Can the trabecular bone score be considered as a major clinical risk factor of osteoporotic fractures? A meta-like analysis.

To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist. Out of these factors many of them are indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 cross-sectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest compared with the middle TBS tertile was 1.55[1.46-1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

Two groups of Schistosoma japonicum infected patients (acute and chronic ) and non-infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard deviation of the optical density in ELISA of acute, chronic and negative groups for IgA anti-SEA were 583±124.7, 98.2±78.8 and 82.2±39. 3, respectively. There was a statistically significance between acute patients and chronic patients (P<0.01). The means and standard deviation of IgG and IgM antibodies to KLH were 501.5±150.6, 113.0±79.1, 28.8±56.3 and 413.6±148.5, 70.2±14.8, 65.3±45.3, respectively. The detection results of IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant difference (P>0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%, respectively. Therefore, this study showed that the detection of IgA to SEA is also a useful new method for the serological differentiation of acute and chronic schistosomiasis japonica in humans.

Creació de material docent digital per l'assignatura transversal de Geoarqueologia

En aquest projecte hem seguit desenvolupant i ampliant els continguts d’una assignatura de caràcter transversal entre Geologia i Arqueologia Prehistòrica aplicada als estudis universitaris. Aquesta ampliació s’ha dut a terme amb la creació d'un recull de fitxes amb les dades més rellevants d’alguns sepulcres megalítics de Catalunya fent especial esment als materials petris utilitzats en la seva construcció de per tal de poder desenvolupar i contextualitzar els resultats que s’assoleixin durant el curs. Cadascuna de les fitxes inclou per cada megàlit: 1) una situació geogràfica, 2) una part de descripció des del punt de vista arqueològic i 3) una part geològica amb la situació, descripció dels elements petris de les lloses tant a visu com al microscopi petrogràfic i una localització probable de l’àrea de procedència de les lloses. Això suposa un aprofundiment i ampliació de l'oferta pedagògica proposada que permet experimentar una metodologia d’ensenyament universitari més pràctica, aplicada i interactiva i s’emmarca en l’eix temàtic al voltant del qual es desenvolupa l’assignatura.

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women.

SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

Lipid composition of fingermark residue and donor classification using GC/MS

Lipids available in fingermark residue represent important targets for enhancement and dating techniques. While it is well known that lipid composition varies among fingermarks of the same donor (intra-variability) and between fingermarks of different donors (inter-variability), the extent of this variability remains uncharacterised. Thus, this worked aimed at studying qualitatively and quantitatively the initial lipid composition of fingermark residue of 25 different donors. Among the 104 detected lipids, 43 were reported for the first time in the literature. Furthermore, palmitic acid, squalene, cholesterol, myristyl myristate and myristyl myristoleate were quantified and their correlation within fingermark residue was highlighted. Ten compounds were then selected and further studied as potential targets for dating or enhancement techniques. It was shown that their relative standard deviation was significantly lower for the intra-variability than for the inter-variability. Moreover, the use of data pretreatments could significantly reduce this variability. Based on these observations, an objective donor classification model was proposed. Hierarchical cluster analysis was conducted on the pre-treated data and the fingermarks of the 25 donors were classified into two main groups, corresponding to "poor" and "rich" lipid donors. The robustness of this classification was tested using fingermark replicates of selected donors. 86% of these replicates were correctly classified, showing the potential of such a donor classification model for research purposes in order to select representative donors based on compounds of interest.

Structural prediction of peptides bound to MHC class I.

An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values &lt; or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values &lt; or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.

La définition des interfaces pour améliorer la qualité: l'exemple de l'anorexie en hospitalisation somatique [Defining interfaces to improve quality of care: the example of anorexia nervosa in acute somatic hospitalisation]

Specialisation in medicine requires multidisciplinary approaches, and hence coordination in collaborations of the different partners involved. These integrated approaches, sometimes called "disease management", fit particularly well to chronic diseases. Our institution introduced an integrated approach for taking care of the acute somatic hospitalisation of patients suffering from anorexia nervosa. Interfaces with the different partners were defined, specifying tasks, rights, and duties of each person, care givers or patients. This initiative allows now to identify any deviation occurring in the process of care or hole in the care system, so that it can be corrected and recurrence prevented. This model will be extended to other complex and multidisciplinary care processes and other services in our institution.

How does monetary policy change? evidence on inflation targeting countries

We examine the evolution of monetary policy rules in a group of inflation targeting countries (Australia, Canada, New Zealand, Sweden and the United Kingdom) applying moment- based estimator at time-varying parameter model with endogenous regressors. Using this novel flexible framework, our main findings are threefold. First, monetary policy rules change gradually pointing to the importance of applying time-varying estimation framework. Second, the interest rate smoothing parameter is much lower that what previous time-invariant estimates of policy rules typically report. External factors matter for all countries, albeit the importance of exchange rate diminishes after the adoption of inflation targeting. Third, the response of interest rates on inflation is particularly strong during the periods, when central bankers want to break the record of high inflation such as in the U.K. or in Australia at the beginning of 1980s. Contrary to common wisdom, the response becomes less aggressive after the adoption of inflation targeting suggesting the positive effect of this regime on anchoring inflation expectations. This result is supported by our finding that inflation persistence as well as policy neutral rate typically decreased after the adoption of inflation targeting.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis.

Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures.Introduction Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach.Methods We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions.Results Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]).Conclusions This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

INTRODUCTION: The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. METHODS: Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. RESULTS: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. CONCLUSIONS: Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.

Allelic Diversity at the Merozoite Surface Protein-1 (MSP-1) Locus in Natural Plasmodium falciparum Populations: a Brief Overview

The merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum codes for a major asexual blood-stage antigen currently proposed as a major malaria vaccine candidate. The protein, however, shows extensive polymorphism, which may compromise its use in sub-unit vaccines. Here we compare the patterns of allelic diversity at the MSP-1 locus in wild isolates from three epidemiologically distinct malaria-endemic areas: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest that MSP-1 is under selective pressure in the local parasite population. Nevertheless, the finding that similar MSP-1 type frequencies were found in 1994 and 1996 argues against the prominence of short-term frequency-dependent immune selection of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolates from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not among those from Brazil and Vietnam, shows significant deviation from that expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epidemiological consequences of these findings are discussed

Volumetric quantification of atherosclerotic plaque in CT considering partial volume effect.

Coronary artery calcification (CAC) is quantified based on a computed tomography (CT) scan image. A calcified region is identified. Modified expectation maximization (MEM) of a statistical model for the calcified and background material is used to estimate the partial calcium content of the voxels. The algorithm limits the region over which MEM is performed. By using MEM, the statistical properties of the model are iteratively updated based on the calculated resultant calcium distribution from the previous iteration. The estimated statistical properties are used to generate a map of the partial calcium content in the calcified region. The volume of calcium in the calcified region is determined based on the map. The experimental results on a cardiac phantom, scanned 90 times using 15 different protocols, demonstrate that the proposed method is less sensitive to partial volume effect and noise, with average error of 9.5% (standard deviation (SD) of 5-7mm(3)) compared with 67% (SD of 3-20mm(3)) for conventional techniques. The high reproducibility of the proposed method for 35 patients, scanned twice using the same protocol at a minimum interval of 10 min, shows that the method provides 2-3 times lower interscan variation than conventional techniques.

Evolutionary ecology of learning: insights from fruit flies

Ecologically and evolutionarily oriented research on learning has traditionally been carried out on vertebrates and bees. While less sophisticated than those animals, fruit flies (Drosophila) are capable of several forms of learning, and have an advantage of a short generation time, which makes them an ideal system for experimental evolution studies. This review summarizes the insights into evolutionary questions about learning gained in the last decade from evolutionary experiments on Drosophila. These experiments demonstrate that Drosophila have the genetic potential to evolve substantially improved learning performance in ecologically relevant learning tasks. In at least one set of selected populations the improved learning generalized to another task than that used to impose selection, involving a different behavior, different stimuli, and a different sensory channel for the aversive reinforcement. This improvement in learning ability was associated with reduction in other fitness-related traits, such as larval competitive ability and lifespan, pointing out to evolutionary trade-offs of improved learning. These trade-offs were confirmed by other evolutionary experiments where reduction in learning performance was observed as a correlated response to selection for tolerance to larval nutritional stress or for delayed aging. Such trade-offs could be one reason why fruit flies have not fully used up their evolutionary potential for learning ability. Finally, another evolutionary experiment with Drosophila provided the first direct evidence for the long-standing ideas that learning can under some circumstances accelerate and in other slow down genetically-based evolutionary change. These results demonstrate the usefulness of fruit flies as a model system to address evolutionary questions about learning.

The metaphysics of quantum gravity : a causal approach

The dissertation investigates some relevant metaphysical issues arising in the context of spacetime theories. In particular, the inquiry focuses on general relativity and canonical quantum gravity. A formal definition of spacetime theory is proposed and, against this framework, an analysis of the notions of general covariance, symmetry and background independence is performed. It is argued that many conceptual issues in general relativity and canonical quantum gravity derive from putting excessive emphasis on general covariance as an ontological prin-ciple. An original metaphysical position grounded in scientific essential- ism and causal realism (weak essentialism) is developed and defended. It is argued that, in the context of general relativity, weak essentialism supports spacetime substantivalism. It is also shown that weak essentialism escapes arguments from metaphysical underdetermination by positing a particular kind of causation, dubbed geometric. The proposed interpretive framework is then applied to Bohmian mechanics, pointing out that weak essentialism nicely fits into this theory. In the end, a possible Bohmian implementation of loop quantum gravity is considered, and such a Bohmian approach is interpreted in a geometric causal fashion. Under this interpretation, Bohmian loop quantum gravity straightforwardly commits us to an ontology of elementary extensions of space whose evolution is described by a non-local law. The causal mechanism underlying this evolution clarifies many conceptual issues related to the emergence of classical spacetime from the quantum regime. Although there is as yet no fully worked out physical theory of quantum gravity, it is argued that the proposed approach sets up a standard that proposals for a serious ontology in this field should meet.

IPH response to 'Towards a Childcare Strategy' (Northern Ireland)

The remit of the Institute of Public Health in Ireland (IPH) is to promote cooperation for public health between Northern Ireland and the Republic of Ireland in the areas of research and information, capacity building and policy advice. Our approach is to support Departments of Health and their agencies in both jurisdictions, and maximise the benefits of all-island cooperation to achieve practical benefits for people in Northern Ireland and the Republic of Ireland. Giving every child the best start in life is recognised by governments worldwide as the most effective way to improve life chances and health outcomes.  This is one of IPH’s key strategic action areas in our Business Plan and we endorse the need for early intervention, particularly in tackling health inequalities and improving the health and wellbeing of children in the most disadvantaged communities.  International evidence is increasingly pointing towards investment in the early years as a critical component of any sensible approach to improving population health and tackling health inequalities across the life course (WHO, 2008 and Marmot, 2010).  It is also apparent that Northern Ireland public policy is now reorienting towards achieving better and fairer outcomes in the early years, as demonstrated through the recent draft public health strategy (DHSSPS, 2012a) and the draft early years strategy (Department of Education, 2012).