The histone deactylase SIRT6 is a novel tumor suppressor that regulates cancer metabolism.

Report for the scientific sojourn carried out at the University of Aarhus, Denmark, from 2010 to 2012. Reprogramming of cellular metabolism is a key process during tumorigenesis. This metabolic adaptation is required in order to sustain the energetic and anabolic demands of highly proliferative cancer cells. Despite known for decades (Warburg effect), the precise molecular mechanisms regulating this switch remained unexplored. We have identify SIRT6 as a novel tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of this sirtuin in non-transformed cells leads to tumor formation without activation of known oncogenes, indicating that SIRT6 functions as a first-hit tumor suppressor. Furthermore, transformed SIRT6-deficient cells display increased glycolysis and tumor growth in vivo, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. We provide data demonstrating that the glycolytic switch towards aerobic glycolysis is the main driving force for tumorigenesis in SIRT6-deficient cells, since inhibition of glycolysis in these cells abrogates their tumorigenic potential. By using a conditional SIRT6-targeted allele, we show that deletion of SIRT6 in vivo increases the number, size and aggressiveness of tumors, thereby confirming a role of SIRT6 as a tumor suppressor in vivo. In addition, we describe a new role for SIRT6 as a regulator of ribosome biogenesis by co-repressing MYC transcriptional activity. Therefore, by repressing glycolysis and ribosomal gene expression, SIRT6 inhibits tumor establishment and progression. Further validating these data, SIRT6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict both prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our results provide a potential Achilles’ hill to tackle cancer metabolism.

Performance evaluation of primary care services for the treatment of tuberculosis

Objective Evaluating the performance of primary care services for the treatment of tuberculosis according to the assessment referential of health services (structure/process) in Cabedelo, a port city in the state of Paraíba. Method An evaluation quantitative, cross-sectional study, in which were carried out 117 interviews with health professionals using a structured instrument. The analysis was based on the construction of indicators using a standardized value for the reduced variable (z=1). Results The structural indicators showed regular performance for the following variables: professional training, access to record instruments and coordination with other services. The process indicators related to external actions and information about the disease had unsatisfactory performance. The directly observed treatment and the flows of reference/counter-reference had regular performance. Conclusion The focused professional qualification, the fragmentation of practices and the unsystematic home care constitute obstacles for carrying out actions aimed at providing expanded, continuous and resolute care.



Iowa's Workforce and the Economy, 2008

A discussion of Iowa's key economic indicators as well as commentary on various apsects of the statewide econony.

Diabetic patients who report receiving processes of diabetic care do not express a better quality of life

Background: Chronic disease management initiatives emphasize patient-centered care, and quality of life (QoL) is increasingly considered a representative outcome in that context. In this study we evaluated the association between receipt of processes of diabetic care and QoL. Methods: This cross-sectional population-based study (2011) used self-reported data from non-institutionalized, adult diabetics, recruited from randomly selected community pharmacies in Vaud. Outcomes included the physical and mental composites of the SF-36 (PCS, MCS) and the disease-specific Audit of Diabetes-Dependent QoL (ADDQoL). Main exposure variables were receipt of six diabetes processes-of care in the past 12 months. We also evaluated whether the association between care received and QoL was congruent with the chronic care model, when assessed by the Patient Assessment of Chronic Illness Care (PACIC). We used linear regressions to examine the association between process measures and the three composites of health-related QoL. Analyses were adjusted for age, gender, socioeconomic status, living companion, BMI, alcohol, smoking, physical activity, co-morbidities and diabetes mellitus (DM) characteristics (type, insulin use, complications, duration). Results: Mean age of the 519 diabetic patients was 64.4 years (SD 11.3), 60% were male and 73% had a living companion; 87% reported type 2 DM, half of respondents required insulin treatment, 48% had at least one DM complication, and 48% had DM over 10 years. Crude overall mean QoL scores were PCS: 43.4 (SD 10.5), MCS: 47.0 (SD 11.2) and ADDQoL: -1.56 (SD 1.6). In bivariate analyses, patients who received the influenza vaccine versus those who did not, had lower ADDQoL and PCS scores; there were no other indicator differences. In adjusted models including all processes, receipt of influenza vaccine was associated with lower ADDQoL (β= - 0.41, p=.01); there were no other associations between process indicators and QoL composites. There was no process association even when these were reported as combined measures of processes of care. PACIC score was associated only with the MCS (β= 1.57, p=.004). Conclusions: Process indicators for diabetes care did not show an association with QoL. This may represent an effect lag time between time of process received and quality of life; or that treatment may be related with inconvenience and patient worry. Further research is needed to explore these unexpected findings.

Eusociality and cooperation.

The evolution of eusociality, here defined as the emergence of societies with reproductive division of labour and cooperative brood care, was first seen as a challenge to Darwin's theory of evolution by natural selection. Why should individuals permanently forgo direct reproduction to help other individuals to reproduce? Kin selection, the indirect transmission of genes through relatives, is the key process explaining the evolution of permanently nonreproductive helpers. However, in some taxa helpers delay reproduction until a breeding opportunity becomes available. Overall, eusociality evolved when ecological conditions promote stable associations of related individuals that benefit from jointly exploiting and defending common resources. High levels of cooperation and robust mechanisms of division of labour are found in many animal societies. However, conflicts among individuals are still frequent when group members that are not genetically identical compete over reproduction or resource allocation.

Project Newsletter Iowa Public Health Tracking, June 2013

The Data Warehouse Replacement Project includes updated County Health Snapshot reports. The snapshots provide an overview of key health indicators for local communities. They contain county-level measures that are organized into eight categories. The categories are asthma, cancer, health behaviors and outcomes, heart disease and other chronic conditions, infectious disease, mortality and injury prevention, population statistics and reproductive outcomes. The updated county health snapshots include almost forty new chronic disease indicators in addition to all of the indicators in the existing snapshots.There will be two different reports available in the Data Warehouse replacement system. One of the reports is a multi-year county health snapshot. This report has a similar format to the previous county health snapshot report in the current Data Warehouse. It will display multiple years of data for a single county. The data will be for the most current year available and the two years prior. The state values for the current year will also be included.

Iowa's Workforce and the Economy, 2013

A discussion of Iowa's key economic indicators as well as commentary on various aspects of the statewide economy.

Implementation of Benchmark Project Recommendations for Iowa DOT Offices of Construction, Addendum to HR-381, 1996

This report describes the continuation of the development of performance measures for the Iowa Department of Transportation (DOT) Offices of Construction. Those offices are responsible for administering transportation construction projects for the Iowa DOT. Researchers worked closely with the Benchmark Steering Team which was formed during Phase I of this project and is composed of representatives of the Offices of Construction. The research team conducted a second survey of Offices of Construction personnel, interviewed numerous members of the Offices and continued to work to improve the eight key processes identified during Phase I of this research. The eight key processes include Inspection of Work, Resolution of Technical Issues, Documentation of Work Progress and Pay Quantities, Employee Training and Development, Continuous Feedback for Improved Contract Documents, Provide Safe Traffic Control, External/Public Communication, and Providing Pre-Letting Information. Three to four measurements were specified for each key process. Many of these measurements required opinion surveys of employees, contractors, and others. During Phase II, researchers concentrated on conducting surveys, interviewing respondents to improve future surveys, and facilitating Benchmark Steering Team monthly meetings. Much effort was placed on using the information collected during the first year's research to improve the effectiveness and efficiency of the Offices of Construction. The results from Process Improvement Teams that studied Traffic Control and Resolution of Technical Issues were used to improve operations.

Characteristics and quality of care of diabetic patients residing int the canton of Vaud

Introduction: Within the framework of the «Programme cantonal Diabète», we aimed at collecting data to 1) describe the population of diabetic patients in the canton of Vaud, and 2) assess the quality of their care. Methods: A cross-sectional study was conducted in the fall of 2011. Out of 140 randomly selected community pharmacies registered in the canton of Vaud, 56 accepted to participate in patients' recruitment. Noninstitutionalized adult diabetic patients (disease duration >12 months) visiting a pharmacy with a prescription for oral anti-diabetic drugs, insulin, glycemic strips or glucose meter were eligible. Patients not residing in the canton of Vaud, not speaking and understanding French well enough, presenting obvious cognitive impairment, and women with gestational diabetes, were excluded. Using a self-administered questionnaire, data was collected on patients' characteristics and diabetes as well as various process (e.g. recommended annual screenings) and outcomes quality of care indicators. Descriptive analyses were performed. Results: A total of 406 patients with diabetes participated. Mean age was 64 years, 41% were women and 63% were married. Patients reported type 1, 2 and other types of diabetes in 13%, 69% and 19%, respectively. They were treated with oral anti-diabetic drugs, insulin or both in 50%, 23% and 27% of the cases. Half of the patients did not report any diabetes-related complication. Glucose self-monitoring was reported by 82% of the patients. Of those who were aware of HbA1C (n = 218), 98% reported at least one HbA1C control during the last 12 months. During that same time frame, 97% and 95% reported at least one blood pressure and weight measure, 94% reported having had a cholesterol check, 74%, 68% and 64% had eyes, feet and urine screening respectively. 62% of the patients had been immunized against influenza. At least 76% of the patients had a minimum of 5 of the 7 described process indicators performed during the last 12 months. Among patients who knew the value (n = 145), mean HbA1C was 7.4 (SD 1.2). Conclusion: This study targeting community-based diabetic patients shows that while routine clinical and laboratory tests were annually performed in the vast majority of patients, feet and urine screening, as well as influenza immunization, were less often reported by patients. The proportion of patients with diabetes having had at least 5 out of the 7 annual screenings performed was nevertheless very high.

KPI definition for measuring customer extranet benefits for a forest company

Tutkimuksen tavoitteena oli määrittää hyötyjä, joita Stora Enso on saavuttanut ottamalla käyttöön extranet-järjestelmän, jonka avulla asiakkaat voivat seurata toimitusketjuaan. Tässä tutkimuksessa keskityttiin taloudellisten hyötyjen määrittämiseen ja aineettomien hyötyjen tutkiminen rajattiintyön ulkopuolelle. Samalla tuli kehittää mittarit itsepalveluasteiden laskemiseksi tietyille toiminnoille, joita asiakkaat voivat hyödyntää järjestelmässä. Myös toiminnot, joita järjestelmässä pääasiassa käytetään, tuli määrittää kvantitatiivisen tutkimuksen avulla. Myyntihenkilöstön haastattelut toimivat apuna laskettaessa taloudellisia hyötyjä. Teoriaosuudessa käsitellään yleisesti sähköisiä palveluita erityisesti yritysten välistä kaupankäyntiä koskevalla alueella. Myös toimitusketjua ja tunnusluku mittareiden rakentamista on esitelty yleisellä tasolla teoriaosassa. Työn keskeisimmät tulokset ovat itsepalveluasteiden mittarit, niiden avulla lasketut itsepalveluasteet sekä taloudelliset hyödyt, joita yrityson saavuttanut järjestelmän käyttöönoton jälkeen.

Ship Leases under IAS 17, case Fortum Shipping

International accounting standards will be applied from the1st of January 2005 in accounting of member states of the EU with a view of harmonizing the accounting practices in Europe, and on the long term even more widely. The purpose of adopting IAS accounting standards is to make the financial statements and financial information received from companies more comparable and more transparent for investors and other interest groups. IAS 17 introduces the treatment of a lease agreement in the light of the new accounting standards. Finnish companies have used finance leases widely as an alternative, off-balance sheet form of financing capital investments consistently with Finnish GAAP. Along with the appliance of IAS 17 the off-balance-sheet financing possibility of leases classified as finance leases will no longer exist. IAS 17 states that finance leases are going to be recognized in the balance sheet as both assets, in form of fixed assets, and loans in liabilities classified as long and short term loans. IAS 17 will make two major changes to the income statement. Firstly, the lease payments formerly treated as variable costs are moved below the operating profit level to finance costs. Secondly, the depreciations from the leased assets are also introduced. The effects to the case company's, Fortum Shipping's, income statement and balance sheet are remarkable. Along with the appliance of IAS Fortum Shipping's net assets are somewhat going to be doubled, the amount of liabilities increases significantly and the earnings before interests and taxes increases moderately. The preceding factors have a big effect on the case company's financial key figures. So, the IAS originated effects on balance sheet and income statement have essential impacts on a company's key financial indicators. Most significant changes can be found in key ratios measuring profitability, capital structure, and efficiency. This means that when comparing the IAS calculated profits of companies with the profits calculated prior with Finnish GAAP, the analysis should be made with prudence because the figures are not comparable on straight-forward basis.

Keeping the balance? Management of oxidative stress, body mass and reproduction under energetic constraints by dispersing and philopatric collared flycatchers.

Dispersal, i.e. individual movement between breeding sites, is a key process for metapopulation dynamics and gene flow. Its success can be modulated by phenotypic differences between dispersing and philopatric individuals, or dispersal syndromes. However, the environmental (external) and physiological (internal) constraints underlying such syndromes remain poorly known. This project aimed at clarifying the impact of environmental variation and oxidative constraints, linked to the reactive oxygen species produced during respiration, on phenotypes associated to dispersal in a passerine bird, the collared flycatcher Ficedula albicollis. Energetic demand was experimentally (i) increased through a wing load manipulation or (ii) relieved through food supplementation. The oxidative balance of breeding flycatchers was influenced by complex interactions of dispersal status and extrinsic factors (breeding density, year, experimental treatments). Interestingly, antioxidant capacity was influenced both by permanent individual differences and by food availability, whereas measures of pro-oxidants were highly variables within individuals. Environmental variation and energetic constraints also modulated the differences in reproduction associated with dispersal: dispersing and philopatric birds differ in their management of the oxidative balance when it is competing with reproductive investment. This thesis highlights that reaction norms, rather than fixed differences, often shape traits associated to dispersal. ----- Le déplacement d'un individu entre sites de reproduction, ou dispersion, est un processus clé pour la dynamique des métapopulations et les flux de gènes. Son succès peut être modulé par des différences de phénotype, ou syndromes de dispersion. Cependant, les contraintes environnementales et physiologiques qui sous-tendent ces syndromes restent mal connues. Ce projet vise à clarifier l'impact des variations environnementales et des contraintes oxydatives (liées aux espèces réactives de l'oxygène produites durant la respiration) sur les phénotypes associés à la dispersion chez un passereau, le gobemouche à collier Ficedula albicollis. La demande énergétique a été expérimentalement (i) augmentée en manipulant la surface alaire ou (ii) diminuée par une supplémentation en nourriture. L'équilibre oxydo-réducteur des gobemouches en reproduction est influencé par des interactions complexes entre statut de dispersion et facteurs extrinsèques (densité de couples reproducteurs, année, traitement expérimental). La capacité antioxydante dépend principalement de différences permanentes entre individus, alors que les pro-oxydants présentent de grandes variations intra-individu. Environnement et contraintes énergétiques modulent aussi les différences de reproduction liées à la dispersion : les oiseaux dispersants et philopatriques diffèrent dans leur gestion de l'équilibre oxydo-réducteur lorsqu'il est en compétition avec l'investissement reproducteur. Ce travail souligne que les traits associés à la dispersion sont souvent déterminés par des normes de réaction à l'environnement et non des différences fixées entre individus.

Effectiveness of Pilotage

The objective of the pilotage effectiveness study was to come up with a process descrip-tion of the pilotage procedure, to design performance indicators based on this process description, to be used by Finnpilot, and to work out a preliminary plan for the imple-mentation of the indicators within the Finnpilot organisation. The theoretical aspects of pilotage as well as the guidelines and standards used were determined through a literature review. Based on the literature review, a process flow model with the following phases was created: the planning of pilotage, the start of pilo-tage, the act of pilotage, the end of pilotage and the closing of pilotage. The model based on the literature review was tested through interviews and observation of pilotage. At the same time an e-mail survey directed at foreign pilotage organisations, which included a questionnaire concerning their standards and management systems, operations procedures, measurement tools and their attitude to the passage planning, was conducted. The main issues in the observations and interviews were the passage plan and the bridge team co-operation. The phases of the pilotage process model emerged in both the pilotage activities and the interviews whereas bridge team co-operation was relatively marginal. Most of the pilotage organisations, who responded to the query, also use some standard-based management system. All organisations who answered the survey use some sort of a pilotage process model. According to the query, the main measuring tools for pilotage are statistical information concerning pilotage and the organisations, the customer feedback surveys, and financial results. Attitudes to-wards passage planning were mostly positive among the organisations. A workshop with pilotage experts was arranged where the process model constructed on the basis of the literature review was tuned to match practical pilotage. In the workshop it was determined that certain phases and the corresponding tasks, through which pilo-tage can be described as a process, were identifiable in all pilotage. The result of the workshop was a complemented process model, which separates incoming and outgoing traffic, as well as the fairway pilotage and harbour pilotage from each other. Addition-ally indicators divided according to the data gathering method were defined. Data con-cerning safety and traffic flow is gathered in the form of customer feedback. The pilot's own perceptions of the pilotage process are gathered through self-assessment. The measurement data which is connected to the phases of the pilotage process is generated e.g. by gathering statistics of the success of the pilot dispatches, the accuracy of the pi-lotage and the incidents that occurred during the pilotage, near misses, deviations and accidents. The measurement data is collected via the PilotWeb at the closing of the pilo-tage. A separate project and a project group with pilots also participating will be established for the deployment of the performance indicators. The phases of the project are: the definition phase, the implementation phase and the deployment phase. The purpose of the definition phase is to prepare questions for ship commanders concerning the cus-tomer feedback questionnaire and also to work out the self-assessment queries and the queries concerning the process indicators.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Suorituskyvyn mittaaminen metsäkoneyrityksissä

Tutkimuksessa selvitettiin kyselytutkimuksella yritysseurannan nykytilaa Koneyrittäjien liiton jäseninä olevissa metsäkoneyrityksissä ja haastateltiin sekä käytiin keskusteluja metsäkonealan asiantuntijoiden kanssa. Työn tuloksena tehtiin ehdotus metsäkoneyrityksille soveltuvan seurantatyökalun tietosisällöstä ja hahmoteltiin työkalun rakenne. Vain 54 prosentilla yrityksistä oli järjestelmällistä yritystoiminnan seurantaa. Yleisin syy seuraamattomuudelle oli ajan puute. Niissä yrityksissä, joilla oli järjestelmällistä seurantaa, talouden tunnusluvuista aktiivisimmin seurattiin liikevoittoa. Puunkorjuuprosessia kuvaavista tunnusluvuista aktiivisimmin seurattiin puunkorjuun tuottavuutta. Ehdotetussa työkalussa rajauduttiin suorituskyvyn taloudelliseen ja prosessinäkökulmaan. Prosessinäkökulmassa keskityttiin puunkorjuuprosessiin ja tutkittiin, kuinka uuden StanForD2010 –tiedonsiirtostandardin avulla puunkorjuun tunnuslukujen tuottaminen voitaisiin automatisoida. Seurantatyökalun sisällöksi ehdotettiin yhteensä 43 talouden ja puun-korjuuprosessin tunnuslukua. Lisäksi ehdotettiin, että yrityksen suorituskykyä kuvaamaan laskettaisiin yrityskohtaisesti valittavista tunnusluvuista johdettu yksi tunnusluku – kokonaissuorituskykyindeksi. Ehdotettu seurantatyökalu mahdollistaa suorituskyvyn mittaamisen tehostamisen metsäkoneyrityksissä. Työkalusta puuttuvat asiakas- ja henkilöstö- sekä oppimisnäkökulmat, joten jatkossa onkin selvitettävä näiden näkökulmien liittäminen työkaluun.