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We present a multiwavelength analysis based on archival radio, optical, and X-ray data of the complex radio source 3C 196.1, whose host is the brightest cluster galaxy of a z = 0.198 cluster. HST data show Hα+[N ii] emission aligned with the jet 8.4 GHz radio emission. An Hα+[N ii] filament coincides with the brightest X-ray emission, the northern hotspot. Analysis of the X-ray and radio images reveals cavities located at galactic and cluster scales. The galactic-scale cavity is almost devoid of 8.4 GHz radio emission and the southwestern Hα+[N ii] emission is bounded (in projection) by this cavity. The outer cavity is cospatial with the peak of 147 MHz radio emission, and hence we interpret this depression in X-ray surface brightness as being caused by a buoyantly rising bubble originating from an active galactic nuclei outburst ∼280 Myr ago. A Chandra snapshot observation allowed us to constrain the physical parameters of the cluster, which has a cool core with a low central temperature ∼2.8 keV, low central entropy index ∼13 keV cm2 and a short cooling time of ∼500 Myr, which is < 0.05 of the age of the universe at this redshift. By fitting jumps in the X-ray density, we found Mach numbers between 1.4 and 1.6, consistent with a shock origin. We also found compelling evidence of a past merger, indicated by a morphology reminiscent of gas sloshing in the X-ray residual image. Finally, we computed the pressures, enthalpies Ecav and jet powers Pjet associated with the cavities: Ecav ∼ 7 × 1058 erg, Pjet ∼ 1.9 × 1044 erg s−1 for the inner cavity and Ecav ∼ 3 × 1060 erg, Pjet ∼ 3.4 × 1044 erg s−1 for the outer cavity. [ABSTRACT FROM AUTHOR]

We present multiwavelength imaging observations of PKS 1045−188, 8C 1849+670, and PKS 2216−038, three radio-loud active galactic nuclei from the MOJAVE-Chandra Sample that straddle the Fanaroff-Riley (FR) boundary between low- and high-power jets. These hybrid sources provide an excellent opportunity to study jet emission mechanisms and the influence of the external environment. We used archival VLA observations, and new Hubble and Chandra observations to identify and study the spectral properties of five knots in PKS 1045−188, two knots in 8C 1849+670, and three knots in PKS 2216−038. For the seven X-ray visible knots, we constructed and fit the broadband spectra using synchrotron and inverse Compton/cosmic microwave background (IC/CMB) emission models. In all cases, we found that the lack of detected optical emission ruled out the X-ray emission from the same electron population that produces radio emission. All three sources have high total extended radio power, similar to that of FR II sources. We find this is in good agreement with previously studied hybrid sources, where high-power hybrid sources emit X-rays via IC/CMB and the low-power hybrid sources emit X-rays via synchrotron emission. This supports the idea that it is total radio power rather than FR morphology that determines the X-ray emission mechanism. We found no significant asymmetries in the diffuse X-ray emission surrounding the host galaxies. Sources PKS 1045−188 and 8C 1849+670 show significant differences in their radio and X-ray termination points, which may result from the deceleration of highly relativistic bulk motion. [ABSTRACT FROM AUTHOR]

Ocular graft versus host disease (OGvHD) develops after allogeneic hematopoietic stem cell transplantation (HSCT) and manifests as ocular surface inflammatory disease. This study evaluated the efficacy of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) to inhibit OGvHD. A major histocompatibility mismatch chronic OGvHD murine model was evaluated. 7 days after HSCT, mice were dosed subconjunctivally with scAAV8-HLA-G1/5 (1 x 10 9 vg/eye), topical cyclosporine (twice daily), or left untreated. Body weights and tear production (red thread test) were recorded, and eyelid, corneal opacity, and corneal fluorescein retention were scored through day 44 after HSCT. Tissues were collected for vector biodistribution, ocular histology, and immunofluorescence. Compared with untreated HSCT eyes, those dosed with scAAV8-HLA-G1/5 had significantly reduced clinical inflammatory signs of OGvHD. On histology, eyes that received scAAV8-HLA-G1/5 or cyclosporine had a significantly lower mean limbal mononuclear cell count when compared with non-treated HSCT eyes. HLA-G immunofluorescence was detected in the subconjunctiva and peripheral cornea in HSCT animals treated with scAAV8-HLA-G1/5. Vector genomes were detected in the lacrimal gland, but not in the other tested organs. These results provide evidence that subconjunctival AAV targets ocular surface and corneal disease and support that HLA-G-based gene therapy may be an effective treatment for OGvHD., Competing Interests: M.L.H. and B.C.G. are coinventors of the AAV-HLA-G technology evaluated herein and are listed on a patent (pending) that is owned by the University of North Carolina and North Carolina State University. M.L.H. and B.C.G. are co-founders of Astro Therapeutics (which has licensed the HLA-G technology evaluated herein) and co-founders of Bedrock Therapeutics., (© 2023 The Author(s).)

Animal faecal contamination of surface waters poses a human health risk, as they may contain pathogenic bacteria or viruses. Of the numerous animal species residing along surface waterways in Australia, macropod species are a top contributor to wild animals' faecal pollution load. We characterised the gut microbiota of 30 native Australian Eastern Grey Kangaroos from six geographical regions (five kangaroos from each region) within South East Queensland in order to establish their bacterial diversity and identify potential novel species-specific bacteria for the rapid detection of faecal contamination of surface waters by these animals. Using three hypervariable regions (HVRs) of the 16S rRNA gene (i.e., V1-V3, V3-V4, and V5-V6), for their effectiveness in delineating the gut microbial diversity, faecal samples from each region were pooled and microbial genomic DNA was extracted, sequenced, and analysed. Results indicated that V1-V3 yielded a higher taxa richness due to its larger target region (~480 bp); however, higher levels of unassigned taxa were observed using the V1-V3 region. In contrast, the V3-V4 HVR (~569 bp) attained a higher likelihood of a taxonomic hit identity to the bacterial species level, with a 5-fold decrease in unassigned taxa. There were distinct dissimilarities in beta diversity between the regions, with the V1-V3 region displaying the highest number of unique taxa ( n = 42), followed by V3-V4 ( n = 11) and V5-V6 ( n = 8). Variations in the gut microbial diversity profiles of kangaroos from different regions were also observed, which indicates that environmental factors may impact the microbial development and, thus, the composition of the gut microbiome of these animals.

Adherent-invasive Escherichia coli (AIEC) strains carry virulence genes (VGs) which are rarely found in strains other than E. coli . These strains are abundantly found in gut mucosa of patients with inflammatory bowel disease (IBD); however, it is not clear whether their prevalence in the gut is affected by the diet of the individual. Therefore, in this study, we compared the population structure of E. coli and the prevalence of AIEC as well as the composition of gut microbiota in fecal samples of healthy participants ( n = 61) on either a vegan ( n = 34) or omnivore ( n = 27) diet to determine whether diet is associated with the presence of AIEC. From each participant, 28 colonies of E. coli were typed using Random Amplified Polymorphic DNA (RAPD)-PCR. A representative of each common type within an individual was tested for the presence of six AIEC-associated VGs. Whole genomic DNA of the gut microbiota was also analyzed for its diversity profiles, utilizing the V5-V6 region of the16S rRNA gene sequence. There were no significant differences in the abundance and diversity of E. coli between the two diet groups. The occurrence of AIEC-associated VGs was also similar among the two groups. However, the diversity of fecal microbiota in vegans was generally higher than omnivores, with Prevotella and Bacteroides dominant in both groups. Whilst 88 microbial taxa were present in both diet groups, 28 taxa were unique to vegans, compared to seven unique taxa in the omnivores. Our results indicate that a vegan diet may not affect the number and diversity of E. coli populations and AIEC prevalence compared to omnivores. The dominance of Prevotella and Bacteroides among omnivores might be accounted for the effect of diet in these groups.

Hexadentate bis(amidines) form versatile networks of hydrogen bonds both in solid state and solution, as revealed by X-ray crystallography, IR, and NMR spectroscopy. Moreover, the corresponding bis(amidinates) produce blue and green emissions in THF solution. Tethered tetradentate bis(amidines) have emerged in coordination chemistry, enantioselective catalysis, as building blocks for polyfunctional heterocycles, and in photoluminescent materials. The next generation of flexible bis(amidine)/bis(amidinate) platforms with up to six N -donor sites has now been established.

Despite the development of prominent theoretical models of goal motivation and its importance in daily life, research has rarely examined goal dysregulation processes in clinical depression. Here we aimed to investigate problematic aspects of goal regulation in clinically depressed adults, relative to controls. Depressed participants (n = 42) were recruited from two Improving Access to Psychological Therapy clinics in north-west England. Control participants (n = 51) were recruited from the same region. Participants generated personal approach goals (e.g., improve my marathon time) and avoidance goals (e.g., avoid getting upset over little things) and completed self-report measures of goal attainment likelihood and depressive symptoms. Participants also completed a measure of ease of disengagement from unattainable goals and re-engagement with new goals. Compared to controls, depressed participants reported fewer approach goals (but not more avoidance goals), rated their approach goal (rewarding) outcomes as less likely to happen and avoidance goal (threatening) outcomes as more likely to happen. Depressed participants also reported greater ease of disengagement from unattainable goals and more difficulty re-engaging with new goals than controls. Our findings extend current knowledge of the psychopathology of depression from a goal regulation perspective, suggesting that pessimism around goal pursuit accompanies fewer approach goal pursuits and a general tendency to disengage when difficulties are encountered., Competing Interests: The authors have declared that no competing interests exist.

Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales. The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas. Recent theory and simulations instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds--a departure from the 'hot mode' accretion model--although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z = 0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma. Under the right conditions, thermal instabilities produce a rain of cold clouds that fall towards the galaxy's centre, sustaining star formation amid a kiloparsec-scale molecular nebula that is found at its core. The observations show that these cold clouds also fuel black hole accretion, revealing 'shadows' cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole, which serves as a bright backlight. Corroborating evidence from prior observations of warmer atomic gas at extremely high spatial resolution, along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it.

Background: Important residency curricular elements, including scholarship, quality improvement (QI), and community health, often exist as independent components. We developed a curriculum to train residents to become community-responsive physicians that included longitudinal care at a community health center (CHC) with a unique community-partnered project (CPP). We evaluated outcomes of one CPP and delineated challenges in implementing the curriculum., Methods: After performing a needs assessment, the resident-CHC team designed a QI intervention to improve documentation of smoking status and cessation counseling. A chart review of 100 random patients assessed pre- and post-intervention documentation. Patient focus groups were held to guide the development of the final intervention, which included medical assistant (MA) education, appropriate patient education materials, and a visual communication system for MAs and providers. Curriculum evaluation via interviews with residency and community partners was done periodically throughout the 2-year process., Results: Focus group participants saw clinicians as a resource for quitting but did not want to talk about quitting at every visit. We reviewed 317 patient visits pre-QI intervention and 191 post-QI intervention. There were no significant changes in the percent of visits where smoking status was documented (82% versus 79%); however, smoking cessation counseling during office visits increased significantly (19% to 54%). Key challenges included academic-community communication and resident scheduling and availability., Conclusions: In this CPP curriculum, residents made a difference in practice outcomes, and ongoing attention to challenges assisted with the project's success, possibly enhancing residents' likelihood of incorporating QI and principles of community health into their future careers.

This paper examines the extent to which cognitive abilities relate to differences in trajectories for key economic outcomes as individuals move towards and through their retirement. We look at whether differences in baseline numeracy (measured in the English Longitudinal Study of Ageing in 2002) and broader cognitive ability predict the subsequent trajectories of outcomes such as wealth, retirement income and key dimensions of retirement expectations. Those with lower numeracy are shown to have different wealth trajectories both pre- and post-retirement than their more numerate counterparts, but the distributions of retirement expectations and net replacement rates are similar across numeracy groups.

Background & Aims: Linaclotide, a minimally absorbed, 14-amino acid peptide agonist of guanylate cyclase-C, has shown benefit in a proof-of-concept study for the treatment of patients with irritable bowel syndrome (IBS) with constipation (IBS-C). We assessed the efficacy and safety of linaclotide at a daily dose range of 75-600 μg in IBS-C., Methods: We performed a randomized, double-blind, multicenter, placebo-controlled study of 420 patients with IBS-C given oral linaclotide at doses of 75, 150, 300, or 600 μg or placebo once daily for 12 weeks. End points included change from baseline in daily bowel habits, daily abdominal symptoms, and weekly global assessments, in addition to responder criteria., Results: All doses of linaclotide significantly improved bowel habits, including frequency of spontaneous bowel movements and complete spontaneous bowel movements (primary end point), severity of straining, and stool consistency. Abdominal pain was significantly reduced from baseline, compared with placebo; mean changes in abdominal pain (assessed on a 5-point scale) from baseline were -0.71, -0.71, -0.90, and -0.86 for linaclotide doses of 75, 150, 300, and 600 μg, respectively, compared with -0.49 for placebo. Likewise, most doses of linaclotide significantly improved other abdominal symptoms, including discomfort and bloating, and global measures of IBS-C compared with placebo. Effects were observed within the first week and were sustained throughout 12 weeks of treatment. Except for diarrhea, the incidence of adverse events was similar between placebo and linaclotide groups., Conclusions: Linaclotide, across a wide range of doses, significantly improved symptoms of IBS-C, including abdominal pain and bowel symptoms. Diarrhea was the only dose-dependent adverse event and was usually of mild or moderate severity., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Thirty low-birthweight (less than 1500g) infants (15 with bronchopulmonary dysplasia (BPD), and 15 controls less than or equal to 5 days O2) and 15 fullterm controls were evaluated at 10 to 12 years of age. BPD children weighted less than fullterm children and had smaller head circumferences than either preterm or fullterm controls. They also had significantly more neurological abnormality than both control groups. BPD children and preterm controls had lower WISC-R arithmetic scores and lower Beery VMI scores, as well as greater need of resources and special education compared with fullterm controls. BPD survivors at 10 to 12 years of age continue to manifest sequelae related to their early pulmonary disease.