Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system

Adaptive planning for resilient urban water systems under an uncertain future

Water planners are familiar with some form of variability in climate and demand. However, the uncertainty associated with the frequency and magnitude of the variations, coupled with broader performance expectations, means that long term deterministic planning needs to give way to a new approach. The structured adaptive planning process proposed in this paper aims to meet those objectives and accommodate the uncertainty in the future by developing a portfolio of measures that are both flexible to gradual changes in trends and robust to sudden shocks. A step-by-step process of the planning framework is presented. This is followed by a case study of the inputs and results based on its implementation by the Melbourne water businesses

The effect of sea temperature and food availability on the spawning success of Cape Anchovy engraulis capensis in the Southern Benguela

Data on the thermal structure, copepod biomass and production, and total number of eggs of the Cape anchovy Engraulis capensis were obtained from monthly surveys during the periods August 1993 – March1994 and September 1994 – March 1995 on the western Agulhas Bank and off the South-Western Cape, South Africa. Previous work suggested that anchovy spawn on the western Agulhas Bank in temperaturesbetween 16 and 19°C, where they feed predominantly on copepods. This study shows that the western Bank is a more suitable spawning area for anchovy, having greater thermal stability, a larger area of 16–19°Cwater and a more consistent food environment than off the South-Western Cape. Also, copepod production on the western Bank was highest in 16–19°C water. To identify factors controlling the area of this watermass, a cluster analysis was used on a suite of hydrographic variables. Three periods were identified: winter (August-September), spring (October-December) and summer (January-March), reflecting changes in theextent of the 16–19°C water and anchovy spawning, both of which peaked during spring. Spring was further characterized by infrequent surface upwelling. During summer, upwelling frequently reached the surface andthe upwelling front migrated offshore, constricting the area of 16–19°C water. It is hypothesized that spawning success in anchovy is dependent upon the extent of suitable spawning habitat, both spatially (16–19°Cwater) and temporally (spring). To put this concept into a predictive framework, the number of anchovy eggs was regressed against the area of 16–19°C water; a significant, positive relationship (p < 0.001, r2 = 0.56, n = 17) was found. An implication of the hypothesis is that the duration of spawning may be important to recruitment

Super-resolving phase measurements with a multi-photon entangled state

Using a linear optical elements and post-selection, we construct an entangled polarization state of three photons in the same spatial mode. This state is analogous to a ``photon-number path entangled state'' and can be used for super-resolving interferometry. Measuring a birefringent phase shift, we demonstrate two- and three-fold improvements in phase resolution.Comment: 4 pages, 3 figure

A proposal for selective resuscitation of adult cardiac arrest patients in a pandemic

Allocation of limited resources in pandemics begs for ethical guidance. The issue of ventilator allocation in pandemics has been reviewed by many medical ethicists, but as localities activate crisis standards of care, and health care workers are infected from patient exposure, the decision to pursue cardiopulmonary resuscitation (CPR) must also be examined to better balance the increased risks to healthcare personnel with the very low resuscitation rates of patients infected with coronavirus disease 2019 (COVID‐19). A crisis standard of care that is equitable, transparent, and mindful of both human and physical resources will lessen the impact on society in this era of COVID‐19. This paper builds on previous work of ventilator allocation in pandemic crises to propose a literature‐based, justice‐informed ethical framework for selecting treatment options for CPR. The pandemic affects regions differently over time, so these suggested guidelines may require adaptation to local practice variations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156457/3/emp212096_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156457/2/emp212096.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156457/1/emp212096-sup-0001-Appendix.pd

Quantum states made to measure

Recent progress in manipulating quantum states of light and matter brings quantum-enhanced measurements closer to prospective applications. The current challenge is to make quantum metrologic strategies robust against imperfections.Comment: 4 pages, 3 figures, Commentary for Nature Photonic

A life cycle stakeholder management framework for enhanced collaboration between stakeholders with competing interests

This is a postprint version of the Book Chapter. Information regarding the official publication is available from the link below - Copyright @ 2011 SpringerImplementation of a Life Cycle Sustainability Management (LCSM) strategy can involve significant challenges because of competing or conflicting objectives between stakeholders. These differences may, if not identified and managed, hinder successful adoption of sustainability initiatives. This article proposes a conceptual framework for stakeholder management in a LCSM context. The framework identifies the key sustainability stakeholder groups and suggests strategic ambiguity as a management tool to harness dysfunctional conflict into constructive collaboration. The framework is of practical value as it can be used as a guideline by managers who wish to improve collaboration with stakeholders along the supply chain. The article also fills a gap in the academic literature where there is only limited research on sustainability stakeholder management through strategic ambiguity

An international internet survey of the experiences of 1,714 mothers with a late stillbirth: The STARS cohort study

Background: Stillbirth occurring after 28 weeks gestation affects between 1.5-4.5 per 1,000 births in high-income countries. The majority of stillbirths in this setting occur in women without risk factors. In addition, many established risk factors such as nulliparity and maternal age are not amenable to modification during pregnancy. Identification of other risk factors which could be amenable to change in pregnancy should be a priority in stillbirth prevention research. Therefore, this study aimed to utilise an online survey asking women who had a stillbirth about their pregnancy in order to identify any common symptoms and experiences. Methods: A web-based survey. Results: A total of 1,714 women who had experienced a stillbirth >3 weeks prior to enrolment completed the survey. Common experiences identified were: perception of changes in fetal movement (63 % of respondents), reports of a "gut instinct" that something was wrong (68 %), and perceived time of death occurring overnight (56 %). A quarter of participants believed that their baby's death was due to a cord issue and another 18 % indicated that they did not know the reason why their baby died. In many cases (55 %) the mother believed the cause of death was different to that told by clinicians. Conclusions: This study confirms the association between altered fetal movements and stillbirth and highlights novel associations that merit closer scrutiny including a maternal gut instinct that something was wrong. The potential importance of maternal sleep is highlighted by the finding of more than half the mothers believing their baby died during the night. This study supports the importance of listening to mothers' concerns and symptoms during pregnancy and highlights the need for thorough investigation of stillbirth and appropriate explanation being given to parents