95 research outputs found

    Relationship between bullet diameter and bullet defect diameter in human calvariums

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    Existing literature on the relationship between bullet diameter and bullet defect diameter in the human calvarium is summarized and discussed. The hypothesis, derived from the literature, that bullet deformation influences bullet defect diameter was studied in a small controlled experiment. The mean defect size caused by non-deforming projectiles was found to be smaller than the mean defect size caused by deforming projectiles of equal original mass and size. The p value of the difference between the two means, measured in two different ways, was found to be 0.002 for both in a Mann-Whitney U test and was significant if the confidence level is set at 5%

    Comparison and interpretation of impressed marks left by a firearm on cartridge cases - Towards an operational implementation of a likelihood ratio based technique.

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    Firearm examination is subject to increased scrutiny regarding its foundational validity and inherent subjective nature. The increased use of automatic comparison systems may help to reduce subjectivity. In this paper, we present the performance and limits of an automatic comparison system that assigns a weight to the forensic findings for the comparisons between firing pin marks, breechface marks, or a combination of the two. This weight is expressed by a likelihood ratio (LR) based on 3D topographical measurements coupled with a bi-dimensional statistical model. As the performance of such systems may depend on the reference databases used to inform the model, we investigated the impact of the brand of ammunition and the number of samples. We show that reference databases used to calculate LRs should ideally consist of the same type of ammunition as is seen in the case under investigation and that 7 specimens fired by the same firearm are enough to obtain rates of misleading evidence of a similar magnitude compared to those obtained when far more specimens (60) are used. Additionally, the automatic system was used to assess the outcomes of 7 cases with known same-source or different-source ground truths. These cases were also examined by 8 qualified firearm examiners. In all cases, the experts' appraisals were in line with the ground truth. The automatic system showed some limitations in cases were the data were not sufficient to calculate a robust LR, but also that it can assist and enhance the examiners in their decision process

    The governance of urban green spaces in selected EU-cities : Policies, Practices, Actors, Topics

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    In a time of continuing urbanization, there is an increasing focus on developing attractive and healthy urban environments. Green spaces, ranging from woodlands and parks to allotment gardens and green roofs, provide a range of ecosystem services that contribute to better cities (Lovell and Taylor, 2013). The Green Infrastructure and Urban Biodiversity for Sustainable Urban Development and the Green Economy project (GREEN SURGE in brief), funded under the EU’s 7th Framework Programme for research, will identify, develop and test ways of linking green spaces, biodiversity, people and the green economy in order to meet the major urban challenges related to land use conflicts, climate change adaptation, demographic changes and human health and well being. The contents of this report are based on work conducted in Work Package 6, one of the eight Work Packages of GREEN SURGE. Work Package 6 focuses on governance arrangements for urban green spaces. In this report, we discuss the findings of the GREEN SURGE Work Package 6 Tier 1 research on identifying and conceptualising innovative participatory governance arrangements in regards to the management of urban green infrastructure

    The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis

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    Aberrant activity of the glucocorticoid (GC)/glucocorticoid receptor (GR) endocrine system has been linked to obesity-related metabolic dysfunction. Traditionally, the GC/GR axis has been believed to play a crucial role in adipose tissue formation and function in both, white (WAT) and brown adipose tissue (BAT). While recent studies have challenged this notion for WAT, the contribution of GC/GR signaling to BAT-dependent energy homeostasis remained unknown. Here, we have generated and characterized a BAT-specific GR-knockout mouse (GRBATKO), for the first time allowing to genetically interrogate the metabolic impact of BAT-GR. The HPA axis in GRBATKO mice was intact, as was the ability of mice to adapt to cold. BAT-GR was dispensable for the adaptation to fasting–feeding cycles and the development of diet-induced obesity. In obesity, glucose and lipid metabolism, insulin sensitivity, and food intake remained unchanged, aligning with the absence of changes in thermogenic gene expression. Together, we demonstrate that the GR in UCP1-positive BAT adipocytes plays a negligible role in systemic metabolism and BAT function, thereby opposing a long-standing paradigm in the field

    The cadherin–catenin complex in laryngeal squamous cell carcinoma

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    Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, β-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of β-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of β-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of β-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues

    The cadherin–catenin complex in nasopharyngeal carcinoma

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    Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze β-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. β-Catenin and E-cadherin expression were examined in 18 nasopharyngeal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clinical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. β-catenin was detected in membrane and cytoplasm in all cases of nasopharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, β-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carcinoma tissues. E-cadherin expression was associated with β-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic β-catenin in nasopharyngeal carcinoma may impair cell–cell adhesion, promoting invasive behavior and a metastatic tumor phenotype

    Local therapy of cancer with free IL-2

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    This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is attained. Analysis of the results of local IL-2 therapy in 288 cases of cancer in human patients shows that there were 27% Complete Regressions (CR), 23% Partial Regressions (PR), 18% Stable Disease (SD), and 32% Progressive Disease (PD). In all tumors analyzed, local IL-2 therapy was more effective than systemic IL-2 treatment. Intratumoral IL-2 applications are more effective than peritumoral application or application at a distant site. Tumor regression induced by intratumoral IL-2 application may be a fast process (requiring about a week) in the case of a highly vascular tumor since IL-2 induces vascular leakage/edema and consequently massive tumor necrosis. The latter then stimulates an immune response. In less vascular tumors or less vascular tumor sites, regression may require 9–20 months; this regression is mainly caused by a cytotoxic leukocyte reaction. Hence the disadvantageous vascular leakage syndrome complicating systemic treatment is however advantageous in local treatment, since local edema may initiate tumor necrosis. Thus the therapeutic effect of local IL-2 treatment is not primarily based on tumor immunity, but tumor immunity seems to be useful as a secondary component of the IL-2 induced local processes. If local IL-2 is combined with surgery, radiotherapy or local chemotherapy the therapeutic effect is usually greater than with either therapy alone. Hence local free IL-2 application can be recommended as an addition to standard treatment protocols. Local treatment with free IL-2 is straightforward and can readily be applied even during surgical interventions. Local IL-2 treatment is usually without serious side effects and besides minor complaints it is generally well supported. Only small quantities of IL-2 are required. Hence the therapy is relatively cheap. A single IL-2 application of 4.5 million U IL-2 costs about 70 Euros. Thus combined local treatment may offer an alternative in those circumstances when more expensive forms of treatment are not available, for instance in resource poor countries

    Advancing co-production for transformative change by synthesizing guidance from case studies on the sustainable management and governance of natural resources.

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    Co-production has become paramount for scientists, practitioners and social groups of Indigenous peoples and local communities of rural and urban areas to deliver transformative changes that enhance sustainability. Coproduction should result in knowledge that is credible, legitimate and usable to enable sustainable outcomes effectively. However, this is not always the case due to challenges related to differences between scientific and Indigenous and local knowledge, as well as inherent power imbalances. The literature emphasises that these challenges are often triggered by rigid scientific theories and postures, dominant practices, and time-money limitations that co-production projects involve. This happens despite the adoption of guidelines recommended in the literature. We investigate the role of these challenges and guidelines in the generation of credible, legitimate, usable, and effective knowledge. We analyse this role in 13 co-production cases focused on sustainable transformative changes linked with the management and governance of natural resources across the globe. Despite challenges varying between groups and contexts, credibility, usability, and effectiveness are promoted simultaneously, especially when co-production empowers social actors via legitimate processes. Scientists and practitioners do so, through creative and flexible reshaping of existing knowledge and worldviews with a focus on common goals that link sustainability and livelihoods. They conceptualise a mutual understanding of knowledge and that is deemed trustworthy feasible to use in their socioecological context. Our findings complement existing scholarship on co-production, exploring the credibility of situated knowledge and its practical effectiveness together with its commonly addressed legitimacy and usability. A focus on the practices of different actors, including dynamics that are external to co-production, and changes in the scientific and social status quo, are needed to advance co-production effectiveness

    Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

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