Understanding National Nonprofit Data Environments.

We develop the concept of the nonprofit data environment as all data collected and reported in a country resulting from law implemented into practice. We map data environments across 20 countries and propose explanations for differences between the information nongovernmental organizations report (collected) and what is made publicly available (reported). Domestic factors including regime type, civil society autonomy, and regulatory quality increase the amount of information collected and released publicly. Exposure to international political forces, including aid flows and globalization, increases the gap, which runs counter to expectations of greater openness with global engagement. Our findings point to the need for a better understanding of patterns in non-profit organizations (NPOs) data environments; while all governments collect information, countries with similar legal codes have widely varying data environments. This matters for NPOs as their ability to learn and improve depends on access to quality data and coincides with a feared global political backlash.

Did the UN convention on the rights of the child reduce child mortality around the world? An interrupted time series analysis.

BACKGROUND: Child mortality has been reduced by more than 50 % over the past 30 years. A range of secular economic and social developments have been considered to explain this phenomenon. In this paper, we examine the association between ratification of the Convention on the Rights of the Child (CRC), which was specifically put in place to ensure the well-being of children, and declines in child mortality. METHODS: Data come from three sources: the United Nations Treaty Series Database, the World Bank World Development Indicators database and, the Polity IV database. Because CRC was widely ratified, leaving few control cases, we used interrupted times series analyses, which uses the trend in the health outcome before policy exposure to mathematically determine what the trend in the health outcome would have been after the policy exposure, if it had continued 'as is' - meaning, if the policy exposure had not occurred. RESULTS: CRC ratification was associated with declining child mortality. CRC ratification was associated with a significant change in shorter-term child mortality trends in all groups except high-income, non-democratic countries and low-imcome democratic countries. CRC ratification was associated with long-term child mortality trends in all groups except middle-income, non-democratic countries. CONCLUSIONS: Child mortality rates would likely have declined even in the absence of CRC ratification, but CRC is associated with a larger decline. Our findings provide a way to assess the effects of widely-held societal norms on health and demonstrate the moderating effects of democracy and income level.

Rotational Pedicle Myocutaneous Forearm Fillet Flap Used to Fill Forequarter Amputation Defect: Indications and Uses.

A full-thickness fourth-degree burn to a large area of the upper extremity may require a forequarter amputation. Whereas our case describes a burn injury, forequarter amputations may more commonly be done in oncological surgery. In addition to the challenge of providing well-vascularized tissue coverage, the burn patient may also pose the complication of respiratory compromise in a systemically ill person. Fillet flaps have often been utilized as "spare part" reconstruction. Although previous forequarter amputations have been covered with free myocutanous forearm fillet flaps, we devised a rotational pedicle myocutaneous forearm fillet flap that might be less complex than a microvascular reconstruction. This article describes the technique and advantages of the pedicle fillet flap of the upper limb. This technique eliminates the risks of delayed warm ischemia time and avoids additional morbidity of donor sites. Although we sought to find a simpler, more rapid procedure for a burn patient, the pedicle forearm fillet flap has applications for both burn and oncological forequarter amputation defects. It provides a good combination of large tissue coverage with maximum perfusion of muscle bulk. The pedicle flap also enabled us to keep the distal part vascularized and to "bank" it for later use when the recipient area was well vascularized and free of infection.

Chapter 3. The adenoviral vector angiogenesis/lymphangiogenesis assay.

Adenoviral vectors expressing vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A(164)) offer a powerful method for elucidating the mechanisms of pathological angiogenesis and lymphangiogenesis and for evaluating the effectiveness of pro- and anti-angiogenesis therapies. When injected into any of a variety of tissues in nude mice or rats, adenoviral vectors expressing VEGF-A(164) (Ad-VEGF-A(164)) induce the formation of six structurally and functionally distinct types of new blood vessels: mother vessels (MV), capillaries, glomeruloid microvascular proliferations (GMP), vascular malformations (VM), feeding arteries (FA), and draining veins (DV). Each of these abnormal vessel types may be found in tumors and in other examples of pathological angiogenesis. In addition, Ad-VEGF-A(164) induces the formation of highly abnormal and poorly functional "giant" lymphatics. The Ad-VEGF-A(164) assay has provided a means of elucidating the steps and mechanisms by which each type of new blood and lymphatic vessel forms, and for generating at defined times and in large numbers each of these different types of vessels for molecular study. Ear injection sites are advantageous in that the angiogenic and lymphangiogenic responses can be followed visually over time in intact animals, thus providing a convenient, inexpensive global screening assay for assessing the efficacy and toxicity of anti- or pro-angiogenic therapies. The assay can be readily extended to the study of the new blood vessels/lymphatics induced by adenoviral vectors expressing other growth factors and cytokines.

Permeability properties of tumor surrogate blood vessels induced by VEGF-A.

Malignant tumors generate new blood vessels by secreting growth factors, particularly members of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) family. Overall, the new blood vessels that form are hyperpermeable to plasma proteins, a property that is thought to be important for generating new stroma. However, tumor blood vessels are structurally heterogeneous and include microvessels of at least the following distinct types: mother vessels (MV), glomeruloid microvascular proliferations (GMP), arterio-venous-like vascular malformations and capillaries. Our goal was to determine whether macromolecular tracers leaked from all or from only a subset of these vessel types and to elucidate the extravasation pathways. As blood vessels are only a minor component of tumors, and therefore, difficult to study in situ, we used an adenoviral vector to express VEGF-A164, the most important member of the VPF/VEGF family, in mouse tissues. So expressed, VEGF-A164 induces large numbers of surrogate vessels of each type found in tumors in a highly reproducible manner. Overall permeability to plasma proteins was assessed qualitatively with Evan's blue dye and quantitatively with a dual tracer method employing radioactive albumin. Leaky vessels were identified by confocal microscopy (FITC-dextran) and by electron microscopy (ferritin). MV, and to a lesser extent GMP, were found to be hyperpermeable but capillaries and vascular malformations were not. Ferritin extravasated primarily by two trans-cellular routes, vesiculo-vacuolar organelles (VVOs) and fenestrae. This occurred despite a considerable reduction in VVO frequency as VVO membranes translocated to the plasma membrane during MV formation. However, reduction in the number and complexity of VVOs was offset by extensive endothelial cell thinning and a greatly shortened extravasation pathway. Extrapolating these findings to tumors predicts that only a subset of tumor vessels, MV and GMP, is hyperpermeable, and that measures of overall vessel permeability greatly underestimate the permeability of individual MV and GMP.

Identification of viral genes essential for replication of murine gamma-herpesvirus 68 using signature-tagged mutagenesis.

Gamma-herpesviruses, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus are important human pathogens, because they are involved in tumor development. Murine gamma-herpesvirus-68 (MHV-68 or gammaHV-68) has emerged as a small animal model system for the study of gamma-herpesvirus pathogenesis and host-virus interactions. To identify the genes required for viral replication in vitro and in vivo, we generated 1,152 mutants using signature-tagged transposon mutagenesis on an infectious bacterial artificial chromosome of MHV-68. Almost every ORF was mutated by random insertion. For each ORF, a mutant with an insertion proximal to the N terminus of each ORF was examined for the ability to grow in fibroblasts. Our results indicate that 41 genes are essential for in vitro growth, whereas 26 are nonessential and 6 attenuated. Replication-competent mutants were pooled to infect mice, which led to the discovery of ORF 54 being important for MHV-68 to replicate in the lung. This genetic analysis of a tumor-associated herpesvirus at the whole genome level validates signature-tagged transposon mutagenesis screening as an effective genetic system to identify important virulent genes in vivo and define interactions with the host immune system.