A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer.

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

Socioeconomic groups and cancer risk at death in the Swiss Canton of Vaud.

Data collected by the Cancer Registry of the Canton of Vaud, Switzerland, were used to estimate proportional mortality ratios (PMR) and mortality odds ratios (MOR) for various neoplasms according to social class and sector of occupation (agriculture versus others). Mortality ratios were elevated in lower social classes for cancers of the lung (MOR = 1.18 for social class IV or V vs I or II) and other sites strictly related to tobacco (mouth or pharynx, oesophagus and larynx; MOR = 1.70), and (though not significantly) for cancers of the stomach (MOR = 1.16) and uterus (MOR = 1.30 for cervix and 1.47 for corpus uteri). Furthermore, there was a strong negative social class gradient for thyroid cancer (a neoplasm with particularly elevated incidence and mortality in Switzerland), probably attributable to higher prevalence of iodine deficiency in lower social classes (MOR = 3.17). Positive social class gradients emerged for cancers of the intestines (MOR = 0.77 for social class IV or V), skin (MOR = 0.74) and prostate (MOR = 0.87). Agricultural workers showed decreased ratios for cancers of the lung (MOR = 0.75), cervix uteri (MOR = 0.72) and prostate (MOR = 0.80), and excess mortality from cancers of the upper digestive and respiratory sites (MOR = 1.22), stomach (MOR = 1.18), testis (MOR = 2.05) and lympho-haematopoietic neoplasms, particularly myeloma (MOR = 2.14).

An international university network for online teaching of pathology in Frenchspeaking countries

Introduction: Building online courses is a highly time consuming task for teachers of a single university. Universities working alone create high-quality courses but often cannot cover all pathological fields. Moreover this often leads to duplication of contents among universities, representing a big waste of teacher time and energy. We initiated in 2011 a French university network for building mutualized online teaching pathology cases, and this network has been extended in 2012 to Quebec and Switzerland. Method: Twenty French universities (see & for details), University Laval in Quebec and University of Lausanne in Switzerland are associated to this project. One e-learning Moodle platform (http://moodle.sorbonne-paris-cite.fr/) contains texts with URL pointing toward virtual slides that are decentralized in several universities. Each university has the responsibility of its own slide scanning, slide storage and online display with virtual slide viewers. The Moodle website is hosted by PRES Sorbonne Paris Cité, and financial supports for hardware have been obtained from UNF3S (http://www.unf3s.org/) and from PRES Sorbonne Paris Cité. Financial support for international fellowships has been obtained from CFQCU (http://www.cfqcu.org/). Results: The Moodle interface has been explained to pathology teachers using web-based conferences with screen sharing. The teachers added then contents such as clinical cases, selfevaluations and other media organized in several sections by student levels and pathological fields. Contents can be used as online learning or online preparation of subsequent courses in classrooms. In autumn 2013, one resident from Quebec spent 6 weeks in France and Switzerland and created original contents in inflammatory skin pathology. These contents are currently being validated by senior teachers and will be opened to pathology residents in spring 2014. All contents of the website can be accessed for free. Most contents just require anonymous connection but some specific fields, especially those containing pictures obtained from patients who agreed for a teaching use only, require personal identification of the students. Also, students have to register to access Moodle tests. All contents are written in French but one case has been translated into English to illustrate this communication (http://moodle.sorbonne-pariscite.fr/mod/page/view.php?id=261) (use "login as a guest"). The Moodle test module allows many types of shared questions, making it easy to create personalized tests. Contents that are opened to students have been validated by an editorial committee composed of colleagues from the participating institutions. Conclusions: Future developments include other international fellowships, the next one being scheduled for one French resident from May to October 2014 in Quebec, with a study program centered on lung and breast pathology. It must be kept in mind that these e-learning programs highly depend on teachers' time, not only at these early steps but also later to update the contents. We believe that funding resident fellowships for developing online pathological teaching contents is a win-win situation, highly beneficial for the resident who will improve his knowledge and way of thinking, highly beneficial for the teachers who will less worry about access rights or image formats, and finally highly beneficial for the students who will get courses fully adapted to their practice.

Predictive accuracy of original and recalibrated Framingham risk score in the Swiss population.

OBJECTIVE: To compare the predictive accuracy of the original and recalibrated Framingham risk function on current morbidity from coronary heart disease (CHD) and mortality data from the Swiss population. METHODS: Data from the CoLaus study, a cross-sectional, population-based study conducted between 2003 and 2006 on 5,773 participants aged 35-74 without CHD were used to recalibrate the Framingham risk function. The predicted number of events from each risk function were compared with those issued from local MONICA incidence rates and official mortality data from Switzerland. RESULTS: With the original risk function, 57.3%, 21.2%, 16.4% and 5.1% of men and 94.9%, 3.8%, 1.2% and 0.1% of women were at very low (<6%), low (6-10%), intermediate (10-20%) and high (>20%) risk, respectively. With the recalibrated risk function, the corresponding values were 84.7%, 10.3%, 4.3% and 0.6% in men and 99.5%, 0.4%, 0.0% and 0.1% in women, respectively. The number of CHD events over 10 years predicted by the original Framingham risk function was 2-3 fold higher than predicted by mortality+case fatality or by MONICA incidence rates (men: 191 vs. 92 and 51 events, respectively). The recalibrated risk function provided more reasonable estimates, albeit slightly overestimated (92 events, 5-95th percentile: 26-223 events); sensitivity analyses showed that the magnitude of the overestimation was between 0.4 and 2.2 in men, and 0.7 and 3.3 in women. CONCLUSION: The recalibrated Framingham risk function provides a reasonable alternative to assess CHD risk in men, but not in women.

A first population-based cohort study of risk factors of stroke mortality in Africa

Background: We are not aware of any population-based cohort study of risk factors of stroke in the African region. We conducted a longitudinal study in the Seychelles (Indian Ocean, east of Kenya), a middle-income island state with majority of the population of African descent. Data in Africa are important for international comparison and for advocacy in the region. Methods: Three population-based examination surveys were performed in 1989, 1994 and 2004 (n_1081, 1067, and 1255, respectively). Baseline data were linked with cause-specific mortality from vital statistics up to May 2007. We considered stroke (any type) as a cause of death if the diagnosis was reported in any of the 4 fields for underlying and concomitant causes of death. Results. Among the 3317 different persons aged 25-64 at baseline, 291 died including 58 with stroke during follow up (mean: 10.2 years). The prevalence of high blood pressure (BP _140/90 mmHg) was 38%. In multivariate Cox regression, stroke mortality was increased by 18% and 35% for a 10-mmHg increase in systolic, respectively diastolic BP (p_0.001). The hazard ratios were 2.4 (95% CI: 1.7-3.3) for a 10-year age increase, 0.32 (0.15- 0.67) for a 1-mmol HDL-cholesterol increase, 2.2 (1.1- 4.2) for smoking _5 cigarettes vs. no smoking and 1.7 for diabetes (0.93-3.3; p_0.08). No significant association was found for sex, LDL-cholesterol, alcohol intake, and occupation. Conclusion. This first populationbased cohort study in the African region demonstrates high mortality rates from stroke in middle-aged adults and confirms the important role of high BP. This emphasizes the critical importance of reducing BP and other modifiable risk factors in this population.

Risk and global change : developing scientific methods for advocacy and awareness raising

Les catastrophes sont souvent perçues comme des événements rapides et aléatoires. Si les déclencheurs peuvent être soudains, les catastrophes, elles, sont le résultat d'une accumulation des conséquences d'actions et de décisions inappropriées ainsi que du changement global. Pour modifier cette perception du risque, des outils de sensibilisation sont nécessaires. Des méthodes quantitatives ont été développées et ont permis d'identifier la distribution et les facteurs sous- jacents du risque.¦Le risque de catastrophes résulte de l'intersection entre aléas, exposition et vulnérabilité. La fréquence et l'intensité des aléas peuvent être influencées par le changement climatique ou le déclin des écosystèmes, la croissance démographique augmente l'exposition, alors que l'évolution du niveau de développement affecte la vulnérabilité. Chacune de ses composantes pouvant changer, le risque est dynamique et doit être réévalué périodiquement par les gouvernements, les assurances ou les agences de développement. Au niveau global, ces analyses sont souvent effectuées à l'aide de base de données sur les pertes enregistrées. Nos résultats montrent que celles-ci sont susceptibles d'être biaisées notamment par l'amélioration de l'accès à l'information. Elles ne sont pas exhaustives et ne donnent pas d'information sur l'exposition, l'intensité ou la vulnérabilité. Une nouvelle approche, indépendante des pertes reportées, est donc nécessaire.¦Les recherches présentées ici ont été mandatées par les Nations Unies et par des agences oeuvrant dans le développement et l'environnement (PNUD, l'UNISDR, la GTZ, le PNUE ou l'UICN). Ces organismes avaient besoin d'une évaluation quantitative sur les facteurs sous-jacents du risque, afin de sensibiliser les décideurs et pour la priorisation des projets de réduction des risques de désastres.¦La méthode est basée sur les systèmes d'information géographique, la télédétection, les bases de données et l'analyse statistique. Une importante quantité de données (1,7 Tb) et plusieurs milliers d'heures de calculs ont été nécessaires. Un modèle de risque global a été élaboré pour révéler la distribution des aléas, de l'exposition et des risques, ainsi que pour l'identification des facteurs de risque sous- jacent de plusieurs aléas (inondations, cyclones tropicaux, séismes et glissements de terrain). Deux indexes de risque multiples ont été générés pour comparer les pays. Les résultats incluent une évaluation du rôle de l'intensité de l'aléa, de l'exposition, de la pauvreté, de la gouvernance dans la configuration et les tendances du risque. Il apparaît que les facteurs de vulnérabilité changent en fonction du type d'aléa, et contrairement à l'exposition, leur poids décroît quand l'intensité augmente.¦Au niveau local, la méthode a été testée pour mettre en évidence l'influence du changement climatique et du déclin des écosystèmes sur l'aléa. Dans le nord du Pakistan, la déforestation induit une augmentation de la susceptibilité des glissements de terrain. Les recherches menées au Pérou (à base d'imagerie satellitaire et de collecte de données au sol) révèlent un retrait glaciaire rapide et donnent une évaluation du volume de glace restante ainsi que des scénarios sur l'évolution possible.¦Ces résultats ont été présentés à des publics différents, notamment en face de 160 gouvernements. Les résultats et les données générées sont accessibles en ligne (http://preview.grid.unep.ch). La méthode est flexible et facilement transposable à des échelles et problématiques différentes, offrant de bonnes perspectives pour l'adaptation à d'autres domaines de recherche.¦La caractérisation du risque au niveau global et l'identification du rôle des écosystèmes dans le risque de catastrophe est en plein développement. Ces recherches ont révélés de nombreux défis, certains ont été résolus, d'autres sont restés des limitations. Cependant, il apparaît clairement que le niveau de développement configure line grande partie des risques de catastrophes. La dynamique du risque est gouvernée principalement par le changement global.¦Disasters are often perceived as fast and random events. If the triggers may be sudden, disasters are the result of an accumulation of actions, consequences from inappropriate decisions and from global change. To modify this perception of risk, advocacy tools are needed. Quantitative methods have been developed to identify the distribution and the underlying factors of risk.¦Disaster risk is resulting from the intersection of hazards, exposure and vulnerability. The frequency and intensity of hazards can be influenced by climate change or by the decline of ecosystems. Population growth increases the exposure, while changes in the level of development affect the vulnerability. Given that each of its components may change, the risk is dynamic and should be reviewed periodically by governments, insurance companies or development agencies. At the global level, these analyses are often performed using databases on reported losses. Our results show that these are likely to be biased in particular by improvements in access to information. International losses databases are not exhaustive and do not give information on exposure, the intensity or vulnerability. A new approach, independent of reported losses, is necessary.¦The researches presented here have been mandated by the United Nations and agencies working in the development and the environment (UNDP, UNISDR, GTZ, UNEP and IUCN). These organizations needed a quantitative assessment of the underlying factors of risk, to raise awareness amongst policymakers and to prioritize disaster risk reduction projects.¦The method is based on geographic information systems, remote sensing, databases and statistical analysis. It required a large amount of data (1.7 Tb of data on both the physical environment and socio-economic parameters) and several thousand hours of processing were necessary. A comprehensive risk model was developed to reveal the distribution of hazards, exposure and risk, and to identify underlying risk factors. These were performed for several hazards (e.g. floods, tropical cyclones, earthquakes and landslides). Two different multiple risk indexes were generated to compare countries. The results include an evaluation of the role of the intensity of the hazard, exposure, poverty, governance in the pattern and trends of risk. It appears that the vulnerability factors change depending on the type of hazard, and contrary to the exposure, their weight decreases as the intensity increases.¦Locally, the method was tested to highlight the influence of climate change and the ecosystems decline on the hazard. In northern Pakistan, deforestation exacerbates the susceptibility of landslides. Researches in Peru (based on satellite imagery and ground data collection) revealed a rapid glacier retreat and give an assessment of the remaining ice volume as well as scenarios of possible evolution.¦These results were presented to different audiences, including in front of 160 governments. The results and data generated are made available online through an open source SDI (http://preview.grid.unep.ch). The method is flexible and easily transferable to different scales and issues, with good prospects for adaptation to other research areas. The risk characterization at a global level and identifying the role of ecosystems in disaster risk is booming. These researches have revealed many challenges, some were resolved, while others remained limitations. However, it is clear that the level of development, and more over, unsustainable development, configures a large part of disaster risk and that the dynamics of risk is primarily governed by global change.

Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.

Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.

A proposal for an international retinoblastoma staging system.

BACKGROUND: Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease. PROCEDURE: A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and II patients. RESULTS: The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage I: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricular or cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and II eyes. CONCLUSIONS: The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease.

Quantitative Ultrasound of the Heel and Fracture Risk Assessment: an Updated Meta-Analysis

Objectives: Quantitative ultrasound (QUS) is an attractive method for assessing fracture risk because it is portable, inexpensive, without ionizing radiation, and available in areas of the world where DXA is not readily accessible or affordable. However, the diversity of QUS scanners and variability of fracture outcomes measured in different studies is an important obstacle to widespread utilisation of QUS for fracture risk assessment. We aimed in this review to assess the predictive power of heel QUS for fractures considering different characteristics of the association (QUS parameters and fracture outcomes measured, QUS devices, study populations, and independence from DXA-measured bone density).Materials/Methods : We conducted an inverse-variance randomeffects 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 : 21 studies including 55,164 women and 13,742 men were included with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fractures. 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). Validated devices from different manufacturers predicted fracture risks with a similar performance (meta-regression p-values>0.05 for difference of devices). There was no sign of publication bias among the studies. QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip DXA 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 QUS of the heel using validated devices predicts risk of different fracture outcomes in elderly men and women. Further research and international collaborations are needed for standardisation of QUS parameters across various manufacturers and inclusion of QUS in fracture risk assessment tools. Disclosure of Interest : None declared.

Cross-Sectional and Longitudinal Associations between Body Mass Index and Cardiometabolic Risk Factors in Adolescents in a Country of the African Region.

We assessed the association between several cardiometabolic risk factors (CRFs) (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, uric acid, and glucose) in 390 young adults aged 19-20 years in Seychelles (Indian Ocean, Africa) and body mass index (BMI) measured either at the same time (cross-sectional analysis) or at the age of 12-15 years (longitudinal analysis). BMI tracked markedly between age of 12-15 and age of 19-20. BMI was strongly associated with all considered CRFs in both cross-sectional and longitudinal analyses, with some exceptions. Comparing overweight participants with those having a BMI below the age-specific median, the odds ratios for high blood pressure were 5.4/4.7 (male/female) cross-sectionally and 2.5/3.9 longitudinally (P < 0.05). Significant associations were also found for most other CRFs, with some exceptions. In linear regression analysis including both BMI at age of 12-15 and BMI at age of 19-20, only BMI at age of 19-20 remained significantly associated with most CRFs. We conclude that CRFs are predicted strongly by either current or past BMI levels in adolescents and young adults in this population. The observation that only current BMI remained associated with CRFs when including past and current levels together suggests that weight control at a later age may be effective in reducing CRFs in overweight children irrespective of past weight status.

Official Positions for FRAX® clinical regarding prior fractures from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The 2010 Position Development Conference addressed four questions related to the impact of previous fractures on 10-year fracture risk as calculated by FRAX(®). To address these questions, PubMed was searched on the keywords "fracture, epidemiology, osteoporosis." Titles of retrieved articles were reviewed for an indication that risk for future fracture was discussed. Abstracts of these articles were reviewed for an indication that one or more of the questions listed above was discussed. For those that did, the articles were reviewed in greater detail to extract the findings and to find additional past work and citing works that also bore on the questions. The official positions and the supporting literature review are presented here. FRAX(®) underestimates fracture probability in persons with a history of multiple fractures (good, A, W). FRAX(®) may underestimate fracture probability in individuals with prevalent severe vertebral fractures (good, A, W). While there is evidence that hip, vertebral, and humeral fractures appear to confer greater risk of subsequent fracture than fractures at other sites, quantification of this incremental risk in FRAX(®) is not possible (fair, B, W). FRAX(®) may underestimate fracture probability in individuals with a parental history of non-hip fragility fracture (fair, B, W). Limitations of the methodology include performance by a single reviewer, preliminary review of the literature being confined to titles, and secondary review being limited to abstracts. Limitations of the evidence base include publication bias, overrepresentation of persons of European descent in the published studies, and technical differences in the methods used to identify prevalent and incident fractures. Emerging topics for future research include fracture epidemiology in non-European populations and men, the impact of fractures in family members other than parents, and the genetic contribution to fracture risk.

Covariance Matrix Estimation and Mean-Variance Optimization in application to International Diversification

Tutkimus keskittyy kansainväliseen hajauttamiseen suomalaisen sijoittajan näkökulmasta. Tutkimuksen toinen tavoite on selvittää tehostavatko uudet kovarianssimatriisiestimaattorit minimivarianssiportfolion optimointiprosessia. Tavallisen otoskovarianssimatriisin lisäksi optimoinnissa käytetään kahta kutistusestimaattoria ja joustavaa monimuuttuja-GARCH(1,1)-mallia. Tutkimusaineisto koostuu Dow Jonesin toimialaindekseistä ja OMX-H:n portfolioindeksistä. Kansainvälinen hajautusstrategia on toteutettu käyttäen toimialalähestymistapaa ja portfoliota optimoidaan käyttäen kahtatoista komponenttia. Tutkimusaieisto kattaa vuodet 1996-2005 eli 120 kuukausittaista havaintoa. Muodostettujen portfolioiden suorituskykyä mitataan Sharpen indeksillä. Tutkimustulosten mukaan kansainvälisesti hajautettujen investointien ja kotimaisen portfolion riskikorjattujen tuottojen välillä ei ole tilastollisesti merkitsevää eroa. Myöskään uusien kovarianssimatriisiestimaattoreiden käytöstä ei synnytilastollisesti merkitsevää lisäarvoa verrattuna otoskovarianssimatrisiin perustuvaan portfolion optimointiin.

Official Positions for FRAX® Bone Mineral Density and FRAX® simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.