456 research outputs found

    Unification of Radio Galaxies and Their Accretion/Jet Properties

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    We investigate the relation between black hole mass, M_bh, and jet power, Q_jet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in M_bh-Q_jet plane, which strongly supports the unification scheme of FR I/BL Lac and FR II/radio quasar. The Eddington ratio distribution of BL Lacs and radio quasars exhibits a bimodal nature with a rough division at L_bol/L_Edd~0.01, which imply that they may have different accretion modes. We calculate the jet power extracted from advection dominated accretion flow (ADAF), and find that it require dimensionless angular momentum of black hole j~0.9-0.99 to reproduce the dividing line between FR I/II or BL Lac/radio quasar if dimensionless accretion rate mdot=0.01 is adopted, which is required by above bimodal distribution of Eddington ratios. Our results suggest that black holes in radio galaxies are rapidly spinning.Comment: To appear JAA in Jun

    Ultrathin compound semiconductor on insulator layers for high performance nanoscale transistors

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    Over the past several years, the inherent scaling limitations of electron devices have fueled the exploration of high carrier mobility semiconductors as a Si replacement to further enhance the device performance. In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied, combining the high mobility of III-V semiconductors and the well-established, low cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored. Besides complexity, high defect densities and junction leakage currents present limitations in the approach. Motivated by this challenge, here we utilize an epitaxial transfer method for the integration of ultrathin layers of single-crystalline InAs on Si/SiO2 substrates. As a parallel to silicon-on-insulator (SOI) technology14,we use the abbreviation "XOI" to represent our compound semiconductor-on-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsOx layer (~1 nm thick). The fabricated FETs exhibit an impressive peak transconductance of ~1.6 mS/{\mu}m at VDS=0.5V with ON/OFF current ratio of greater than 10,000 and a subthreshold swing of 107-150 mV/decade for a channel length of ~0.5 {\mu}m

    Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.

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    BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR. RESULTS: Pfmdr1-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two pfmdr1 gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (P < 0.0001). Among the main pfmdr1 haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (P = 0.04). At the pfatp6 locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the pfatp6 E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The pfk13 variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the pfk13 locus occurring at low frequency were observed. CONCLUSIONS: Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries

    Antimalarial treatment in infants.

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    INTRODUCTION: Malaria in infants is common in high-transmission settings, especially in infants >6 months. Infants undergo physiological changes impacting pharmacokinetics and pharmacodynamics of anti-malarial drugs and, consequently, the safety and efficacy of malaria treatment. Yet, treatment guidelines and evidence on pharmacological interventions for malaria often fail to address this vulnerable age group. This review aims to summarize the available data on anti-malarial treatment in infants. AREAS COVERED: The standard recommended treatments for severe and uncomplicated malaria are generally safe and effective in infants. However, infants have an increased risk of drug-related vomiting and have distinct pharmacokinetic parameters of antimalarials compared with older patients. These include larger volumes of distribution, higher clearance rates, and immature enzyme systems. Consequently, infants with malaria may be at increased risk of treatment failure and drug toxicity. EXPERT OPINION: Knowledge expansion to optimize treatment can be achieved by including more infants in antimalarial drug trials and by reporting separately on treatment outcomes in infants. Additional evidence on the efficacy, safety, tolerability, acceptability, and effectiveness of ACTs in infants is needed, as well as population pharmacokinetics studies on antimalarials in the infant population

    Outer membrane protein folding from an energy landscape perspective

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    The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Melioidosis presenting with mediastinal lymphadenopathy masquerading as malignancy: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Melioidosis, endemic in Thailand and in the Northern Territory of Australia is an emerging infectious disease in India which can present with varied forms. A case of melioidosis, presenting as a rare anterior mediastinal mass which can masquerade as malignancy or tuberculosis, is described here. With treatment, our patient initially showed an increase in the size of mediastinal node and development of new submandibular node.. To the best of our knowledge, this phenomenon has not been documented in the literature and the same is highlighted in this case report. </p> <p>Case Presentation</p> <p>A 43-year-old Asian man with diabetes presented with fever, loss of appetite, weight loss for one month and painful swelling below his left mandible for five days. An examination revealed an enlarged left submandibular lymph node and bilateral axillary lymph nodes. A chest X-ray showed mediastinal widening. Computed tomography of his thorax showed a lobulated heterogeneously enhancing anterior mediastinal mass encasing the superior vena cava suggestive of malignancy. An excision biopsy of the lymph node showed granulomas suggestive of tuberculosis but bone marrow culture and lymph node aspirate culture grew <it>Burkholderia pseudomallei</it>. He was treated with parenteral ceftazidime and amoxicillin-clavulanic acid. During the course of treatment, he developed an enlargement of the submandibular lymph node on the opposite side. It gradually subsided with the continuation of therapy orally with a combination of cotrimoxazole and doxycycline for six months. A repeat computed tomography chest scan showed resolution of the mediastinal mass.</p> <p>Conclusion</p> <p>Melioidosis can present as a mediastinal mass that mimics tuberculosis or malignancy. During the initial phase of treatment of melioidosis, the appearance of new lymph nodes or an increase in the size of the existing lymph nodes does not mean treatment failure. Inexperienced clinicians may consider this as treatment failure and may switch treatment. To the best of our knowledge, this is the first report documenting this phenomenon in melioidosis cases.</p

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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