Effects of Placental Transfusion on Neonatal and 18 Month Outcomes in Preterm Infants: A Randomized Controlled Trial

Objective: To assess the effect of delayed cord clamping (DCC) vs immediate cord clamping (ICC) on intraventricular hemorrhage (IVH), late onset sepsis (LOS), and 18-month motor outcomes in preterm infants. Study Design: Women (n = 208) in labor with singleton fetuses (\u3c32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (\u3c10 seconds). The primary outcomes were IVH, LOS, and motor outcomes at 18-22 months corrected age. Intention-to-treat was used for primary analyses. Results: Cord clamping time was 32 ± 16 (DCC) vs 6.6 ± 6 (ICC) seconds. Infants in the DCC and ICC groups weighed 1203 ± 352 and 1136 ± 350 g and mean gestational age was 28.3 ± 2 and 28.4 ± 2 weeks, respectively. There were no differences in rates of IVH or LOS between groups. At 18-22 months, DCC was protective against motor scores below 85 on the Bayley Scales of Infant Development, Third Edition (OR 0.32, 95% CI 0.10-0.90, P = .03). There were more women with preeclampsia in the ICC group (37% vs 22%, P = .02) and more women in the DCC group with premature rupture of membranes/preterm labor (54% vs 75%, P = .002). Preeclampsia halved the risk of IVH (OR 0.50, 95% CI 0.2-1.0) and premature rupture of membranes/preterm labor doubled the risk of IVH (OR 2.0, 95% CI 1.2-4.3). Conclusions: Although DCC did not alter the incidence of IVH or LOS in preterm infants, it improved motor function at 18-22 months corrected age

Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial

Objective To evaluate whether placental transfusion influences brain myelination at 4 months of age. Study design A partially blinded, randomized controlled trial was conducted at a level III maternity hospital in the US. Seventy-three healthy term pregnant women and their singleton fetuses were randomized to either delayed umbilical cord clamping (DCC, \u3e5 minutes) or immediate clamping (ICC, \u3c20 \u3eseconds). At 4 months of age, blood was drawn for ferritin levels. Neurodevelopmental testing (Mullen Scales of Early Learning) was administered, and brain myelin content was measured with magnetic resonance imaging. Correlations between myelin content and ferritin levels and group-wise DCC vs ICC brain myelin content were completed. Results In the DCC and ICC groups, clamping time was 172 ± 188 seconds vs 28 ± 76 seconds (P \u3c .002), respectively; the 48-hour hematocrit was 57.6% vs 53.1% (P \u3c .01). At 4 months, infants with DCC had significantly greater ferritin levels (96.4 vs 65.3 ng/dL, P = .03). There was a positive relationship between ferritin and myelin content. Infants randomized to the DCC group had greater myelin content in the internal capsule and other early maturing brain regions associated with motor, visual, and sensory processing/function. No differences were seen between groups in the Mullen testing. Conclusion At 4 months, infants born at term receiving DCC had greater ferritin levels and increased brain myelin in areas important for early life functional development. Endowment of iron-rich red blood cells obtained through DCC may offer a longitudinal advantage for early white matter development

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator

The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2β2-specific activators, here we perform structure/function analysis of the 2-hydroxybiphenyl group of SC4, an activator with tendency for α2-selectivity that is also capable of potently activating β2 complexes. Substitution of the LHS 2-hydroxyphenyl group with polar-substituted cyclohexene-based probes resulted in two AMPK agonists, MSG010 and MSG011, which did not display α2-selectivity when screened against a panel of AMPK complexes. By radiolabel kinase assay, MSG010 and MSG011 activated α2β2γ1 AMPK with one order of magnitude greater potency than the pan AMPK activator MK-8722. A crystal structure of MSG011 complexed to AMPK α2β1γ1 revealed a similar binding mode to SC4 and the potential importance of an interaction between the SC4 2-hydroxyl group and α2-Lys31 for directing α2-selectivity. MSG011 induced robust AMPK signalling in mouse primary hepatocytes and commonly used cell lines, and in most cases this occurred in the absence of changes in phosphorylation of the kinase activation loop residue α-Thr172, a classical marker of AMP-induced AMPK activity. These findings will guide future design of α2β2-selective AMPK activators, that we hypothesise may avoid off-target complications associated with indiscriminate activation of AMPK throughout the body

280 one-opposition near-Earth asteroids recovered by the EURONEAR with the <i>Isaac Newton</i> Telescope

Context. One-opposition near-Earth asteroids (NEAs) are growing in number, and they must be recovered to prevent loss and mismatch risk, and to improve their orbits, as they are likely to be too faint for detection in shallow surveys at future apparitions. Aims. We aimed to recover more than half of the one-opposition NEAs recommended for observations by the Minor Planet Center (MPC) using the Isaac Newton Telescope (INT) in soft-override mode and some fractions of available D-nights. During about 130 h in total between 2013 and 2016, we targeted 368 NEAs, among which 56 potentially hazardous asteroids (PHAs), observing 437 INT Wide Field Camera (WFC) fields and recovering 280 NEAs (76% of all targets). Methods. Engaging a core team of about ten students and amateurs, we used the THELI, Astrometrica, and the Find_Orb software to identify all moving objects using the blink and track-and-stack method for the faintest targets and plotting the positional uncertainty ellipse from NEODyS. Results. Most targets and recovered objects had apparent magnitudes centered around V ~ 22.8 mag, with some becoming as faint as V ~ 24 mag. One hundred and three objects (representing 28% of all targets) were recovered by EURONEAR alone by Aug. 2017. Orbital arcs were prolonged typically from a few weeks to a few years; our oldest recoveries reach 16 years. The O−C residuals for our 1854 NEA astrometric positions show that most measurements cluster closely around the origin. In addition to the recovered NEAs, 22 000 positions of about 3500 known minor planets and another 10 000 observations of about 1500 unknown objects (mostly main-belt objects) were promptly reported to the MPC by our team. Four new NEAs were discovered serendipitously in the analyzed fields and were promptly secured with the INT and other telescopes, while two more NEAs were lost due to extremely fast motion and lack of rapid follow-up time. They increase the counting to nine NEAs discovered by the EURONEAR in 2014 and 2015. Conclusions. Targeted projects to recover one-opposition NEAs are efficient in override access, especially using at least two-meter class and preferably larger field telescopes located in good sites, which appear even more efficient than the existing surveys

Opportunity Mars Rover mission: Overview and selected results from Purgatory ripple to traverses to Endeavour crater

Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony‐iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional‐scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour&rsquo;s rim that will be markedly different from anything examined to date.Additional co-authors: RM Haberle, KE Herkenhoff, JA Herman, KD Iagnemma, BL Jolliff, JR Johnson, G Klingelhöfer, AH Knoll, AT Knudson, R Li, SM McLennan, DW Mittlefehldt, RV Morris, TJ Parker, MS Rice, LA Soderblom, SW Squyres, RJ Sullivan, MJ Wolf

Caring for Caregivers (C4C): study protocol for a pilot feasibility randomised control trial of Positive Written Disclosure for older adult caregivers of people with psychosis

Background: The caregivers of people who experience psychosis are themselves at risk of developing physical and mental health problems. This risk is increased for older adult caregivers who also have to manage the lifestyle and health changes associated with ageing. As a consequence, older adult caregivers are in particular need of support; we propose a Written Emotional Disclosure (WED) intervention, called Positive Written Disclosure (PWD). Methods/design: This is a pilot randomised controlled trial of PWD compared to a neutral writing control and a no writing condition. We aim to recruit 60 participants, 20 in each arm. This study will utilise a mixed-methods approach and collect quantitative (questionnaires) and qualitative (interviews) data. Quantitative data will be collected at baseline and 1, 3, and 6 months post baseline. Participants who complete a writing task (PWD or neutral writing control) will be invited to complete an exit interview to discuss their experiences of the intervention and study. The study is supported by a patient and public involvement group. Discussion: The results of this trial will determine whether a definitive trial is justified. If so, the quantitative and qualitative findings will be used to refine the intervention and study protocols

Implementation of the CALM intervention for anxiety disorders: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Investigators recently tested the effectiveness of a collaborative-care intervention for anxiety disorders: Coordinated Anxiety Learning and Management(CALM) []) in 17 primary care clinics around the United States. Investigators also conducted a qualitative process evaluation. Key research questions were as follows: (1) What were the facilitators/barriers to implementing CALM? (2) What were the facilitators/barriers to sustaining CALM after the study was completed?</p> <p>Methods</p> <p>Key informant interviews were conducted with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic administrators, and 8 clinic staff) and 14 study-trained anxiety clinical specialists (ACSs) who coordinated the collaborative care and provided cognitive behavioral therapy. The interviews were semistructured and conducted by phone. Data were content analyzed with line-by-line analyses leading to the development and refinement of themes.</p> <p>Results</p> <p>Similar themes emerged across stakeholders. Important facilitators to implementation included the perception of "low burden" to implement, provider satisfaction with the intervention, and frequent provider interaction with ACSs. Barriers to implementation included variable provider interest in mental health, high rates of part-time providers in clinics, and high social stressors of lower socioeconomic-status patients interfering with adherence. Key sustainability facilitators were if a clinic had already incorporated collaborative care for another disorder and presence of onsite mental health staff. The main barrier to sustainability was funding for the ACS.</p> <p>Conclusions</p> <p>The CALM intervention was relatively easy to incorporate during the effectiveness trial, and satisfaction was generally high. Numerous implementation and sustainability barriers could limit the reach and impact of widespread adoption. Findings should be interpreted with the knowledge that the ACSs in this study were provided and trained by the study. Future research should explore uptake of CALM and similar interventions without the aid of an effectiveness trial.</p

Alcohol use and misuse: What are the contributions of occupation and work organization conditions?

<p>Abstract</p> <p>Background</p> <p>This research examines the specific contribution of occupation and work organization conditions to alcohol use and misuse. It is based on a social-action model that takes into account agent personality, structures of daily life, and macro social structures.</p> <p>Methods</p> <p>Data come from a representative sample of 10,155 workers in Quebec, Canada. Multinomial regression models corrected for sample design effect have been used to predict low-risk and high-risk drinking compared to non-drinkers. The contribution of occupation and work organization conditions (skill used, decision authority, physical and psychological demands, hours worked, irregular work schedule, harassment, unionization, job insecurity, performance pay, prestige) have been adjusted for family situation, social network outside the workplace, and individual characteristics.</p> <p>Results</p> <p>Compared to non-qualified blue-collars, both low-risk and high-risk drinking are associated with qualified blue-collars, semi-qualified white-collars, and middle managers; high-risk drinking is associated with upper managers. For constraints-resources related to work organization conditions, only workplace harassment is an important determinant of both low-risk and high-risk drinking, but it is modestly moderated by occupation. Family situation, social support outside work, and personal characteristics of individuals are also associated with alcohol use and misuse. Non-work factors mediated/suppressed the role of occupation and work organization conditions.</p> <p>Conclusion</p> <p>Occupation and workplace harassment are important factors associated with alcohol use and misuse. The results support the theoretical model conceptualizing alcohol use and misuse as being the product of stress caused by constraints and resources brought to bear simultaneously by agent personality, structures of daily life, and macro social structures. Occupational alcohol researchers must expand their theoretical perspectives to avoid erroneous conclusions about the specific role of the workplace.</p