The Impact of Insurance on the Law of Torts

An experimental study of "Model-on-Demand" (MoD) identification is made on a pilot-scale brine-water mixing tank. MoD estimation is compared against semi-physical modeling techniques using identification data generated from a systematically designed m-level Pseudo Random Sequence (PRS) input. The estimated models are the basis for evaluating the usefulness of MoD-based Model Predictive Control (MPC). For this application, MoD-MPC is shown to provide better performance at high bandwidths compared to a linear MPC controller

Characterizing urinary hCG beta cf patterns during pregnancy

Objective: Elevated concentrations of hCG beta core fragment (hCG beta cf) are known to cause false-negative results in qualitative urine pregnancy test devices, but the pattern of urinary hCG beta cf during normal pregnancy has not been well characterized. Here, we evaluate the relationship between urine hCG, hCG beta cf, and hCG free beta subunit (hCG beta) during pregnancy. Design and methods: Banked second trimester urine specimens from 100 pregnant women were screened for high concentrations of hCG beta cf using a qualitative point-of-care device known to demonstrate false-negative results in the presence of elevated hCG beta cf concentrations. Additional first and third trimester specimens from the same pregnancy were obtained from 10 women who generated negative/faint positive results, 5 women who generated intermediate positive results, and 10 women who generated strong positive results on the point-of care device. Intact hCG, hCG beta cf, hCG beta, and specific gravity were quantified in these 75 specimens. Results: Urinary hCG beta cf concentrations were greater than intact hCG concentrations at all times. A strong correlation (r(2) = 0.70) was observed between urine intact hCG and hCG beta cf concentrations. A poor correlation was observed between specific gravity and intact hCG (r(2) = 0.32), hCG beta (r(2) = 0.32), and hCG beta cf (r(2) = 0.32). The highest hCG beta cf concentrations were observed between 10 and 16 weeks gestation but individual women demonstrated very different patterns of hCG beta cf excretion. Conclusions: Urine specimens with elevated hCG beta cf are frequently encountered during pregnancy but hCG beta cf excretion patterns are unpredictable. Manufacturers and clinicians must appreciate that hCG beta cf is the major immunoreactive component in urine during pregnancy and must design and interpret qualitative urine hCG test results accordingly. (C) 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Peer reviewe

European randomized study of prostate cancer screening: first-year results of the Finnish trial

Approximately 20 000 men 55–67 years of age from two areas in Finland were identified from the Population Registry and randomized either to the screening arm (1/3) or the control arm (2/3) of a prostate cancer screening trial. In the first round, the participation rate in the screening arm was 69%. Of the 5053 screened participants, 428 (8.5%) had a serum prostate-specific antigen (PSA) concentration of 4.0 ng/ml or higher, and diagnostic examinations were performed on 399 of them. A total of 106 cancers were detected among them corresponding to a positive predictive value of 27%, which is comparable with mammography screening for breast cancer. The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml−1 or higher was 2.1%. Approximately nine out of ten screen-detected prostate cancers were localized (85% clinical stage T1–T2) and well or moderately differentiated (42% World Health Organization (WHO) grade I and 50% grade II), which suggests a higher proportion of curable cancers compared with cases detected by other means. © 1999 Cancer Research Campaig

Gender has to be taken into account in diagnosing adult growth hormone deficiency by the GHRH plus arginine test

Objective: Data on the effect of gender on the interpretation of the GHRH plus arginine stimulation test (GHRH + ARG test) is controversial. We validated the GHRH + ARG stimulation test in control subjects and patients with organic or idiopathic pituitary disease and a suspicion of adult growth hormone deficiency (AGHD) using the Immulite 2000 XPi GH assay. Design: We studied 126 apparently healthy adults (median age 38.8 years) and 34 patients with a suspicion of AGHD (median age 42.2 years). Identification of AGHD with the GHRH + ARG test was investigated with commonly accepted BMI-related consensus cut-off limits for peak GH concentrations. Serum samples collected during the GHRH + ARG test were analysed for GH in 2014-2015. Serum IGF-1 concentrations were studied as a reference. Results: In 14 of 65 (22%) control males the GH peak value was below the BMI-related cut-off limits for GH sufficiency indicating a false diagnosis of AGHD. All control females had a normal GHRH + ARG response. Median peak GH response was significantly (p <0.001) higher in female (39.3 mu g/L) than in male controls (21 mu g/L). According to consensus cut-offs all but one young female patient had a deficient response compatible with a diagnosis of AGHD. Conclusions: The GH response to stimulation by GHRH + ARG is gender-dependent, being lower in healthy males than in females. Gender should be considered when defining cut-off limits for peak GH concentrations in the GHRH + ARG test. The presently used BMI-related cut-off levels will lead to a significant misclassification of males as GH deficient.Peer reviewe

Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

<p>Abstract</p> <p>Background</p> <p>MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA) leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126.</p> <p>Methods and result</p> <p>Rats were subjected to a 2-h middle cerebral artery occlusion (MCAO) followed by reperfusion for 48-h and the ischemic area was calculated. The expression of phosphorylated ERK1/2 and Elk-1, and of endothelin ET_Aand ET_B, angiotensin AT₁, and 5-hydroxytryptamine 5-HT_1Breceptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue. The expression of endothelin ET_Breceptor was analyzed by quantitative Western blot. We demonstrate that there is an increase in the number of contractile smooth muscle receptors in the MCA and in micro- vessels within the ischemic region. The enhanced expression occurs in the smooth muscle cells as verified by co-localization studies. This receptor upregulation is furthermore associated with enhanced expression of pERK1/2 and of transcription factor pElk-1 in the vascular smooth muscle cells. Blockade of transcription with the MEK1 inhibitor U0126, given at the onset of reperfusion or as late as 6 hours after the insult, reduced transcription (pERK1/2 and pElk-1), the enhanced vascular receptor expression, and attenuated the cerebral infarct and improved neurology score.</p> <p>Conclusion</p> <p>Our results show that MCAO results in upregulation of cerebrovascular ET_B, AT₁and 5-HT_1Breceptors. Blockade of this event with a MEK1 inhibitor as late as 6 h after the insult reduced the enhanced vascular receptor expression and the associated cerebral infarction.</p

Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women

Objectives: Maternal serum inhibin-A , pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine arter y pulsatility inde x (UtA PI) were analysed to study thei r ability to predict pre-eclampsia (PE). Study design: Serial serum samples for the nested case-control study were collected prospectively at 12-14, 18-20 and 26-28 weeks of gestation from 11 women who later developed early-onset PE (EO PE , diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE , diagnosis 2 34 + 0 weeks) and 89 controls. Main outcome measures: Gestational age-adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester bio-markers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under cu r v e (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated . Results: A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513-0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562-0.840 and 0.798, 0.686-0.909, respectively). At 26-28 weeks PAPP-A2 and inhibin-A predicted a l l PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726-0.896) and LO PE (0.824, 0.733-0.914). Conclusions: At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be usef u l for short-term prediction of PE.Peer reviewe