Direct and indirect effects of Johne's disease on farm and animal productivity in an Irish dairy herd

Johne's disease (JD) is caused by infection with the organism Mycobacterium avium spp. paratuberculosis, leading to chronic diarrhoea and ill thrift in adult cattle. JD is considered to adversely affect farm performance and profitability. This retrospective case study was undertaken on a single commercial dairy herd in the south west of Ireland. Animal production records were interrogated to assess the effect of JD on milk yield (total kg per lactation), somatic cell count (the geometric mean over the lactation), reasons for culling, cull price and changes in herd parity structure over time. JD groups were defined using clinical signs and test results. One control animal was matched to each case animal on parity number and year. Specific lactations (clinical, pre-clinical and test-positive only) from 1994 to 2004 were compared between JD case and control cows. A significantly lower milk yield (1259.3 kg/lactation) was noted from cows with clinical JD in comparison to their matched control group. Clinical animals had an average cull price of €516 less than animals culled without signs of clinical disease. In contrast, little effect was noted for sub-clinical infections. These direct effects of JD infections, in combination with increased culling for infertility and increasing replacement rates, had a negative impact on farm production. Results from this study provide preliminary information regarding the effects of JD status on both herd and animal-level performance in Ireland

Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

Background: Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. Methods: This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. Results: The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. Conclusions: In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical methods and outcome metrics suitable for performing that testing are also described. This approach has potential benefits but requires broad testing, in multiple patient samples, to determine its clinical value. The usefulness of the approach is likely to be context-specific, depending on the characteristics of the available data and the research question being asked of it

Generalized quark-antiquark potential at weak and strong coupling

We study a two-parameter family of Wilson loop operators in N=4 supersymmetric Yang-Mills theory which interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines. These observables capture a natural generalization of the quark-antiquark potential. We calculate these loops on the gauge theory side to second order in perturbation theory and in a semiclassical expansion in string theory to one-loop order. The resulting determinants are given in integral form and can be evaluated numerically for general values of the parameters or analytically in a systematic expansion around the 1/2 BPS configuration. We comment about the feasibility of deriving all-loop results for these Wilson loops.Comment: 43 pages: 15 comprising the main text and 25 for detailed appendice

Comparison of m-mode echocardiographic left ventricular mass measured using digital and strip chart readings: The Atherosclerosis Risk in Communities (ARIC) study

BACKGROUND: Epidemiological and clinical studies frequently use echocardiography to measure LV wall thicknesses and chamber dimension for estimating quantitative measures of LV mass. While echocardiographic M-mode LV images have traditionally been measured using hand-held calipers and strip-chart paper tracings, digitized M-mode LV image measurements made directly on the computer screen using electronic calipers have become standard practice. We sought to determine if systematic differences in LV mass occur between the two methods by comparing LV mass measured from simultaneous M-mode strip chart recordings and digitized recordings. METHODS: The Atherosclerosis Risk in Communities study applied the latter method. To determine if systematic differences in LV mass occur between the two methods, LV mass was measured from simultaneous M-mode strip chart recordings and digitized recordings. RESULTS: We found no difference in LV mass (p > .25) and a strong correlation in LV mass between the two methods (r = 0.97). Neither age, sex, nor hypertension status affected the correlation of LV mass between the two methods. CONCLUSIONS: We conclude that digital estimates of LV mass provide unbiased estimates comparable to the strip-chart method

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

Inactivation of respiratory syncytial virus by zinc finger reactive compounds

<p>Abstract</p> <p>Background</p> <p>Infectivity of retroviruses such as HIV-1 and MuLV can be abrogated by compounds targeting zinc finger motif in viral nucleocapsid protein (NC), involved in controlling the processivity of reverse transcription and virus infectivity. Although a member of a different viral family (<it>Pneumoviridae</it>), respiratory syncytial virus (RSV) contains a zinc finger protein M2-1 also involved in control of viral polymerase processivity. Given the functional similarity between the two proteins, it was possible that zinc finger-reactive compounds inactivating retroviruses would have a similar effect against RSV by targeting RSV M2-1 protein. Moreover, inactivation of RSV through modification of an internal protein could yield a safer whole virus vaccine than that produced by RSV inactivation with formalin which modifies surface proteins.</p> <p>Results</p> <p>Three compounds were evaluated for their ability to reduce RSV infectivity: 2,2'-dithiodipyridine (AT-2), tetraethylthiuram disulfide and tetramethylthiuram disulfide. All three were capable of inactivating RSV, with AT-2 being the most potent. The mechanism of action of AT-2 was analyzed and it was found that AT-2 treatment indeed results in the modification of RSV M2-1. Altered intramolecular disulfide bond formation in M2-1 protein of AT-2-treated RSV virions might have been responsible for abrogation of RSV infectivity. AT-2-inactivated RSV was found to be moderately immunogenic in the cotton rats <it>S.hispidus </it>and did not cause a vaccine-enhancement seen in animals vaccinated with formalin-inactivated RSV. Increasing immunogenicity of AT-2-inactivated RSV by adjuvant (Ribi), however, led to vaccine-enhanced disease.</p> <p>Conclusions</p> <p>This work presents evidence that compounds that inactivate retroviruses by targeting the zinc finger motif in their nucleocapsid proteins are also effective against RSV. AT-2-inactivated RSV vaccine is not strongly immunogenic in the absence of adjuvants. In the adjuvanted form, however, vaccine induces immunopathologic response. The mere preservation of surface antigens of RSV, therefore may not be sufficient to produce a highly-efficacious inactivated virus vaccine that does not lead to an atypical disease.</p

Reduced susceptibility to pyrethroid insecticide treated nets by the malaria vector Anopheles gambiae s.l. in western Uganda

<p>Abstract</p> <p>Background</p> <p>Pyrethroid insecticide-treated mosquito nets are massively being scaled-up for malaria prevention particularly in children under five years of age and pregnant mothers in sub-Saharan Africa. However, there is serious concern of the likely evolution of widespread pyrethroid resistance in the malaria vector <it>Anopheles gambiae s.l</it>. due to the extensive use of pyrethroid insecticide-treated mosquito nets. The purpose of this study was to ascertain the status of pyrethroid resistance in <it>An. gambiae s.l</it>. in western Uganda.</p> <p>Methods</p> <p>Wild mosquitoes (1–2 days old) were exposed in 10 replicates to new nets impregnated with K-othrine (Deltamethrin 25 mg/m²), Solfac EW50 (Cyfluthrin 50 mg/m²) and Fendona 6SC (Cypermethrin 50 mg/m²) and observed under normal room temperature and humidity (Temperature 24.8°C���27.4°C, Humidity 65.9–45.7). A similar set of mosquitoes collected from the control area 80 km away were exposed to a deltamethrin 25 mg/m²impregnated net at the same time and under the same conditions. The 10-year mean KDT₅₀and mortality rates for each of the three pyrethroid insecticides were compared using the Student <it>t</it>-test.</p> <p>Results</p> <p>A significant increase in the mean knockdown time (KDT₅₀) and mean mortality rate were observed in almost all cases an indication of reduced susceptibility. The overall results showed a four-fold increase in the mean knockdown time (KDT₅₀) and 1.5-fold decrease in mortality rate across the three pyrethroid insecticides. There was a significant difference in the 10-year mean KDT₅₀between deltamethrin and cyfluthrin; deltamethrin and cypermethrin, but no significant difference between cyfluthrin and cypermethrin. The 10-year mean difference in KDT50 for mosquitoes exposed to deltamethrin from the control site was significantly different from that of mosquitoes from the intervention site (p<0.05, t=3.979, 9df). The 10-year mean difference in mortality rate between deltamethrin (84.64%); cyfluthrin (74.18%); cypermethrin (72.19%) and the control (90.45%) showed a significant decline in mortality across all the three insecticides.</p> <p>Conclusion</p> <p>Generally the results showed a trend of increase in mosquito resistance status with cross-resistance against all the three pyrethroid insecticides. This study reveals for the first time the development of pyrethroid resistance in <it>An. gambiae s.l</it>. in Western Uganda. It is therefore strongly recommended that the impact of this development on malaria control efforts be closely monitored and alternative fabric treatments be considered before this problem curtails community wide implementation of this malaria control strategy in Uganda.</p

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

Effects of tutor-related behaviours on the process of problem-based learning

Tutors in a Problem-Based Learning (PBL) curriculum are thought to play active roles in guiding students to develop frameworks for use in the construction of knowledge. This implies that both subject-matter expertise and the ability of tutors to facilitate the learning process must be important in helping students learn. This study examines the behavioural effects of tutors in terms of subject-matter expertise, social congruence and cognitive congruence on students’ learning process and on their final achievement. The extent of students’ learning at each PBL phase was estimated by tracking the number of relevant concepts recalled at the end of each learning phase, while student achievement was based on students’ ability to describe and elaborate upon the relationship between relevant concepts learned. By using Analysis of Covariance, social congruence of the tutor was found to have a significant influence on learning in each PBL phase while all of the tutor-related behaviours had a significant impact on student achievement. The results suggest that the ability of tutors to communicate informally with students and hence create a less threatening learning environment that promotes a free flow exchange of ideas, has a greater impact on learning at each of the PBL phases as compared to tutors’ subject-matter expertise and their ability to explain concepts in a way that is easily understood by students. The data presented indicates that these tutor-related behaviours are determinants of learning in a PBL curriculum, with social congruence having a greater influence on learning in the different PBL phases