The role of micro-organisms (Staphylococcus aureus and Candida albicans) in the pathogenesis of breast pain and infection in lactating women: study protocol

Background: The CASTLE (Candida and Staphylococcus Transmission: Longitudinal Evaluation) study will investigate the micro-organisms involved in the development of mastitis and &ldquo;breast thrush&rdquo; among breastfeeding women. To date, the organism(s) associated with the development of breast thrush have not been identified. The CASTLE study will also investigate the impact of physical health problems and breastfeeding problems on maternal psychological health in the early postpartum period.Methods/Design: The CASTLE study is a longitudinal descriptive study designed to investigate the role of Staphylococcus spp (species) and Candida spp in breast pain and infection among lactating women, and to describe the transmission dynamics of S. aureus and Candida spp between mother and infant. The relationship between breastfeeding and postpartum health problems as well as maternal psychological well-being is also being investigated. A prospective cohort of four hundred nulliparous women who are at least thirty six weeks gestation pregnant are being recruited from two hospitals in Melbourne, Australia (November 2009 to June 2011). At recruitment, nasal, nipple (both breasts) and vaginal swabs are taken and participants complete a questionnaire asking about previous known staphylococcal and candidal infections. Following the birth, participants are followed-up six times: in hospital and then at home weekly until four weeks postpartum. Participants complete a questionnaire at each time points to collect information about breastfeeding problems and postpartum health problems. Nasal and nipple swabs and breast milk samples are collected from the mother. Oral and nasal swabs are collected from the baby. A telephone interview is conducted at eight weeks postpartum to collect information about postpartum health problems and breastfeeding problems, such as mastitis and nipple and breast pain.Discussion: This study is the first longitudinal study of the role of both staphylococcal and candidal colonisation in breast infections and will help to resolve the current controversy about which is the primary organism in the condition known as breast thrush. This study will also document transmission dynamics of S. aureus and Candida spp between mother and infant. In addition, CASTLE will investigate the impact of common maternal physical health symptoms and the effect of breastfeeding problems on maternal psychological well-being.<br /

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

A flexible automotive systems architecture for next generation ADAS

The evolution of Advanced Driver Assistance Systems (ADASs) increasingly paves the way towards autonomous driving. The increase in sensor data to be processed as well as the complexity of processing algorithms demands more powerful processing platforms. Additionally, aspects like functional safety and platform security have to be taken into account. Algorithms should be re-usable to facilitate rapid development. Current solutions are very much focused on single sub-systems and incompatible with next generation processing platforms available for ADASs. In this paper we therefore propose a novel architecture for future ADAS development, taking into account the aforementioned aspects. We also outline tools to aid developers in dealing with the real-time and functional safety aspects of ADASs. The utilization of the presented architecture in the EU-funded project ADAS&ME is also described

Design of a 2D MEMS micromirror with indirect static actuation

We present the design of a 2D MEMS micromirror with indirect static actuation based on gyroscopic effects. Additionally to the primary resonant oscillation we introduce a second one, disturbing the angular momentum of the former. This under special conditions leads to a directed torque about a third axis. This concept thus uses only resonant actuation by still enabling static deflection, potentially being more energy efficient compared to current technologies. After discussion of the used manufacturing process, the MEMS design workflow and the resulting fully functional micromirror design is shown. In first experimental results we then show a proof of concept for the manufactured micromirror devices

A Novel Indirect Quasi-Static Actuation Concept for 2D MEMS Micromirrors

We present a 2D MEMS raster scanning micromirror based on a novel actuation concept for the (quasi-)static axis. This is based on the distortion of the angular momentum generated by the primary resonant axis using a secondary oscillation. After introducing a model of the device dynamics using a rigid body approximation, several simulation studies are carried out to investigate the nonlinear dynamics of such a device. In the next step, a fully operational MEMS design is shown, that is actuated by piezoelectric as well as electromagnetic drive schemes. After manufacturing, we performed a series of experiments to obtain the characteristics of the resonant as well as the quasistatic axis, proving the viability of the proposed actuation concept

Simulation of nanostructures for sensor and circuit applications

The simulation of nanostructures for sensor and circuit applications requires new concepts, namely electronic structure calculations based on the atomic configuration of the involved materials. We give a short overview of the available concepts. Semi-empirical methods and the density functional theory are highlighted. The concepts are illustrated by several examples. Presenting results obtained from metal nanowires, CNT-metal-contacts and strained CNTs, we demonstrate that electronic structure calculations based on quantum theory are essential for an adequate simulation of nanostructures

Mobile communication and control for Smart Microfluidic Systems

This paper provides an approach for the integration of control and communication electronics for a Smart Microfluidic System by the use of a mobile phone. Aspects of the integration include pump control, power supply and user interface for an existing microfluidic platform

The effect of <em>LPA</em> Thr3888Pro on lipoprotein(a) and coronary artery disease is modified by the <em>LPA</em> KIV-2 variant 4925G&gt;A.

Background and aims: High lipoprotein(a) [Lp(a)] concentrations are associated with increased coronary artery disease (CAD) risk. Lp(a) is regulated mainly genetically by the LPA gene but involved genetic variants have not been fully elucidated. Improved understanding of the entanglements of genetic Lp(a) regulation may enhance genetic prediction of Lp(a) and CAD risk. We investigated an interaction between the well-known LPA missense SNP rs41272110 (known as Thr3888Pro) and the frequent LPA splicing mutation KIV-2 4925G&gt;A. Methods: Effects on Lp(a) concentrations were investigated by multiple quantile regression in the German Chronic Kidney Disease (GCKD) study, KORA-F3 and KORA-F4 (ntotal = 10,405) as well as in the UK Biobank (UKB) 200k exome dataset (n = 173,878). The impact of the interaction on CAD risk was assessed by survival analysis in UKB. Results: We observed a significant SNP-SNP interaction in all studies (p = 1.26e-05 to 3.03e-04). In quantile regression analysis, rs41272110 as a predictor shows no impact on Lp(a) (β = −0.06 [-0.79; 0.68], p = 0.879), but in a joint model including both SNPs as predictors, rs41272110 is associated with markedly higher Lp(a) (β = +9.40 mg/dL [6.45; 12.34], p = 4.07e-10). Similarly, rs41272110 shows no effect on CAD in UKB (HR = 1.01 [0.97; 1.04], p = 0.731), while rs41272110 carriers not carrying 4925G&gt;A show an increased CAD risk (HR = 1.10 [1.04; 1.16], p = 6.9e-04). This group corresponds to 4% of the population. Adjustment for apolipoprotein(a) isoforms further modified the effect estimates markedly. Conclusions: This work emphasizes the complexity of the genetic regulation of Lp(a) and the importance to account for genetic subgroups in Lp(a) association studies and when interpreting genetic cardiovascular risk profiles

The kringle IV type 2 domain variant 4925G&gt;A causes the elusive association signal of the <em>LPA</em> pentanucleotide repeat.

Lipoprotein(a) [Lp(a)] concentrations are regulated by the LPA gene mainly via the large kringle IV-type 2 (KIV-2) copy number variation and multiple causal variants. Early studies suggested an effect of long pentanucleotide repeat (PNR) alleles (10 and 11 repeats, PNR10 and PNR11) in the LPA promoter on gene transcription and found an association with lower Lp(a). Subsequent in-vitro studies showed no effects on mRNA transcription, but the association with strongly decreased Lp(a) remained consistent. We investigated the isolated and combined effect of PNR10, PNR11 and the frequent splice site variant KIV-2 4925G&gt;A on Lp(a) concentrations in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study by multiple quantile regression in single-SNP and joint models. Data on Lp(a), apolipoprotein(a) Western blot isoforms and variant genotypes were available for n=2,858 individuals. We found a considerable linkage disequilibrium (LD) between KIV-2 4925G&gt;A and the alleles PNR10 and PNR11. In single variant analysis adjusted for age, sex, and the shorter apo(a) isoform we determined that both PNR alleles were associated with a highly significant Lp(a) decrease (PNR10: β=-14.43 mg/dL, 95% CI: -15.84,-13.02, p=3.33e-84; PNR11: β=-17.21 mg/dL, 95% CI: -20.19,-14.23, p=4.01e-29). However, a joint model, adjusting the PNR alleles additionally for 4925G&gt;A abolished the effect on Lp(a) (PNR10: β=+0.44 mg/dL, 95% CI: -1.73,2.60, p=0.69; PNR11: β=-1.52 mg/dL, 95% CI: -6.05,3.00, p=0.51). Collectively, we conclude that the previously reported Lp(a) decrease observed in pentanucleotide alleles PNR10 or PNR11 carriers results from an LD with the frequent splicing mutation KIV-2 4925G&gt;A