Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy

GSK (ClinicalTrials.gov identifier NCT01573767

Canrightiopsis, a new Early Cretaceous fossil with Clavatipollenites-type pollen bridge the gap between extinct Canrightia and extant Chloranthaceae

Canrightiopsis with three species (C. intermedia, C. crassitesta, C. dinisii) is described from the Early Cretaceous of Portugal based on small, one-seeded berries. The fruits are derived from bisexual flowers with three stamens borne on one side of the ovary. There are no traces of a perianth. Pollen is of the Clavatipollenites-type, monocolpate, semitectate, reticulate-columellate with heterobrochate reticulum and muri with beaded supratectal ornamentation. The ovary is unilocular with a single pendant, orthotropous and bitegmic ovule. The seed is endotestal. The endotesta consists of one layer of palisade-shaped crystal cells with fibrous infillings. The fruit wall has resin bodies or cavities from presumed ethereal oil cells sometimes seen as stomata-like structures on the fruit surface. A phylogenetic analysis resolves Canrightiopsis as a close relative of extant Chloranthaceae, particularly close to extant Chloranthus and Sarcandra. All three taxa share the one-sided position of the stamens on the ovary. An evolutionary sequence from fossil Canrightia to fossil Canrightiopsis and extant Chloranthus and Sarcandra is suggested by loss of perianth, reduction in number of ovules and stamens and displacement of stamens to one side of the ovary. Canrightiopsis also shares several critical features with extant Ascarina including monoaperturate pollen and beaded supratectal ornamentation of the pollen wall.Swiss Light Source (European Union) [20110963, 20130185]; Swedish Research Council [621-2011-5431]; CretaCarbo project [PTDC/CTE-GIX/113983/2009]info:eu-repo/semantics/publishedVersio

Clinical and scientific progress related to the interface between cardiology and psychology: lessons learned from 35 years of experience at the Thoraxcenter of the Erasmus Medical Center in Rotterdam

In November 1975, as the first in the Netherlands, a full-time psychologist was employed at the Department of Cardiology of the Thoraxcenter of the Erasmus Medical Center. This innovative decision was consistent with a view to treat the patient as a whole rather than the heart as a single body part in need of repair, combined with the understanding that the heart and mind interact to affect health. The present selective review addresses the broad range of contributions of 35 years of psychology to clinical cardiology and cardiovascular research with a focus on research, teaching, psychological screening and patient care. The review ends with lessons to be learned and challenges for the future with respect to improving the care and management of patients with heart disease in order to enhance secondary prevention and the role of behavioural and psychological factors in this endeavour

Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This 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.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Energy spectra of quantum rings

Ring geometries have fascinated experimental and theoretical physicists over many years. Open rings connected to leads allow the observation of the Aharonov-Bohm effect, a paradigm of quantum mechanical phase coherence. The phase coherence of transport through a quantum dot embedded in one arm of an open ring has been demonstrated. The energy spectrum of closed rings has only recently been analysed by optical experiments and is the basis for the prediction of persistent currents and related experiments. Here we report magnetotransport experiments on a ring-shaped semiconductor quantum dot in the Coulomb blockade regime. The measurements allow us to extract the discrete energy levels of a realistic ring, which are found to agree well with theoretical expectations. Such an agreement, so far only found for few-electron quantum dots, is here extended to a many-electron system. In a semiclassical language our results indicate that electron motion is governed by regular rather than chaotic motion, an unexplored regime in many-electron quantum dots.Comment: 10 pages, 4 figure

Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section

BACKGROUND: Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section. METHODS: Study was performed on 120 cesarean section parturients divided into six groups, identified as B(8), B(10 )and B (12.5 )8.10 and 12.5 mg of bupivacaine mg and FB(8), FB(10 )and FB (12.5 )received a combination of 12.5 μg intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain. RESULTS: Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl. CONCLUSION: Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects

Thermal Giant Gravitons

We study the giant graviton solution as the AdS_5 X S^5 background is heated up to finite temperature. The analysis employs the thermal brane probe technique based on the blackfold approach. We focus mainly on the thermal giant graviton corresponding to a thermal D3-brane probe wrapped on an S^3 moving on the S^5 of the background at finite temperature. We find several interesting new effects, including that the thermal giant graviton has a minimal possible value for the angular momentum and correspondingly also a minimal possible radius of the S^3. We compute the free energy of the thermal giant graviton in the low temperature regime, which potentially could be compared to that of a thermal state on the gauge theory side. Moreover, we analyze the space of solutions and stability of the thermal giant graviton and find that, in parallel with the extremal case, there are two available solutions for a given temperature and angular momentum, one stable and one unstable. In order to write down the equations of motion, action and conserved charges for the thermal giant graviton we present a slight generalization of the blackfold formalism for charged black branes. Finally, we also briefly consider the thermal giant graviton moving in the AdS_5 part.Comment: v1: 32 pages + 11 pages appendices, 13 figures, v2: typos fixed in Sec.2 and other misprints, references adde

Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes

The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes.Research in the senior author’s laboratory is supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. Further support was provided by a research fellowship from the German Research Foundation ( DFG PA2369/1-1 to M.P.), a British Heart Foundation PhD Studentship ( FS/11/77/39327 to A.B.), a Clinician Scientist Award from the National Institute for Health Research UK ( CS-2015-15-023 to M.R.N.K.), and the Qatar Foundation (to M.R.N.K.). The Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute is supported by core funding from the Wellcome Trust and MRC

Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension

<p>Abstract</p> <p>Background</p> <p>Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.</p> <p>Methods</p> <p>We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2_CR, u-ENaC_β-CR), prostaglandin E2 (u-PGE₂) and cyclic AMP (u-cAMP), fractional sodium excretion (FE_Na), free water clearance (C_H2O), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).</p> <p>Results</p> <p>At baseline, no differences in u-AQP2_CRor u-ENaC_β-CRwere measured between patients and controls. U-AQP2_CRincreased significantly more after saline in patients than controls, whereas u-ENaC_β-CRincreased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE₂, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2_CRresponse.</p> <p>Conclusions</p> <p>No differences were found in u-AQP2_CRand u-ENaC_β-CRbetween patients and controls at baseline. However, in response to saline, u-AQP2_CRwas abnormally increased in patients, whereas the u-ENaC_β-CRresponse was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent.</p> <p>Clinicaltrial.gov identifier</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=00345124">NCT00345124</a>.</p