Dynamic characterisation of a heritage structure with limited accessibility using ambient vibrations

Historic Cairo has been a UNESCO World Heritage Site since 1979. It has more than 600 historic structures, which require extensive studies to sustain their cultural, religious, and economic values. The main aim of this paper is to undertake dynamic investigation tests for the dome of Fatima Khatun, a historic mausoleum in Historic Cairo dating back to the 13th century and consisting of mainly bricks and stones. The challenge was that the structure was difficult to access, and only a small portion of the top was accessible for the attachment of accelerometers. Current dynamic identification procedures typically adopt methods in which the sensors are arranged at optimal locations and permit direct assessment of the natural frequencies, mode shapes, and damping ratios of a structure. Approaches that allow for the evaluation of dynamic response for structures with limited accessibility are lacking. To this end, in addition to in situ dynamic investigation tests, a numerical model was created based on available architectural, structural, and material documentation to obtain detailed insight into the dominant modes of vibration. The free vibration analysis of the numerical model identified the dynamic properties of the structure using reasonable assumptions on boundary conditions. System identification, which was carried out using in situ dynamic investigation tests and input from modelling, captured three experimental natural frequencies of the structure with their mode shapes and damping ratios. The approach proposed in this study informs and directs structural restoration for the mausoleum and can be used for other heritage structures located in congested historic sites

The impact of iron overload and its treatment on quality of life: results from a literature review

BACKGROUND: To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. METHODS: A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. RESULTS: Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. CONCLUSION: A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL

Changes in liver mitochondrial plasticity induced by brain tumor

BACKGROUND: Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. METHODS: Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H(2)Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. CONCLUSION: This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation

Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers.</p> <p>Methods</p> <p>From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit.</p> <p>Results</p> <p>In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054).</p> <p>Conclusions</p> <p>Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.</p

Financial feasibility of end-user designed rainwater harvesting and greywater reuse systems for high water use households

© 2017, The Author(s). Water availability pressures, competing end-uses and sewers at capacity are all drivers for change in urban water management. Rainwater harvesting (RWH) and greywater reuse (GWR) systems constitute alternatives to reduce drinking water usage and in the case of RWH, reduce roof runoff entering sewers. Despite the increasing popularity of installations in commercial buildings, RWH and GWR technologies at a household scale have proved less popular, across a range of global contexts. For systems designed from the top-down, this is often due to the lack of a favourable cost-benefit (where subsidies are unavailable), though few studies have focused on performing full capital and operational financial assessments, particularly in high water consumption households. Using a bottom-up design approach, based on a questionnaire survey with 35 households in a residential complex in Bucaramanga, Colombia, this article considers the initial financial feasibility of three RWH and GWR system configurations proposed for high water using households (equivalent to >203L per capita per day). A full capital and operational financial assessment was performed at a more detailed level for the most viable design using historic rainfall data. For the selected configuration (‘Alt 2’), the estimated potable water saving was 44% (equivalent to 131m3/year) with a rate of return on investment of 6.5% and an estimated payback period of 23years. As an initial end-user-driven design exercise, these results are promising and constitute a starting point for facilitating such approaches to urban water management at the household scale

Modeling double strand break susceptibility to interrogate structural variation in cancer

Abstract Background Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). Results We used experimentally quantified DSB frequencies in cell lines with matched chromatin and sequence features to derive the first quantitative genome-wide models of DSB susceptibility. These models are accurate and provide novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type-specific processes. Using model predictions as a proxy for susceptibility to DSBs in tumors, many SV-enriched regions appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of these regions show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation and are therefore credible targets of positive selection in tumors. These putatively positively selected SV hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel coldspot regions appear to be subject to purifying selection in tumors and are enriched for active promoters and enhancers. Conclusions We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumors

Pesticide use and opportunities of exposure among farmers and their families: cross-sectional studies 1998-2006 from Hebron governorate, occupied Palestinian territory

<p>Abstract</p> <p>Background</p> <p>Adverse health effects caused by pesticide exposure have been reported in occupied Palestinian territory and the world at large. The objective of this paper is to compare patterns of pesticide use in Beit-U'mmar village, West Bank, between 1998 and 2006.</p> <p>Methods</p> <p>We studied two populations in Beit-U'mmar village, comprised of: 1) 61 male farmers and their wives in 1998 and 2) 250 male farmers in 2006. Both populations completed a structured interview, which included questions about socio-demographic factors, types of farming tasks, as well as compounds, quantities, and handling of pesticides. Using the 1998 population as a reference, we applied generalized linear regression models (GLM) and 95% confidence intervals (CI) in order to estimate prevalence differences (PD) between the two populations.</p> <p>Results</p> <p>In 1998, farmers used 47 formulated pesticides on their crops. In 2006, 16 of these pesticides were still in use, including five internationally banned compounds. There were positive changes with less use of large quantities of pesticides (>40 units/year) (PD -51; CI -0.60, -0.43), in applying the recommended dosage of pesticides (PD +0.57; CI +0.48, +0.68) and complying with the safety period (PD +0.89; CI+0.83, +0.95). Changes also included farmers' habits while applying pesticides, such as less smoking (PD -0.20; CI-0.34, -0.07) and eating at the work place (PD -0.33; CI-0.47, -0.19). No significant changes were found from 1998 to 2006 regarding use of personal protective equipment, pesticide storage, farmers' habits after applying pesticides, and in using some highly hazardous pesticides.</p> <p>Conclusions</p> <p>The results were based on two cross-sectional surveys and should be interpreted with caution due to potential validity problems. The results of the study suggest some positive changes in the handling of pesticides amongst participants in 2006, which could be due to different policy interventions and regulations that were implemented after 1998. However, farm workers in Beit -U'mmar village are still at risk of health effects because of ongoing exposure to pesticides. To the best of our knowledge, no studies on long-term changes in pesticide use have been reported from developing countries.</p

Derivation of a Myeloid Cell-Binding Adenovirus for Gene Therapy of Inflammation

The gene therapy field is currently limited by the lack of vehicles that permit efficient gene delivery to specific cell or tissue subsets. Native viral vector tropisms offer a powerful platform for transgene delivery but remain nonspecific, requiring elevated viral doses to achieve efficacy. In order to improve upon these strategies, our group has focused on genetically engineering targeting domains into viral capsid proteins, particularly those based on adenovirus serotype 5 (Ad5). Our primary strategy is based on deletion of the fiber knob domain, to eliminate broad tissue specificity through the human coxsackie-and-adenovirus receptor (hCAR), with seamless incorporation of ligands to re-direct Ad tropism to cell types that express the cognate receptors. Previously, our group and others have demonstrated successful implementation of this strategy in order to specifically target Ad to a number of surface molecules expressed on immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid cell-binding peptide (MBP), with the sequence WTLDRGY, and demonstrated that MBP can be successfully incorporated into a knob-deleted Ad5. The resulting virus, Ad.MBP, results in specific binding to primary myeloid cell types, as well as significantly higher transduction of these target populations ex vivo, compared to unmodified Ad5. These data are the first step in demonstrating Ad targeting to cell types associated with inflammatory disease