WALLABY Early Science - I. The NGC 7162 Galaxy Group

We present Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY) early science results from the Australian Square Kilometre Array Pathfinder (ASKAP) observations of the NGC 7162 galaxy group. We use archival HIPASS and Australia Telescope Compact Array (ATCA) observations of this group to validate the new ASKAP data and the data reduction pipeline ASKAPsoft. We detect six galaxies in the neutral hydrogen (HI) 21-cm line, expanding the NGC 7162 group membership from four to seven galaxies. Two of the new detections are also the first HI detections of the dwarf galaxies, AM 2159-434 and GALEXASC J220338.65-431128.7, for which we have measured velocities of $cz=2558$ and $cz=2727$ km s$^{-1}$, respectively. We confirm that there is extended HI emission around NGC 7162 possibly due to past interactions in the group as indicated by the $40^{\circ}$ offset between the kinematic and morphological major axes for NGC 7162A, and its HI richness. Taking advantage of the increased resolution (factor of $\sim1.5$) of the ASKAP data over archival ATCA observations, we fit a tilted ring model and use envelope tracing to determine the galaxies' rotation curves. Using these we estimate the dynamical masses and find, as expected, high dark matter fractions of $f_{\mathrm{DM}}\sim0.81-0.95$ for all group members. The ASKAP data are publicly available.Comment: 20 pages, 11 figures, accepted for publication in MNRA

The impact of opiate substitution treatment on mortality risk in drug addicts: a natural experiment study

Background Opiate substitution treatment (OST) is the main treatment for people addicted to heroin and other opioid drugs. However, there is limited information on how the delivery of this treatment affects mortality risk.Objectives To investigate the associations of mortality risk with periods during treatment and following cessation of treatment, medication type, co-prescription of other medication and dosing regimens during titration and detoxification. The trends with time of prescribed medication, dose and treatment duration were also explored.Design Prospective longitudinal observational study.Setting UK primary care between 1998 and 2014.Participants A total of 12,780 patients receiving methadone, buprenorphine or dihydrocodeine.Main outcome measures All-cause mortality relating to 657 deaths and drug-related poisoning relating to 113 deaths.Data sources Clinical Practice Research Datalink with linked information on cause of death from the Office for National Statistics.Results For both outcomes, the lowest mortality risk was observed after 4 weeks of treatment and the highest risk was observed in the first 4 weeks following cessation of treatment [e.g. for drug-related poisoning, incidence rate ratio (IRR) 8.15, 95% confidence interval (CI) 5.45 to 12.19]. There was evidence that the treatment period risks varied with OST medication. The largest difference in risk was for the first 4 weeks of treatment for both outcomes, with patients on buprenorphine being at lower risk than those on methadone (e.g. for drug-related poisoning, IRR 0.08, 95% CI 0.01 to 0.48). The co-prescription of benzodiazepines was associated with linearly increasing the risk of drug-related deaths by dose (IRR 2.02, 95% CI 1.66 to 2.47), whereas z-drugs (zolpidem, zopiclone and zaleplon) were associated with increased risk of both all-cause (IRR 1.83, 95% CI 1.59 to 2.12) and drug-related (IRR 3.31, 95% CI 2.45 to 4.47) mortality. There was weak evidence that higher initial and final doses were associated with increased all-cause mortality risk. In the first 4 weeks of treatment, the risk increased by 4% for each 5-mg increment in methadone dose (1-mg increase in buprenorphine) (hazard ratio 1.04, 95% CI 1.00 to 1.09). In the first 4 weeks after treatment ceased, a similar increment in final dose increased the risk by 3% (hazard ratio 1.03, 95% CI 0.99 to 1.07). There were too few deaths to evaluate the effects on drug-related poisoning. The proportion of OST patients receiving buprenorphine increased between 1998 and 2006. Median treatment duration was consistently shorter for buprenorphine than for methadone for each year studied (overall median duration of 48 and 106 days, respectively).Limitations As this was an observational study, the possibility remains of bias from unmeasured factors, which covariate adjustment and inverse probability weighting can eliminate only partially.Conclusions Using buprenorphine as an alternative to methadone may not reduce mortality overall despite resulting in lower IRRs from shorter treatment duration. Clinical guidance needs to consider strengthening warnings about the co-prescription of a range of drugs for OST patients.Future work Our analyses need to be replicated using other clinical data sets in the UK and in other countries. New interventions and trials are required to investigate improving the retention of OST patients in primary care.Funding The National Institute for Health Research Health Services and Delivery Research programme

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50

We present dynamical modeling of the broad line region (BLR) in the Seyfert 1 galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN Monitoring Project (LAMP) 2011. We model the reverberation mapping data directly, constraining the geometry and kinematics of the BLR, as well as deriving a black hole mass estimate that does not depend on a normalizing factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of 25\pm10 degrees above the plane. We also constrain the inclination angle to be 9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the virial black hole mass estimate from traditional reverberation mapping analysis, we find the normalizing constant (virial coefficient) to be log10(f) = 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74 based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies. While our dynamical model includes the possibility of a net inflow or outflow in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure

Antibiotic susceptibilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 mu g ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung

Effects of home-based EEG neurofeedback training as a non-pharmacological intervention for Parkinson's disease

Objectives Aberrant movement-related cortical activity has been linked to impaired motor function in Parkinson's disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. Effective non-pharmacological treatments could help reduce reliance on drugs. This experiment reports the first study of home-based electroencephalographic (EEG) neurofeedback training as a non-pharmacological candidate treatment for PD. Our primary aim was to test the feasibility of our EEG neurofeedback intervention in a home setting. Methods Sixteen people with PD received six home visits comprising symptomology self-reports, a standardised motor assessment, and a precision handgrip force production task while EEG was recorded (visits 1, 2 and 6); and 3 × 1-hr EEG neurofeedback training sessions to supress the EEG mu rhythm before initiating handgrip movements (visits 3 to 5). Results Participants successfully learned to self-regulate mu activity, and this appeared to expedite the initiation of precision movements (i.e., time to reach target handgrip force off-medication pre-intervention = 628 ms, off-medication post-intervention = 564 ms). There was no evidence of wider symptomology reduction (e.g., Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III Motor Examination, off-medication pre-intervention = 29.00, off-medication post intervention = 30.07). Interviews indicated that the intervention was well-received. Conclusion Based on the significant effect of neurofeedback on movement-related cortical activity, positive qualitative reports from participants, and a suggestive benefit to movement initiation, we conclude that home-based neurofeedback for people with PD is a feasible and promising non-pharmacological treatment that warrants further research

The selection landscape and genetic legacy of ancient Eurasians

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans

Improving our understanding of the in vivo modelling of psychotic disorders: a systematic review and meta-analysis

Psychotic disorders represent a severe category of mental disorders affecting about one percent of the population. Individuals experience a loss or distortion of contact with reality alongside other symptoms, many of which are still not adequately managed using existing treatments. While animal models of these disorders could offer insights into these disorders and potential new treatments, translation of this knowledge has so far been poor in terms of informing clinical trials and practice. The aim of this project was to improve our understanding of these pre-clinical studies and identify potential weaknesses underlying translational failure. I carried out a systematic search of the literature to provide an unbiased summary of publications reporting animal models of schizophrenia and other psychotic disorders. From these publications, data were extracted to quantify aspects of the field including reported quality of studies, study characteristics and behavioural outcome data. The latter of these data were then used to calculate estimates of efficacy using random-effects meta-analysis. Having identified 3847 publications of relevance, including 852 different methods used to induce the model, over 359 different outcomes tested in them and almost 946 different treatments reported to be administered. I show that a large proportion of studies use simple pharmacological interventions to induce their models of these disorders, despite the availability of models using other interventions that are arguably of higher translational relevance. I also show that the reported quality of these studies is low, and only 22% of studies report taking measures to reduce the risk of biases such as randomisation and blinding, which has been shown to affect the reliability of results drawn. Through this work it becomes apparent that the literature is incredibly vast for studies looking at animal models of psychotic disorders and that some of the relevant work potentially overlaps with studies describing other conditions. This means that drawing reliable conclusions from these data is affected by what is made available in the literature, how it is reported and identified in a search and the time that it takes to reach these conclusions. I introduce the idea of using computer-assisted tools to overcome one of these problems in the long term. Translation of results from studies looking at animals modelling uniquely-human psychotic disorders to clinical successes might be improved by better reporting of studies including publishing of all work carried out, labelling of studies more uniformly so that it is identifiable, better reporting of study design including improving on reporting of measures taken to reduce the risk of bias and focusing on models with greater validity to the human condition

Pneumococcal Capsular Polysaccharide Structure Predicts Serotype Prevalence

There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement

WALLABY early science – I. The NGC 7162 galaxy group

We present Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY) early science results from the Australian Square Kilometre Array Pathfinder (ASKAP) observations of the NGC 7162 galaxy group. We use archival HIPASS and Australia Telescope Compact Array (ATCA) observations of this group to validate the new ASKAP data and the data reduction pipeline ASKAP soft. We detect six galaxies in the neutral hydrogen (H i) 21-cm line, expanding the NGC 7162 group membership from four to seven galaxies. Two of the new detections are also the first H i detections of the dwarf galaxies, AM 2159-434 and GALEXASC J220338.65-431128.7, for which we have measured velocities of cz = 2558 and cz = 2727 km s−1, respectively. We confirm that there is extended H i emission around NGC 7162 possibly due to past interactions in the group as indicated by the 40° offset between the kinematic and morphological major axes for NGC 7162A, and its H i richness. Taking advantage of the increased resolution (factor of ∼1.5) of the ASKAP data over archival ATCA observations, we fit a tilted ring model and use envelope tracing to determine the galaxies’ rotation curves. Using these we estimate the dynamical masses and find, as expected, high dark matter fractions of fDM ∼ 0.81−0.95 for all group members. The ASKAP data are publicly available.Publisher PDFPeer reviewe

Ecological compatibility of GM crops and biological control

Insect-resistant and herbicide-tolerant genetically modified (GM) crops pervade many modern cropping systems (especially field-cropping systems), and present challenges and opportunities for developing biologically based pest-management programs. Interactions between biological control agents (insect predators, parasitoids, and pathogens) and GM crops exceed simple toxicological relationships, a priority for assessing risk of GM crops to non-target species. To determine the compatibility of biological control and insect-resistant and herbicide-tolerant GM crop traits within integrated pest-management programs, this synthesis prioritizes understanding the bi-trophic and prey/host-mediated ecological pathways through which natural enemies interact within cropland communities, and how GM crops alter the agroecosystems in which natural enemies live. Insect-resistant crops can affect the quantity and quality of non-prey foods for natural enemies, as well as the availability and quality of both target and non-target pests that serve as prey/hosts. When they are used to locally eradicate weeds, herbicide-tolerant crops alter the agricultural landscape by reducing or changing the remaining vegetational diversity. This vegetational diversity is fundamental to biological control when it serves as a source of habitat and nutritional resources. Some inherent qualities of both biological control and GM crops provide opportunities to improve upon sustainable IPM systems. For example, biological control agents may delay the evolution of pest resistance to GM crops, and suppress outbreaks of secondary pests not targeted by GM plants, while herbicide-tolerant crops facilitate within-field management of vegetational diversity that can enhance the efficacy of biological control agents. By examining the ecological compatibility of biological control and GM crops, and employing them within an IPM framework, the sustainability and profitability of farming may be improved