Spatially and genetically distinct African trypanosome virulence variants defined by host interferon-g response

We describe 2 spatially distinct foci of human African trypansomiasis in eastern Uganda. The Tororo and Soroti foci of <i>Trypanosoma brucei rhodesiense</i> infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon (IFN)–γ concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN-γ response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN-γ in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. <i>brucei rhodesiense</i>

Observation of Bose-Einstein Condensation in a Strong Synthetic Magnetic Field

Extensions of Berry's phase and the quantum Hall effect have led to the discovery of new states of matter with topological properties. Traditionally, this has been achieved using gauge fields created by magnetic fields or spin orbit interactions which couple only to charged particles. For neutral ultracold atoms, synthetic magnetic fields have been created which are strong enough to realize the Harper-Hofstadter model. Despite many proposals and major experimental efforts, so far it has not been possible to prepare the ground state of this system. Here we report the observation of Bose-Einstein condensation for the Harper-Hofstadter Hamiltonian with one-half flux quantum per lattice unit cell. The diffraction pattern of the superfluid state directly shows the momentum distribution on the wavefuction, which is gauge-dependent. It reveals both the reduced symmetry of the vector potential and the twofold degeneracy of the ground state. We explore an adiabatic many-body state preparation protocol via the Mott insulating phase and observe the superfluid ground state in a three-dimensional lattice with strong interactions.Comment: 6 pages, 5 figures. Supplement: 6 pages, 4 figure

Documentation of best interest by intensivists: a retrospective study in an Ontario critical care unit

<p>Abstract</p> <p>Background</p> <p>Intensive care physicians often must rely on substitute decision makers to address all dimensions of the construct of "best interest" for incapable, critically ill patients. This task involves identifying prior wishes and to facilitate the substitute decision maker's understanding of the incapable patient's condition and their likely response to treatment. We sought to determine how well such discussions are documented in a typical intensive care unit.</p> <p>Methods</p> <p>Using a quality of communication instrument developed from a literature search and expert opinion, 2 investigators transcribed and analyzed 260 handwritten communications for 105 critically ill patients who died in the intensive care unit between January and June 2006. Cohen's kappa was calculated before analysis and then disagreements were resolved by consensus. We report results on a per-patient basis to represent documented communication as a process leading up to the time of death in the ICU. We report frequencies and percentages for discrete data, median (m) and interquartile range (IQR) for continuous data.</p> <p>Results</p> <p>Our cohort was elderly (m 72, IQR 58-81 years) and had high APACHE II scores predictive of a high probability of death (m 28, IQR 23-36). Length of stay in the intensive care unit prior to death was short (m 2, IQR 1-5 days), and withdrawal of life support preceded death for more than half (n 57, 54%). Brain death criteria were present for 18 patients (17%). Although intensivists' communications were timely (median 17 h from admission to critical care), the person consenting on behalf of the incapable patient was explicitly documented for only 10% of patients. Life support strategies at the time of communication were noted in 45% of charts, and options for their future use were presented in 88%. Considerations relevant to determining the patient's best interest in relation to the treatment plan were not well documented. While explicit survival estimates were noted in 50% of charts, physicians infrequently documented their own predictions of the patient's functional status (20%), anticipated need for chronic care (0%), or post ICU quality of life (3%). Similarly, documentation of the patient's own perspectives on these ranged from 2-18%.</p> <p>Conclusions</p> <p>Intensivists' documentation of their communication with substitute decision makers frequently outlined the proposed plan of treatment, but often lacked evidence of discussion relevant to whether the treatment plan was expected to improve the patient's condition. Legislative standards for determination of best interest, such as the Health Care Consent Act in Ontario, Canada, may provide guidance for intensivists to optimally document the rationales for proposed treatment plans.</p

Gastrointestinal stromal tumour and hypoglycemia in a Fjord pony: Case report

<p>Abstract</p> <p>Background</p> <p>Neoplasia may cause hypoglycemia in different species including the horse, but hypoglycemia has not previously been reported in the horse associated with gastrointestinal stromal tumours.</p> <p>Case presentation</p> <p>A case of a gastrointestinal stromal tumour in a Fjord pony with severe recurrent hypoglycemia is presented. The mechanism causing the hypoglycemia was not established.</p> <p>Conclusion</p> <p>This case indicates that a gastrointestinal stromal tumour may cause hypoglycemia also in the horse.</p

Real-Time PyMOL Visualization for Rosetta and PyRosetta

Computational structure prediction and design of proteins and protein-protein complexes have long been inaccessible to those not directly involved in the field. A key missing component has been the ability to visualize the progress of calculations to better understand them. Rosetta is one simulation suite that would benefit from a robust real-time visualization solution. Several tools exist for the sole purpose of visualizing biomolecules; one of the most popular tools, PyMOL (Schrödinger), is a powerful, highly extensible, user friendly, and attractive package. Integrating Rosetta and PyMOL directly has many technical and logistical obstacles inhibiting usage. To circumvent these issues, we developed a novel solution based on transmitting biomolecular structure and energy information via UDP sockets. Rosetta and PyMOL run as separate processes, thereby avoiding many technical obstacles while visualizing information on-demand in real-time. When Rosetta detects changes in the structure of a protein, new coordinates are sent over a UDP network socket to a PyMOL instance running a UDP socket listener. PyMOL then interprets and displays the molecule. This implementation also allows remote execution of Rosetta. When combined with PyRosetta, this visualization solution provides an interactive environment for protein structure prediction and design

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Clustering More than Two Million Biomedical Publications: Comparing the Accuracies of Nine Text-Based Similarity Approaches

We investigate the accuracy of different similarity approaches for clustering over two million biomedical documents. Clustering large sets of text documents is important for a variety of information needs and applications such as collection management and navigation, summary and analysis. The few comparisons of clustering results from different similarity approaches have focused on small literature sets and have given conflicting results. Our study was designed to seek a robust answer to the question of which similarity approach would generate the most coherent clusters of a biomedical literature set of over two million documents.We used a corpus of 2.15 million recent (2004-2008) records from MEDLINE, and generated nine different document-document similarity matrices from information extracted from their bibliographic records, including titles, abstracts and subject headings. The nine approaches were comprised of five different analytical techniques with two data sources. The five analytical techniques are cosine similarity using term frequency-inverse document frequency vectors (tf-idf cosine), latent semantic analysis (LSA), topic modeling, and two Poisson-based language models--BM25 and PMRA (PubMed Related Articles). The two data sources were a) MeSH subject headings, and b) words from titles and abstracts. Each similarity matrix was filtered to keep the top-n highest similarities per document and then clustered using a combination of graph layout and average-link clustering. Cluster results from the nine similarity approaches were compared using (1) within-cluster textual coherence based on the Jensen-Shannon divergence, and (2) two concentration measures based on grant-to-article linkages indexed in MEDLINE.PubMed's own related article approach (PMRA) generated the most coherent and most concentrated cluster solution of the nine text-based similarity approaches tested, followed closely by the BM25 approach using titles and abstracts. Approaches using only MeSH subject headings were not competitive with those based on titles and abstracts

Human resources issues and Australian Disaster Medical Assistance Teams: results of a national survey of team members

Background: Calls for disaster medical assistance teams (DMATs) are likely to continue in response to international disasters. As part of a national survey, this study was designed to evaluate Australian DMAT experience in relation to the human resources issues associated with deployment.\ud \ud Methods: Data was collected via an anonymous mailed survey distributed via State and Territory representatives on the Australian Health Protection Committee, who identified team members associated with Australian DMAT deployments from the 2004 South East Asian Tsunami disaster.\ud \ud Results: The response rate for this survey was 50% (59/118). Most personnel had deployed to the Asian Tsunami affected areas with DMAT members having significant clinical and international experience. While all except one respondent stated they received a full orientation prior to deployment, only 34% of respondents (20/59) felt their role was clearly defined pre deployment. Approximately 56% (33/59) felt their actual role matched their intended role and that their clinical background was well suited to their tasks. Most respondents were prepared to be available for deployment for 1 month (34%, 20/59). The most common period of notice needed to deploy was 6–12 hours for 29% (17/59) followed by 12–24 hours for 24% (14/59). The preferred period of overseas deployment was 14–21 days (46%, 27/59) followed by 1 month (25%, 15/59) and the optimum shift period was felt to be 12 hours by 66% (39/59). The majority felt that there was both adequate pay (71%, 42/59) and adequate indemnity (66%, 39/59). Almost half (49%, 29/59) stated it was better to work with people from the same hospital and, while most felt their deployment could be easily covered by staff from their workplace (56%, 33/59) and caused an inconvenience to their colleagues (51%, 30/59), it was less likely to interrupt service delivery in their workplace (10%, 6/59) or cause an inconvenience to patients (9%, 5/59). Deployment was felt to benefit the affected community by nearly all (95%, 56/59) while less (42%, 25/59) felt that there was a benefit for their own local community. Nearly all felt their role was recognised on return (93%, 55/59) and an identical number (93%, 55/59) enjoyed the experience. All stated they would volunteer again, with 88% strongly agreeing with this statement.\ud \ud Conclusions: This study of Australian DMAT members provides significant insights into a number of human resources issues and should help guide future deployments. The preferred 'on call' arrangements, notice to deploy, period of overseas deployment and shift length are all identified. This extended period of operations needs to be supported by planning and provision of rest cycles, food, temporary accommodation and rest areas for staff. The study also suggests that more emphasis should be placed on team selection and clarification of roles. While the majority felt that there was both adequate pay and adequate indemnity, further work clarifying this, based on national conditions of service should be, and are, being explored currently by the state based teams in Australia. Importantly, the deployment was viewed positively by team members who all stated they would volunteer again, which allows the development of an experienced cohort of team members