Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms

Nonlinear Dynamics of the Perceived Pitch of Complex Sounds

We apply results from nonlinear dynamics to an old problem in acoustical physics: the mechanism of the perception of the pitch of sounds, especially the sounds known as complex tones that are important for music and speech intelligibility

Can we use medical examiners' records for suicide surveillance and prevention research in Nova Scotia?

Introduction: Medical examiners' records can contribute to our understanding of the extent of suicide in a population, as well as associated sociodemographic and other factors

What influences withdrawal because of rejection of telehealth - the whole systems demonstrator evaluation

Purpose: The widespread deployment of telehealth (TH) has been conducted in the absence of any clear understanding of how acceptable these devices are to patients. One potential limitation of the widespread deployment of TH is that patients may refuse. Moreover an understanding of the reasons for refusing to use TH devices will provide an understanding of the barriers. Design/methodology/approach: This investigation from the Whole Systems Demonstrator (WSD) programme, a pragmatic cluster randomised controlled trial into the effectiveness of TH, examined reasons for patients in the intervention cohort of the trial refusing TH, and the potential barriers to its deployment. Findings: Active rejection of the TH intervention was the most frequent reason for withdrawal. After examination of trial-related, health, socio-demographic, cognitive, emotional and behavioural factors, patients diagnosed with diabetes, as opposed to heart failure or chronic obstructive pulmonary disease, and patients' beliefs about the acceptability of the intervention predicted whether or not they withdrew from the trial because of the intervention. Originality/value: Beliefs that the TH intervention resulted in increased accessibility to care, satisfaction with equipment and fewer concerns about the privacy, safety and discomfort associated with using TH equipment predicted continued participation in the WSD trial. Findings suggest that potentially modifiable beliefs about TH predict those more likely to reject the intervention. These findings have important implications for understanding individual differences in the acceptance of TH and subsequent success in mainstreaming TH in healthcare services. © Emerald Group Publishing Limited

Men’s strategies for preserving emotional well-being in advanced prostate cancer: an interpretative phenomenological analysis

Objective This study explores men with advanced prostate cancers’ own practices for promoting and maintaining emotional well-being using Interpretative Phenomenological Analysis. Design Five men with advanced prostate cancer participated in face-to-face, semi-structured, in-depth interviews. Results Within rich narratives of lost and regained well-being, two super-ordinate themes emerged – ‘living with an imminent and uncertain death’ and ‘holding on to life.’ Well-being was threatened by reduced sense of the future, isolation and uncertainty. Yet, the men pursued well-being by managing their emotions, striving for the future whilst enjoying life in the present, taking care of their families and renegotiating purpose. Running through participant’s accounts was a preference for taking action and problem-solving. Sense of purpose, social connectedness and life-engagement were revealed as concepts central to improving well-being, indicating areas which practitioners could explore with men to help them re-establish personal goals and life-purpose. Conclusions The findings also add weight to the evidence base for the potential value of psychological interventions such as cognitive behaviour therapy and mindfulness in men with prostate cancer

DASI First Results: A Measurement of the Cosmic Microwave Background Angular Power Spectrum

We present measurements of anisotropy in the Cosmic Microwave Background (CMB) from the first season of observations with the Degree Angular Scale Interferometer (DASI). The instrument was deployed at the South Pole in the austral summer 1999--2000, and made observations throughout the following austral winter. We have measured the angular power spectrum of the CMB in the range 100<l<900 with high signal-to-noise. In this paper we review the formalism used in the analysis, in particular the use of constraint matrices to project out contaminants such as ground and point source signals, and to test for correlations with diffuse foreground templates. We find no evidence of foregrounds other than point sources in the data, and find a maximum likelihood temperature spectral index beta = -0.1 +/- 0.2 (1 sigma), consistent with CMB. We detect a first peak in the power spectrum at l approx 200, in agreement with previous experiments. In addition, we detect a peak in the power spectrum at l approx 550 and power of similar magnitude at l approx 800 which are consistent with the second and third harmonic peaks predicted by adiabatic inflationary cosmological models.Comment: 8 pages, 1 figure, minor changes in response to referee comment

First Intrinsic Anisotropy Observations with the Cosmic Background Imager

We present the first results of observations of the intrinsic anisotropy of the cosmic microwave background radiation with the Cosmic Background Imager from a site at 5080 m altitude in northern Chile. Our observations show a sharp decrease in C_l in the range l=400 - 1500. The broadband amplitudes we have measured are deltaT(band) = 58.7 (-6.3, +7.7) microK for l = 603 (-166, +180) and 29.7 (-4.2, +4.8) microK for l = 1190 (-224, +261), where these are half-power widths in l. Such a decrease in power at high l is one of the fundamental predictions of the standard cosmological model, and these are the first observations which cover a broad enough l range to show this decrease in a single experiment. The C_l we have measured enable us to place limits on the density parameter, Omega(tot) = 0.7 (90% confidence).Comment: 5 pages including 2 figures. Corrected an error in the comparison with Boomerang and Maxim

An integrative literature review exploring the impact of alcohol workplace policies

Purpose: Alcohol workplace policies (AWPs) can help organizations to manage and support employees with alcohol-related problems. Over the last two decades, there has been a slow but steady rise of research on AWPs with some indication that these can contribute to reducing employee excessive consumption. However, there does not appear to be any empirical literature reviews to consolidate and evaluate what this body of evidence says regarding the impact of these policies. The following review seeks to address this gap. Design/methodology/approach: Five electronic databases were searched for papers published between January 1996 and January 2020. To capture additional relevant papers (including those from non-peer reviewed sources), the search was extended to Google Scholar, professional and human resource management websites, trade publications and the website of one United Kingdom (UK)-based alcohol charity. Inclusion and exclusion criteria were used to systematically screen the paper titles, abstracts and full-text records. 14 papers were deemed eligible and therefore included in the integrative review. After extracting data, all 14 papers were appraised for quality and then analysed using the narrative synthesis guide by Popay et al. (2006). Findings: Five themes were identified, namely, Associations between Policy and Consumption Levels/Patterns, Deterrence, Policy and Programme Type, Knowledge and Understanding and Enforcement and Discipline. These themes encapsulated what the included papers concluded about the impact and associated benefits or challenges of AWPs. Research limitations/implications: This review identifies that despite the benefits of AWPs, up to 40% of workplaces do not have these policies in place. Future research needs to explicitly explore the reasons for this. Practical implications: This review highlights that AWPs can benefit employees and workplaces. Therefore, organizations are encouraged to develop and implement AWPs to support health improvement and prevention of alcohol problems in the workplace. Originality/value: This review provides a current synthesis of literature published over the last two decades regarding the impact of AWPs on employees and workplaces

Information-theoretic significance of the Wigner distribution

A coarse grained Wigner distribution p_{W}(x,u) obeying positivity derives out of information-theoretic considerations. Let p(x,u) be the unknown joint PDF (probability density function) on position- and momentum fluctuations x,u for a pure state particle. Suppose that the phase part Psi(x,z) of its Fourier transform F.T.[p(x,u)]=|Z(x,z)|exp[iPsi(x,z)] is constructed as a hologram. (Such a hologram is often used in heterodyne interferometry.) Consider a particle randomly illuminating this phase hologram. Let its two position coordinates be measured. Require that the measurements contain an extreme amount of Fisher information about true position, through variation of the phase function Psi(x,z). The extremum solution gives an output PDF p(x,u) that is the convolution of the Wigner p_{W}(x,u) with an instrument function defining uncertainty in either position x or momentum u. The convolution arises naturally out of the approach, and is one-dimensional, in comparison with the two-dimensional convolutions usually proposed for coarse graining purposes. The output obeys positivity, as required of a PDF, if the one-dimensional instrument function is sufficiently wide. The result holds for a large class of systems: those whose amplitudes a(x) are the same at their boundaries (Examples: states a(x) with positive parity; with periodic boundary conditions; free particle trapped in a box).Comment: pdf version has 16 pages. No figures. Accepted for publ. in PR