Palaeoclimatic Control on the Composition of Palaeozoic Shales from Southern Ghana, West Africa

The Late Ordovician to Early Cretaceous Sekondian Group of southern Ghana is made up of seven major sedimentary formations. One important feature of the Sekondian Group is the abundance of fairly fresh plagioclase in the lowest two formations, i.e., the Ajua Shale and Elmina Sandstone, and at the uppermost formation (i.e., Essikado Sandstone); but a virtual absence throughout the rest of the Group. The basal part of the Sekondian Group has been interpreted as of glacial origin whereas the upper formations are thought to have formed in a warmer stage. The abundant plagioclase in the lowest two formations could, therefore, be due to less pervasive chemical weathering rather than erosion of a distinct source. In this paper, geochemical data for fine-grained sedimentary rocks of the Ajua Shale and the Takoradi Shale (that overlie the Elmina Sandstone) formations are used to investigate the influence of palaeoweathering on the composition of the Sekondian Group.The concentrations of the transition trace metals Cr, Ni, V, and Cu, and Cr/V-, Zr/Y-, and Ba/Co-ratios are similar in the samples from both formations and suggest that they were largely derived from the granitoids that intrude the Birimian supracrastal rocks. However, the Takoradi Shale samples are enriched in Rb, Cs, Th, U, and Nb relative to the Ajua Shale samples, and this may be related to differences in the degree of weathering in the source rocks. The Takoradi Shale samples are characterized by high chemical index of alteration (CIA) values and Rb/Sr ratios (CIA > 75; Rb/Sr > 1) indicating high degrees of weathering of their source rocks. In contrast, the Ajua Shale samples have low CIA values and Rb/Sr ratios (CIA < 62; Rb/Sr < 0.5) that indicate low degrees of weathering of their source. The tectonic setting at the time of deposition of both formations was passive margin suggesting that the change in paleoclimatic conditions rather than erosion rates played a more dominant role in the observed compositional changes in these shales

AXL-associated tumor inflammation as a poor prognostic signature in chemotherapy-treated triple-negative breast cancer patients

A subgroup of triple-negative breast cancer (TNBC) shows epithelial-to-mesenchymal transition (EMT) features, which are sustained by the interaction between cancer cells and tumor-associated macrophages (TAMs). In this study, the clinical relevance of 30 EMT-related kinases and the potential cross-talk with TAMs were investigated in a cohort of 203 TNBC patients treated with adjuvant chemotherapy. The prognostic value of the evaluated markers was validated in two independent cohorts of TNBC patients treated with adjuvant chemotherapy (N=95; N=137). In vitro, we investigated the potential synergism between cancer cells and TAMs. We found that the EMT-related kinase AXL showed the highest correlation with the frequency of CD163-positive macrophages (rS=0.503; P<0.0001). Relapsing TNBC patients presented high expression of AXL (P<0.0001) and CD163 (P<0.018), but only AXL retained independent prognostic significance in multivariate analysis (relapse-free survival, P=0.002; overall survival P=0.001). In vitro analysis demonstrated that AXL-expressing TNBC cells were able to polarize human macrophages towards an M2-like phenotype, and modulate a specific pattern of pro-tumor cytokines and chemokines. Selective AXL inhibition impaired the activity of M2-like macrophages, reducing cancer cell invasiveness, and restoring the sensitivity of breast cancer cells to chemotherapeutic drugs. These data suggest that the EMT-related kinase AXL overexpressed in cancer cells has prognostic significance, and contributes to the functional skewing of macrophage functions in TNBC. AXL inhibition may represent a novel strategy to target cancer cells, as well as tumor-promoting TAMs in TNBC

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36−/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Geochemistry of lower proterozoic greywackes from the Birim diamondiferous field, Ghana

The Birim Diamondiferous field from which most of the alluvial diamonds are recovered is underlain by Lower Proterozoic Birimian metasedimentary and associated mafic rocks. Bulk rock geochemistry was carried out on the sandstones from the metasedimentary rocks to constrain the tectonic setting during the early Proterozoic. Bulk rock geochemical studies on greywackes show that they are characterized by moderately low but variable SiO2 contents, generally high Al2O3 and ferromagnesian element (e.g., Fe, Mg, Cr, V, Co, Sc) contents, and K2O/Na20 commonly less than 1. The geochemical data indicate that the greywackes were deposited in an active continental margin environment. The detritus were mainly derived from the upper continental crust but with an admixture of mafic component. Recent studies have shown that some of the mafics/ultramafics are diamondiferous metakimberlites. The inferred tectonic (arc) setting makes the emplacement of the so-called Proterozoic diamondiferous metakimberlites unlikely, if we are to go by the Clifford's Rule. However, if these ultramafic rocks are really metakimberlites and the source of the diamonds, then the Clifford's Rule may not be applicable in the Ghanaian situation, and the Birim field may be one of the few exceptions to this general rule. This would, then, present a typical example of subduction zone related diamondiferous kimberlites. Keywords: Birim Diamondiferous field, Birimian, geochemistry, Ghana, tectornc settingAfrican Journal of Science and Technology Vol. 5(2) 2004: 9-1

Socio-cultural determinants of timely and delayed treatment of Buruli ulcer: implications for disease control

INTRODUCTION: Public health programmes recommend timely medical treatment for Buruli ulcer (BU) infection to prevent pre-ulcer conditions from progressing to ulcers, to minimise surgery, disabilities and the socio-economic impact of BU. Clarifying the role of socio-cultural determinants of timely medical treatment may assist in guiding public health programmes to improve treatment outcomes. This study clarified the role of socio-cultural determinants and health system factors affecting timely medical treatment for BU in an endemic area in Ghana. METHODS: A semi-structured explanatory model interview based on the explanatory model interview catalogue (EMIC) was administered to 178 BU-affected persons. Based on research evidence, respondents were classified as timely treatment (use of medical treatment 3 months from awareness of disease) and delayed treatment (medical treatment 3 months after onset of disease and failure to use medical treatment). The outcome variable, timely treatment was analysed with cultural epidemiological variables for categories of distress, perceived causes of BU, outside-help and reasons for medical treatment in logistic regression models. The median time for the onset of symptoms to treatment was computed in days. Qualitative phenomenological analysis of respondents’ narratives clarified the meaning, context and dynamic features of the relationship of explanatory variables with timely medical treatment. RESULTS: The median time for initiating treatment was 25 days for pre-ulcers, and 204 days for ulcers. Income loss and use of herbalists showed significantly negative associations with timely treatment. Respondents’ use of herbalists was often motivated by the desire for quick recovery in order to continue with work and because herbalists were relatives and easily accessible. However, drinking unclean water was significantly associated with timely treatment and access to health services encouraged timely treatment (OR 8.5, p = 0.012). Findings show that health system factors of access are responsible for non-compliance to treatment regimes. CONCLUSIONS: Findings highlight the importance of an integrated approach to BU control and management considering the social and economic features that influence delayed treatment and factors that encourage timely medical treatment. This approach should consider periodic screening for early case-detection, collaboration with private practitioners and traditional healers, use of mobile services to improve access, adherence and treatment outcomes

Lipid-Lowering Effects of Tetradecylthioacetic Acid in Antipsychotic-Exposed, Female Rats: Challenges with Long-Term Treatment

Background: Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. Aims: In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Methods: Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. Results: The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. Conclusion: TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a more valid long-term rat model for antipsychotic-induced metabolic adverse effects is required