Point-counterpoint: Should we be performing metagenomic next-generation sequencing for infectious disease diagnosis in the clinical laboratory?

With established applications of next-generation sequencing in inherited diseases and oncology, clinical laboratories are evaluating the use of metagenomics for identification of infectious agents directly from patient samples, to aid in the diagnosis of infections. Metagenomic next-generation sequencing for infectious diseases promises an unbiased approach to detection of microbes that does not depend on growth in culture or the targeting of specific pathogens. However, the issues of contamination, interpretation of results, selection of databases used for analysis, and prediction of antimicrobial susceptibilities from sequencing data remain challenges. In this Point-Counterpoint, Steve Miller and Charles Chiu discuss the pros of using direct metagenomic sequencing, while Kyle Rodino and Melissa Miller argue for the use of caution

Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation

Ground-based observations of Saturn’s auroral ionosphere over three days:trends in H3+ temperature, density and emission with Saturn local time and planetary period oscillation

On 19–21 April 2013, the ground-based 10-m W.M. Keck II telescope was used to simultaneously measure View the MathML sourceH3+ emissions from four regions of Saturn’s auroral ionosphere: (1) the northern noon region of the main auroral oval; (2) the northern midnight main oval; (3) the northern polar cap and (4) the southern noon main oval. The View the MathML sourceH3+ emission from these regions was captured in the form of high resolution spectral images as the planet rotated. The results herein contain twenty-three View the MathML sourceH3+ temperatures, column densities and total emissions located in the aforementioned regions – ninety-two data points in total, spread over timescales of both hours and days. Thermospheric temperatures in the spring-time northern main oval are found to be cooler than their autumn-time southern counterparts by tens of K, consistent with the hypothesis that the total thermospheric heating rate is inversely proportional to magnetic field strength. The main oval View the MathML sourceH3+ density and emission is lower at northern midnight than it is at noon, in agreement with a nearby peak in the electron influx in the post-dawn sector and a minimum flux at midnight. Finally, when arranging the northern main oval View the MathML sourceH3+ parameters as a function of the oscillation period seen in Saturn’s magnetic field – the planetary period oscillation (PPO) phase – we see a large peak in View the MathML sourceH3+ density and emission at ∼115° northern phase, with a full-width at half-maximum (FWHM) of ∼44°. This seems to indicate that the influx of electrons associated with the PPO phase at 90° is responsible at least in part for the behavior of all View the MathML sourceH3+ parameters. A combination of the View the MathML sourceH3+ production and loss timescales and the ±10° uncertainty in the location of a given PPO phase are likely, at least in part, to be responsible for the observed peaks in View the MathML sourceH3+ density and emission occurring at a later time than the peak precipitation expected at 90° PPO phase

Anti-Nirvana: crime, culture and instrumentalism in the age of insecurity

‘Anti-Nirvana’ explores the relationship between consumer culture, media and criminal motivations. It has appeared consistently on the list of the top-ten most-read articles in this award-winning international journal, and it mounts a serious neo-Freudian challenge to the predominant naturalistic notion of ‘resistance’ at the heart of liberal criminology and media studies. It is also cited in the Oxford Handbook of Criminology and other criminology texts as a persuasive argument in support of the theory that criminality amongst young people is strongly linked to the acquisitive values of consumerism and the images of possessive individualism that dominate mass media

Processing Images from the Zwicky Transient Facility

The Zwicky Transient Facility is a new robotic-observing program, in which a newly engineered 600-MP digital camera with a pioneeringly large field of view, 47~square degrees, will be installed into the 48-inch Samuel Oschin Telescope at the Palomar Observatory. The camera will generate $\sim 1$~petabyte of raw image data over three years of operations. In parallel related work, new hardware and software systems are being developed to process these data in real time and build a long-term archive for the processed products. The first public release of archived products is planned for early 2019, which will include processed images and astronomical-source catalogs of the northern sky in the $g$ and $r$ bands. Source catalogs based on two different methods will be generated for the archive: aperture photometry and point-spread-function fitting.Comment: 6 pages, 4 figures, submitted to RTSRE Proceedings (www.rtsre.org

Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock

AbstractIn mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed ∼650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology

Hydrodynamic Hunters

The Gram-negative Bdellovibrio bacteriovorus (BV) is a model bacterial predator that hunts other bacteria and may serve as a living antibiotic. Despite over 50 years since its discovery, it is suggested that BV probably collides into its prey at random. It remains unclear to what degree, if any, BV uses chemical cues to target its prey. The targeted search problem by the predator for its prey in three dimensions is a difficult problem: it requires the predator to sensitively detect prey and forecast its mobile prey’s future position on the basis of previously detected signal. Here instead we find that rather than chemically detecting prey, hydrodynamics forces BV into regions high in prey density, thereby improving its odds of a chance collision with prey and ultimately reducing BV’s search space for prey. We do so by showing that BV’s dynamics are strongly influenced by self-generated hydrodynamic flow fields forcing BV onto surfaces and, for large enough defects on surfaces, forcing BV in orbital motion around these defects. Key experimental controls and calculations recapitulate the hydrodynamic origin of these behaviors. While BV’s prey (Escherichia coli) are too small to trap BV in hydrodynamic orbit, the prey are also susceptible to their own hydrodynamic fields, substantially confining them to surfaces and defects where mobile predator and prey density is now dramatically enhanced. Colocalization, driven by hydrodynamics, ultimately reduces BV’s search space for prey from three to two dimensions (on surfaces) even down to a single dimension (around defects). We conclude that BV’s search for individual prey remains random, as suggested in the literature, but confined, however—by generic hydrodynamic forces—to reduced dimensionality

HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

<p>Abstract</p> <p>Background</p> <p>The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.</p> <p>Methods</p> <p>HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.</p> <p>Results</p> <p>Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.</p> <p>Conclusion</p> <p>HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.</p

Designing a complex intervention for dementia case management in primary care

Background: Community-based support will become increasingly important for people with dementia, but currently services are fragmented and the quality of care is variable. Case management is a popular approach to care co-ordination, but evidence to date on its effectiveness in dementia has been equivocal. Case management interventions need to be designed to overcome obstacles to care co-ordination and maximise benefit. A successful case management methodology was adapted from the United States (US) version for use in English primary care, with a view to a definitive trial. Medical Research Council guidance on the development of complex interventions was implemented in the adaptation process, to capture the skill sets, person characteristics and learning needs of primary care based case managers. Methods: Co-design of the case manager role in a single NHS provider organisation, with external peer review by professionals and carers, in an iterative technology development process. Results: The generic skills and personal attributes were described for practice nurses taking up the case manager role in their workplaces, and for social workers seconded to general practice teams, together with a method of assessing their learning needs. A manual of information material for people with dementia and their family carers was also created using the US intervention as its source. Conclusions: Co-design produces rich products that have face validity and map onto the complexities of dementia and of health and care services. The feasibility of the case manager role, as described and defined by this process, needs evaluation in ‘real life’ settings