Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Effects of Screening and Brief Intervention Training on Resident and Faculty Alcohol Intervention Behaviours: A Pre- Post-Intervention Assessment

Background: Many hazardous and harmful drinkers do not receive clinician advice to reduce their drinking. Previous studies suggest under-detection and clinician reluctance to intervene despite awareness of problem drinking (PD). The Healthy Habits Project previously reported chart review data documenting increased screening and intervention with hazardous and harmful drinkers after training clinicians and implementing routine screening. This report describes the impact of the Healthy Habits training program on clinicians\u27 rates of identification of PD, level of certainty in identifying PD and the proportion of patients given advice to reduce alcohol use, based on self-report data using clinician exit questionnaires. Methods: 28 residents and 10 faculty in a family medicine residency clinic completed four cycles of clinician exit interview questionnaires before and after screening and intervention training. Rates of identifying PD, level of diagnostic certainty, and frequency of advice to reduce drinking were compared across intervention status (pre vs. post). Findings were compared with rates of PD and advice to reduce drinking documented on chart review. Results: 1,052 clinician exit questionnaires were collected. There were no significant differences in rates of PD identified before and after intervention (9.8% vs. 7.4%, p = .308). Faculty demonstrated greater certainty in PD diagnoses than residents (p = .028) and gave more advice to reduce drinking (p = .042) throughout the program. Faculty and residents reported higher levels of diagnostic certainty after training (p = .039 and .030, respectively). After training, residents showed greater increases than faculty in the percentage of patients given advice to reduce drinking (p = .038), and patients felt to be problem drinkers were significantly more likely to receive advice to reduce drinking by all clinicians (50% vs. 75%, p = .047). The number of patients receiving advice to reduce drinking after program implementation exceeded the number of patients felt to be problem drinkers. Recognition rates of PD were four to eight times higher than rates documented on chart review (p = .028). Conclusion: This program resulted in greater clinician certainty in diagnosing PD and increases in the number of patients with PD who received advice to reduce drinking. Future programs should include booster training sessions and emphasize documentation of PD and brief intervention

A ship rain gauge for use in high wind speeds.

A ship rain gauge has been developed that can be used under high wind speeds such as those experienced by ships at sea. The instrument has an improved aerodynamic design and an additional lateral collecting surface, which is effective especially with high wind speeds. The ship rain gauge has been calibrated at sea against a specially designed optical disdrometer. An accuracy of 2%–3% has been obtained for 6-hourly sums. The ship rain gauge has also successfully been tested at a test site of the German Weather Service and presently is used on research vessels and voluntary observing ship

Hospital Performance, the Local Economy, and the Local Workforce: Findings from a US National Longitudinal Study

Blustein and colleagues examine the associations between changes in hospital performance and their local economic resources. Locationally disadvantaged hospitals perform poorly on key indicators, raising concerns that pay-for-performance models may not reduce inequality

RON5 is critical for organization and function of the Toxoplasma moving junction complex

Apicomplexans facilitate host cell invasion through formation of a tight-junction interface between parasite and host plasma membranes called the moving junction (MJ). A complex of the rhoptry neck proteins RONs 2/4/5/8 localize to the MJ during invasion where they are believed to provide a stable anchoring point for host penetration. During the initiation of invasion, the preformed MJ RON complex is injected into the host cell where RON2 spans the host plasma membrane while RONs 4/5/8 localize to its cytosolic face. While much attention has been directed toward an AMA1-RON2 interaction supposed to occur outside the cell, little is known about the functions of the MJ RONs positioned inside the host cell. Here we provide a detailed analysis of RON5 to resolve outstanding questions about MJ complex organization, assembly and function during invasion. Using a conditional knockdown approach, we show loss of RON5 results in complete degradation of RON2 and mistargeting of RON4 within the parasite secretory pathway, demonstrating that RON5 plays a key role in organization of the MJ RON complex. While RON8 is unaffected by knockdown of RON5, these parasites are unable to invade new host cells, providing the first genetic demonstration that RON5 plays a critical role in host cell penetration. Although invasion is not required for injection of rhoptry effectors into the host cytosol, parasites lacking RON5 also fail to form evacuoles suggesting an intact MJ complex is a prerequisite for secretion of rhoptry bulb contents. Additionally, while the MJ has been suggested to function in egress, disruption of the MJ complex by RON5 depletion does not impact this process. Finally, functional complementation of our conditional RON5 mutant reveals that while proteolytic separation of RON5 N- and C-terminal fragments is dispensable, a portion of the C-terminal domain is critical for RON2 stability and function in invasion

Time and Encoding Effects in the Concealed Knowledge Test

Although the traditional “lie detector” test is used frequently in forensic contexts, it has (like most test of deception) some limitations. The concealed knowledge test (CKT) focuses on participants’ recognition of privileged knowledge rather than lying per-se and has been studied extensively using a variety of measures. A “guilty” suspect’s interaction with and memory of crimescene items may vary. Furthermore, memory for crimescene items may diminish over time. The interaction of encoding quality and test delay on CKT efficiency has been previously implied, but not yet demonstrated. We used a response-time based CKT to detect concealed knowledge from shallow and deep study procedures after 10-min, 24-h, and 1-week delays. Results show that more elaborately encoded information afforded higher detection accuracy than poorly encoded items. Although classification accuracy following deep study was unaffected by delay, detection of poorly elaborated information was initially high, but compromised after 1 week. Thus, choosing optimal test items requires considering both test delay and initial encoding level

The Dispersal Ecology of Rhodesian Sleeping Sickness Following Its Introduction to a New Area

Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir) from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was “seasonally flooding grassland” or “woodlands and dense savannah.” Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more ‘suitable’ areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread

Field observations of canopy flows over complex terrain

The investigation of airflow over and within forests in complex terrain has been, until recently, limited to a handful of modelling and laboratory studies. Here, we present an observational dataset of airflow measurements inside and above a forest situated on a ridge on the Isle of Arran, Scotland. The spatial coverage of the observations all the way across the ridge makes this a unique dataset. Two case studies of across-ridge flow under near-neutral conditions are presented and compared with recent idealized two-dimensional modelling studies. Changes in the canopy profiles of both mean wind and turbulent quantities across the ridge are broadly consistent with these idealized studies. Flow separation over the lee slope is seen as a ubiquitous feature of the flow. The three-dimensional nature of the terrain and the heterogeneous forest canopy does however lead to significant variations in the flow separation across the ridge, particularly over the less steep western slope. Furthermore, strong directional shear with height in regions of flow separation has a significant impact on the Reynolds stress terms and other turbulent statistics. Also observed is a decrease in the variability of the wind speed over the summit and lee slope, which has not been seen in previous studies. This dataset should provide a valuable resource for validating models of canopy flow over real, complex terrain

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition