Blood lead levels in 2018/2019 compared to 1987/1988 in the German population-based KORA study

INTRODUCTION: Lead exposure remains of continuing concern due to its known and suspected impacts on human health and has been designated as a priority substance for investigation in human biomonitoring studies by the EU. The aims of this study were to measure blood lead levels (BLL) in a population based cohort of middle-aged individuals without major current exposures to lead, and to compare these to historical blood lead levels obtained thirty years earlier. METHODS: The population-based KORA study from 1984 to 2001 included inhabitants of the Augsburg Region, Germany. During 2018 to 2019, a subsample of these participants (KORA-Fit) was invited for interview regarding demographic and lifestyle factors, physical examination and blood withdrawal. Blood samples were stored at -80C prior to measurement of BLL via graphite furnace atomic absorption spectroscopy (GF-AAS). Descriptive and multivariable analyses were performed. RESULTS: BLLs were measured in 3033 eligible persons aged 54 to 73, establishing a geometric mean (GM) BLL of 24.8 μg/l in 2018/19. Of these, 555 (18%) had BLL above proposed 95th percentile reference values of the German Environment Agency. Only small differences were found in BLL stratified by sociodemographic categories, however regular smokers had higher GM BLL (26.1 μg/l) compared to never smokers (23.7 μg/l), and an increasing BLL with increased wine consumption was noted. For 556 individuals, BLLs (GM: 54.0 μg/l) reduced by 35% in men and 50% in women compared to levels in 1987/88 with only 1.4% of individuals having an unchanged or increased BLL. DISCUSSION: KORA-Fit provided contemporary normative data for BLL in a Western European population without major current sources of lead exposure. Mean BLLs have fallen since the 1980s using historical BLL data which is likely linked to the ban of leaded gasoline. Nevertheless, BLLs in this population remain elevated at levels associated with morbidity and mortality

A new approach to cure and reinforce cold-cured acrylics

Purpose: The low degree of polymerization of cold-cured acrylics has resulted in inferior mechanical properties and fracture vulnerability in orthodontics removable appliances. Methods: In this study, the effect of reinforcement by various concentrations of chopped E-glass fibers (0%, 1%, 2%, 3% and 5% by weight of resin powder) and post-curing microwave irradiation (800 W for 3 min) on the flexural strength of cold-cured acrylics was evaluated at various storage conditions (at room temperature for 1 day and 7 days; at water storage for 7, 14 and 30 days). Results: The data was analyzed by using 1-way and 2-way ANOVA, and a Tukey post hoc test (α = .05). The specimens with chopped E-glass fibers treated with post-curing microwave irradiation significantly increased the flexural strength of cold-cured PMMA. The optimal concentration might be 2% fibers under irradiation. Conclusions: The exhibited reinforcement effect lasted in a consistent trend for 14 days in water storage. A new fiber-acrylic mixing method was also developed. © 2012 The Author(s).published_or_final_versio

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

The minimal computational substrate of fluid intelligence

The quantification of cognitive powers rests on identifying a behavioural task that depends on them. Such dependence cannot be assured, for the powers a task invokes cannot be experimentally controlled or constrained a priori, resulting in unknown vulnerability to failure of specificity and generalisability. Evaluating a compact version of Raven's Advanced Progressive Matrices (RAPM), a widely used clinical test of fluid intelligence, we show that LaMa, a self-supervised artificial neural network trained solely on the completion of partially masked images of natural environmental scenes, achieves human-level test scores a prima vista, without any task-specific inductive bias or training. Compared with cohorts of healthy and focally lesioned participants, LaMa exhibits human-like variation with item difficulty, and produces errors characteristic of right frontal lobe damage under degradation of its ability to integrate global spatial patterns. LaMa's narrow training and limited capacity -- comparable to the nervous system of the fruit fly -- suggest RAPM may be open to computationally simple solutions that need not necessarily invoke abstract reasoning.Comment: 26 pages, 5 figure

Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering

In developmental biology, gradients of bioactive signals direct the formation of structural transitions in tissue that are key to physiological function. Failure to reproduce these native features in an in vitro setting can severely limit the success of bioengineered tissue constructs. In this report, we introduce a facile and rapid platform that uses magnetic field alignment of glycosylated superparamagnetic iron oxide nanoparticles, pre-loaded with growth factors, to pattern biochemical gradients into a range of biomaterial systems. Gradients of bone morphogenetic protein 2 in agarose hydrogels were used to spatially direct the osteogenesis of human mesenchymal stem cells and generate robust osteochondral tissue constructs exhibiting a clear mineral transition from bone to cartilage. Interestingly, the smooth gradients in growth factor concentration gave rise to biologically-relevant, emergent structural features, including a tidemark transition demarcating mineralized and non-mineralized tissue and an osteochondral interface rich in hypertrophic chondrocytes. This platform technology offers great versatility and provides an exciting new opportunity for overcoming a range of interfacial tissue engineering challenges

Changes in and predictors of length of stay in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England: a population-based

BACKGROUND Decreases in length of stay (LOS) in hospital after breast cancer surgery can be partly attributed to the change to less radical surgery, but many other factors are operating at the patient, surgeon and hospital levels. This study aimed to describe the changes in and predictors of length of stay (LOS) in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England. METHODS Cases of female invasive breast cancer diagnosed in two English cancer registry regions were linked to Hospital Episode Statistics data for the period 1st April 1997 to 31st March 2005. A subset of records where women underwent mastectomy or breast conserving surgery (BCS) was extracted (n = 44,877). Variations in LOS over the study period were investigated. A multilevel model with patients clustered within surgical teams and NHS Trusts was used to examine associations between LOS and a range of factors. RESULTS Over the study period the proportion of women having a mastectomy reduced from 58% to 52%. The proportion varied from 14% to 80% according to NHS Trust. LOS decreased by 21% from 1997/98 to 2004/05 (LOSratio = 0.79, 95%CI 0.77-0.80). BCS was associated with 33% shorter hospital stays compared to mastectomy (LOSratio = 0.67, 95%CI 0.66-0.68). Older age, advanced disease, presence of comorbidities, lymph node excision and reconstructive surgery were associated with increased LOS. Significant variation remained amongst Trusts and surgical teams. CONCLUSION The number of days spent in hospital after breast cancer surgery has continued to decline for several decades. The change from mastectomy to BCS accounts for only 9% of the overall decrease in LOS. Other explanations include the adoption of new techniques and practices, such as sentinel lymph node biopsy and early discharge. This study has identified wide variation in practice with substantial cost implications for the NHS. Further work is required to explain this variation

Awe and Wonder in Scientific Practice: Implications for the Relationship Between Science and Religion

This paper examines the role of awe and wonder in scientific practice. Drawing on evidence from psychological research and the writings of scientists and science communicators, I argue that awe and wonder play a crucial role in scientific discovery. They focus our attention on the natural world, encourage open-mindedness, diminish the self (particularly feelings of self-importance), help to accord value to the objects that are being studied, and provide a mode of understanding in the absence of full knowledge. I will flesh out implications of the role of awe and wonder in scientific discovery for debates on the relationship between science and religion. Abraham Heschel argued that awe and wonder are religious emotions because they reduce our feelings of self-importance, and thereby help to cultivate the proper reverent attitude towards God. Yet metaphysical naturalists such as Richard Dawkins insist that awe and wonder need not lead to any theistic commitments for scientists. The awe some scientists experience can be regarded as a form of non-theistic spirituality, which is neither a reductive naturalism nor theism. I will attempt to resolve the tension between these views by identifying some common ground

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

The discursive construction of childhood and youth in AIDS interventions in Lesotho's education sector: Beyond global-local dichotomies

This is the post-print version of this article. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning D,Society and Space 28(5) 791 – 810, 2010, available from the link below. Copyright @ 2010 Pion.In southern Africa interventions to halt the spread of AIDS and address its social impacts are commonly targeted at young people, in many cases through the education sector. In Lesotho, education-sector responses to AIDS are the product of negotiation between a range of ‘local’ and ‘global’ actors. Although many interventions are put forward as government policy and implemented by teachers in schools, funding is often provided by bilateral and multilateral donors, and the international ‘AIDS industry’—in the form of UN agencies and international NGOs—sets agendas and makes prescriptions. This paper analyses interviews conducted with policy makers and practitioners in Lesotho and a variety of documents, critically examining the discourses of childhood and youth that are mobilised in producing changes in education policy and practice to address AIDS. Focusing on bursary schemes, life-skills education, and rights-based approaches, the paper concludes that, although dominant ‘global’ discourses are readily identified, they are not simply imported wholesale from the West, but rather are transformed through the organisations and personnel involved in designing and implementing interventions. Nonetheless, the connections through which these discourses are made, and children are subjectified, are central to the power dynamics of neoliberal globalisation. Although the representations of childhood and youth produced through the interventions are hybrid products of local and global discourses, the power relations underlying them are such that they, often unintentionally, serve a neoliberal agenda by depicting young people as individuals in need of saving, of developing personal autonomy, or of exercising individual rights.RGS-IB

Deep forecasting of translational impact in medical research

The value of biomedical research--a $1.7 trillion annual investment--is ultimately determined by its downstream, real-world impact. Current objective predictors of impact rest on proxy, reductive metrics of dissemination, such as paper citation rates, whose relation to real-world translation remains unquantified. Here we sought to determine the comparative predictability of future real-world translation--as indexed by inclusion in patents, guidelines or policy documents--from complex models of the abstract-level content of biomedical publications versus citations and publication meta-data alone. We develop a suite of representational and discriminative mathematical models of multi-scale publication data, quantifying predictive performance out-of-sample, ahead-of-time, across major biomedical domains, using the entire corpus of biomedical research captured by Microsoft Academic Graph from 1990 to 2019, encompassing 43.3 million papers across all domains. We show that citations are only moderately predictive of translational impact as judged by inclusion in patents, guidelines, or policy documents. By contrast, high-dimensional models of publication titles, abstracts and metadata exhibit high fidelity (AUROC > 0.9), generalise across time and thematic domain, and transfer to the task of recognising papers of Nobel Laureates. The translational impact of a paper indexed by inclusion in patents, guidelines, or policy documents can be predicted--out-of-sample and ahead-of-time--with substantially higher fidelity from complex models of its abstract-level content than from models of publication meta-data or citation metrics. We argue that content-based models of impact are superior in performance to conventional, citation-based measures, and sustain a stronger evidence-based claim to the objective measurement of translational potential