Abstract
We present 1–7 GHz high-resolution radio imaging (VLA and e-MERLIN) and spatially resolved ionized gas kinematics for 10 z < 0.2 type 2 ‘obscured’ quasars (log LAGN/erg s−1 ≳ 45) with ...moderate radio luminosities ($\log L_{\rm {1.4\,GHz}}$/W Hz−1 = 23.3–24.4). These targets were selected to have known ionized outflows based on broad O iii emission-line components (full width at half-maximum ≈ 800–1800 km s−1). Although ‘radio-quiet’ and not ‘radio AGN’ by many traditional criteria, we show that for nine of the targets, star formation likely accounts for ≲10 per cent of the radio emission. We find that ∼80–90 per cent of these nine targets exhibit extended radio structures on 1–25 kpc scales. The quasars’ radio morphologies, spectral indices, and position on the radio size–luminosity relationship reveals that these sources are consistent with being low power compact radio galaxies. Therefore, we favour radio jets as dominating the radio emission in the majority of these quasars. The radio jets we observe are associated with morphologically and kinematically distinct features in the ionized gas, such as increased turbulence and outflowing bubbles, revealing jet–gas interaction on galactic scales. Importantly, such conclusions could not have been drawn from current low-resolution radio surveys such as FIRST. Our observations support a scenario where compact radio jets, with modest radio luminosities, are a crucial feedback mechanism for massive galaxies during a quasar phase.
Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit ...the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
ABSTRACT
We use a sample of powerful $z\, \approx \, 0.1$ type 2 quasars (‘obscured’; log LAGN/erg s$^{-1}\, \gtrsim \, 45$), which host kpc-scale ionized outflows and jets, to identify possible ...signatures of AGN feedback on the total molecular gas reservoirs of their host galaxies. Specifically, we present Atacama Pathfinder EXperiment (APEX) observations of the CO(2–1) transition for nine sources and the CO(6–5) for a subset of three. We find that the majority of our sample reside in starburst galaxies (average specific star formation rates – sSFR – of 1.7 Gyr−1), with the seven CO-detected quasars also having large molecular gas reservoirs (average Mgas = 1.3 × 1010 M⊙), even though we had no pre-selection on the star formation or molecular gas properties. Despite the presence of quasars and outflows, we find that the molecular gas fractions (Mgas/M⋆ = 0.1–1.2) and depletion times (Mgas/SFR = 0.16–0.95 Gyr) are consistent with those expected for the overall galaxy population with matched stellar masses and sSFRs. Furthermore, for at least two of the three targets with the required measurements, the CO(6–5)/CO(2–1) emission-line ratios are consistent with star formation dominating the CO excitation over this range of transitions. The targets in our study represent a gas-rich phase of galaxy evolution with simultaneously high levels of star formation and nuclear activity; furthermore, the jets and outflows do not have an immediate appreciable impact on the global molecular gas reservoirs.
Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of ...single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy.
Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS).
Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR partial (PR) or complete response (CR) was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis.
Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.
A signature of EeV protons of Galactic origin Tinyakov, P. G; Urban, F. R; Ivanov, D ...
Monthly Notices of the Royal Astronomical Society,
08/2016, Volume:
460, Issue:
4
Journal Article
Peer reviewed
Open access
We investigate signatures that would be produced in the spectrum and sky distribution of ultra-high energy cosmic rays (UHECR) by a population of the Galactic sources of high-energy protons in the ...energy range around 1 EeV, i.e. around the diffusive-to-ballistic transition. In this regime, the CR flux has to be calculated numerically. We employ the approach that consists in backtracking anti-protons from Earth through the Galaxy and integrating the source emissivity along the trajectory. This approach makes evident two generic features of the transition region: sharp increase of the total flux as the energy decreases across the transition region, and its strong anisotropy (appearance of a bright compact spot) all the way until the onset of the diffusive regime. We then discuss and compare several methods to experimentally detect or constrain these features. We find that a few per cent admixture of the Galactic protons can in principle be detected by the current UHECR experiments.
Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin ...with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics.
Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis.
At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression.
Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics.
There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.
The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: ...the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.
ABSTRACT
We present the first results from the Quasar Feedback Survey, a sample of 42 z < 0.2, O iii luminous AGNs ( LO III > 1042.1 ergs s−1) with moderate radio luminosities (i.e. L1.4GHz > ...1023.4 W Hz−1; median L1.4GHz = 5.9 × 1023 W Hz−1). Using high spatial resolution (∼0.3–1 arcsec), 1.5–6 GHz radio images from the Very Large Array, we find that 67 per cent of the sample have spatially extended radio features on ∼1–60 kpc scales. The radio sizes and morphologies suggest that these may be lower radio luminosity versions of compact, radio-loud AGNs. By combining the radio-to-infrared excess parameter, spectral index, radio morphology, and brightness temperature, we find radio emission in at least 57 per cent of the sample that is associated with AGN-related processes (e.g. jets, quasar-driven winds, or coronal emission). This is despite only 9.5–21 per cent being classified as radio-loud using traditional criteria. The origin of the radio emission in the remainder of the sample is unclear. We find that both the established anticorrelation between radio size and the width of the O iii line, and the known trend for the most O iii luminous AGNs to be associated with spatially extended radio emission, also hold for our sample of moderate radio luminosity quasars. These observations add to the growing evidence of a connection between the radio emission and ionized gas in quasar host galaxies. This work lays the foundation for deeper investigations into the drivers and impact of feedback in this unique sample.
Increasing numbers of genes are being implicated in Mendelian disorders and incorporated into clinical test panels. However, lack of evidence supporting the gene-disease relationship can hinder ...interpretation. We explored the utility of testing 51 additional genes for hypertrophic cardiomyopathy (HCM), one of the most commonly tested Mendelian disorders.
Using genome sequencing data from 240 sarcomere gene negative HCM cases and 6229 controls, we undertook case-control and individual variant analyses to assess 51 genes that have been proposed for HCM testing.
We found no evidence to suggest that rare variants in these genes are prevalent causes of HCM. One variant, in a single case, was categorized as likely to be pathogenic. Over 99% of variants were classified as a variant of uncertain significance (VUS) and 54% of cases had one or more VUS.
For almost all genes, the gene-disease relationship could not be validated and lack of evidence precluded variant interpretation. Thus, the incremental diagnostic yield of extending testing was negligible, and would, we propose, be outweighed by problems that arise with a high rate of uninterpretable findings. These findings highlight the need for rigorous, evidence-based selection of genes for clinical test panels.
Background: Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the ...pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. Methods: Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra- pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. Results: HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. Conclusion: Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP, tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound. Keywords: Acute pancreatitis, HIV, AIDS defining malignancies
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