134 research outputs found
Will REDD+ safeguards mitigate corruption? Qualitative evidence from Southeast Asia
High levels of faith and finance are being invested in REDD+ as a promising global climate change mitigation policy. Since its inception in 2007, corruption has been viewed as a potential impediment to the achievement of REDD+ goals, partly motivating ‘safeguards’ rolled out as part of national REDD+ readiness activities. We compare corruption mitigation measures adopted as part of REDD+ safeguards, drawing on qualitative case evidence from three Southeast Asian countries that have recently piloted the scheme: Indonesia, the Philippines, and Vietnam. We find that while REDD+ safeguards adopt a conventional principal-agent approach to tackling corruption in the schemes, our case evidence confirms our theoretical expectation that REDD+ corruption risks are perceived to arise not only from principal-agent type problems: they are also linked to embedded pro-corruption social norms. This implies that REDD+ safeguards are likely to be at best partially effective against corruption, and at worst will not mitigate corruption at all
Chinese multinationals: host country factors and foreign direct investment location
The study of Chinese multinationals (MNEs) is becoming one of the most promising research topics in the international business literature. After outlining the distinctive characteristics of the internationalization process of Chinese MNEs, this chapter analyzes the influence of various host country factors on the location of Chinese outward foreign direct investment (FDI). From a sample of 189 outward FDI decisions made by 35 mainland Chinese firms in 63 countries, our results show that host market size and the existence of overseas Chinese in the host country are positively associated with the number of Chinese FDIs. However, greater difficulty in doing business and host country political risk have no effect
Tetrahydrouridine Inhibits Cell Proliferation through Cell Cycle Regulation Regardless of Cytidine Deaminase Expression Levels
Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells
Environmental NGOs at a crossroads?
Article published as introduction to the Special Issue 'Environmental Politics at a crossroads', edited by Nathalie Berny & Christopher Rootes, Environmental Politics vol.27.no.6, November 201
Dirty and 40 days in the wilderness: Eliciting childbirth and postnatal cultural practices and beliefs in Nepal.
Background: Pregnancy and childbirth are socio-cultural events that carry varying meanings across different societies and cultures. These are often translated into social expectations of what a particular society expects women to do (or not to do) during pregnancy, birth and/or the postnatal period. This paper reports a study exploring beliefs around childbirth in Nepal, a low-income country with a largely Hindu population. The paper then sets these findings in the context of the wider global literature around issues such as periods where women are viewed as polluted (or dirty even) after childbirth. Methods: A qualitative study comprising five in-depth face-to-face interviews and 14 focus group discussions with mainly women, but also men and health service providers. The qualitative findings in Nepal were compared and contrasted with the literature on practices and cultural beliefs related to the pregnancy and childbirth period across the globe and at different times in history. Results: The themes that emerged from the analysis included: (a) cord cutting & placenta rituals; (b) rest & seclusion; (c) purification, naming & weaning ceremonies and (d) nutrition and breastfeeding. Physiological changes in mother and baby may underpin the various beliefs, ritual and practices in the postnatal period. These practices often mean women do not access postnatal health services. Conclusions: The cultural practices, taboos and beliefs during pregnancy and around childbirth found in Nepal largely resonate with those reported across the globe. This paper stresses that local people’s beliefs and practices offer both opportunities and barriers to health service providers. Maternity care providers need to be aware of local values, beliefs and traditions to anticipate and meet the needs of women, gain their trust and work with them
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
The Wnt-dependent signaling pathways as target in oncology drug discovery
Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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