The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature.

The clinical utility of microarray technologies when used in the context of prenatal diagnosis lies in the technology's ability to detect sub-microscopic copy number changes that are associated with clinically significant outcomes. We have carried out a systematic review of the literature to calculate the utility of prenatal microarrays in the presence of a normal conventional karyotype. Amongst 12362 cases in studies that recruited cases from all prenatal ascertainment groups, 295/12362 (2.4%) overall were reported to have copy number changes with associated clinical significance (pCNC), 201/3090 (6.5%) when ascertained with an abnormal ultrasound, 50/5108 (1.0%) when ascertained because of increased maternal age and 44/4164 (1.1%) for all other ascertainment groups (e.g. parental anxiety, abnormal serum screening result etc). When additional prenatal microarray studies are included in which ascertainment was restricted to fetuses with abnormal ultrasound scans, 262/3730 (7.0%) were reported to have pCNCs. This article is protected by copyright. All rights reserved

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

The phonon theory of liquid thermodynamics

Heat capacity of matter is considered to be its most important property because it holds information about system's degrees of freedom as well as the regime in which the system operates, classical or quantum. Heat capacity is well understood in gases and solids but not in the third state of matter, liquids, and is not discussed in physics textbooks as a result. The perceived difficulty is that interactions in a liquid are both strong and system-specific, implying that the energy strongly depends on the liquid type and that, therefore, liquid energy can not be calculated in general form. Here, we develop a phonon theory of liquids where this problem is avoided. The theory covers both classical and quantum regimes. We demonstrate good agreement of calculated and experimental heat capacity of 21 liquids, including noble, metallic, molecular and hydrogen-bonded network liquids in a wide range of temperature and pressure.Comment: 7 pages, 4 figure

92-Gene Molecular Profiling in Identification of Cancer Origin: A Retrospective Study in Chinese Population and Performance within Different Subgroups

BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE) samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC). A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85) have a high chance (agreement rate = 95%) of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM) makes the THEROS CancerTYPE ID® accessible to almost all of the cancer patients with different tumor statuses

Regulatory control and the costs and benefits of biochemical noise

Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a mathematical model that makes it possible to quantify the effect of protein concentration fluctuations on the growth rate of a population of genetically identical cells. The model predicts that the population's growth rate depends on how the growth rate of a single cell varies with protein concentration, the variance of the protein concentration fluctuations, and the correlation time of these fluctuations. The model also predicts that when the average concentration of a protein is close to the value that maximizes the growth rate, fluctuations in its concentration always reduce the growth rate. However, when the average protein concentration deviates sufficiently from the optimal level, fluctuations can enhance the growth rate of the population, even when the growth rate of a cell depends linearly on the protein concentration. The model also shows that the ensemble or population average of a quantity, such as the average protein expression level or its variance, is in general not equal to its time average as obtained from tracing a single cell and its descendants. We apply our model to perform a cost-benefit analysis of gene regulatory control. Our analysis predicts that the optimal expression level of a gene regulatory protein is determined by the trade-off between the cost of synthesizing the regulatory protein and the benefit of minimizing the fluctuations in the expression of its target gene. We discuss possible experiments that could test our predictions.Comment: Revised manuscript;35 pages, 4 figures, REVTeX4; to appear in PLoS Computational Biolog

Early Lyme disease with spirochetemia - diagnosed by DNA sequencing

<p>Abstract</p> <p>Background</p> <p>A sensitive and analytically specific nucleic acid amplification test (NAAT) is valuable in confirming the diagnosis of early Lyme disease at the stage of spirochetemia.</p> <p>Findings</p> <p>Venous blood drawn from patients with clinical presentations of Lyme disease was tested for the standard 2-tier screen and Western Blot serology assay for Lyme disease, and also by a nested polymerase chain reaction (PCR) for <it>B. burgdorferi </it>sensu lato 16S ribosomal DNA. The PCR amplicon was sequenced for <it>B. burgdorferi </it>genomic DNA validation. A total of 130 patients visiting emergency room (ER) or Walk-in clinic (WALKIN), and 333 patients referred through the private physicians' offices were studied. While 5.4% of the ER/WALKIN patients showed DNA evidence of spirochetemia, none (0%) of the patients referred from private physicians' offices were DNA-positive. In contrast, while 8.4% of the patients referred from private physicians' offices were positive for the 2-tier Lyme serology assay, only 1.5% of the ER/WALKIN patients were positive for this antibody test. The 2-tier serology assay missed 85.7% of the cases of early Lyme disease with spirochetemia. The latter diagnosis was confirmed by DNA sequencing.</p> <p>Conclusion</p> <p>Nested PCR followed by automated DNA sequencing is a valuable supplement to the standard 2-tier antibody assay in the diagnosis of early Lyme disease with spirochetemia. The best time to test for Lyme spirochetemia is when the patients living in the Lyme disease endemic areas develop unexplained symptoms or clinical manifestations that are consistent with Lyme disease early in the course of their illness.</p

Design as a provocation to support discussion about euthanasia: The Plug

Design as a provocation to support discussion about euthanasia: The Plu

Misaligned Protoplanetary Disks in a Young Binary System

Many extrasolar planets follow orbits that differ from the nearly coplanar and circular orbits found in our solar system; orbits may be eccentric or inclined with respect to the host star's equator, and the population of giant planets orbiting close to their host stars suggests significant orbital migration. There is currently no consensus on what produces such orbits. Theoretical explanations often invoke interactions with a binary companion star on an orbit that is inclined relative to the planet's orbital plane. Such mechanisms require significant mutual inclinations between planetary and binary star orbital planes. The protoplanetary disks in a few young binaries are misaligned, but these measurements are sensitive only to a small portion of the inner disk, and the three-dimensional misalignment of the bulk of the planet-forming disk mass has hitherto not been determined. Here we report that the protoplanetary disks in the young binary system HK Tau are misaligned by 60{\deg}-68{\deg}, so one or both disks are significantly inclined to the binary orbital plane. Our results demonstrate that the necessary conditions exist for misalignment-driven mechanisms to modify planetary orbits, and that these conditions are present at the time of planet formation, apparently due to the binary formation process.Comment: Published in Nature, July 31 2014. 18 pages. This version has slight differences from the final published version. Final version is available at http://www.nature.com/nature/journal/v511/n7511/full/nature13521.htm