Phragmén–Lindelöf Principles for Generalized Analytic Functions on Unbounded Domains

We prove versions of the Phragmén–Lindelöf strong maximum principle for generalized analytic functions defined on unbounded domains. A version of Hadamard’s three-lines theorem is also derived

Livestock trade networks for guiding animal health surveillance

BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

A national clinician–educator program: a model of an effective community of practice

Background: The increasing complexity of medical training often requires faculty members with educational expertise to address issues of curriculum design, instructional methods, assessment, program evaluation, faculty development, and educational scholarship, among others. Discussion: In 2007, The Royal College of Physicians & Surgeons of Canada responded to this need by establishing the first national clinician–educator program. We define a clinician–educator and describe the development of the program. Adopting a construct from the business community, we use a community of practice framework to describe the benefits (with examples) of this program and challenges in developing it. The benefits of the clinician–educator program include: improved educational problem solving, recognition of educational needs and development of new projects, enhanced personal educational expertise, maintenance of professional satisfaction and retention of group members, a positive influence within the Royal College, and a positive influence within other Canadian academic institutions. Summary: Our described experience of a social reorganization – a community of practice – suggests that the organizational and educational benefits of a national clinician–educator program are not theoretical, but real

Optimism/pessimism and health-related quality of life during pregnancy across three continents: a matched cohort study in China, Ghana, and the United States

<p>Abstract</p> <p>Background</p> <p>Little is known about how optimism/pessimism and health-related quality of life compare across cultures.</p> <p>Methods</p> <p>Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.). Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors. A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies. Anovas with post-hoc pairwise comparisons were used to compare results across the cohorts. Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism.</p> <p>Results</p> <p>LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis. Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001). Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure. U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample.</p> <p>Conclusion</p> <p>This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women. Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.</p

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Biophysically Realistic Filament Bending Dynamics in Agent-Based Biological Simulation

An appealing tool for study of the complex biological behaviors that can emerge from networks of simple molecular interactions is an agent-based, computational simulation that explicitly tracks small-scale local interactions – following thousands to millions of states through time. For many critical cell processes (e.g. cytokinetic furrow specification, nuclear centration, cytokinesis), the flexible nature of cytoskeletal filaments is likely to be critical. Any computer model that hopes to explain the complex emergent behaviors in these processes therefore needs to encode filament flexibility in a realistic manner. Here I present a numerically convenient and biophysically realistic method for modeling cytoskeletal filament flexibility in silico. Each cytoskeletal filament is represented by a series of rigid segments linked end-to-end in series with a variable attachment point for the translational elastic element. This connection scheme allows an empirically tuning, for a wide range of segment sizes, viscosities, and time-steps, that endows any filament species with the experimentally observed (or theoretically expected) static force deflection, relaxation time-constant, and thermal writhing motions. I additionally employ a unique pair of elastic elements – one representing the axial and the other the bending rigidity– that formulate the restoring force in terms of single time-step constraint resolution. This method is highly local –adjacent rigid segments of a filament only interact with one another through constraint forces—and is thus well-suited to simulations in which arbitrary additional forces (e.g. those representing interactions of a filament with other bodies or cross-links / entanglements between filaments) may be present. Implementation in code is straightforward; Java source code is available at www.celldynamics.org

From working collections to the World Germplasm Project: agricultural modernization and genetic conservation at the Rockefeller Foundation

This paper charts the history of the Rockefeller Foundation’s participation in the collection and long-term preservation of genetic diversity in crop plants from the 1940s through the 1970s. In the decades following the launch of its agricultural program in Mexico in 1943, the Rockefeller Foundation figured prominently in the creation of world collections of key economic crops. Through the efforts of its administrators and staff, the foundation subsequently parlayed this experience into a leadership role in international efforts to conserve so-called plant genetic resources. Previous accounts of the Rockefeller Foundation’s interventions in international agricultural development have focused on the outcomes prioritized by foundation staff and administrators as they launched assistance programs and especially their characterization of the peoples and ‘‘problems’’ they encountered abroad. This paper highlights instead how foundation administrators and staff responded to a newly emergent international agricultural concern—the loss of crop genetic diversity. Charting the foundation’s responses to this concern, which developed only after agricultural modernization had begun and was understood to be produced by the successes of the foundation’s own agricultural assistance programs, allows for greater interrogation of how the foundation understood and projected its central position in international agricultural research activities by the 1970s.Research for this article was supported in part by a grant-in-aid from the Rockefeller Archive Center

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences