CO2 conversion to phenyl isocyanates by uranium(vi) bis(imido) complexes.

Uranium(vi) trans-bis(imido) complexes [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(NPhR)] react with CO2 to eliminate phenyl isocyanates and afford uranium(vi) trans-[O[double bond, length as m-dash]U[double bond, length as m-dash]NR]2+ complexes, including [U(κ4-{(tBu2ArO)2Me2-cyclam})(NPh)(O)] that was crystallographically characterized. DFT studies indicate that the reaction proceeds by endergonic formation of a cycloaddition intermediate; the secondary reaction to form a dioxo uranyl complex is both thermodynamically and kinetically hindered

Managing healthcare budgets in times of austerity: the role of program budgeting and marginal analysis

Given limited resources, priority setting or choice making will remain a reality at all levels of publicly funded healthcare across countries for many years to come. The pressures may well be even more acute as the impact of the economic crisis of 2008 continues to play out but, even as economies begin to turn around, resources within healthcare will be limited, thus some form of rationing will be required. Over the last few decades, research on healthcare priority setting has focused on methods of implementation as well as on the development of approaches related to fairness and legitimacy and on more technical aspects of decision making including the use of multi-criteria decision analysis. Recently, research has led to better understanding of evaluating priority setting activity including defining ‘success’ and articulating key elements for high performance. This body of research, however, often goes untapped by those charged with making challenging decisions and as such, in line with prevailing public sector incentives, decisions are often reliant on historical allocation patterns and/or political negotiation. These archaic and ineffective approaches not only lead to poor decisions in terms of value for money but further do not reflect basic ethical conditions that can lead to fairness in the decision-making process. The purpose of this paper is to outline a comprehensive approach to priority setting and resource allocation that has been used in different contexts across countries. This will provide decision makers with a single point of access for a basic understanding of relevant tools when faced with having to make difficult decisions about what healthcare services to fund and what not to fund. The paper also addresses several key issues related to priority setting including how health technology assessments can be used, how performance can be improved at a practical level, and what ongoing resource management practice should look like. In terms of future research, one of the most important areas of priority setting that needs further attention is how best to engage public members

Operando Spectroscopic Studies of Cu–SSZ-13 for NH3–SCR deNOx Investigates the Role of NH3 in Observed Cu(II) Reduction at High NO Conversions

The small pore zeolite chabazite (SSZ-13) in the copper exchanged form is a very efficient material for the selective catalytic reduction by ammonia (NH 3 ) of nitrogen oxides (NOx) from the exhaust of lean burn engines, typically diesel powered vehicles. The full mechanism occurring during the NH 3 –SCR process is currently debated with outstanding questions including the nature and role of the catalytically active sites. Time-resolved operando spectroscopic techniques have been used to provide new level of insights in to the mechanism of NH 3 –SCR, to show that the origin of stable Cu(I) species under SCR conditions is potentially caused by an interaction between NH 3 and the Cu cations located in eight ring sites of the bulk of the zeolite and is independent of the NH 3 –SCR of NOx occurring at Cu six ring sites within the zeolite

TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

© 2016 Thorburn 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. Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/- , TLR4-/- , TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the suppression of asthma by S. pneumoniae, and potentially other immunoregulatory therapies

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

On-chip manipulation of single photons from a diamond defect

Operating reconfigurable quantum circuits with single photon sources is a key goal of photonic quantum information science and technology. We use an integrated waveguide device containing directional couplers and a reconfigurable thermal phase controller to manipulate single photons emitted from a chromium related color center in diamond. Observation of both a wavelike interference pattern and particlelike sub-Poissionian autocorrelation functions demonstrates coherent manipulation of single photons emitted from the chromium related center and verifies wave particle duality. © 2013 American Physical Society

Asthma symptoms associated with depression and lower quality of life: a population survey

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Objective: To identify any association between asthma and depression and quality of life. Design and setting: A face-to-face Health Omnibus Survey of a random and representative sample of the South Australian population in August 1998. Participants: 3010 randomly selected participants aged 15 years and over. Main outcome measures: Prevalence of doctor-diagnosed asthma, and scores for depression (measured by PRIME-MD instrument) and quality of life (measured by SF-36) in affected participants. Results: The prevalence of asthma was 9.9%. The prevalence of major depression was significantly higher for those who experienced dyspnoea, wakening at night with asthma, and morning symptoms of asthma. Quality-of-life scores were also lower for the same groups. Conclusions: Depression is a serious but potentially remediable comorbidity with asthma that may affect appropriate diagnosis and outcome.Robert D Goldney, Richard Ruffin, Laura J Fisher and David H Wilso

Cross-adaptation from heat stress to hypoxia: A systematic review and exploratory meta-analysis

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Cross-adaptation (CA) refers to the successful induction of physiological adaptation under one environmental stressor (e.g., heat), to enable subsequent benefit in another (e.g., hypoxia). This systematic review and exploratory meta-analysis investigated the effect of heat acclimation (HA) on physiological, perceptual and physical performance outcome measures during rest, and submaximal and maximal intensity exercise in hypoxia. Database searches in Scopus and MEDLINE were performed. Studies were included when they met the Population, Intervention, Comparison, and Outcome criteria, were of English-language, peer-reviewed, full-text original articles, using human participants. Risk of bias and study quality were assessed using the COnsensus based Standards for the selection of health status Measurement INstruments checklist. Nine studies were included, totalling 79 participants (100 % recreationally trained males). The most common method of HA included fixed-intensity exercise comprising 9 ± 3 sessions, 89 ± 24-min in duration and occurred within 39 ± 2 °C and 32 ± 13 % relative humidity. CA induced a moderate, beneficial effect on physiological measures at rest (oxygen saturation: g = 0.60) and during submaximal exercise (heart rate: g = −0.65, core temperature: g = −0.68 and skin temperature: g = −0.72). A small effect was found for ventilation (g = 0.24) and performance measures (peak power: g = 0.32 and time trial time: g = −0.43) during maximal intensity exercise. No effect was observed for perceptual outcome measures. CA may be appropriate for individuals, such as occupational or military workers, whose access to altitude exposure prior to undertaking submaximal activity in hypoxic conditions is restricted. Methodological variances exist within the current literature, and females and well-trained individuals have yet to be investigated. Future research should focus on these cohorts and explore the mechanistic underpinnings of CA.Funding sources: None. Acknowledgments: The authors would like to thank Para-Monte, the Adam Savory Altitude Awareness Charity, Eastbourne, East Sussex (https://www.para-monte.org/) for their charitable support that has underpinned our hypoxic research

Purtscher-like retinopathy following valsalva maneuver effect: case report

<p>Abstract</p> <p>Introduction</p> <p>Purtscher's retinopathy is a rare condition that is noted in cases related to various types of trauma. The characteristic finding in the fundus is the presence of multiple Purtscher flecken. Purtscher-like retinopathy has a similar presentation in the fundus, but without an association with trauma.</p> <p>Case presentation</p> <p>A 43-year old Malay man presented with a sudden onset of central foggy vision in the left eye after holding his breath for two minutes while catching a falling object. It was not associated with floaters, flashes of light, or head trauma. His vision in the right eye was 6/6, and in his left eye it was finger counting. He had bilateral temporal sub-conjunctival hemorrhages. An examination of his left fundus revealed multiple white cotton wool spots and dot-blot retinal hemorrhages with diffuse retinal edema at the posterior pole. His right fundus was noted to have only mild temporal peri-papillary edema associated with a few dot-blot hemorrhages. Fundus fluorescein angiography showed good arterial perfusion and no evidence of leaking or neo-vascularization. A diagnosis of Purtscher-like retinopathy was made, and the patient was treated with indomethacin tablets for six weeks. At his six-week follow-up examination, his left eye visual acuity had improved to 6/12. His bilateral sub-conjunctival hemorrhage had resolved. His left fundus showed residual multiple cotton wool spots and reduced retinal edema.</p> <p>Conclusions</p> <p>Treatment with non-steroidal anti-inflammatory drugs seems to be effective in reducing edema in patients with Purtscher-like retinopathy.</p