A Critical Role for Induced IgM in the Protection against West Nile Virus Infection

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578–2586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM−/−) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM−/− mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM−/− mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection

Development of a quality of life questionnaire for patients with pancreatic neuroendocrine tumours (the PANNET module)

Gastrinoma; Insulinoma; Pancreatic neuroendocrine tumourGastrinoma; Insulinoma; Tumor neuroendocrino pancreáticoGastrinoma; Insulinoma; Tumor neuroendocrí pancreàticPancreatic neuroendocrine tumours (panNET) are heterogeneous neoplasms usually characterised by slow growth and secretion of hormones, which often cause symptoms. The effect of these symptoms on quality of life (QoL) has not previously been examined in detail. EORTC (European Organisation for Research and Treatment of Cancer) guidelines were followed in phases 1–3 to produce a potential module of questions usable for trials in panNET, focusing on three common types of panNET. For two less common types, a list of symptoms was constructed. Following an extensive literature search and phase 1a interviews with patients and healthcare workers, a long list of potential issues (169) was obtained. This list was shown to 12 patients from three countries in phase 1b interviews to check that no items were missed. The list was reduced to 57 issues. The list of issues was converted to questions, mainly from existing validated questions within the EORTC item library. The list of questions was then used in a phase 3 international study in eight countries using seven languages. A provisional module of 24 items is presented for use in nonfunctioning panNET, gastrinoma and insulinoma. This module increases knowledge concerning QoL in this condition and may be a useful adjunct in clinical trials. A phase 4 trial is being considered for validation of this questionnaire

Propuesta de creación de una empresa de capacitación y facilitación de empleo para personas con discapacidad para las empresas de la ciudad de Guayaquil

La inclusión de las personas con discapacidad en el ámbito laboral y productivo de las empresas, se ha tornado muy complejo, por cuanto existen nuevas regulaciones y leyes que estas empresas deben cumplir de forma obligatoria, esto ha hecho que las empresas seleccionen personal con discapacidad solo para cumplir con la ley. Las personas con discapacidad, en su gran mayoría, solo pueden aspirar a puestos de trabajo en donde prima la mano de obra sobre el intelecto (guardianía, limpieza, etc.). Esta investigación proporciona una visión optimista de que con una correcta capacitación de acuerdo a las habilidades y destrezas del individuo con discapacidad, y un buen asesoramiento a la empresa contratante, se puede armonizar la relación entre estos dos actores de la sociedad. La propuesta de diseño de una empresa que brinde los servicios de asesoramiento y capacitación es viable, por cuanto el financiamiento de estos servicios podrá ser a través de la ayuda gubernamental que se está brindando con los organismos competentes, por lo tanto es un proyecto con fines de lucro y con un enfoque real de ayuda social. Las personas con discapacidad que son micro empresarios también podrán acceder con el mismo financiamiento a estas capacitaciones de acuerdo al diseño de la estrategia comercial de la empresa. El propósito de esta investigación y posterior diseño de la empresa es ofrecer un elemento de ayuda a resolver el problema que se estaría presentando en las actuales circunstancias en Guayaquil y en el país

Interaction of stress and magnetic properties in patterned copper-nickel-copper thin films

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 135-137).In recent years, the epitaxial Cu/Ni/Cu thin film system has been extensively studied, due to its wide range of perpendicular magnetization. It has proved to be a model system to explore the interactions of strain, surface energies and magnetic properties. For that reason, is also an ideal system to explore the effects of patterning. It is expected that the miniaturization of patterned magnetic devices will be accompanied by a transition from polycrystalline to epitaxial films. This transition will require a detailed theoretical understanding of the interaction of strain and magnetic properties in patterned epitaxial magnetic thin films. The Cu/Ni/Cu film system is used in this work to explore a triaxial model for an orthorhombic symmetry of strain. By patterning the Cu/Ni into nanolines and measuring the resulting magnetic anisotropy, the validity of the model has been tested. It has been shown that upon patterning certain thicknesses of nickel into nanolines, the easy axis of magnetization shifts from out of the film plane to in-plane, transverse to the line direction, an observation at odds with the direction of magnetization predicted by shape considerations alone. This transition is explained by the dominant magnetoelastic energy for the Cu/Ni/Cu nanoline system.(cont.) The resulting anisotropy values are consistent with strain relief values predicted by finite element modeling. In addition, the low temperature properties of the Cu/Ni/Cu epitaxial film system have been explored. The variation of the overall magnetic anisotropy as a function of temperature is found to be proportional to the cube of the reduced magnetization. In addition, the easy axis of magnetization for certain thicknesses of nickel has been found to shift from in-plane to perpendicular with the reduction of temperature.by Elizabeth Friend.Ph.D

Thresholds for clinical importance for four key domains of the EORTC QLQ-C30 : physical functioning, emotional functioning, fatigue and pain

Background The EORTC QLQ-C30 is one of the most widely used quality of life questionnaires in cancer research. Availability of thresholds for clinical importance for the individual questionnaire domains could help to increase its interpretability. The aim of our study was to identify thresholds for clinical importance for four EORTC QLQ-C30 scales: Physical Functioning (PF), Emotional Functioning (EF), Pain (PA) and Fatigue (FA). Methods We recruited adult cancer patients from Austria, the Netherlands, Poland and the UK. No restrictions were placed on diagnosis or type or stage of treatment. Patients completed the QLQ-C30 and three anchor items reflecting potential attributes of clinically important levels of PF, EF, PA and FA. We merged the anchor items assessing perceived burden, limitations in daily activities and need for help into a dichotomous external criterion to estimate thresholds for clinical importance using Receiver Operator Characteristic (ROC) analysis. Results In our sample of 548 cancer patients (mean age 60.6 years; 54 % female), the QLQ-C30 scales showed high diagnostic accuracy in identifying patients reporting burden, limitations and/or need for help related to PF, EF, PA and FA. All areas under the curve were above 0.86. Conclusions We were able to estimate thresholds for clinical importance for four QLQ-C30 scales. When used in daily clinical practice, these thresholds can help to identify patients with clinically important problems requiring further exploration and possibly intervention by health care professionals

An interdisciplinary framework for measuring and supporting adherence in HIV prevention trials of ARV‐based vaginal rings

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138229/1/jia29158.pd

Assessing metabolism and function of normothermically perfused ex vivo livers by multinuclear MR imaging and spectroscopy

Synopsis Liver transplantation is the only cure for end-stage liver disease. Unfortunately, 20% of patients die waiting for a donor. New techniques for preserving transplant livers, such as normothermic machine perfusion (NMP), provide an opportunity to utilise ‘marginal’ (currently discarded) donated livers if their viability can be assessed accurately. We present initial results from a CE-marked NMP system that we adapted for use in an MRI scanner. We demonstrate the power of NMP-MRI to assess structure and metabolism in a freshly donated pig liver, dynamically over a 10-hour period. Our protocol includes H imaging, P spectroscopy, and hyperpolarised C spectroscopy.This work was funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z) and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)

A Highly Emissive Surface Layer in Mixed-Halide Multication Perovskites.

Mixed-halide lead perovskites have attracted significant attention in the field of photovoltaics and other optoelectronic applications due to their promising bandgap tunability and device performance. Here, the changes in photoluminescence and photoconductance of solution-processed triple-cation mixed-halide (Cs0.06 MA0.15 FA0.79 )Pb(Br0.4 I0.6 )3 perovskite films (MA: methylammonium, FA: formamidinium) are studied under solar-equivalent illumination. It is found that the illumination leads to localized surface sites of iodide-rich perovskite intermixed with passivating PbI2 material. Time- and spectrally resolved photoluminescence measurements reveal that photoexcited charges efficiently transfer to the passivated iodide-rich perovskite surface layer, leading to high local carrier densities on these sites. The carriers on this surface layer therefore recombine with a high radiative efficiency, with the photoluminescence quantum efficiency of the film under solar excitation densities increasing from 3% to over 45%. At higher excitation densities, nonradiative Auger recombination starts to dominate due to the extremely high concentration of charges on the surface layer. This work reveals new insight into phase segregation of mixed-halide mixed-cation perovskites, as well as routes to highly luminescent films by controlling charge density and transfer in novel device structures

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd