leading to unusual mixtures. These chemically peculiar stars can be identified from the presence of unusual lines in their spectra. Some hot subdwarf stars show extraordinary abundances of elements such as lead, zirconium and strontium, while the abundance of helium ranges from practically zero to almost 100 percent across the hot subdwarf population. A sequence of extreme horizontal branch star models was generated by producing a number of post-common envelope objects from red giants. The evolution of these subdwarf progenitors was computed with the MESA stellar evolution code from immediately after envelope ejection right up to the ignition of helium in the core. Envelope abundances were calculated at the zero age horizontal branch for models both with and without the presence of diffusion. A small number of simulations also looked at the effects on radiative levitation of these abundances, to test how well diffusion physics is able to reproduce observational data

Feasibility of Photofrin II as a radiosensitizing agent in solid tumors - Preliminary results

Background: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. Material and Methods: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. Results: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of > 45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. Conclusion: The early follow-up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent

Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown

Psychometric properties of three measures of “Facebook engagement and/or addiction” among a sample of English speaking Pakistani university students

For researchers interested in measuring the construct of “Facebook engagement and/or addiction,” there are a number of existing measures including the Bergen Facebook Addiction Scale, the Facebook Intensity Scale, and the Addictive Tendencies Scale. Currently, there is limited data on the psychometric properties of these three scales, especially among South Asian samples. The present aim was to address this shortfall. A sample of 308 English-speaking Pakistani university students completed the scales, in their original English versions, on two occasions separated by four weeks. Results demonstrated that for each of the scales, across both administrations, satisfactory psychometric properties were found, including internal reliability, temporal stability, and construct validity. Moreover, for these three scales, using confirmatory factor analysis, a one-factor structure was generally found to be a good description of the data for both male and female samples. These data provide further evidence for the reliability and validity of three scales concerned with “Facebook engagement and/or addiction.

Risk measures for direct real estate investments with non-normal or unknown return distributions

The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate. We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification

High-throughput, quantitative analyses of genetic interactions in E. coli.

Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

Dissolution dominating calcification process in polar pteropods close to the point of aragonite undersaturation

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Omega_Ar). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Omega_Ar,0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Var levels slightly above 1 and lower at Omega_Ar levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Var derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Omega_Ar levels close to 1, with net shell growth ceasing at an Omega_Ar of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean