491 research outputs found
Thoracic Pressure Does Not Impact CSF Pressure via Compartment Compliance
Space acquired neuro-ocular syndrome (SANS) remains a difficult risk to characterize due to the complex multi-factorial etiology related to physiological responses to the spaceflight environment. Fluid shift and the resultant change on the Cardiovascular (CV) and cerebral spinal fluid systems (CSF) in the absence of gravity continue to be considered a contributing factor to the progression of SANS. In this study, we utilize a computational model of the CSF and CV interface to establish the sensitivity that intracranial pressure, and subsequently the optic nerve sheath pressure, exhibits due to variations in thoracic pressure, assuming the cranial perfusion pressure, i.e. mean arterial pressure (MAP) to central venous pressure (CVP), is known. Methods: The GRC Cross cutting computational modeling project created as model of the CSF and CV interaction within the cranial vault by extending the work of Stevens et al. [1] by modifying the representative anatomy to include a separate venous sinus, jugular veins, secondary veins and extra jugular pathways [2-3] to more adequately represent the vascular drainage pathways from the cranial vault (Figure 1). Assuming the MAP, CVP and thoracic pressure are known, we initiated this enhanced computational model assuming a supine positon and utilized a linear ramp to vary the thoracic pressure from the assumed supine state to the target pressure corresponding to set MAP and CVP values. The model generates the time based CSF pressure values (Figure2). Results and Conclusions: Following this analysis, CSF pressure shows significant independence from thoracic pressure changes (16 mmHg in thoracic pressure produces < 1mmHg change in CSF pressure), being mostly dependent on perfusion pressure. Similarly fluid redistribution is not predicted to be impacted over a level of 1mL. We note that this simulation represents an acute changes (order of 10's of minutes) and does not represent the long term effects
Trees and Tradition in Early Ireland
Old and Middle Irish nature poetry has long been appreciated for the vividness of its description of the natural world. In this paper, we will show that the inventory of trees and bushes upon which poets drew was based less upon direct observation of nature than upon a traditional taxonomy found in a completely different genre, the law tracts dating back to the seventh century, notably the tree list edited by Fergus Kelly in 1976 from Bretha Comaithchesa ‘Judgments Concerning Neighborhood Law’. Thus, the economic and aesthetic value of trees and bushes as discussed in law tracts and nature poetry were part of a single continuous tradition of taxonomy and silviculture stretching over at least 500 years. We will end by discussing the relationship between this tradition and the Ogam letter names (McManus 1997).
Reduced Expression of miRNA-27a Modulates Cisplatin Resistance in Bladder Cancer by Targeting the Cystine/Glutamate Exchanger SLC7A11
Purpose: Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome.
Experimental Design: miRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material.
Results: A panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine.
Conclusion: Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease
Poetry meets design pedagogy in The WoW Project: Collaborations on ‘The Moving Poet’ to ‘start the conversation’
Recommended from our members
Fast gas chromotography with luminol detection for measurement of nitrogen dioxide and PANs.
Fast capillary gas chromatography has been coupled to a luminol-based chemiluminescence detection system for the rapid monitoring of nitrogen dioxide and peroxyacyl nitrates. A first-generation instrument was described recently (Gaffney et al., 1998). This system is capable of monitoring nitrogen dioxide and peroxyacyl nitrates (PANs; to and including the C4 species) with 1-min time resolution. This is an improvement by a factor of five over gas chromatography methods with electron capture detection. In addition, the luminol method is substantially less expensive than laser fluorescent detection or mass spectroscopic methods. Applications in aircraft-based research have been published electronically and will appear shortly in Environmental Science and Technology (Gaffney et al., 1999a). An improved version of the instrument that has been designed and built makes use of a Hammamatsu photon-counting system. Detection limits of this instrumentation are at the low tens of ppt. The range of the instrument can be adjusted by modifying sampling volumes and detection counting times. A review of past work and of recent application of the instrumentation to field measurements of nitrogen dioxide and PANs is presented. The data clearly indicate that the luminol approach can determine the target species with time resolution of less than 1 min. Examples of applications for estimation of peroxyacetyl radical concentrations and nitrate radical formation rates are also presented. This instrumentation can further be used for evaluation of surfaces for loss of nitrogen dioxide and PANs, phenomena of possible importance for sampling interfaces and chamber wall design. Our high-frequency field data clearly indicate that the ''real world'' is not well mixed and that turbulent mixing and plume-edge chemistries might play an important role in urban- and regional-scale interactions. Dynamic flow systems might be required to evaluate such effects in new-generation chamber studies
The role of maternal stress in early pregnancy in the aetiology of gastroschisis : An incident case control study
We wish to thank all the women who took the time to take part in this study, the research nurses who undertook interviews and data collection: Sandra Edwards-Fenton, Anne Chamberlain, Marit Bodley, Sharon Brown, Isobel Clegg, Catherine Collins and the British Isles Network of Congenital Anomaly Registers (BINOCAR) for their support in facilitating this study.Peer reviewedPublisher PD
Effects of high volume saline enemas vs no enema during labour – The N-Ma Randomised Controlled Trial [ISRCTN43153145]
BACKGROUND: Enemas are used during labour in obstetric settings with the belief that they reduce puerperal and neonatal infections, shorten labour duration, and make delivery cleaner for attending personnel. However, a systematic review of the literature found insufficient evidence to support the use of enemas. The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates. METHODS: Design: RCT (randomised controlled trial; randomized clinical trial). Outcomes: Clinical diagnosis of maternal or neonatal infections, labour duration, delivery types, episiotomy rates, and prescription of antibiotics Setting: Tertiary care referral hospital at the Javeriana University (Bogotá, Colombia) that attended 3170 births during study period with a caesarean section rate of 26%. Participants: 443 women admitted for delivery to the obstetrics service (February 1997 to February 1998) and followed for a month after delivery. Inclusion criteria were women with: low risk pregnancy and expected to remain in Bogotá during follow up; gestational age ≥ 36 weeks; no pelvic or systemic bacterial infection; intact membranes; cervix dilatation ≤7 cm. Intervention: 1 litre saline enema, versus no enema, allocated following a block random allocation sequence and using sealed opaque envelopes. RESULTS: Allocation provided balanced groups and 86% of the participants were followed up for one month. The overall infection rate for newborns was 21%, and 18% for women. We found no significant differences in puerperal or neonatal infection rates (Puerperal infection: 41/190 [22%] with enema v 26/182 [14%] without enema; RR 0.66 CI 95%: 0.43 to 1.03; neonatal infection 38/191 [20%] with enema v 40/179 [22%] without enema; RR 1.12, 95% CI 95% 0.76 to 1.66), and median labour time was similar between groups (515 min. with enema v 585 min. without enema; P = 0.24). Enemas didn't significantly change episiorraphy dehiscence rates (21/182 [12%] with enema v 32/190 [17%] without enema; P = 0.30). CONCLUSION: This RCT found no evidence to support routine use of enemas during labour. Although these results cannot rule out a small clinical effect, it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit
PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study
OBJECTIVES: To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions.
DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019.
SETTING: Community hospitals and academic medical centers in the United States.
PARTICIPANTS: ICU clinical pharmacists.
INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance.
MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated 5,822,539 CA), resource utilization (12,630 interventions; 9,680,036 cost avoidance), prophylaxis (1,639 interventions; 1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; 418 per intervention, 7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is 3.3:1 and 3.3:1 and $9.6:1
The Color of Childhood: The Role of the Child/Human Binary in the Production of Anti-Black Racism
The binary between the figure of the child and the fully human being is invoked with regularity in analyses of race, yet its centrality to the conception of race has never been fully explored. For most commentators, the figure of the child operates as a metaphoric or rhetorical trope, a non-essential strategic tool in the perpetuation of White supremacy. As I show in the following, the child/human binary does not present a contingent or merely rhetorical construction but, rather, a central feature of racialization. Where Black peoples are situated as objects of violence it is often precisely because Blackness has been identified with childhood and childhood is historically identified as the archetypal site of naturalized violence and servitude. I proceed by offering a historical account of how Black peoples came to inherit the subordination and dehumanization of European childhood and how White youth were subsequently spared through their partial categorization as adults
- …