Targeted Disruption of Toxoplasma gondii Serine Protease Inhibitor 1 Increases Bradyzoite Cyst Formation In Vitro and Parasite Tissue Burden in Mice

As an intracellular protozoan parasite, Toxoplasma gondii is likely to exploit proteases for host cell invasion, acquisition of nutrients, avoidance of host protective responses, escape from the parasitophorous vacuole, differentiation, and other activities. T. gondii serine protease inhibitor 1 (TgPI1) is the most abundantly expressed protease inhibitor in parasite tachyzoites. We show here that alternative splicing produces two TgPI1 isoforms, both of which are secreted via dense granules into the parasitophorous vacuole shortly after invasion, become progressively more abundant over the course of the infectious cycle, and can be detected in the infected host cell cytoplasm. To investigate TgPI1 function, the endogenous genomic locus was disrupted in the RH strain background. ΔTgPI1 parasites replicate normally as tachyzoites but exhibit increased bradyzoite gene transcription and labeling of vacuoles with Dolichos biflorus lectin under conditions promoting in vitro differentiation. The differentiation phenotype can be partially complemented by either TgPI1 isoform. Mice infected with the ΔTgPI1 mutant display ∼3-fold-increased parasite burden in the spleen and liver, and this in vivo phenotype is also complemented by either TgPI1 isoform. These results demonstrate that TgPI1 influences both parasite virulence and bradyzoite differentiation, presumably by inhibiting parasite and/or host serine proteases

Capturing Saddam Hussein: How the full story got away, and what conflict journalism can learn from it

The capture of Saddam Hussein in December 2003 was reported with a sense of triumph which must have greatly satisfied the United States forces occupying Iraq. This was the victory they had been looking for; the seminal moment which signalled that the invasion had been a success. But the reporting of that event was also a missed opportunity: an example of incomplete story telling. In this article, I use my personal experience of reporting on the event for the BBC as a starting point to examine what it, and the way it was covered, tell us about the omissions which are frequently a feature of conflict reporting. The article argues that the way in which reporters had to work in Iraq then meant that they did not convey all of the event’s wider implications, and suggests how that might be improved

Macroscopic Quantum Fluctuations in the Josephson Dynamics of Two Weakly Linked Bose-Einstein Condensates

We study the quantum corrections to the Gross-Pitaevskii equation for two weakly linked Bose-Einstein condensates. The goals are: 1) to investigate dynamical regimes at the borderline between the classical and quantum behaviour of the bosonic field; 2) to search for new macroscopic quantum coherence phenomena not observable with other superfluid/superconducting systems. Quantum fluctuations renormalize the classical Josephson oscillation frequencies. Large amplitude phase oscillations are modulated, exhibiting collapses and revivals. We describe a new inter-well oscillation mode, with a vanishing (ensemble averaged) mean value of the observables, but with oscillating mean square fluctuations. Increasing the number of condensate atoms, we recover the classical Gross-Pitaevskii (Josephson) dynamics, without invoking the symmetry-breaking of the Gauge invariance.Comment: Submitte

The XMM-Newton serendipitous ultraviolet source survey catalogue

The XMM-Newton Serendipitous Ultraviolet Source Survey (XMM-SUSS) is a catalogue of ultraviolet (UV) sources detected serendipitously by the Optical Monitor (XMM-OM) on-board the XMM-Newton observatory. The catalogue contains ultraviolet-detected sources collected from 2,417 XMM-OM observations in 1-6 broad band UV and optical filters, made between 24 February 2000 and 29 March 2007. The primary contents of the catalogue are source positions, magnitudes and fluxes in 1 to 6 passbands, and these are accompanied by profile diagnostics and variability statistics. The XMM-SUSS is populated by 753,578 UV source detections above a 3 sigma signal-to-noise threshold limit which relate to 624,049 unique objects. Taking account of substantial overlaps between observations, the net sky area covered is 29-54 square degrees, depending on UV filter. The magnitude distributions peak at 20.2, 20.9 and 21.2 in UVW2, UVM2 and UVW1 respectively. More than 10 per cent of sources have been visited more than once using the same filter during XMM-Newton operation, and > 20 per cent of sources are observed more than once per filter during an individual visit. Consequently, the scope for science based on temporal source variability on timescales of hours to years is broad. By comparison with other astrophysical catalogues we test the accuracy of the source measurements and define the nature of the serendipitous UV XMM-OM source sample. The distributions of source colours in the UV and optical filters are shown together with the expected loci of stars and galaxies, and indicate that sources which are detected in multiple UV bands are predominantly star-forming galaxies and stars of type G or earlier.Comment: Accepted for publication in MNRA

A randomised controlled trial of patient led training in medical education: protocol

<p>Abstract</p> <p>Background</p> <p>Estimates suggest that approximately 1 in 10 patients admitted to hospital experience an adverse event resulting in harm. Methods to improve patient safety have concentrated on developing safer systems of care and promoting changes in professional behaviour. There is a growing international interest in the development of interventions that promote the role of patients preventing error, but limited evidence of effectiveness of such interventions. The present study aims to undertake a randomised controlled trial of patient-led teaching of junior doctors about patient safety.</p> <p>Methods/Design</p> <p>A randomised cluster controlled trial will be conducted. The intervention will be incorporated into the mandatory training of junior doctors training programme on patient safety. The study will be conducted in the Yorkshire and Humber region in the North of England. Patients who have experienced a safety incident in the NHS will be recruited. Patients will be identified through National Patient Safety Champions and local Trust contacts. Patients will receive training and be supported to talk to small groups of trainees about their experiences. The primary aim of the patient-led teaching module is to increase the awareness of patient safety issues amongst doctors, allow reflection on their own attitudes towards safety and promote an optimal culture among the doctors to improve safety in practice. A mixture of qualitative and quantitative methods will be used to evaluate the impact of the intervention, using the Attitudes to Patient Safety Questionnaire (APSQ) as our primary quantitative outcome, as well as focus groups and semi-structured interviews.</p> <p>Discussion</p> <p>The research team face a number of challenges in developing the intervention, including integrating a new method of teaching into an existing curriculum, facilitating effective patient involvement and identifying suitable outcome measures.</p> <p>Trial Registration</p> <p>Current controlled Trials: <a href="http://www.controlled-trials.com/ISRCTN94241579">ISRCTN94241579</a></p

The density and peculiar velocity fields of nearby galaxies

We review the quantitative science that can be and has been done with redshift and peculiar velocity surveys of galaxies in the nearby universe. After a brief background setting the cosmological context for this work, the first part of this review focuses on redshift surveys. The practical issues of how redshift surveys are carried out, and how one turns a distribution of galaxies into a smoothed density field, are discussed. Then follows a description of major redshift surveys that have been done, and the local cosmography out to 8,000 km/s that they have mapped. We then discuss in some detail the various quantitative cosmological tests that can be carried out with redshift data. The second half of this review concentrates on peculiar velocity studies, beginning with a thorough review of existing techniques. After discussing the various biases which plague peculiar velocity work, we survey quantitative analyses done with peculiar velocity surveys alone, and finally with the combination of data from both redshift and peculiar velocity surveys. The data presented rule out the standard Cold Dark Matter model, although several variants of Cold Dark Matter with more power on large scales fare better. All the data are consistent with the hypothesis that the initial density field had a Gaussian distribution, although one cannot rule out broad classes of non-Gaussian models. Comparison of the peculiar velocity and density fields constrains the Cosmological Density Parameter. The results here are consistent with a flat universe with mild biasing of the galaxies relative to dark matter, although open universe models are by no means ruled out.Comment: In press, Physics Reports. 153 pages. gzip'ed postscript of text plus 20 embedded figures. Also available via anonymous ftp at ftp://eku.ias.edu/pub/strauss/review/physrep.p

Special Issue: Inequality and Race in the Histories of Archaeology

This special issue gathers together a selection of short articles reflecting on the historical construction of inequality and race in the histories of archaeology. The articles also suggest ways in which the discipline might grapple with the—often obvious, sometimes subtle—consequences of that historical process. Solicited via an open call for papers in the summer of 2020 (one made with the aim of speedy publication), the breadth of the topics discussed in the articles reflect how inequality and race have become more prominent research themes within the histories of archaeology in the previous five-to-ten years. At the same time, the pieces show how research can—and should—be connected to attempts to promote social justice and an end to racial discrimination within archaeological practice, the archaeological profession, and the wider worlds with which the discipline interacts. Published at a time when a pandemic has not only swept the world, but also exposed such inequalities further, the special issue represents a positive intervention in what continues to be a contentious issue

Exploring how the balanced scorecard engages and unfolds:Articulating the visual power of accounting inscriptions

Research on the Balanced Scorecard (BSC) has questioned whether its adoption generates greater integration between financial and nonfinancial performance measures, supports strategy implementation, increases performance and improves strategic decision making. This research has also highlighted how the BSC often generates effects other than these. Building on studies that portray Performance Measurement Systems as intrinsically incomplete practices of representation, the purpose of this article is to investigate how the BSC engages users because of the organizing work that it stimulates around this incompleteness. Our findings allow us to further articulate the power of specific visual elements of the BSC, such as hierarchical trees, wheels, causal and strategy maps. The article provides material that contributes to a better understanding of how the BSC performs multiple roles within organizations beyond a simple representational functionality and unfolds continuously. It contributes to the growing literature on accounting inscriptions, that is, signs producing incomplete representations, by developing an analytical theoretical framework that defines the BSC as a rhetorical machine composed of four key features: (i) a visual performable space (i.e., a schema generating creative engagement); (ii) a method of ordering and innovation; (iii) a means of interrogation and mediation; and (iv) a motivating ritual

Between a rock and a hard place: the need for and challenges to implementation of Rights Based Fisheries Management in small-scale fisheries of Southern Lake Malawi

There has been a decline in commercially valuable fish species, especially the Chambo (Oreochromis spp.), in southern Lake Malawi. Although there might be lack of reliable and scientifically backed evidence, most experts and experienced fishers concur that productivity of most fish stocks in the area is much below par compared to their productivity about two to three decades ago. This leads to the hypotheses that the fish stocks are generally over-exploited. This trend will continue or their productivity will remain at these depressed levels unless appropriate measures are taken. This article argues that Rights Based Management (RBM) could hold the best hope for moving towards sustainable fisheries management in the southern Lake Malawi (Southeast and Southwest Arms) area while recognizing the need for a broad human rights approach for fishing communities. Even then, the implementation of the RBM approach will not be easy given the historical developmental open access management approach and general unorganized characteristics of the small-scale fisheries sector. Of note is that co-management was introduced in area in the early millennium as part of attempts to strengthen user fishing rights, local accountability and stewardship—with mixed results