Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

PMCID: PMC3604109This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Of, By, and For Which People? Government and Contested Heritage in the American Midwest

Two government-owned and managed heritage sites in Indiana, USA, offer an opportunity to explore the role of governments in adjudicating the competing paradigms of value and contested uses. Strawtown Koteewi is a Hamilton County park and Mounds State Park is part of the Indiana Department of Natural Resources statewide park system. Each site has come under scrutiny in recent years. Strawtown Koteewi is one of the most significant sites in the area for understanding the history of Native peoples. After almost a decade of archaeological excavations, several Native American groups, under the auspices of the Native American Graves Protection and Repatriation Act (NAGPRA), initiated repatriation processes for the recovery of human remains, and some objected to the ongoing archaeological research. At Mounds State Park a coalition of citizens opposed a planned dam project intended to ensure a safe and plentiful water supply and to spur economic development in the area. In each case, the government entities have had to navigate the political landscapes of competing claims about the sites. These case studies expose the fissures between authorized heritage discourse and the paradigms of meaning among the diverse constituencies of the sites, and they highlight the tenuous position of public governance in privileging competing cultural, economic, and social interests. While not unique, the state and county agencies’ positions within these fields of power and their strategic choices reveal some of the barriers and constraints that limit their actions as well as the deep-seated ideologies of policies that perpetuate settler colonial politics in the control and interpretation of indigenous heritage

Influences of Excluded Volume of Molecules on Signaling Processes on Biomembrane

We investigate the influences of the excluded volume of molecules on biochemical reaction processes on 2-dimensional surfaces using a model of signal transduction processes on biomembranes. We perform simulations of the 2-dimensional cell-based model, which describes the reactions and diffusion of the receptors, signaling proteins, target proteins, and crowders on the cell membrane. The signaling proteins are activated by receptors, and these activated signaling proteins activate target proteins that bind autonomously from the cytoplasm to the membrane, and unbind from the membrane if activated. If the target proteins bind frequently, the volume fraction of molecules on the membrane becomes so large that the excluded volume of the molecules for the reaction and diffusion dynamics cannot be negligible. We find that such excluded volume effects of the molecules induce non-trivial variations of the signal flow, defined as the activation frequency of target proteins, as follows. With an increase in the binding rate of target proteins, the signal flow varies by i) monotonically increasing; ii) increasing then decreasing in a bell-shaped curve; or iii) increasing, decreasing, then increasing in an S-shaped curve. We further demonstrate that the excluded volume of molecules influences the hierarchical molecular distributions throughout the reaction processes. In particular, when the system exhibits a large signal flow, the signaling proteins tend to surround the receptors to form receptor-signaling protein clusters, and the target proteins tend to become distributed around such clusters. To explain these phenomena, we analyze the stochastic model of the local motions of molecules around the receptor.Comment: 31 pages, 10 figure

Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.</p> <p>Methods</p> <p>We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.</p> <p>Results</p> <p>According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, <it>P </it>= 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, <it>P </it>= 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, <it>P </it>= 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, <it>P </it>= 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, <it>P </it>= 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, <it>P </it>= 0.001).</p> <p>Conclusions</p> <p>The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.</p

Use of multi-trait and random regression models to identify genetic variation in tolerance to porcine reproductive and respiratory syndrome virus

Background: A host can adopt two response strategies to infection: resistance (reduce pathogen load) and tolerance (minimize impact of infection on performance). Both strategies may be under genetic control and could thus be targeted for genetic improvement. Although there is evidence that supports a genetic basis for resistance to porcine reproductive and respiratory syndrome (PRRS), it is not known whether pigs also differ genetically in tolerance. We determined to what extent pigs that have been shown to vary genetically in resistance to PRRS also exhibit genetic variation in tolerance. Multi-trait linear mixed models and random regression sire models were fitted to PRRS Host Genetics Consortium data from 1320 weaned pigs (offspring of 54 sires) that were experimentally infected with a virulent strain of PRRS virus to obtain genetic parameter estimates for resistance and tolerance. Resistance was defined as the inverse of within-host viral load (VL) from 0 to 21 (VL21) or 0 to 42 (VL42) days post-infection and tolerance as the slope of the reaction-norm of average daily gain (ADG21, ADG42) on VL21 or VL42. Results: Multi-trait analysis of ADG associated with either low or high VL was not indicative of genetic variation in tolerance. Similarly, random regression models for ADG21 and ADG42 with a tolerance slope fitted for each sire did not result in a better fit to the data than a model without genetic variation in tolerance. However, the distribution of data around average VL suggested possible confounding between level and slope estimates of the regression lines. Augmenting the data with simulated growth rates of non-infected half-sibs (ADG0) helped resolve this statistical confounding and indicated that genetic variation in tolerance to PRRS may exist if genetic correlations between ADG0 and ADG21 or ADG42 are low to moderate. Conclusions: Evidence for genetic variation in tolerance of pigs to PRRS was weak when based on data from infected piglets only. However, simulations indicated that genetic variance in tolerance may exist and could be detected if comparable data on uninfected relatives were available. In conclusion, of the two defense strategies, genetics of tolerance is more difficult to elucidate than genetics of resistance.</p

The psychophysics of uneconomical choice: non-linear reward evaluation by a nectar feeder

Uneconomical choices by humans or animals that evaluate reward options challenge the expectation that decision-makers always maximize the return currency. One possible explanation for such deviations from optimality is that the ability to sense differences in physical value between available alternatives is constrained by the sensory and cognitive processes for encoding profitability. In this study, we investigated the capacity of a nectarivorous bat species (Glossophaga commissarisi) to discriminate between sugar solutions with different concentrations. We conducted a two-alternative free-choice experiment on a population of wild electronically tagged bats foraging at an array of computer-automated artificial flowers that recorded individual choices. We used a Bayesian approach to fit individual psychometric functions, relating the strength of preferring the higher concentration option to the intensity of the presented stimulus. Psychometric analysis revealed that discrimination ability increases non-linearly with respect to intensity. We combined this result with a previous psychometric analysis of volume perception. Our theoretical analysis of choice for rewards that vary in two quality dimensions revealed regions of parameter combinations where uneconomic choice is expected. Discrimination ability may be constrained by non-linear perceptual and cognitive encoding processes that result in uneconomical choice

Cell surface antigens in renal tumour cells: detection by immunoluminescence and enzymatic analysis

Two renal cell carcinoma cell lines (49RC 43STR and 75RC 2STR) were characterized by detection of the cell surface proteins: CD44(var), intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator (uPA) and its receptor and aminopeptidase N (APN). To detect their localization the immunoluminescent technique was used. In addition, the enzyme activity of uPA and APN was investigated in cell suspensions as well as in monolayers. The latter procedure was more advantageous since the additional use of HPLC permits a single registration of the fluorescent hydrolysis-product AMC (7-amino-4-methylcoumarin) without interference by cellular autofluorescence or non-reacted fluorescent substrate. Unlike 75RC 2STR, the cell line 49RC 43STR expressed high levels of uPA and APN. Contrary to that the cell line 75RC 2STR expressed high levels of ICAM-1 and CD44(v6), whereas 49RC 43STR showed a low level of ICAM-1 and no distinct light signal with anti-CD44(v6). The uPA activity was measured directly as well as indirectly (via plasmin) with the substrate Z-Gly-Gly-Arg-AMC. Both activator and plasmin activity were inhibited by D-Val-Phe-Lys-CMK and phenylmethylsulfonyl fluoride. The anti-catalytic antibody to uPA and that to uPA receptor were found to be inhibiting the uPA activity in a concentration-dependent manner. APN activity was assayed using alanine-p-nitroanilide. Peptidase activity was effectively inhibited by 1,10-phenanthroline and partly inhibited by ethylenediamine-tetraacetic acid. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Sharing clinical information across care settings: the birth of an integrated assessment system

Background: Population ageing, the emergence of chronic illness, and the shift away from institutional care challenge conventional approaches to assessment systems which traditionally are problem and setting specific

Surveillance of antenatal influenza vaccination: validity of current systems and recommendations for improvement

Abstract Background: Although influenza vaccination is recommended during pregnancy as standard of care, limited surveillance data are available for monitoring uptake. Our aim was to evaluate the validity of existing surveillance in Western Australia for measuring antenatal influenza immunisations. Methods: The self-reported vaccination status of 563 women who delivered between April and October 2013 was compared against three passive data collection sources: a state-wide antenatal influenza vaccination database maintained by the Department of Health, a public maternity hospital database, and a private health service database. Sensitivity, specificity, and positive and negative predictive values were calculated for each system using self-report as the “gold standard.” Results: The state-wide antenatal vaccination database detected 45.7 % (95 % CI: 40.1–51.4 %) of influenza vaccinations, the public maternity hospital database detected 66.7 % (95 % CI: 55.1–76.9 %), and the private health service database detected 29.1 % (95 % CI: 20.5–39.4 %). Specificity exceeded 90 % and positive predictive values exceeded 80 % for each system. Sensitivity was lowest for women whose antenatal care was provided by a private obstetrician. Conclusions: Existing resources for surveillance of antenatal influenza vaccinations detect 29–67 % of vaccinations. Considering the importance of influenza immunisation as a public health intervention, particularly in pregnant women, improvements to routine monitoring of influenza vaccination is warranted

Novel standards in the measurement of rat insulin granules combining electron microscopy, high-content image analysis and in silico modelling

Knowledge of number, size and content of insulin secretory granules is pivotal for understanding the physiology of pancreatic beta cells. Here we re-evaluated key structural features of rat beta cells, including insulin granule size, number and distribution as well as cell size