Pulsatile flow does not improve efficacy in ex vivo lung perfusion.

Introduction Ex vivo lung perfusion (EVLP) has the potential to increase the donor pool for lung transplantation by facilitating extended evaluation of marginal organs. Current methodology employs continuous flow pumps for perfusion. In vivo, continuous flow has been shown to increase pulmonary vascular resistance (PVR). Thus, pulsatile flow EVLP may reduce PVR and improve organ preservation by providing physiologic flow morphology. Methods Lung blocks harvested from male, Yorkshire pigs were allocated into continuous (CF, n=3) and pulsatile flow (PF, n=4) groups. Lungs were ventilated at 4-5 mL/kg, 30% FiO2 and perfused with an acellular, albumin-based solution corrected for osmolarity, acid/base balance, and CO2 concentration (=19 hours at 30°C). Prostaglandin E2 and 30% albumin were infused continuously at 250 ?g/hr and 100 mL/hr, respectively. Hemodynamic, respiratory, and blood gas parameters were recorded hourly. Parenchymal biopsies were used for quantification of wet: dry ratio and IL-6, IL-8, and TNF-a using ELISA. Results ?PO2/FoO2 in mmHg was 261±47 and 313±37 at baseline and 174±36 and 152±36 at hour 12 for CF and PF, respectively. Wet: dry ratio was 5.53±0.56 and 6.06±0.09 at baseline and 5.27±0.48 and 5.12±0.40 at hour 12 for CF and PF, respectively. Average PVR in Woods Units was 15.17±1.33 and 13.60±1.91 over the 12 hour test period for CF and PF groups, respectively. Peak airway pressure (PAWP) in cm H2O was 17±1.15 and 16±0.75 at baseline and 21±1.67 and 21±0.41 at hour 12 for CF and PF, respectively. There were no discernable differences in TNF-a, IL-6, and IL-8 concentrations, PVR, ?PO2/FiO2, wet: dry ratio, and PAWP between CF and PF. Conclusion EVLP system successfully maintained lungs up to 19 hours using a modified perfusate. These data suggest PF does not offer benefits over CF for prolonged ex vivo lung preservation

Social adaptation can reduce the strength of social–ecological feedbacks from ecosystem degradation

Feedbacks between people and ecosystems are central to the study of social–ecological systems (SES) but remain poorly understood. It is commonly assumed that changes in ecosystems leading to a reduction in ecosystem services will trigger human responses that seek to restore service provision. Other responses are possible, however, but remain less studied. We evaluated the effect of environmental change, specifically the degradation of coral reefs, on the supply of and demand for a cultural ecosystem service (CES); that is, recreation. We found that declines in coral cover reduced demand for recreational ecosystem services but had no apparent effect on the benefits received from recreation. While this finding seems counter-intuitive given previous experimental data that suggest ecosystem quality affects people's satisfaction, our analysis suggests that social adaptation could have mediated the anticipated negative impact of environmental change on CES benefits. We propose four mechanisms that may explain this effect and that require further research: spatial diversification; (service) substitution; shifting baselines; and time-delayed effects. Our findings emphasize the importance of human culture and perception as influences on human responses to environmental change, and the relevance of the more subjective elements of social systems for understanding social–ecological feedbacks

Radiation-hard ASICs for optical data transmission in the ATLAS pixel detector

We have developed two radiation-hard ASICs for optical data transmission in the ATLAS pixel detector at the LHC at CERN: a driver chip for a Vertical Cavity Surface Emitting Laser (VCSEL) diode for 80 Mbit/s data transmission from the detector, and a Bi-Phase Mark decoder chip to recover the control data and 40 MHz clock received optically by a PIN diode. We have successfully implemented both ASICs in 0.25 um CMOS technology using enclosed layout transistors and guard rings for increased radiation hardness. We present results from prototype circuits and from irradiation studies with 24 GeV protons up to 57 Mrad (1.9 x 10e15 p/cm2).Comment: 8th Tropical Seminar on Innovative Particle and Radiation Detectors, Siena, Italy (2002

An Animal Cell Mutant With a Deficiency in Acyl/Alkyl-Dihydroxyacetone- Phosphate Reductase Activity. Effects on the Biosynthesis of Ether-Linked and Diacyl Glycerolipids

In the accompanying paper (James, P. F., and Zoeller, R. A. (1997) J. Biol. Chem. 272, 23532-23539), we reported the isolation of a series of mutants from the fibroblast-like cell line, CHO-K1, that are deficient in the incorporation of the long chain fatty alcohol, hexadecanol, into complex lipids. All but one of these mutants, FAA.K1B, were deficient in long-chain- fatty alcohol oxidase (FAO) activity. We have further characterized this FAO+ isolate. FAA.K1B cells displayed a 40% decrease in [9,103H]hexadecanol uptake when compared with the parent strain. Although incorporation of hexadecanol into the phospholipid fraction was decreased by 52%, the cells accumulated label in alkylglycerol (20-fold over wild type). The increase in 1-alkylglycerol labeling corresponded to a 4-fold increase in alkylglycerol mass. Short term labeling with 32P1 showed a 45-50% decrease in overall phospholipid biosynthesis in FAA.K1B. Both diacyl- and ether-linked species were affected, suggesting a general defect in phospholipid biosynthesis. Mutant cells were able to partially compensate for the decreased biosynthesis by decreasing the turnover of the phospholipid pools. The primary lesion in FAA.K1B was identified as a 95% reduction in acyl/alkyl-dihydroxyacetone- phospbate reductase activity. Whole cell homogenates from FAA.K1B were unable to reduce either acyl-dihydroxyacetone phosphate (DHAP) or alkyl-DHAP, supporting the notion that the reduction of these two compounds is catalyzed by a single enzyme. These data suggest that the biosynthesis of diacyl phospholipids, in Chinese hamster ovary cells, begins with the acylation of dihydroxyacetone phosphate as well as glycero-3-phosphate and that the \u27DHAP pathway\u27 contributes significantly to diacyl glycerolipid biosynthesis. Also, the severe reduction in acyl/alkyl-DHAP reductase activity in FAA.K1B resulted in only a moderate decrease in ether lipid biosynthesis. These latter data together with the observed increase in alkylglycerol levels sup port the existence of a shunt pathway that is able to partially bypass the enzymatic lesion

Insights from twenty years of comparative research in Pacific Large Ocean States

Under global environmental change, understanding the interactions between people and nature has become critical for human survival. Comparative research can identify trends within social-ecological systems providing key insights for both environmental and developmental research. Island systems, with clear land boundaries, have been proposed as ideal case studies for comparative research, but it is unclear to what extent their potential has been fulfilled. To summarize existing research and identify potential gaps and new directions, we reviewed comparative environmental and developmental research on Pacific Large Ocean States. A diversity of case study locations and research themes were addressed within the sample of reviewed studies. Within the reviewed literature climate change, energy infrastructure, trade and fisheries were key themes of environmental and developmental research compared between island systems. Research was biased towards wealthier Pacific Large Ocean States and those with a relatively higher degree of socio-economic development. Our review highlights the potential value of a stronger a priori inclusion of spatial scale and conceptual frameworks, such as spatial resilience, to facilitate generalization from case studies

Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.Portuguese Fundacao para Ciencia e Tecnologia (FCT) [PTDC/EXPL/MARBIO/0430/2013]; CCMAR FCT Plurianual financing [UID/Multi/04326/2013]; FCT [SFRH/BD/111226/2015, SFRH/BD/108842/2015, SFRH/BPD/89889/2012]; FCT-IF Starting Grant [IF/01274/2014]info:eu-repo/semantics/publishedVersio

Longitudinal assessment of PCBs and chlorinated pesticides in pregnant women from Western Canada

BACKGROUND: Maternal exposures to organochlorines prior to pregnancy are considered a risk to neonatal welfare, specifically in relation to neurocognitive functions. There is growing interest in the evaluation of maternal blood testing as a marker for fetal exposure as well as the variable geographic distribution of these priority chemicals. METHODS: Three hundred and twenty-three women in the second trimester of pregnancy entered the study at a prenatal clinic providing genetic counselling information. Subjects who had an indication for genetic amniocentesis based on late maternal age were eligible to participate. Two hundred and thirty-eight completed an environmental questionnaire. A sample of amniotic fluid was taken for karyotype analysis in 323 women and blood samples during pregnancy (209), at birth (105) and from the umbilical cord (97) and breast milk (47) were also collected. These samples were tested for 29 PCB congeners and organochlorine pesticides. RESULTS: The concentrations of PCB 153 in these media were relatively low in relation to other studies. Σ PCBs measurements in samples taken during the second trimester of pregnancy, at birth and in the umbilical cord were strongly correlated. Specific measurements of PCB 153 and PCB 180 among those subjects with completed sampling of blood samples from mothers and cord samples were significantly correlated. The concentrations of PCBs and pesticides did not differ in relation to prior spontaneous abortion history. There were no organochlorines present in the amniotic fluid at the current level of quantification. CONCLUSION: Pregnant women from the Western Canada region of Calgary, Alberta are exposed to relatively low concentrations of organochlorines. Measurement of maternal blood during the second trimester of pregnancy can reliably estimate the fetal exposure to PCBs. This estimate is reliable for Group 2 and 3 PCBs as well as PCB 153 and PCB 180. The amniotic fluid does not contain measurable concentrations of pesticides and PCBs under the conditions of the levels of quantification