313 research outputs found
Changes in social inequality with respect to health-related living conditions of 6-year-old children in East Germany after re-unification
BACKGROUND: Since Germany re-unified in 1990, substantial social and economic changes have happened in East Germany, the former socialist German Democratic Republic (GDR). The aim of this study was to investigate the influence of these socio-economic changes in East Germany on the association between social status, measured by parental educational level, and health-related living conditions of children during the ten-year period after re-unification. METHODS: In total, 25,864 6-year-old school beginner children (51.2% male and 48.8% female) participated in cross-sectional studies which have been repeated every year from 1991 to 2000 in East Germany. Parental educational level as a social indicator was the independent variable. Dependent variables included not employed parents, small living space and health-related living conditions (e. g. damp housing, single oven heating and living at busy road). The relationships were described by odds ratios using logistic regression. RESULTS: A large overall effect of parental educational level on health-related living conditions was observed. The time trends showed that the situation regarding small living space, damp housing conditions and single oven heating improved from 1991 to 2000, while regarding not employed parents (1996–2000) and living at busy road (1991–2000) did not, but even deteriorated. 6-year old children with low parental educational level, who lived at the time of re-unification, were often under damp housing conditions and with single oven heating at homes. Nevertheless, this social inequality has almost vanished ten years later. In contrast, we found an increasing gap between low and high parental educational level with respect to the proportion of parents who were not employed (22%: 4% gain), or lived under cramped housing conditions (22%: 37% reduction), or close to a busy road (7% gain: 2% reduction). CONCLUSION: The social inequalities which already existed under the socialist system in East Germany persisted in the system of social market economy between 1991 and 2000. 6-year-old children from families with the lowest social status were living under the worst domestic conditions (e. g. living at busy road, having damp housing conditions, single oven heating and small living space) and for some conditions (e. g. living at busy road and having small living space) the gap betweenlow and high social status was even bigger in 2000 than in 1991
Autism as a disorder of neural information processing: directions for research and targets for therapy
The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself
Impacts of climate change on plant diseases – opinions and trends
There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods
Placentation defects are highly prevalent in embryonic lethal mouse mutants.
Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation
Tendon–bone contact pressure and biomechanical evaluation of a modified suture-bridge technique for rotator cuff repair
The aim of the study was to evaluate the time-zero mechanical and footprint properties of a suture-bridge technique for rotator cuff repair in an animal model. Thirty fresh-frozen sheep shoulders were randomly assigned among three investigation groups: (1) cyclic loading, (2) load-to-failure testing, and (3) tendon–bone interface contact pressure measurement. Shoulders were cyclically loaded from 10 to 180 N and displacement to gap formation of 5- and 10-mm at the repair site. Cycles to failure were determined. Additionally, the ultimate tensile strength and stiffness were verified along with the mode of failure. The average contact pressure and pressure pattern were investigated using a pressure-sensitive film system. All of the specimens resisted against 3,000 cycles and none of them reached a gap formation of 10 mm. The number of cycles to 5-mm gap formation was 2,884.5 ± 96.8 cycles. The ultimate tensile strength was 565.8 ± 17.8 N and stiffness was 173.7 ± 9.9 N/mm. The entire specimen presented a unique mode of failure as it is well known in using high strength sutures by pulling them through the tendon. We observed a mean contact pressure of 1.19 ± 0.03 MPa, applied on the footprint area. The fundamental results of our study support the use of a suture-bridge technique for optimising the conditions of the healing biology of a reconstructed rotator cuff tendon. Nevertheless, an individual estimation has to be done if using the suture-bridge technique clinically. Further investigation is necessary to evaluate the cell biological healing process in order to achieve further sufficient advancements in rotator cuff repair
Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines
Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al
Dynamic causal modelling for EEG and MEG
Dynamic Causal Modelling (DCM) is an approach first introduced for the analysis of functional magnetic resonance imaging (fMRI) to quantify effective connectivity between brain areas. Recently, this framework has been extended and established in the magneto/encephalography (M/EEG) domain. DCM for M/EEG entails the inversion a full spatiotemporal model of evoked responses, over multiple conditions. This model rests on a biophysical and neurobiological generative model for electrophysiological data. A generative model is a prescription of how data are generated. The inversion of a DCM provides conditional densities on the model parameters and, indeed on the model itself. These densities enable one to answer key questions about the underlying system. A DCM comprises two parts; one part describes the dynamics within and among neuronal sources, and the second describes how source dynamics generate data in the sensors, using the lead-field. The parameters of this spatiotemporal model are estimated using a single (iterative) Bayesian procedure. In this paper, we will motivate and describe the current DCM framework. Two examples show how the approach can be applied to M/EEG experiments
HIV-1 Nef Protein Structures Associated with Brain Infection and Dementia Pathogenesis
The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein
What Is ‘Value’ and How Can We Capture It from the Product Value Chain?
The mobile phone industry is based upon the rapid development of handsets and the high turnover of devices in order to drive sales. Phones are often used for shorter periods of time than their designed life, and when discarded it is often through channels that result in lost resource. This unsustainable business model places strain on resources and creates adverse environmental and social impacts. Through interrogation of a stock and flow model, a product-service system (PSS) for a small consumer electronic device, a mobile telephone, is proposed. The points at which value may be extracted from the PSS are identified. A quantitative measure of value is proposed in order to allow the evaluation of the most appropriate time to extract it. This value is not solely monetary, but is derived from the combination of indicators which encompass environmental, economic, and technological factors. A worked example is presented, in which it is found that the precious metals within the phone are the main determinants for value extraction. These metals are found in the printed circuit board, leading to a requirement to design phones for ease of extraction of these components in order to access the value within
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