A state-of-the-art multi-criteria model for drug benefit-risk analysis

Drug benefit-risk analysis is based on firm clinical evidence related to various safety and efficacy outcomes, such as tolerability, treatment response, and adverse events. In this paper, we propose a new approach for constructing a supporting multi-criteria model that fully takes into account this evidence. Our approach is based on the Stochastic Multicriteria Acceptability Analysis (SMAA) methodology, which allows us to compute the typical value judgments that support a decision, to quantify uncertainty, and to compute a comprehensive benefit-risk profile. As an example, we constructed a multi-criteria model for the therapeutic group of second-generation antidepressants. We analyzed Fluoxetine, Paroxetine, Sertraline, and Venlafaxine according to relative efficacy and absolute rates of several common adverse drug reactions using meta-analytical data from the literature. Our model showed that there are clear trade-offs among the four drugs. Based on our experiences from this study, SMAA appears to be a suitable approach for quantifying trade-offs and decision uncertainty in drug benefit-risk analysis.

Sidosryhmäjohtamisen hyvät käytänteet ja haasteet rakennusprojekteissa

Tiivistelmä. Sidosryhmäjohtaminen on kriittinen osa projektijohtamista. Rakennusprojektien onnistumisen kannalta erityisen tärkeää on hyvä sidosryhmäjohtaminen, sillä sidosryhmiä on lukuisia ja rakennusprojektit ovat monimutkaisia. Vaikka sidosryhmäjohtamiseen on olemassa monenlaisia lähestymistapoja ja työkaluja, se ei siltikään ole helppoa rakennusprojekteissa. Tässä kandidaatintyössä pyritään selvittämään rakennusprojektien sidosryhmäjohtamisen hyviä käytänteitä sekä haasteita. Työn tavoitteena on toimia tietolähteenä projektien sidosryhmäjohtamisesta kiinnostuneille. Työn tutkimusmenetelmänä on kirjallisuuskatsaus. Tutkimuksen olennaisimpana löydöksenä oli, että sidosryhmien analysointi on yleisin johtamiskeino rakennusprojekteissa, sillä sen avulla projektin johto tietää, miten huomioida kutakin sidosryhmää. Haasteena kuitenkin on se, että laajojen projektien sidosryhmiä on lukuisia ja niiden asema projektin suhteen vaihtelee. Tämä monimutkaistaa analysointia ja tekee siitä työlästä. Jatkotutkimuksessa voitaisiin tutkia sidosryhmäjohtamista rakennusprojekteissa erityisesti sidosryhmien näkökulmasta ja sidosryhmäjohtamisen työkalujen käytännön soveltuvuuksia eri kokoisissa rakennusprojekteissa. Tätä työtä voidaan hyödyntää tietopakettina projektijohtamisen opiskelussa tai projektijohtajien kertauskoulutuksessa yleisellä tasolla. Tutkimuksen sisältö on hyödynnettävissä monentyyppisissä projekteissa kuitenkin muistaen, että esitettyjä keinoja tulee soveltaa osin projektikohtaisesti.Good practices and challenges of stakeholder management in construction projects. Abstract. Stakeholder management is a critical part of project management. Good and effective stakeholder management is particularly important for the success of construction projects, given the large number of stakeholders and the complexity of construction projects. Although there is a variety of approaches and tools for stakeholder management available, it is still not easy in construction projects. This thesis aims to identify good practices and challenges of stakeholder management in construction projects. The aim is to serve as a source of information for those interested in stakeholder management in projects. The research method used is a literature review. The main finding of the research was that stakeholder analysis is the most common management tool in construction projects, as it allows the project management to know how to take each stakeholder into account. The challenge, however, is that there are many stakeholders in large-scale projects and their position towards the project varies. This complicates the analysis and makes it more demanding. Further research could explore stakeholder management in construction projects from the perspective of stakeholders and also the practical applicability of stakeholder management tools in construction projects of different sizes. This work could be used as a knowledge package in project management studies or in refresher training for project managers in general. The content of the study can be used in many types of projects, remembering that the methods presented must be applied to some extent on a projectspecific basis

Evaluation of scalarization methods and NSGA-II/SPEA2 genetic algorithms for multi-objective optimization of green supply chain design

This paper considers supply chain design in green logistics. We formulate the choice of an environmentally conscious chain design as a multi-objective optimization (MOO) problem and approximate the Pareto front using the weighted sum and epsilon constraint scalarization methods as well as with two popular genetic algorithms, NSGA-II and SPEA2. We extend an existing case study of green supply chain design in the South Eastern Europe region by optimizing simultaneously costs, CO2 and fine dust (also known as PM - Particulate Matters) emissions. The results show that in the considered case the scalarization methods outperform genetic algorithms in finding efficient solutions and that the CO2 and PM emissions can be lowered by accepting a marginal increase of costs over their global minimum

Terveyden edistäminen on kunnan tehtävä

Ensisijainen vastuu terveyden edistämisestä on kunnalla. Kunnassa tehdään päätökset siitä, miten terveyden edistäminen toteutuu kunnan alueella

Macrophage Subset Sensitivity to Endotoxin Tolerisation by Porphyromonas gingivalis

Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14hi and CD14lo M1- and M2-like MΦs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and vitamin D3, respectively. MΦ subsets were pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity

Flood Impacts on Road Transportation Using Microscopic Traffic Modelling Techniques

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordThis paper proposes a novel methodology for modelling the impacts of floods on traffic. Often, flooding is a complex combination of various causes (coastal, fluvial and pluvial). Further, transportation systems are very sensitive to external disturbances. The interactions between these two complex and dynamic systems have not been studied in detail so far. To address this issue, this paper proposes a methodology for a dynamic integration of a flood model (MIKE FLOOD) and a microscopic traffic simulation model (SUMO). The flood modelling results indicate which roads are inundated for a period of time. The traffic on these links will be halted or delayed according to the flood characteristics—extent, propagation and depth. As a consequence, some of the trips need to be cancelled; some need to be rerouted to unfavourable routes; and some are indirectly affected. A comparison between the baseline and a flood scenario yields the impacts of that flood on traffic, estimated in terms of lost business hours, additional fuel consumption and additional CO2 emissions. The proposed methodology will be further developed as a workable tool to evaluate the flooding impact on transportation network at city scale automatically.Research on the PEARL (Preparing for Extreme And Rare events in coastaL regions) project is funded by the European Commission through Framework Programme 7, Grant Number 603663

Reduced propagation loss in silicon strip and slot waveguides coated by atomic layer deposition

When silicon strip and slot waveguides are coated with a 50nm amorphous titanium dioxide (TiO2) film, measured losses at a wavelength of 1.55μm can be as low as (2±1)dB/cm and (7±2)dB/cm, respectively. We use atomic layer deposition (ALD), estimate the effect of ALD growth on the surface roughness, and discuss the effect on the scattering losses. Because the gap between the rails of a slot waveguide narrows by the TiO2 deposition, the effective slot width can be back-end controlled. This is useful for precise adjustment if the slot is to be filled with, e. g., a nonlinear organic material or with a sensitizer for sensors applications

Self – perceived and clinically diagnosed dental and periodontal health status among young adults and their implications for epidemiological surveys

BACKGROUND: Clinical (normative) and subjective (self-assessment) evaluation of caries and periodontal diseases have been reported to demonstrate a significant disparity. The dental public health team is obligated to recognize and understand this gap. The objectives of the study were to investigate the practical values of using questionnaires (self–perceived assessment) as compared to clinical examinations (normative assessment) and to evaluate the implications of the results in understanding the public's perception of oral health. METHODS: The investigation was performed on 4920, 21 year-old Israeli adults upon release from compulsory military service between 1996 and 1998. Participants were asked to fill in a questionnaire inquiring how they would rate their personal dental and periodontal health levels. Clinical examinations, employing the DMFT and CPITN indices, were performed to determine normative oral health status. Perceived and normative assessments were compared for sensitivity, specificity, positive and negative predictive values and overall proportions using the clinical examinations as a gold standard. RESULTS: The sensitivity (disease perception) for dental status was found to be 0.34, while the specificity (health perception) was found to be 0.83. The positive predictive value for perceived dental status was found to be 0.68, whereas the negative predictive value was found to be 0.54. The sensitivity for perceived periodontal status was found to be 0.28, while the specificity was found to be 0.83. The positive predictive value for perceived periodontal status was found to be 0.05, whereas the negative predictive value was found to be 0.97. Regarding the overall proportions, a large discrepancy was found between self–assessment and professional assessment for both dental and periodontal health status. CONCLUSIONS: Self-assessment questionnaires were of low value in evaluating oral health status both in the individual and public levels, though perception levels of health were higher than that of disease. Findings reflects a low level of awareness of the public that may influence care-seeking behavior and highlight the importance of oral health promotion and the crucial need for public health action

Psychiatric disorders are a common prognostic marker for worse outcome in patients with idiopathic intracranial hypertension

Objective: Idiopathic intracranial hypertension (IIH) is aetiologically unknown disorder that associates with endocrinological disturbances, including dysfunction of hypothalamic-pituitary-adrenal-axis. Neuroendocrinological dysfunctions have also been characterized in psychiatric disorders, and therefore we investigated the presence of psychiatric disorders of patients with IIH in a well-defined cohort.Patients and methods: A total of 51 patients with IIH were included. Patient demographics, symptoms, imaging data, ophthalmological and clinical findings were collected.Results: At the time of diagnosis the mean age was 32.5years (SD 10.7), the body mass index was 37.1 kg/m(2) (SD 7.4), and the opening pressure 29.1 mmHg (SD 6.2). A total of 88.2% of patients were female and 45.1% were diagnosed with a psychiatric co-morbidity prior to IIH diagnosis. The mean follow-up time was 4.4 years (SD 5.4). The overall treatment outcome was significantly poorer on a group of patients with psychiatric diagnosis when compared to individuals without such history (p = 0.001), but there were no differences in the resolution of papilledema (p = 0.405). Patients with IIH and psychiatric disorders had more often empty sella on their imaging at diagnosis when compared to patients without psychiatric co-morbidity (p = 0.044).Conclusion: Psychiatric disorders are highly prevalent in patients with IIH and associate with worse subjective outcomes. These findings advocate for monitoring the mental health of patients with IIH and warrant further multidisciplinary research to understand the potentially underlying psychosocial and neuroendocrinological mechanisms