A rare combination of strong spin-orbit coupling and electron-electron correlations makes the iridate Mott insulator Sr2 IrO4 a promising host for novel electronic phases of matter. The resemblance ...of its crystallographic, magnetic and electronic structures to La2 CuO4 , as well as the emergence on doping of a pseudogap region and a low-temperature d-wave gap, has particularly strengthened analogies to cuprate high-Tc superconductors. However, unlike the cuprate phase diagram, which features a plethora of broken symmetry phases in a pseudogap region that includes charge density wave, stripe, nematic and possibly intra-unit-cell loop-current orders, no broken symmetry phases proximate to the parent antiferromagnetic Mott insulating phase in Sr2 IrO4 have been observed so far, making the comparison of iridate to cuprate phenomenology incomplete. Using optical second-harmonic generation, we report evidence of a hidden non-dipolar magnetic order in Sr2 IrO4 that breaks both the spatial inversion and rotational symmetries of the underlying tetragonal lattice. Four distinct domain types corresponding to discrete 90°-rotated orientations of a pseudovector order parameter are identified using nonlinear optical microscopy, which is expected from an electronic phase that possesses the symmetries of a magneto-electric loop-current order. The onset temperature of this phase is monotonically suppressed with bulk hole doping, albeit much more weakly than the Néel temperature, revealing an extended region of the phase diagram with purely hidden order. Driving this hidden phase to its quantum critical point may be a path to realizing superconductivity in Sr2 IrO4 .
Over recent years there has been a growing need for patients to be sent home from hospital with prescribed opioids for ongoing management of their acute pain. Increasingly complex surgery is being ...performed on a day-stay or 23-hour-stay basis and inpatients after major surgery and trauma are now discharged at a much earlier stage than in the past. However, prescription of opioids to be self-administered at home is not without risk. In addition to the potential for acute adverse effects, including opioid-induced ventilatory impairment and impairment of driving skills, a review of the literature shows that opioid use continues in some patients for some years after surgery. There are also indications that over-prescription of discharge opioids occur with a significant amount not consumed, resulting in a potentially large pool of unused opioid available for later use by either the patient or others in the community. Concerns about the potential for harm arising from prescription of opioids for ongoing acute pain management after discharge are relatively recent. However, at a time when serious problems resulting from the non-medical use of opioids have reached epidemic proportions in the community, all doctors must be aware of the potential risks and be able to identify and appropriately manage patients where there might be a risk of prolonged opioid use or misuse. Anaesthetists are ideally placed to exercise stewardship over the use of opioids, so that these drugs can maintain their rightful place in the post-discharge analgesic pharmacopoeia.
Priorities for peri‐operative research in Africa Biccard, B.M.; Biccard, BM; Torborg, AM ...
Anaesthesia,
January 2020, 2020-Jan, 2020-01-00, 20200101, Letnik:
75, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Summary
Deaths following surgery are the third largest contributor to deaths globally, and in Africa are twice the global average. There is a need for a peri‐operative research agenda to ensure ...co‐ordinated, collaborative research efforts across Africa in order to decrease peri‐operative mortality. The objective was to determine the top 10 research priorities for peri‐operative research in Africa. A Delphi technique was used to establish consensus on the top research priorities. The top 10 research priorities identified were (1) Develop training standards for peri‐operative healthcare providers (surgical, anaesthesia and nursing) in Africa; (2) Develop minimum provision of care standards for peri‐operative healthcare providers (surgical, anaesthesia and nursing) in Africa; (3) Early identification and management of mothers at risk from peripartum haemorrhage in the peri‐operative period; (4) The role of communication and teamwork between surgical, anaesthetic, nursing and other teams involved in peri‐operative care; (5) A facility audit/African World Health Organization situational analysis tool audit to assess emergency and essential surgical care, which includes anaesthetic equipment available and level of training and knowledge of peri‐operative healthcare providers (surgeons, anaesthetists and nurses); (6) Establishing evidence‐based practice guidelines for peri‐operative physicians in Africa; (7) Economic analysis of strategies to finance access to surgery in Africa; (8) Establishment of a minimum dataset surgical registry; (9) A quality improvement programme to improve implementation of the surgical safety checklist; and (10) Peri‐operative outcomes associated with emergency surgery. These peri‐operative research priorities provide the structure for an intermediate‐term research agenda to improve peri‐operative outcomes across Africa.
We report in this paper that highly purified Escherichia coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase are inactivated by O2- with second order rate constants in ...the range of 10(6) to 10(7) M-1 s-1. Each of these enzymes belongs to the hydro-lyase class and contains catalytically active 4Fe-4S clusters. Simultaneous with inactivation by O2- is the release of iron from their clusters. Our working hypothesis is O2- inactivates these enzymes by oxidizing their clusters to an unstable oxidation state, and cluster degradation follows. Consistent with this hypothesis is our observation that spinach dihydroxy-acid dehydratase, a member of the hydro-lyase class that has a catalytically active 2Fe-2S cluster, is not inactivated and does not lose iron in the presence of O2-. Porcine fumarase, a member of the hydro-lyase class that does not contain an Fe-S cluster, is also not inactivated by O2-. We also report the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase, fumarase A, fumarase B, and mammalian aconitase by O2 are close to 2 x 10(2) M-1 s-1, and the rate constants for the inactivation of E. coli dihydroxy-acid dehydratase and mammalian aconitase by H2O2 are about 10(3) M-1 s-1. E. coli dihydroxy-acid dehydratase has been reported previously to be inactivated in vivo when cells are grown in hyperbaric O2, presumably due to the increased O2- generated under these conditions. We report here that E. coli fumarase A, fumarase B, and aconitase are also inactivated in vivo by hyperbaric O2. Thermodynamic parameters for the oxidation of the cluster of aconitase by O2- and O2 are calculated.
An enzyme having the same L-cysteine desulfurization activity previously described for the NifS protein was purified from a strain of Azotobacter vinelandii deleted for the nifS gene. This protein ...was designated IscS to indicate its proposed role in iron-sulfur cluster assembly. Like NifS, IscS is a pyridoxal-phosphate containing homodimer. Information gained from microsequencing of oligopeptides obtained by tryptic digestion of purified IscS was used to design a strategy for isolation and DNA sequence analysis of a 7,886-base pair A. vinelandii genomic segment that includes the iscS gene. The iscS gene is contained within a gene cluster that includes homologs to nifU and another gene contained within the major nif cluster of A. vinelandii previously designated orf6. These genes have been designated iscU and iscA, respectively. Information available from complete genome sequences of Escherichia coli and Hemophilus influenzae reveals that they also encode iscSUA gene clusters. A wide conservation of iscSUA genes in nature and evidence that NifU and NifS participate in the mobilization of iron and sulfur for nitrogenase-specific iron-sulfur cluster formation suggest that the products of the iscSUA genes could play a general role in the formation or repair of iron-sulfur clusters. The proposal that IscS is involved in mobilization of sulfur for iron-sulfur cluster formation in A. vinelandii is supported by the presence of a cysE-like homolog in another gene cluster located immediately upstream from the one containing the iscSUA genes. O-Acetylserine synthase is the product of the cysE gene, and it catalyzes the rate-limiting step in cysteine biosynthesis. A similar cysE-like gene is also located within the nif gene cluster of A. vinelandii. The likely role of such cysE-like gene products is to increase the cysteine pool needed for iron-sulfur cluster formation. Another feature of the iscSUA gene cluster region from A. vinelandii is that E. coli genes previously designated as hscB, hscA, and fdx are located immediately downstream from, and are probably co-transcribed with, the iscSUA genes. The hscB, hscA, and fdx genes are also located adjacent to the iscSUA genes in both E. coli and H. influenzae. The E. coli hscA and hscB gene products have previously been shown to bear primary sequence identity when respectively compared with the dnaK and dnaJ gene products and have been proposed to be members of a heat-shock-cognate molecular chaperone system of unknown function. The close proximity and apparent co-expression of iscSUA and hscBA in A. vinelandii indicate that the proposed chaperone function of the hscBA gene products could be related to the maturation of iron-sulfur cluster-containing proteins. Attempts to place non-polar insertion mutations within either A. vinelandii iscS or hscA revealed that such mutations could not be stably maintained in the absence of the corresponding wild-type allele. These results reveal a very strong selective pressure against the maintenance of A. vinelandii iscS or hscA knock-out mutations and suggest that such mutations are either lethal or highly deleterious. In contrast to iscS or hscA, a strain having a polar insertion mutation within the cysE-like gene was readily isolated and could be stably maintained. These results show that the cysE-like gene located upstream from iscS is not essential for cell growth and that the cysE-like gene and the iscSUA-hscBA-fdx genes are contained within separate transcription units.
Background: The main complication of external ventricular drains (EVD) is infection. Implementation of evidence-based guidelines for central venous catheter (CVC) care resulted in significant ...declines in infections. We tested a comparable approach to EVD infection rates.
Methods: An initial retrospective study evaluated the existing EVD infection rate, and identified contributory risk factors. Based on our results, and in corroboration with existing literature, an EVD care bundle was developed and implemented. A prospective study was then conducted to identify improvement.
Results: A total of 275 EVDs (120 pre- and 155 post-EVD care bundle) inserted over a period of 1532 days were included. Pre-care bundle, the infection rate was 27%, with the predominant factor associated with infection being number cerebrospinal fluid sampling episodes. Following introduction of the EVD care bundle, the infection rate declined to 10% (p < 0.001) with the incidence from 21 to 9 cases per 1,000 EVD-days (p = 0.003). The infection rate was not found to be significantly associated with the number of accesses during this period (p = 0.910).
Conclusions: Introduction of a well-implemented EVD care bundle can significantly decrease EVD infection rates.
Seed‐based seagrass restoration strategies demand precise understanding of the environmental drivers influencing flowering. Flowering varies across diverse spatial and temporal scales, yet ...environmental drivers' effects on these dynamics have received less attention. Lack of knowledge regarding this life‐history stage limits the advancement of seed‐based restoration efforts, especially the establishment of shore‐based seagrass nurseries to enhance seed production.
A systematic literature review on the flowering of the genus Zostera was conducted to develop a conceptual model that links influential environmental drivers with flowering. Additionally, a case study using existing survey data supplemented by additional field surveys was designed to explore the spatio‐temporal variability of flowering along the latitudinal gradient in Australasia for the species Zostera muelleri. Predictive models for flowering times were developed using regional climatic variables, following hypotheses generated from long‐term mesocosm observations.
The review identified the direct and/or indirect effects of temperature, light, tidal variation, nutrients, salinity and grazing pressure on flowering dynamics. Four categories of flowering variables were identified based on their implications on restoration, namely, timing, abundance, the ratio between reproductive and vegetative growth and morphological characteristics. The spathe densities varied significantly among sites along the latitudinal gradient. While first (r2 = 0.71) and peak (r2 = 0.68) flowering times showed significant correlation with latitude, first flowering was equally predicted by mean winter air temperature and mean winter solar radiation (r2 = 0.73), whereas peak flowering time was best predicted by mean winter air temperature (r2 = 0.60).
Accurate predictions of flowering times can improve conservation outcomes by enabling restoration practitioners to forecast flowering times and subsequent wild seed harvesting. The strong correlation between flowering times and climatic variables suggests future shifts in flowering times under climate change are likely, which is crucial knowledge for maintaining the contribution of restoration projects to seagrass conservation.
Telomere-specific clones are a valuable resource for the characterization of chromosomal rearrangements. We previously reported a first-generation set of human telomere probes consisting of 34 ...genomic clones, which were a known distance from the end of the chromosome (∼300 kb), and 7 clones corresponding to the most distal markers on the integrated genetic/physical map (1p, 5p, 6p, 9p, 12p, 15q, and 20q). Subsequently, this resource has been optimized and completed: the size of the genomic clones has been expanded to a target size of 100–200 kb, which is optimal for use in genome-scanning methodologies, and additional probes for the remaining seven telomeres have been identified. For each clone we give an associated mapped sequence-tagged site and provide distances from the telomere estimated using a combination of fiberFISH, interphase FISH, sequence analysis, and radiation-hybrid mapping. This updated set of telomeric clones is an invaluable resource for clinical diagnosis and represents an important contribution to genetic and physical mapping efforts aimed at telomeric regions.
In this paper, I report the purification of a protein from Escherichia coli that is very similar in sequence, molecular weight, and the reactions it can catalyze to the protein encoded by the ...Azotobacter vinelandii nifS gene. This E. coli protein contains pyridoxal phosphate as a cofactor and catalyzes the removal of sulfur from cysteine to form alanine and S0. When dithiothreitol is present along with cysteine, the S0 formed is reduced to S2−. This protein has a reactive sulfhydryl group that is essential for activity. As isolated, this sulfhydryl group appears to be in a disulfide linkage with the sulfhydryl group from the phosphopantetheine moiety of the acyl carrier protein. The purified E. coli protein can mobilize the sulfur from cysteine and contribute it to the formation of a 4Fe-4S cluster on the apoprotein of E. coli dihydroxy-acid dehydratase. A mechanism is proposed for the early stages of the synthesis of Fe-S clusters using this protein and sulfur in the S0 oxidation state.
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