ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.

Study designA longitudinal cohort study.ObjectiveTo define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients.MethodsWe collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls.ResultsStandard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls.ConclusionsLongitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material

An evaluation of a refresher training intervention for HIV lay counsellors in Chongwe District, Zambia

To address a severe shortage of human resources for health, the Zambian Ministry of Health has begun to make use of lay counsellors for HIV counselling and testing. However, their skills and knowledge rarely have been reviewed or refreshed. We conducted a two-day refresher workshop for lay counsellors to review their performance and refresh their skills and knowledge. The objective of this study was to evaluate the refresher training intervention for HIV lay counsellors in the rural district of Chongwe in Zambia. The two-day refreshertraining workshop was held in November 2009. Twenty-five lay counsellors were selected by District Health Office and participated in the workshop. The workshop included: the opening, a pre-training exercise, lectures on quality assurance with regard to testing and safety precautions, lectures on counselling, filling the gap/Q&A session, and a post-training exercise. In both the pre- and post-trainingexercise, participants answered 25 true/false questions and tested 10 blood panel samples to demonstrate their knowledge and skill on HIV counselling and testing. The average overall knowledge test score  increased from 79% to 95% (p<0.001). At the baseline, knowledgetest scores in topic of standard precaution and post-exposure prophylaxis were relatively low (58%) but rose to 95% after the training (p<0.001). The per cent agreement of HIV testing by lay counsellors with reference laboratory was 99.2%. Participants’ knowledge was improved during the workshop and skill at HIV testing was found to remain at a high level of accuracy. Relatively weak knowledge of standard precautions and post-exposure prophylaxis suggests that lay counsellors are at risk of nosocomial infections, particularly in the absence of refresher training interventions. We conclude that the refresher training was effective for improving the knowledge and skills of lay counsellors and provided an opportunity to monitor their performance

Effectiveness and cost of an incentive-based intervention on food safety and income in "dibiteries" in Dakar, Senegal

BACKGROUND: Rapid urbanisation in Sub-Saharan African cities such as Dakar, Senegal, leads to proliferation of informal braised meat restaurants known as "dibiteries". Dibiteries do not often comply with minimal hygiene and food safety standards. The primary objective of this study was to assess the effectiveness and cost of a good hygiene practice intervention, identify factors that incentivize hygiene improvement and how that impacts on dibiteries' income. METHODS: A randomized controlled trial was carried out in Dakar dibiteries. The 120 random samples of braised meat were collected in three phases: (i) one-month pre-intervention, (ii) 2 months post-intervention, (iii) 10 months post-intervention. The trial comprised four groups of 10 dibiteries each: (a) (control) received no intervention, (b) a standardized training module, (c) a hygiene kit, (d) a training module and hygiene kit. Laboratory analysis of samples determined the total aerobic mesophilic flora (TAMF), thermotolerant coliforms (TC) and Staphylococcus aureus (SA). A questionnaire-based survey and focus group discussion were used to identify pre-intervention hygiene practices, and socioeconomic determinants of hygiene management in dibiteries post-intervention, respectively. RESULTS: Samples were found to be contaminated with TAMF, TC and SA. In phase 1, 27 and 13% of the samples contained TC and SA, respectively. In phase 2, no significant improvement of contamination rates was seen. In phase 3, microbiological quality of samples was significantly improved, with only 11.5% showing contamination with any of the bacterial species analysed (p < 0.1). Compared to the control group, only samples from dibiteries in group (b) had significantly reduced bacterial load in phase 3. The cost of intervention and hygiene improvement was estimated at 67 FCFA ($0.12) and 41 FCFA ($ 0.07) / day respectively and did not significantly impact on dibiterie profitability. Incentives to sustainably implement good hygiene practices were mainly linked to access to secure long-term workspaces. CONCLUSION: This intervention may have worked, but globally the results are mixed and not quite significant. However, continuous training in good hygiene practice and access to secure and sustainable infrastructure for dibiterie restaurants are the incentives necessary to achieve sustainable investments and behavioural change. We recommend further intervention refinement and testing other factors for promoting the adoption of good hygiene practices in the dibiteries in relation to consumers health risk

Curvature fluctuations and Lyapunov exponent at Melting

We calculate the maximal Lyapunov exponent in constant-energy molecular dynamics simulations at the melting transition for finite clusters of 6 to 13 particles (model rare-gas and metallic systems) as well as for bulk rare-gas solid. For clusters, the Lyapunov exponent generally varies linearly with the total energy, but the slope changes sharply at the melting transition. In the bulk system, melting corresponds to a jump in the Lyapunov exponent, and this corresponds to a singularity in the variance of the curvature of the potential energy surface. In these systems there are two mechanisms of chaos -- local instability and parametric instability. We calculate the contribution of the parametric instability towards the chaoticity of these systems using a recently proposed formalism. The contribution of parametric instability is a continuous function of energy in small clusters but not in the bulk where the melting corresponds to a decrease in this quantity. This implies that the melting in small clusters does not lead to enhanced local instability.Comment: Revtex with 7 PS figures. To appear in Phys Rev

Human Sclera Maintains Common Characteristics with Cartilage throughout Evolution

BACKGROUND: The sclera maintains and protects the eye ball, which receives visual inputs. Although the sclera does not contribute significantly to visual perception, scleral diseases such as refractory scleritis, scleral perforation and pathological myopia are considered incurable or difficult to cure. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. METHODOLOGY/PRINCIPAL FINDINGS: We have demonstrated microarray data of cultured human infant scleral cells. Hierarchical clustering was performed to group scleral cells and other mesenchymal cells into subcategories. Hierarchical clustering analysis showed similarity between scleral cells and auricular cartilage-derived cells. Cultured micromasses of scleral cells exposed to TGF-betas and BMP2 produced an abundant matrix. The expression of cartilage-associated genes, such as Indian hedge hog, type X collagen, and MMP13, was up-regulated within 3 weeks in vitro. These results suggest that human 'sclera'-derived cells can be considered chondrocytes when cultured ex vivo. CONCLUSIONS/SIGNIFICANCE: Our present study shows a chondrogenic potential of human sclera. Interestingly, the sclera of certain vertebrates, such as birds and fish, is composed of hyaline cartilage. Although the human sclera is not a cartilaginous tissue, the human sclera maintains chondrogenic potential throughout evolution. In addition, our findings directly explain an enigma that the sclera and the joint cartilage are common targets of inflammatory cells in rheumatic arthritis. The present global gene expression database will contribute to the clarification of the pathogenesis of developmental diseases such as high myopia

Big-Data-Driven Materials Science and its FAIR Data Infrastructure

This chapter addresses the forth paradigm of materials research -- big-data driven materials science. Its concepts and state-of-the-art are described, and its challenges and chances are discussed. For furthering the field, Open Data and an all-embracing sharing, an efficient data infrastructure, and the rich ecosystem of computer codes used in the community are of critical importance. For shaping this forth paradigm and contributing to the development or discovery of improved and novel materials, data must be what is now called FAIR -- Findable, Accessible, Interoperable and Re-purposable/Re-usable. This sets the stage for advances of methods from artificial intelligence that operate on large data sets to find trends and patterns that cannot be obtained from individual calculations and not even directly from high-throughput studies. Recent progress is reviewed and demonstrated, and the chapter is concluded by a forward-looking perspective, addressing important not yet solved challenges.Comment: submitted to the Handbook of Materials Modeling (eds. S. Yip and W. Andreoni), Springer 2018/201

Sodium Selenide Toxicity Is Mediated by O2-Dependent DNA Breaks

Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few experiments studied the direct link between this toxic agent and cell death. To address this question, we first screened a systematic collection of Saccharomyces cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor for hydrogen selenide (H2Se/HSe−/Se2−). Among the genes whose deletion caused hypresensitivity, homologous recombination and DNA damage checkpoint genes were over-represented, suggesting that DNA double-strand breaks are a dominant cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly induced DNA phosphodiester-bond breaks via an O2-dependent reaction. The reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl radicals and ruling out participations of superoxide anions or hydrogen peroxide. The •OH signature could indeed be detected by electron spin resonance upon exposure of a solution of sodium selenide to O2. Finally we showed that, in vivo, toxicity strictly depended on the presence of O2. Therefore, by combining genome-wide and biochemical approaches, we demonstrated that, in yeast cells, hydrogen selenide induces toxic DNA breaks through an O2-dependent radical-based mechanism

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. Methods: In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025. Interpretation: On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. Funding: Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK