Projected rapid response of stratospheric temperature to stringent climate mitigation.

Deep, rapid and sustained reductions in greenhouse gas emissions are required to meet the 2015 Paris Agreement climate target. If the world strengthens efforts toward near-term decarbonisation and undertakes major societal transformation, this will be met with requests from policymakers and the public for evidence that our actions are working and there are demonstrable effects on the climate system. Global surface temperature exhibits large internal variability on interannual to decadal timescales, meaning a reduction in the magnitude of surface warming would not be robustly attributable to climate mitigation for some time.

Evaluation of a Simple Low-cost Intervention to Empower People with CKD to Reduce Their Dietary Salt Intake: OxCKD1, a Multicenter Randomized Controlled Trial.

Key Points: A randomized controlled trial demonstrates that a simple and cheap 1-month intervention empowers people with CKD to lower their dietary salt intake. The effect of the intervention persisted after the intervention finished.

Background: To evaluate the efficacy of a simple low-cost intervention to empower people with CKD to reduce their dietary salt intake.

Global temperature modes shed light on the Holocene temperature conundrum.

Reconstructions of the global mean annual temperature evolution during the Holocene yield conflicting results. One temperature reconstruction shows global cooling during the late Holocene. The other reconstruction reveals global warming.

The linearity of the El Niño teleconnection to the Amundsen Sea region.

El Niño Southern Oscillation (ENSO) drives interannual variability in West Antarctic climate through altering atmospheric circulation in the Amundsen Sea region (ASR). The El Niño-ASR teleconnection is known to be strongest in austral winter and spring, but its variation with El Niño amplitude is underexplored. This study uses experiments from the HadGEM3-A climate model to investigate the El Niño-ASR teleconnection for a range of imposed SST perturbations spanning weak (0.

Efficacy of Climate Forcings in PDRMIP Models.

Quantifying the efficacy of different climate forcings is important for understanding the real-world climate sensitivity. This study presents a systematic multimodel analysis of different climate driver efficacies using simulations from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP). Efficacies calculated from instantaneous radiative forcing deviate considerably from unity across forcing agents and models.

Latent tuberculosis may be missed by current screening practices: Analysis of interferon-gamma release assay results from a paediatric refugee clinic.

Aims: (i) To determine the prevalence of latent tuberculosis infection (LTBI) and characteristics associated with LTBI in children attending a paediatric refugee clinic and (ii) to determine whether current New South Wales (NSW) Health screening practices could miss LTBI cases.

Methods: This was a retrospective analysis of tuberculosis (TB) screening data from refugee and asylum seeker children who attended a refugee clinic in a tertiary children's hospital during 2014 and 2015. We determined associations between LTBI and child characteristics at 5% significance levels.

Revisiting the mystery of recent stratospheric temperature trends.

Simulated stratospheric temperatures over the period 1979-2016 in models from the Chemistry-Climate Model Initiative (CCMI) are compared with recently updated and extended satellite observations. The multi-model mean global temperature trends over 1979- 2005 are -0.88 ± 0.

Possible impacts of a future grand solar minimum on climate: Stratospheric and global circulation changes.

A future decline in solar activity would not offset projected global warmingA future decline in solar activity could have larger regional effects in winterTop-down mechanism contributes to Northern Hemisphere regional response.

Regional climate impacts of a possible future grand solar minimum.

Any reduction in global mean near-surface temperature due to a future decline in solar activity is likely to be a small fraction of projected anthropogenic warming. However, variability in ultraviolet solar irradiance is linked to modulation of the Arctic and North Atlantic Oscillations, suggesting the potential for larger regional surface climate effects. Here, we explore possible impacts through two experiments designed to bracket uncertainty in ultraviolet irradiance in a scenario in which future solar activity decreases to Maunder Minimum-like conditions by 2050.

A large ozone-circulation feedback and its implications for global warming assessments.

State-of-the-art climate models now include more climate processes which are simulated at higher spatial resolution than ever. Nevertheless, some processes, such as atmospheric chemical feedbacks, are still computationally expensive and are often ignored in climate simulations. Here we present evidence that how stratospheric ozone is represented in climate models can have a first order impact on estimates of effective climate sensitivity.

Australia's treatment of refugee and asylum seeker children: the views of Australian paediatricians.

Objective: Australia's response to refugees and people seeking asylum is a matter of national debate. We sought to determine the knowledge and attitudes of paediatricians about refugee and asylum seeker issues (both onshore and offshore).

Design, Setting And Participants: In November 2013, we emailed a questionnaire web link to all Australian general and community paediatricians registered with the Royal Australasian College of Physicians.

Amino acid conjugates as kappa opioid receptor agonists.

A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.

Synthesis and evaluation of novel peripherally restricted kappa-opioid receptor agonists.

A series of 3-substituted analogs (3) of the parent kappa agonist, 1, were prepared to limit access to the central nervous system. With the exception of compound 3j, all other compounds bound to the human kappa opioid receptor with high affinity (K(i)=0.31-9.

Arylacetamides as peripherally restricted kappa opioid receptor agonists.

Analogues of the kappa (kappa) opioid receptor agonist, ICI 199441, were prepared. Ki values for these analogues at the cloned human kappa opioid receptor ranged from 0.058 to 25 nM.

[Pro(3)]Dyn A(1-11)-NH(2): a dynorphin analogue with high selectivity for the kappa opioid receptor.

A proline scan at positions 2 and 3 of the opioid peptide dynorphin A(1-11)-NH(2) led to the discovery of the analogue [Pro(3)]Dyn A(1-11)-NH(2). This analogue possesses high affinity and selectivity for the kappa opioid receptor (K(i)(kappa) = 2.7 nM, K(i) ratio kappa/micro/delta = 1/2110/3260).

Determination of loperamide in rat plasma and bovine serum albumin by LC.

A rapid, isocratic liquid chromatographic (LC) method was developed for the determination of loperamide (Lop) in solutions of bovine serum albumin (BSA) and rat plasma. Prior to LC analysis, BSA solutions or rat plasma samples were treated with metaphosphoric acid to precipitate protein. Supernatant was directly injected onto a C18 reverse phase column and loperamide was monitored by a UV detector set at 195 nm.

Mechanism of inhibition of human leucocyte elastase by beta-lactams. 2. Stability, reactivation kinetics, and products of beta-lactam-derived E-I complexes.

The monocyclic beta-lactams reported by Knight et al. [Knight, W. B.

Damnacanthal is a highly potent, selective inhibitor of p56lck tyrosine kinase activity.

Damnacanthal, an anthraquinone isolated from a plant extract, was found to be a potent, selective inhibitor of p56lck tyrosine kinase activity. The structure, potency, and selectivity of damnacanthal were confirmed by independent synthesis and testing. Damnacanthal exhibited an IC50 of 17 nM for inhibition of p56lck autophosphorylation and an IC50 of 620 nM for phosphorylation of an exogenous peptide by p56lck.

Orally active beta-lactam inhibitors of human leukocyte elastase. 3. Stereospecific synthesis and structure-activity relationships for 3,3-dialkylazetidin-2-ones.

The stereospecific synthesis of several 4-[(4-carboxyphenyl)oxy]- 3,3-dialkyl-1-[[(1-phenylalkyl)-amino]carbonyl]azetidin-2-on es 3 is described in which the C-3 alkyl groups were varied from methyl to butyl as well as allyl, benzyl and methoxymethyl. The structure-activity relations for these compounds are discussed in terms of the hydrolytic stability of the beta-lactam ring, their in vitro inhibitory potency for human leukocyte elastase (HLE), and their in vivo oral efficacy in an HLE-mediated hamster lung hemorrhage assay. Further alkyl substitution on the benzylic urea moiety, especially in the R configuration, afforded enhanced HLE inhibition and in vivo efficacy.

Mechanism of inhibition of human leucocyte elastase by monocyclic beta-lactams.

The kinetic and catalytic mechanisms of time-dependent inhibition of human polymorphonuclear leukocyte elastase (HLE) by the monocyclic beta-lactams described by Knight et al. [Knight, W.B.

Orally active beta-lactam inhibitors of human leukocyte elastase. 2. Effect of C-4 substitution.

The effect of changing the C-4 substituent of 3,3-diethyl-1-[(benzylamino)carbonyl]-2-azetidinone on inhibition of HLE and in a model of HLE-induced lung damage in hamsters was explored. Substituents at this position do not appear to interact strongly with HLE with the most potent compounds having k(obs)/[I] = 6900 M-1 s-1. However, substituents at this position had a marked effect on in vivo activity.

Specificity, stability, and potency of monocyclic beta-lactam inhibitors of human leucocyte elastase.

Stable, potent, highly specific, time-dependent monocyclic beta-lactam inhibitors of human leucocyte elastase (HLE) are described. The heavily substituted beta-lactams are stable under physiological conditions including in the presence of enzymes of the digestive tract. The beta-lactams were unstable in base.

Mechanism of inhibition of human leukocyte elastase by two cephalosporin derivatives.

The cephalosporin derivatives L 658758 [1-[[3-(acetoxymethyl)-7 alpha-methoxy-8-oxo-5-thia-1-azabicyclo [4.2.0]oct-2-en-2-yl]carbonyl]proline S,S-dioxide] and L 659286 [1-[[7 alpha-methoxy-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo- 1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-aza-(6R)-bicyclo[4.

PMN elastases: a comparison of the specificity of human isozymes and the enzyme from other species toward substrates and inhibitors.

The human elastases isolated from polymorphonuclear neutrophils (PMN) and purulent sputum displayed identical kinetic constants toward substrates and inhibitors. The elastases from the two sources yield identical N-terminal sequences and were recognized by antiserum prepared against human sputum elastase (HSE) isozyme-4 (I-4). The data support the proposal put forth by Twumasi and Liener (1977, J.