43 research outputs found

    ATP-Binding Cassette Systems of Brucella

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    Brucellosis is a prevalent zoonotic disease and is endemic in the Middle East, South America, and other areas of the world. In this study, complete inventories of putative functional ABC systems of five Brucella species have been compiled and compared. ABC systems of Brucella melitensis 16M, Brucella abortus 9-941, Brucella canis RM6/66, Brucella suis 1330, and Brucella ovis 63/290 were identified and aligned. High numbers of ABC systems, particularly nutrient importers, were found in all Brucella species. However, differences in the total numbers of ABC systems were identified (B. melitensis, 79; B. suis, 72; B. abortus 64; B. canis, 74; B. ovis, 59) as well as specific differences in the functional ABC systems of the Brucella species. Since B. ovis is not known to cause human brucellosis, functional ABC systems absent in the B. ovis genome may represent virulence factors in human brucellosis

    Comparison of clinical and radiological outcomes for the anterior and medial approaches to open reduction in the treatment of bilateral developmental dysplasia of the hip:a systematic review protocol

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    Background: Developmental dysplasia of the hip (DDH) affects 1–3% of newborns and 20% of cases are bilateral. The optimal surgical management strategy for patients with bilateral DDH who fail bracing, closed reduction or present too late for these methods to be used is unclear. There are proponents of both medial approach open reduction (MAOR) and anterior approach open reduction (AOR); however, there is little evidence to inform this debate. Methods: We will perform a systematic review designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search the medical and scientific databases including the grey and difficult to locate literature. The Medical Subject Headings “developmental dysplasia of the hip”, “congenital dysplasia of the hip”, “congenital hip dislocation”, “developmental hip dislocation”, and their abbreviations, “DDH” and “CDH” will be used, along with the qualifier “bilateral”. Reviewers will independently screen records for inclusion and then independently extract data on study design, population characteristics, details of operative intervention and outcomes from the selected records. Data will be synthesised and a meta-analysis performed if possible. If not possible we will analyse data according to Systematic Review without Meta-Analysis guidance. All studies will be assessed for risk of bias. For each outcome measure a summary of findings will be presented in a table with the overall quality of the recommendation assessed using the Grading of Recommendations Assessment Development and Evaluation approach. Discussion: The decision to perform MAOR or AOR in patients with bilateral DDH who have failed conservative management is not well informed by the current literature. High-quality, comparative studies are exceptionally challenging to perform for this patient population and likely to be extremely uncommon. A systematic review provides the best opportunity to deliver the highest possible quality of evidence for bilateral DDH surgical management. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42022362325)

    Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago

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    Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world

    Pathogen Populations Evolve to Greater Race Complexity in Agricultural Systems – Evidence from Analysis of Rhynchosporium secalis Virulence Data

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    Fitness cost associated with pathogens carrying unnecessary virulence alleles is the fundamental assumption for preventing the emergence of complex races in plant pathogen populations but this hypothesis has rarely been tested empirically on a temporal and spatial scale which is sufficient to distinguish evolutionary signals from experimental error. We analyzed virulence characteristics of ∌1000 isolates of the barley pathogen Rhynchosporium secalis collected from different parts of the United Kingdom between 1984 and 2005. We found a gradual increase in race complexity over time with a significant correlation between sampling date and race complexity of the pathogen (r20 = 0.71, p = 0.0002) and an average loss of 0.1 avirulence alleles (corresponding to an average gain of 0.1 virulence alleles) each year. We also found a positive and significant correlation between barley cultivar diversity and R. secalis virulence variation. The conditions assumed to favour complex races were not present in the United Kingdom and we hypothesize that the increase in race complexity is attributable to the combination of natural selection and genetic drift. Host resistance selects for corresponding virulence alleles to fixation or dominant frequency. Because of the weak fitness penalty of carrying the unnecessary virulence alleles, genetic drift associated with other evolutionary forces such as hitch-hiking maintains the frequency of the dominant virulence alleles even after the corresponding resistance factors cease to be used

    Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.

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    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

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    Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

    Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

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    Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

    Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

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    Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≀0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

    Effect of Substituents of Cerium Pyrazolates and Pyrrolates on Carbon Dioxide Activation

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    Homoleptic ceric pyrazolates (pz) Ce(RR’pz)4 (R = R’ = tBu; R = R’ = Ph; R = tBu, R’ = Me) were synthesized by the protonolysis reaction of Ce[N(SiHMe2)2]4 with the corresponding pyrazole derivative. The resulting complexes were investigated in their reactivity toward CO2, revealing a significant influence of the bulkiness of the substituents on the pyrazolato ligands. The efficiency of the CO2 insertion was found to increase in the order of tBu2pz &lt; Ph2pz &lt; tBuMepz &lt; Me2pz. For comparison, the pyrrole-based ate complexes [Ce2(pyr)6(”-pyr)2(thf)2][Li(thf)4]2 (pyr = pyrrolato) and [Ce(cbz)4(thf)2][Li(thf)4] (cbz = carbazolato) were obtained via protonolysis of the cerous ate complex Ce[N(SiHMe2)2]4Li(thf) with pyrrole and carbazole, respectively. Treatment of the pyrrolate/carbazolate complexes with CO2 seemed promising, but any reversibility could not be observed
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