Intestinal absorption of macromolecules during viral enteritis: an experimental study on rotavirus-infected conventional and germ-free mice.

Epithelial transport and degradation of horseradish peroxidase (HRP), a macromolecular tracer, was studied in conventional and germ-free suckling mice following an experimental infection with rotavirus. Conventional and germ-free mice developed diarrhea from days 2 to 8 postinfection (pi), with growth failure. In mucosal homogenates, infectious virus detected by immunofluorescence on MA 104 cells was present from day 2 through day 8 pi in germ-free mice, but persisted longer (day 13 pi) in conventional mice. Only mild histological lesions were observed during diarrhea, but obvious macrovacuolation of epithelial cells and increased cellular density occurred during the convalescence period (days 9 to 13 pi). Intact and degraded HRP fluxes from mucosa to serosa were measured in vitro on segments of jejunum mounted in Ussing chambers. Both groups of mice developed increased HRP permeability during the experimental period, but at different times after inoculation: during the diarrheal period (days 2 and 3 pi) conventional mouse epithelium absorbed five times more HRP than noninfected controls and during the convalescence period (days 9 to 13 pi) HRP absorption in germ-free mice rose 10-fold as compared to its level before infection. In both cases, this increase in HRP permeability was entirely due to an increase in intact HRP absorption, probably via a transcellular route, and occurred without any alteration in degraded HRP transport. These results indicate that in mice, rotavirus infection causes a transient rise in gut permeability to undegraded proteins. The intestinal microflora seems to affect the timing, magnitude, and duration of this increased permeability

Pediatric assent for a study of antiretroviral therapy dosing for children in western Kenya: a case study in international research collaboration

Multinational collaborators in health research face particular ethical challenges when conducting studies involving vulnerable populations such as children. We use an example from our first attempt to implement pediatric assent in the context of a longstanding research and clinical partnership between Kenyan and American medical schools to highlight the ethical and procedural issues related to pediatric assent that must be considered for multinational, pediatric studies. We consider relevant domestic, professional, and international guidelines for assent in pediatric research subjects, and we discuss the particular ethical challenges related to pediatric assent in the Kenyan context. Finally, we propose a way forward for approaching pediatric assent within our collaborative research program in Kenya that may apply to other multinational research partnerships.Fogarty International Center at the National Institutes of Health [R25TW006070]; USAID-AMPATH Partnership, United States Agency for International Developmen

A rapid microwave-assisted procedure for easy access to Nx polydentate ligands for potential application in α-RIT

International audienceHeterocycles bearing a hydrazine moiety react with bisaldehydes or bisketones to afford new Nx polydentate ligands suitable for α-radioimmunotherapy. We developed a fast and efficient method using microwave-assisted technology to obtain chelators with variable size and number of coordination centres which were fully characterized. The complexation efficiency with astatine will be assessed

PhyleasProg: a user-oriented web server for wide evolutionary analyses

Evolutionary analyses of biological data are becoming a prerequisite in many fields of biology. At a time of high-throughput data analysis, phylogenetics is often a necessary complementary tool for biologists to understand, compare and identify the functions of sequences. But available bioinformatics tools are frequently not easy for non-specialists to use. We developed PhyleasProg (http://phyleasprog.inra.fr), a user-friendly web server as a turnkey tool dedicated to evolutionary analyses. PhyleasProg can help biologists with little experience in evolutionary methodologies by analysing their data in a simple and robust way, using methods corresponding to robust standards. Via a very intuitive web interface, users only need to enter a list of Ensembl protein IDs and a list of species as inputs. After dynamic computations, users have access to phylogenetic trees, positive/purifying selection data (on site and branch-site models), with a display of these results on the protein sequence and on a 3D structure model, and the synteny environment of related genes. This connection between different domains of phylogenetics opens the way to new biological analyses for the discovery of the function and structure of proteins

Modification of the trapped field in bulk high-temperature superconductors as a result of the drilling of a pattern of artificial columnar holes

The trapped magnetic field is examined in bulk high-temperature superconductors that are artificially drilled along their c-axis. The influence of the hole pattern on the magnetization is studied and compared by means of numerical models and Hall probe mapping techniques. To this aim, we consider two bulk YBCO samples with a rectangular cross-section that are drilled each by six holes arranged either on a rectangular lattice (sample I) or on a centered rectangular lattice (sample II). For the numerical analysis, three different models are considered for calculating the trapped flux: (i), a two-dimensional (2D) Bean model neglecting demagnetizing effects and flux creep, (ii), a 2D finite-element model neglecting demagnetizing effects but incorporating magnetic relaxation in the form of an E-J power law, and, (iii), a 3D finite element analysis that takes into account both the finite height of the sample and flux creep effects. For the experimental analysis, the trapped magnetic flux density is measured above the sample surface by Hall probe mapping performed before and after the drilling process. The maximum trapped flux density in the drilled samples is found to be smaller than that in the plain samples. The smallest magnetization drop is found for sample II, with the centered rectangular lattice. This result is confirmed by the numerical models. In each sample, the relative drops that are calculated independently with the three different models are in good agreement. As observed experimentally, the magnetization drop calculated in the sample II is the smallest one and its relative value is comparable to the measured one. By contrast, the measured magnetization drop in sample (1) is much larger than that predicted by the simulations, most likely because of a change of the microstructure during the drilling process.Comment: Proceedings of EUCAS 09 conferenc

A Needs Assessment to Build International Research Ethics Capacity at Moi University

International Research Ethics Partnership. This online version is the post-print version (final, peer-reviewed and accepted for publication version) of the published article. For the published version, refer to the article citation within the item record.International collaborators in biomedical sciences face ethical challenges in the design,review, and conduct of research. Challenges include differences in research ethics capacity, cultural differences in interpretation and application of ethical principles, and cooperation between ethics review boards at collaborating institutions. Indiana University School of Medicine (Indianapolis, USA) and Moi University Faculty of Health Sciences (Eldoret, Kenya)developed a Memorandum of Understanding (MOU) to establish greater cooperation between their ethics review boards, followed by a joint needs assessment to assess barriers to implementing the MOU. Focus groups and interviews at each institution revealed that while each side verbalized understanding and respect for the other's culture, there were misunderstandings deeply rooted in each culture that could potentially derail the collaboration. Although the participants at each university agreed on the major principles and issues in research ethics and on the importance attributed to them, a more in-depth evaluation of the responses revealed important differences. Methods to address these misunderstandings are outlined in the recommended Best Practices.Fogarty International Center at the NIH, Indiana University Division of General Internal Medicine and Geriatrics, Indiana University School of Medicine, Indiana University International Development Fund, Indiana Genomics Initiative, Lilly Endowment, Inc

The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children’s rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population

Provider Responses to Patients Controlling Access to their Electronic Health Records: A Prospective Cohort Study in Primary Care

Introduction: Applying Fair Information Practice principles to electronic health records (EHRs) requires allowing patient control over who views their data. Methods: We designed a program that captures patients’ preferences for provider access to an urban health system’s EHR. Patients could allow or restrict providers’ access to all data (diagnoses, medications, test results, reports, etc.) or only highly sensitive data (sexually transmitted infections, HIV/AIDS, drugs/alcohol, mental or reproductive health). Except for information in free-text reports, we redacted EHR data shown to providers according to patients’ preferences. Providers could “Break the Glass” to display redacted information. We prospectively studied this system in one primary care clinic, noting redactions and when users “Broke the Glass,” and surveyed providers about their experiences and opinions. Results: Eight of 9 eligible clinic physicians and all 23 clinic staff participated. All 105 patients who enrolled completed the preference program.. Providers did not know which of their patients were enrolled and nor their preferences for accessing their EHRs. During the six-month prospective study, 92 study patients (88%) returned 261 times during which providers viewed their EHRs 126 times (48%). Providers “broke the glass” 102 times, 92 times for patients not in the study and 10 times for 6 returning study patients, all of whom had restricted EHR access. Providers “broke the glass” for 6 (14%) of 43 returning study patients with redacted data vs. zero among 49 study patients without redactions (p=0.01). Although 54% of providers agreed that patients should have control over who sees their EHR information, 58% believed restricting EHR access could harm provider-patient relationships and 71% felt quality of care would suffer. Conclusions: Patients frequently preferred restricting provider access to their EHRs. Providers infrequently overrode patients’ preferences to view hidden data. Providers believed restricting EHR access would adversely impact patient care. Applying Fair Information Practice principles to EHRs will require balancing patient preferences, providers’ needs, and health care quality.This study was supported in part by grant number 90HT005 from the Office of the National Coordinator for Health Information Technology (ONC) to the Indiana Health Information Technology Corporation. The opinions expressed in this work are the authors’ and do not necessarily reflect the positions of ONC, IHIT, Eskenazi Health, Indiana University, or the Regenstrief Institute, Inc

Bulk high-Tc superconductors with drilled holes: how to arrange the holes to maximize the trapped magnetic flux ?

Drilling holes in a bulk high-Tc superconductor enhances the oxygen annealing and the heat exchange with the cooling liquid. However, drilling holes also reduces the amount of magnetic flux that can be trapped in the sample. In this paper, we use the Bean model to study the magnetization and the current line distribution in drilled samples, as a function of the hole positions. A single hole perturbs the critical current flow over an extended region that is bounded by a discontinuity line, where the direction of the current density changes abruptly. We demonstrate that the trapped magnetic flux is maximized if the center of each hole is positioned on one of the discontinuity lines produced by the neighbouring holes. For a cylindrical sample, we construct a polar triangular hole pattern that exploits this principle; in such a lattice, the trapped field is ~20% higher than in a squared lattice, for which the holes do not lie on discontinuity lines. This result indicates that one can simultaneously enhance the oxygen annealing, the heat transfer, and maximize the trapped field