Detection of Chlamydia trachomatis infections in women by Amplicor PCR: comparison of diagnostic performance with urine and cervical specimens

We used the Roche Amplicor PCR assay to compare urine and cervical swabs as sample material in the detection of Chlamydia trachomatis causing genital infections. The diagnostic performance of Amplicor PCR was compared with that of cell culture and the Gen-Probe PACE 2 assay with cervical specimens. If discrepant from other results, the specimens negative by PCR were diluted and reanalyzed to reveal PCR inhibitors. Of 666 patients, 39 (5.9%) were confirmed to have chlamydial infection. The respective sensitivity and specificity of Amplicor PCR were as follows: urine specimens, 82.0 and 99.7%; cervical specimens, 82.0 and 99.8%. Those for cell culture with cervical specimens were 84.6 and 100%. For the Gen-Probe PACE 2 assay, the sensitivity and specificity with cervical specimens were 79.5 and 100%, respectively. Without the effect of PCR inhibitors, the sensitivity of PCR with urine would have been 97.4%. Provided that the problems currently caused by inhibitors will be solved, the Amplicor PCR assay with urine specimens offers a tempting alternative for the diagnosis of C. trachomatis infection in women.     

Articulating User Needs in Collaborative Design: Towards an Activity-Theoretical Approach

This paper analyses the collaborative design ofa high-technology product, a neuromagnetometerused in the analysis of the activity of thehuman cortex. The producer, Neuromag Company istrying to transform the device from a basicresearch instrument into a means of clinicalpractice. This transition is analyzed as asimultaneous evolution of the product,producer-user network and user activities. Thenetwork is analyzed as a network of activitysystems. Each activity has a historicallyformed object and a motive of its own, as wellas a system of cultural means and expertise. Weuse these to explain and understand theinterests and points of view of the actors inrelation to the product and the contradictionsof the producer-user network. It is suggestedthat the emerging user needs of collectiveactors must be analyzed at three levels. At thefirst level, the use value of the product, itscapacity of solving the vital problems andchallenges of developing user activities, ischaracterized. The second-level analysisconcerns the creation and development of thenecessary complementary tools and services thatmake the implementation and use of the productpossible. This task presupposes collaborationbetween several communities of the innovationnetwork. The third level is the situatedpractical use of the product. In ourexperience, it is advantageous that researcherscontribute with their data to a dialogue inwhich the user needs are articulated.     

The apolipoprotein E phenotype has a strong influence on tracking of serum cholesterol and lipoprotein levels in children: a follow-up study from birth to the age of 11 years

Fatty acid uptake is partly controlled by the FATP gene family, of which at least five members are known in mice. Using the mmFATP1 cDNA as hybridization probe, a 1.6 kb partial cDNA clone was isolated from a human heart cDNA library. With 5' and 3' RACE procedures, the complete cDNA was isolated. Sequence comparisons with its mouse homologues identified this clone as hsFATP4.     

If Virchow and Ehrlich Had Dreamt Together: What the Future Holds for KRAS-Mutant Lung Cancer

Non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) mutations has notoriously challenged oncologists and researchers for three notable reasons: (1) the historical assumption that KRAS is “undruggable”, (2) the disease heterogeneity and (3) the shaping of the tumor microenvironment by KRAS downstream effector functions. Better insights into KRAS structural biochemistry allowed researchers to develop direct KRAS(G12C) inhibitors, which have shown early signs of clinical activity in NSCLC patients and have recently led to an FDA breakthrough designation for AMG-510. Following the approval of immune checkpoint inhibitors for PDL1-positive NSCLC, this could fuel yet another major paradigm shift in the treatment of advanced lung cancer. Here, we review advances in our understanding of the biology of direct KRAS inhibition and project future opportunities and challenges of dual KRAS and immune checkpoint inhibition. This strategy is supported by preclinical models which show that KRAS(G12C) inhibitors can turn some immunologically “cold” tumors into “hot” ones and therefore could benefit patients whose tumors harbor subtype-defining STK11/LKB1 co-mutations. Forty years after the discovery of KRAS as a transforming oncogene, we are on the verge of approval of the first KRAS-targeted drug combinations, thus therapeutically unifying Paul Ehrlich’s century-old “magic bullet” vision with Rudolf Virchow’s cancer inflammation theory.     

Dietary squalene increases tissue sterols and fecal bile acids in the rat

Feeding 1% squalene increased markedly the concentrations of squalene and methyl sterols in each serum lipoprotein class, intestinal mucosa, liver and also in adipose tissue. It also increased cholesterol concentration of the liver and serum VLDL, and esterified cholesterol in serum LDL as well as fecal bile acids. The results suggest that absorbed dietary squalene contributes to some extent to the squalene content of adipose tissue, effectively increases the overall cholesterol synthesis and enhances cholesterol elimination preferentially as fecal bile acids.     

Centroid index: Cluster level similarity measure

In clustering algorithm, one of the main challenges is to solve the global allocation of the clusters instead of just local tuning of the partition borders. Despite this, all external cluster validity indexes calculate only point-level differences of two partitions without any direct information about how similar their cluster-level structures are. In this paper, we introduce a cluster level index called centroid index. The measure is intuitive, simple to implement, fast to compute and applicable in case of model mismatch as well. To a certain extent, we expect it to generalize other clustering models beyond the centroid-based k-means as well.     

K-means: Clustering by gradual data transformation

Traditional approach to clustering is to fit a model (partition or prototypes) for the given data. We propose a completely opposite approach by fitting the data into a given clustering model that is optimal for similar pathological data of equal size and dimensions. We then perform inverse transform from this pathological data back to the original data while refining the optimal clustering structure during the process. The key idea is that we do not need to find optimal global allocation of the prototypes. Instead, we only need to perform local fine-tuning of the clustering prototypes during the transformation in order to preserve the already optimal clustering structure.     

From big smartphone data to worldwide research: The Mobile Data Challenge

This paper presents an overview of the Mobile Data Challenge (MDC), a large-scale research initiative aimed at generating innovations around smartphone-based research, as well as community-based evaluation of mobile data analysis methodologies. First, we review the Lausanne Data Collection Campaign (LDCC), an initiative to collect unique longitudinal smartphone dataset for the MDC. Then, we introduce the Open and Dedicated Tracks of the MDC, describe the specific datasets used in each of them, discuss the key design and implementation aspects introduced in order to generate privacy-preserving and scientifically relevant mobile data resources for wider use by the research community, and summarize the main research trends found among the 100+ challenge submissions. We finalize by discussing the main lessons learned from the participation of several hundred researchers worldwide in the MDC Tracks.