A comparison of two molecular methods for diagnosing leptospirosis from three different sample types in patients presenting with fever in Laos.

OBJECTIVES: To compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to Mahosot Hospital, Vientiane, Laos. METHODS: Serum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test. RESULTS: In all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%-81.8%); 99.6% (99.2%-100%)), buffy coat (58.8% (34.4%-90.9%); 99.9% (99.6%-100%)) and urine samples (45.0% (27.0%-66.7%); 99.6% (99.3%-100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%-100%) vs. 92.5% (92.3%-92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%-29.4%)) and culture (25% (95% CI 13.3%-44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001). CONCLUSIONS: Serum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease

Signature Movements Lead to Efficient Search for Threatening Actions

The ability to find and evade fighting persons in a crowd is potentially life-saving. To investigate how the visual system processes threatening actions, we employed a visual search paradigm with threatening boxer targets among emotionally-neutral walker distractors, and vice versa. We found that a boxer popped out for both intact and scrambled actions, whereas walkers did not. A reverse correlation analysis revealed that observers' responses clustered around the time of the “punch", a signature movement of boxing actions, but not around specific movements of the walker. These findings support the existence of a detector for signature movements in action perception. This detector helps in rapidly detecting aggressive behavior in a crowd, potentially through an expedited (sub)cortical threat-detection mechanism

The General Age of Leadership: Older-Looking Presidential Candidates Win Elections during War

As nation-state leaders age they increasingly engage in inter-state militarized disputes yet in industrialized societies a steady decrease in testosterone associated with aging is observed – which suggests a decrease in dominance behavior. The current paper points out that from modern societies to Old World monkeys increasing both in age and social status encourages dominant strategies to maintain acquired rank. Moreover, it is argued this consistency has shaped an implicit prototype causing followers to associate older age with dominance leadership. It is shown that (i) faces of older leaders are preferred during intergroup conflict and (ii) morphing U.S. Presidential candidates to appear older or younger has an overriding effect on actual election outcomes. This indicates that democratic voting can be systematically adjusted by activating innate biases. These findings appear to create a new line of research regarding the biology of leadership and contextual cues of age

The effect of social context on the use of visual information

Social context modulates action kinematics. Less is known about whether social context also affects the use of task relevant visual information. We tested this hypothesis by examining whether the instruction to play table tennis competitively or cooperatively affected the kind of visual cues necessary for successful table tennis performance. In two experiments, participants played table tennis in a dark room with only the ball, net, and table visible. Visual information about both players’ actions was manipulated by means of self-glowing markers. We recorded the number of successful passes for each player individually. The results showed that participants’ performance increased when their own body was rendered visible in both the cooperative and the competitive condition. However, social context modulated the importance of different sources of visual information about the other player. In the cooperative condition, seeing the other player’s racket had the largest effects on performance increase, whereas in the competitive condition, seeing the other player’s body resulted in the largest performance increase. These results suggest that social context selectively modulates the use of visual information about others’ actions in social interactions

Current understanding of the relationship between cervical manipulation and stroke: what does it mean for the chiropractic profession?

The understanding of the relationship between cervical manipulative therapy (CMT) and vertebral artery dissection and stroke (VADS) has evolved considerably over the years. In the beginning the relationship was seen as simple cause-effect, in which CMT was seen to cause VADS in certain susceptible individuals. This was perceived as extremely rare by chiropractic physicians, but as far more common by neurologists and others. Recent evidence has clarified the relationship considerably, and suggests that the relationship is not causal, but that patients with VADS often have initial symptoms which cause them to seek care from a chiropractic physician and have a stroke some time after, independent of the chiropractic visit

A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV

Sorafenib is a multi-kinase inhibitor with antiangiogenic and antiproliferative activity. The activity of sorafenib in progressive hormone-refractory prostate cancer (HRPC) patients was investigated in a phase II clinical study. Progressive HRPC patients received sorafenib 400 mg bid p.o. continuously. Only patients with no prior chemotherapy, and either one-unidimensional measurable lesion according to RECIST-criteria or increasing prostate-specific antigen (PSA) values reflecting a hormone-refractory situation, were eligible for study entry. The primary study objective was the rate of progression-free survival of ⩾12 weeks (PFS12). Secondary end points were overall response, overall survival, and toxicity. Fifty-seven patients with PC were enrolled. Two patients had to be withdrawn from the set of eligible patients. According to RECIST criteria, 4 patients out of 55 evaluable patients showed stable disease (SD). According to PSA–response, we saw 11 patients with SD PSA and 2 patients were responders at 12 weeks (PFS12=17/55=31%). Among the 257 adverse events, 15 were considered drug related of maximum CTC-grade 3. Twenty-four serious adverse events occurred in 14 patients (14/55=26%). Seven of them were determined to be drug related. No treatment-related death was observed. Sorafenib has antitumour activity in HRPCP when evaluated for RECIST- and PSA-based response. Further investigation as a component of combination regimens is necessary to evaluate its definite or overall clinical benefit for HRPCP

Enveloping Sophisticated Tools into Process-Centered Environments

We present a tool integration strategy based on enveloping pre-existing tools without source code modifications or recompilation, and without assuming an extension language, application programming interface, or any other special capabilities on the part of the tool. This Black Box enveloping (or wrapping) idea has existed for a long time, but was previously restricted to relatively simple tools. We describe the design and implementation of, and experimentation with, a new Black Box enveloping facility intended for sophisticated tools --- with particular concern for the emerging class of groupware applications

Combining modularity, conservation, and interactions of proteins significantly increases precision and coverage of protein function prediction

<p>Abstract</p> <p>Background</p> <p>While the number of newly sequenced genomes and genes is constantly increasing, elucidation of their function still is a laborious and time-consuming task. This has led to the development of a wide range of methods for predicting protein functions in silico. We report on a new method that predicts function based on a combination of information about protein interactions, orthology, and the conservation of protein networks in different species.</p> <p>Results</p> <p>We show that aggregation of these independent sources of evidence leads to a drastic increase in number and quality of predictions when compared to baselines and other methods reported in the literature. For instance, our method generates more than 12,000 novel protein functions for human with an estimated precision of ~76%, among which are 7,500 new functional annotations for 1,973 human proteins that previously had zero or only one function annotated. We also verified our predictions on a set of genes that play an important role in colorectal cancer (<it>MLH1</it>, <it>PMS2</it>, <it>EPHB4 </it>) and could confirm more than 73% of them based on evidence in the literature.</p> <p>Conclusions</p> <p>The combination of different methods into a single, comprehensive prediction method infers thousands of protein functions for every species included in the analysis at varying, yet always high levels of precision and very good coverage.</p

Discovering Networks of Perturbed Biological Processes in Hepatocyte Cultures

The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs and environmental toxicants. The two most prevalent liver culture systems are hepatocyte monolayers (HMs) and collagen sandwiches (CS). Despite their wide use, comprehensive transcriptional programs and interaction networks in these culture systems have not been systematically investigated. We integrated an existing temporal transcriptional dataset for HM and CS cultures of rat hepatocytes with a functional interaction network of rat genes. We aimed to exploit the functional interactions to identify statistically significant linkages between perturbed biological processes. To this end, we developed a novel approach to compute Contextual Biological Process Linkage Networks (CBPLNs). CBPLNs revealed numerous meaningful connections between different biological processes and gene sets, which we were successful in interpreting within the context of liver metabolism. Multiple phenomena captured by CBPLNs at the process level such as regulation, downstream effects, and feedback loops have well described counterparts at the gene and protein level. CBPLNs reveal high-level linkages between pathways and processes, making the identification of important biological trends more tractable than through interactions between individual genes and molecules alone. Our approach may provide a new route to explore, analyze, and understand cellular responses to internal and external cues within the context of the intricate networks of molecular interactions that control cellular behavior