Interaction between the intergalactic medium and central radio source in the NGC 4261 group of galaxies

Using observations from the Chandra and XMM-Newton X-ray observatories, we examine the interaction between the intra-group medium and central radio source in the nearby NGC 4261 galaxy group. We confirm the presence of cavities associated with the radio lobes and estimate their enthalpy to be ~2.4x10^58 erg. The mechanical power output of the jets is >=10^43 erg/s, at least a factor of 60 greater than the cooling luminosity in the region the lobes inhabit. We identify rims of compressed gas enclosing the lobes, but find no statistically significant temperature difference between them and their surroundings, suggesting that the lobe expansion velocity is approximately sonic (Mach<=1.05). The apparent pressure of the radio lobes, based on the synchrotron minimum energy density argument, is a factor of 5 lower than that of the intra-group medium. Pressure balance could be achieved if entrainment of thermal gas provided additional non-radiating particles in the lobe plasma, but the energy required to heat these particles would be ~20 per cent. of the mechanical energy output of the radio source. NGC 4261 has a relatively compact cool core, which should probably be categorised as a galactic corona. The corona is capable of fuelling the active nucleus for considerably longer than the inferred source lifetime, but can be only inefficiently heated by the AGN or conduction. The expansion of the radio lobes has affected the structure of the gas in the galaxy, compressing and moving the material of the corona without causing significant shock heating, and expelling gas from the immediate neighbourhood of the jets. We discuss the possible implications of this environment for the duration of the AGN outburst, and consider mechanisms which might lead to the cessation of nuclear activity.Comment: Accepted for publication in MNRAS, 17 pages, 6 figure

New insights into the evolution of the FR I radio galaxy 3C 270 (NGC 4261) from VLA and GMRT radio observations

We present Giant Metrewave Radio Telescope (GMRT) 240 MHz observations of the nearby luminous FR I radio source 3C 270, in the group-central elliptical NGC 4261. Combining these data with reprocessed Very Large Array (VLA) 1.55 and 4.8 GHz observations, we produce spectral index maps that reveal a constant spectral index along the jets and a gradual steepening from the ends of the jets through the lobes towards the nucleus. A Jaffe & Perola (JP) model fitted to the integrated spectrum of the source gives an asymptotic low-frequency index of $\alpha_{inj}=0.53_{-0.02}^{+0.01}$, while JP models fitted to the observed spectral index trend along the lobes allow us to estimate radiative ages of $\sim29$ Myr and $\sim37$ Myr for the west and east lobes respectively. Our age estimates are a factor of two lower than the 75-Myr upper limit derived from X-ray data (O'Sullivan et al. 2011). We find unlikely the scenario of an early supersonic phase in which the lobe expanded into the ISM at approximately Mach 6 (3500 km s$^{-1}$), and suggest that either the source underwent multiple AGN outbursts with possible large changes in jet power, or possibly that the source age that we find is due to a backflow that transports young electrons from the jet tips through the lobes toward the nucleus relatively quickly. We calculate that in the lobes the energy ratio of non-radiating to radiating particles is $\sim4-24$ indicating significant gas entrainment. If the lobes are in pressure balance with their surroundings, the total energy required to heat the entrained material is $10^{58}$ erg, $\sim$40% of the total enthalpy of the lobes.Comment: 14 pages, 11 figures, 8 tables. Accepted for publication by MNRAS. Revised throughout in response to referee's comment

Evidence of AGN feedback and sloshing in the X-ray luminous NGC 1550 galaxy group

We present results from GMRT and Chandra observations of the NGC 1550 galaxy group. Although previously thought of as relaxed, we show evidence that gas sloshing and active galactic nucleus (AGN) heating have affected the structure of the system. The 610 and 235 MHz radio images show an asymmetric jet-lobe structure with a total size of $\sim$33 kpc, with a sharp kink at the base of the more extended western jet, and bending of the shorter eastern jet as it enters the lobe. The 235$-$610 MHz spectral index map shows that both radio lobes have steep spectral indices ($\alpha_{235}^{610}\geq-1.5$) indicating the presence of an old electron population. The X-ray images reveal an asymmetric structure in the hot gas correlated with the radio structure, as well as potential cavities coincident with the radio lobes, with rims and arms of gas that may have been uplifted by the cavity expansion. The X-ray residual map reveals an arc shaped structure to the east that resembles a sloshing cold front. Radio spectral analysis suggests a radiative age of about 33 Myr for the source, comparable to the sloshing timescale and dynamical estimates of the age of the lobes. An estimate of the mechanical energy required to inflate the cavities suggests that the AGN of NGC 1550 is capable of balancing radiative losses from the intragroup medium (IGM) and preventing excessive cooling, providing that the AGN jets are efficiently coupled to the IGM gas. In conclusion, we find evidence of sloshing motions from both radio and X-ray structures, suggesting that NGC 1550 was perturbed by a minor merger or infalling galaxy about 33 Myr ago.Comment: Accepted for publication in MNRAS, 17 pages with 13 figures and 10 table

Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs

BACKGROUND: Mycobacterium tuberculosis resistance to anti-tuberculosis drugs is a major threat to global public health. Whole genome sequencing (WGS) is rapidly gaining traction as a diagnostic tool for clinical tuberculosis settings. To support this informatically, previous work led to the development of the widely used TBProfiler webtool, which predicts resistance to 14 drugs from WGS data. However, for accurate and rapid high throughput of samples in clinical or epidemiological settings, there is a need for a stand-alone tool and the ability to analyse data across multiple WGS platforms, including Oxford Nanopore MinION. RESULTS: We present a new command line version of the TBProfiler webserver, which includes hetero-resistance calling and will facilitate the batch processing of samples. The TBProfiler database has been expanded to incorporate 178 new markers across 16 anti-tuberculosis drugs. The predictive performance of the mutation library has been assessed using > 17,000 clinical isolates with WGS and laboratory-based drug susceptibility testing (DST) data. An integrated MinION analysis pipeline was assessed by performing WGS on 34 replicates across 3 multi-drug resistant isolates with known resistance mutations. TBProfiler accuracy varied by individual drug. Assuming DST as the gold standard, sensitivities for detecting multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were 94% (95%CI 93-95%) and 83% (95%CI 79-87%) with specificities of 98% (95%CI 98-99%) and 96% (95%CI 95-97%) respectively. Using MinION data, only one resistance mutation was missed by TBProfiler, involving an insertion in the tlyA gene coding for capreomycin resistance. When compared to alternative platforms (e.g. Mykrobe predictor TB, the CRyPTIC library), TBProfiler demonstrated superior predictive performance across first- and second-line drugs. CONCLUSIONS: The new version of TBProfiler can rapidly and accurately predict anti-TB drug resistance profiles across large numbers of samples with WGS data. The computing architecture allows for the ability to modify the core bioinformatic pipelines and outputs, including the analysis of WGS data sourced from portable technologies. TBProfiler has the potential to be integrated into the point of care and WGS diagnostic environments, including in resource-poor settings

Learning while evaluating: the use of an electronic evaluation portfolio in a geriatric medicine clerkship

BACKGROUND: Electronic evaluation portfolios may play a role in learning and evaluation in clinical settings and may complement other traditional evaluation methods (bedside evaluations, written exams and tutor-led evaluations). METHODS: 133 third-year medical students used the McGill Electronic Evaluation Portfolio (MEEP) during their one-month clerkship rotation in Geriatric Medicine between September 2002 and September 2003. Students were divided into two groups, one who received an introductory hands-on session about the electronic evaluation portfolio and one who did not. Students' marks in their portfolios were compared between both groups. Additionally, students self-evaluated their performance and received feedback using the electronic portfolio during their mandatory clerkship rotation. Students were surveyed immediately after the rotation and at the end of the clerkship year. Tutors' opinions about this method were surveyed once. Finally, the number of evaluations/month was quantified. In all surveys, Likert scales were used and were analyzed using Chi-square tests and t-tests to assess significant differences in the responses from surveyed subjects. RESULTS: The introductory session had a significant effect on students' portfolio marks as well as on their comfort using the system. Both tutors and students reported positive notions about the method. Remarkably, an average (± SD) of 520 (± 70) evaluations/month was recorded with 30 (± 5) evaluations per student/month. CONCLUSION: The MEEP showed a significant and positive effect on both students' self-evaluations and tutors' evaluations involving an important amount of self-reflection and feedback which may complement the more traditional evaluation methods

Electrochemical Detection of Single-Nucleotide Polymorphism Associated with Rifampicin Resistance in Mycobacterium tuberculosis Using Solid-Phase Primer Elongation with Ferrocene-Linked Redox-Labeled Nucleotides.

Here, we report the electrochemical detection of single-point mutations using solid-phase isothermal primer elongation with redox-labeled oligonucleotides. A single-base mutation associated with resistance to rifampicin, an antibiotic commonly used for the treatment of Mycobacterium tuberculosis, was used as a model system to demonstrate a proof-of-concept of the approach. Four 5'-thiolated primers, designed to be complementary with the same fragment of the target sequence and differing only in the last base, addressing the polymorphic site, were self-assembled via chemisorption on individual gold electrodes of an array. Following hybridization with single-stranded DNA, Klenow (exo-) DNA polymerase-mediated primer extension with ferrocene-labeled 2'-deoxyribonucleoside triphosphates (dNFcTPs) was only observed to proceed at the electrode where there was full complementarity between the surface-tethered probe and the target DNA being interrogated. We tested all four ferrocenylethynyl-linked dNTPs and optimized the ratio of labeled/natural nucleotides to achieve maximum sensitivity. Following a 20 min hybridization step, Klenow (exo-) DNA polymerase-mediated primer elongation at 37 °C for 5 min was optimal for the enzymatic incorporation of a ferrocene-labeled nucleotide, achieving unequivocal electrochemical detection of a single-point mutation in 14 samples of genomic DNA extracted from Mycobacterium tuberculosis strains. The approach is rapid, cost-effective, facile, and can be extended to multiplexed electrochemical single-point mutation genotyping

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TO

Costs and effects of a 'healthy living' approach to community development in two deprived communities: findings from a mixed methods study

Background: Inequalities in health have proved resistant to 'top down' approaches. It is increasingly recognised that health promotion initiatives are unlikely to succeed without strong local involvement at all stages of the process and many programmes now use grass roots approaches. A healthy living approach to community development (HLA) was developed as an innovative response to local concerns about a lack of appropriate services in two deprived communities in Pembrokeshire, West Wales. We sought to assess feasibility, costs, benefits and working relationships of this HLA. Methods: The HLA intervention operated through existing community forums and focused on the whole community and its relationship with statutory and voluntary sectors. Local people were trained as community researchers and gathered views about local needs though resident interviews. Forums used interview results to write action plans, disseminated to commissioning organisations. The process was supported throughout through the project. The evaluation used a multi-method before and after study design including process and outcome formative and summative evaluation; data gathered through documentary evidence, diaries and reflective accounts, semi-structured interviews, focus groups and costing proformas. Main outcome measures were processes and timelines of implementation of HLA; self reported impact on communities and participants; community-agency processes of liaison; costs. Results: Communities were able to produce and disseminate action plans based on locally-identified needs. The process was slower than anticipated: few community changes had occurred but expectations were high. Community participants gained skills and confidence. Cross-sector partnership working developed. The process had credibility within service provider organisations but mechanisms for refocusing commissioning were patchy. Intervention costs averaged £58,304 per community per annum. Conclusions: The intervention was feasible and inexpensive, with indications of potential impact at individual, community and policy planning levels. However, it is a long term process which requires sustained investment and must be embedded in planning and service delivery processes.12 page(s

In vitro enamel thickness measurements with ultrasound

In the work described here, agreement between ultrasound and histologic measurements of enamel thickness in vitro was investigated. Fifteen extracted human premolars were sectioned coronally to produce 30 sections. The enamel thickness of each specimen was measured with a 15-MHz hand-held ultrasound probe and verified with histology. The speed of sound in enamel was established. Bland–Altman analysis, intra-class correlation coefficient and Wilcoxon sign rank test were used to assess agreement. The mean speed of sound in enamel was 6191 ± 199 m s−1. Bland–Altman limits of agreement were −0.16 to 0.18 mm when the speed of sound for each specimen was used, and −0.17 to 0.21 mm when the mean speed of sound was used. Intra-class correlation coefficient agreement was 0.97, and the Wilcoxon sign rank test yielded a p-value of 0.55. Using the speed of sound for each specimen results in more accurate measurement of enamel thickness. Ultrasound measurements were in good agreement with histology, which highlights its potential for monitoring the progressive loss of enamel thickness in erosive tooth surface loss