Developing a discrimination rule between breast cancer patients and controls using proteomics mass spectrometric data: A three-step approach

To discriminate between breast cancer patients and controls, we used a three-step approach to obtain our decision rule. First, we ranked the mass/charge values using random forests, because it generates importance indices that take possible interactions into account. We observed that the top ranked variables consisted of highly correlated contiguous mass/charge values, which were grouped in the second step into new variables. Finally, these newly created variables were used as predictors to find a suitable discrimination rule. In this last step, we compared three different methods, namely Classification and Regression Tree ( CART), logistic regression and penalized logistic regression. Logistic regression and penalized logistic regression performed equally well and both had a higher classification accuracy than CART. The model obtained with penalized logistic regression was chosen as we hypothesized that this model would provide a better classification accuracy in the validation set. The solution had a good performance on the training set with a classification accuracy of 86.3%, and a sensitivity and specificity of 86.8% and 85.7%, respectively

18S is an appropriate housekeeping gene for in vitro hypoxia experiments

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Poisson transition rates from time-domain measurements with finite bandwidth

In time-domain measurements of a Poisson two-level system, the observed transition rates are always smaller than those of the actual system, a general consequence of finite measurement bandwidth in an experiment. This underestimation of the rates is significant even when the measurement and detection apparatus is ten times faster than the process under study. We derive here a quantitative form for this correction using a straightforward state-transition model that includes the detection apparatus, and provide a method for determining a system's actual transition rates from bandwidth-limited measurements. We support our results with computer simulations and experimental data from time-domain measurements of quasiparticle tunneling in a single-Cooper-pair transistor.Comment: 4 pages, 5 figure

Pregnancy outcomes in Benghazi, Libya, before and during the armed conflict in 2011

Stressful life events experienced by pregnant women may lead to adverse obstetric outcomes. This study in Benghazi compared the rates of preterm, low-birth-weight and caesarean-section births at Al-Jamhouria hospital in the months before and during the armed conflict in Libya in 2011. Data were collected on all women admitted to the delivery ward during February to May 2011 (the months of the most active fighting in the city) (n = 7096), and October to December 2010 (the months immediately before the war) (n = 5935). Compared with the preceding months there was a significant rise during the conflict in the rate of deliveries involving preterm (3.6% versus 2.5%) and low-birth-weight (10.1% versus 8.5%) infants and caesarean sections (26.9% versus 25.3%). Psychosocial stress may have been a factor (among others) in an increase in negative pregnancy outcomes, and obstetric hospitals should be aware of these issues in times of war

Diphtheria antitoxin levels in the Netherlands: a population-based study.

In a population-based study in the Netherlands, diphtheria antitoxin antibodies were measured with a toxin-binding inhibition assay in 9, 134 sera from the general population and religious communities refusing vaccination. The Dutch immunization program appears to induce long-term protection against diphtheria. However, a substantial number of adults born before the program was introduced had no protective diphtheria antibody levels. Although herd immunity seems adequate, long-term population protection cannot be assured. As more than 60% of orthodox reformed persons have antibody levels lower than 0.01 IU/ml, introduction of diphtheria into religious communities refusing vaccination may constitute a danger of spread of the bacterium

Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX

Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer

Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa

Background: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. Methods: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. Results: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. Conclusion: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women

Surface enhanced raman scattering artificial nose for high dimensionality fingerprinting

Label-free surface-enhanced Raman spectroscopy (SERS) can interrogate systems by directly fingerprinting its components’ unique physicochemical properties. In complex biological systems however, this can yield highly overlapping spectra that hinder sample identification. Here, we present an artificial-nose inspired SERS fingerprinting approach where spectral data is obtained as a function of sensor surface chemical functionality. Supported by molecular dynamics modelling, we show that mildly selective self-assembled monolayers can influence the strength and configuration in which analytes interact with plasmonic surfaces, diversifying the resulting SERS fingerprints. Since each sensor generates a modulated signature, the implicit value of increasing the dimensionality of datasets is shown using cell lysates for all possible combinations of up to 9 fingerprints. Reliable improvements in mean discriminatory accuracy towards 100% is achieved with each additional surface functionality. This arrayed label-free platform illustrates the wide-ranging potential of high dimensionality artificial-nose based sensing systems for more reliable assessment of complex biological matrices