Genetic control of iron concentration in Mesoamerican and Andean common bean seeds

The objective of this work was to evaluate the main differences in the genetic control of the iron concentration in Mesoamerican and Andean common bean seeds, in early generations, and to select recombinants with a high iron concentration in the seeds. F1, F1 reciprocal, F2, F2 reciprocal, and backcross (BC11 and BC12) generations were produced by crosses between Mesoamerican (CNFP 10104 x CHC 01-175) and Andean (Cal 96 x Hooter) inbred lines. The expression of significant maternal effect was observed for the Mesoamerican gene pool. Iron concentration was higher in the seed coat of Mesoamerican common bean seeds (54.61 to 67.92%) and in the embryo of Andean common bean seeds (69.40 to 73.44%). High broad-sense heritability was obtained for iron concentration in Mesoamerican and Andean common bean seeds. Gains with the selection of higher magnitude, from 20.39 to 24.58%, are expected in Mesoamerican common bean seeds. Iron concentration in common bean seeds showed a continuous distribution in F2, which is characteristic of quantitative inheritance in Mesoamerican and Andean common bean seeds. Recombinants with high iron concentration in seeds can be selected in both Mesoamerican and Andean common bean hybrids.

Biological control of white mold by Trichoderma harzianum in common bean under field conditions

Abstract: The objective of this work was to evaluate Trichoderma harzianum isolates for biological control of white mold in common bean (Phaseolus vulgaris). Five isolates were evaluated for biocontrol of white mold in 'Perola' common bean under field conditions, in the 2009 and 2010 crop seasons. A commercial isolate (1306) and a control treatment were included. Foliar applications at 2x109 conidia mL-1 were performed at 42 and 52 days after sowing (DAS), in 2009, and at 52 DAS in 2010. The CEN287, CEN316, and 1306 isolates decreased the number of Sclerotinia sclerotiorum apothecia per square meter in comparison to the control, in both crop seasons. CEN287, CEN316, and 1306 decreased white mold severity during the experimental period, when compared to the control.

Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods: Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 20032004 season. Interventions: intramuscular administration of influença vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results: Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion: This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route

Combined effect of tobacco and alcohol on laryngeal cancer risk : a case-control study

OBJECTIVE: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. METHODS: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). CONCLUSIONS: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Control of gene expression in melanocytes and RPE by conserved distal regulatory elements

Résumé Durant le développement embryonnaire, les cellules pigmentaires des mammifères se développent à partir de deux origines différentes : les melanocytes se développent à partir de la crête neurale alors que les cellules de la rétine pigmentaire (RP) ont une origine neuronale. Un grand nombre de gènes sont impliqués dans la pigmentation dont les gènes de la famille tyrosinase à savoir Tyr, Tyrp1 et Dct. Certaines études ont suggéré que les gènes de la pigmentation sont régulés de manière différentielle dans les mélanocytes et dans la RP. Dans ce travail, les gènes de la famille tyrosinase ont été étudiés comme modèle de la régulation des gènes de la pigmentation par des éléments régulateurs agissant à distance. II a été montré que le promoteur du gène Tyrp1pouvait induire l'expression d'un transgène uniquement dans la RP alors que ce gène est aussi exprimé dans les mélanocytes comme le montre le phénotype des souris mutantes pour Tyrp1. Ce résultat suggère que les éléments régulateurs du promoteur sont suffisants pour l'expression dans la RP mais pas pour l'expression dans les mélanocytes. J'ai donc cherché à identifier la séquence qui régule l'expression dans les mélanocytes. Un chromosome artificiel bactérien (CAB) contenant le gène Tyrp1 s'est avéré suffisant pour induire l'expression dans les mélanocytes, comme démontré par la correction du phénotype mutant. La séquence de ce CAB contient plusieurs régions très conservées qui pourraient représenter de nouveaux éléments régulateurs. Par la suite, j'ai focalisé mon analyse sur une séquence située à -I5 kb qui s'est révélée être un amplificateur spécifique aux mélanocytes comme démontré par des expériences de cultures cellulaire et de transgenèse. De plus, une analyse poussée de cet élément a révélé que le facteur de transcription Sox 10 représentait un transactivateur de cet amplificateur. Comme pour Tyrp1, la régulation du gène tyrosinase est contrôlée par différents éléments régulateurs dans les mélanocytes et la RP. Il a été montré que le promoteur de tyrosinase n'était pas suffisant pour une forte expression dans les mélanocytes et la RP. De plus, l'analyse de la région située en amont a révélé la présence d'un amplificateur nécessaire à l'expression dans les mélanocytes à la position -15 kb. Cet amplificateur n'est toutefois pas actif dans la RP mais agit comme un répresseur dans ces cellules. Ces résultats indiquent que certains éléments nécessaires à l'expression dans les deux types de cellules pigmentaires sont absents de ces constructions. Comme pour Tyrp1, j'ai en premier lieu démontré qu'un CAB était capable de corriger le phénotype albinique, puis ai inséré un gène reporter (lacZ) dans le CAB par recombinaison homologue et ai finalement analysé l'expression du reporter en transgenèse. Ces souris ont montré une expression forte du lacZ dans les mélanocytes et la RP, ce qui indique que le CAB contient les séquences régulatrices nécessaires à l'expression correcte de tyrosinase. Afin de localiser plus précisément les éléments régulateurs, j'ai ensuite généré des délétions dans le CAB et analysé l'expression du lacZ en transgenèse. La comparaison de séquences génomiques provenant de différentes espèces a permis par la suite d'identifier des régions représentant de nouveaux éléments régulateurs potentiels. En utilisant cette approche, j'ai identifié une région qui se comporte comme un amplificateur dans la RP et qui est nécessaire à l'expression de tyrosinase dans ce tissu. De plus, j'ai identifié les facteurs de transcription Mitf et Sox10 comme transactivateurs de l'amplificateur spécifique aux mélanocytes situé à -15 kb. L'identification et la caractérisation des ces éléments régulateurs des gènes tyrosinase et Tyrp1confirme donc que la régulation différentielle des gènes dans les mélanocytes et la RP est liée à des éléments régulateurs séparés. Summary Pigment cells of mammals originate from two different lineages: melanocytes arise from the neural crest, whereas cells of the retinal pigment epithelium (RPE) originate from the optic cup of the developing forebrain. A large set of genes are involved in pigmentation, including the members of the tyrosinase gene family, namely tyrosinase, Tyrp1 and Dct. Previous studies have suggested that pigmentation genes are differentially regulated in melanocytes and RPE. In this work, the tyrosinase gene family was used as a model for studying the involvement of distal regulatory elements in pigment cell-specific gene expression. The promoter of the Tyrp1 gene has been shown to drive detectable transgene expression only to the RPE, even though the gene is also expressed in melanocytes as evident from Tyrp1-mutant mice. This indicates that the regulatory elements responsible for Tyrp1 gene expression in the RPE are not sufficient for expression in melanocytes. I thus searched for a putative melanocyte-specific regulatory sequence and demonstrate that a bacterial artificial chromosome (BAC) containing the Tyrp1 gene and surrounding sequences is able to target transgenic expression to melanocytes and to rescue the Tyrp1 b (brown) phenotype. This BAC contains several highly conserved non-coding sequences that might represent novel regulatory elements. I further focused on a sequence located at -15 kb which I identified as amelanocyte-specific enhancer as shown by cell culture and transgenic mice. In addition, further functional analysis identified the transcription factor Sox10 as being able to bind and transactivate this enhancer. As for Tyrp1, tyrosinase gene regulation is mediated by different cis-regulatory elements in melanocytes and RPE. It was shown that the tyrosinase promoter was not sufficient to confer strong and specific expression in melanocytes and RPE. Moreover, analysis of tyrosinase upstream sequence, revealed the presence of a specific enhancer at position -15 kb which was necessary to confer strong expression in melanocytes. This enhancer element however failed to act as an enhancer in the RPE, but rather repressed expression. This indicates that some regulatory elements required for tyrosinase expression in both RPE and melanocytes are still missing from these constructs. As for Tyrp1, I first demonstrated that a BAC containing the Tyr gene is able to rescue the Tyr c (albino) phenotype in mice, then I inserted a lacZ reporter gene in the BAC by homologous recombination, and finally analysed the pattern of lacZ expression in transgenic mice. These mice showed strong lacZ expression in both RPE and melanocytes, indicating that the BAC contains the regulatory sequences required for proper tyrosinase expression. In order to localize more precisely these regulatory elements, I have then generated several deletions in the BAC and analysed lacZ expression in transgenic mice. Multi-species comparative genomic analysis then allowed identifying conserved sequences that potentially represent novel regulatory elements. Using this experimental approach, I identified a region that behaves as a RPE-specific enhancer and that is required for tyrosinase expression in the retina] pigment epithelium. In addition, I identified the transcription factors Mitf and Sox l0 as being transactivators of the melanocyte-specific enhancer located at -l5 kb. The identification and characterization of these tyrosinase and Tyrp1 distal regulatory element supports the idea that separate regulatory sequences mediate differential gene expression in melanocytes and RPE.

R&D Performance Analysis: Case Studies on the Challenges and Promotion of the Evaluation and Measurement of R&D

Due to the intense international competition, demanding, and sophisticated customers, and diverse transforming technological change, organizations need to renew their products and services by allocating resources on research and development (R&D). Managing R&D is complex, but vital for many organizations to survive in the dynamic, turbulent environment. Thus, the increased interest among decision-makers towards finding the right performance measures for R&D is understandable. The measures or evaluation methods of R&D performance can be utilized for multiple purposes; for strategic control, for justifying the existence of R&D, for providing information and improving activities, as well as for the purposes of motivating and benchmarking. The earlier research in the field of R&D performance analysis has generally focused on either the activities and considerable factors and dimensions - e.g. strategic perspectives, purposes of measurement, levels of analysis, types of R&D or phases of R&D process - prior to the selection of R&Dperformance measures, or on proposed principles or actual implementation of theselection or design processes of R&D performance measures or measurement systems. This study aims at integrating the consideration of essential factors anddimensions of R&D performance analysis to developed selection processes of R&D measures, which have been applied in real-world organizations. The earlier models for corporate performance measurement that can be found in the literature, are to some extent adaptable also to the development of measurement systemsand selecting the measures in R&D activities. However, it is necessary to emphasize the special aspects related to the measurement of R&D performance in a way that make the development of new approaches for especially R&D performance measure selection necessary: First, the special characteristics of R&D - such as the long time lag between the inputs and outcomes, as well as the overall complexity and difficult coordination of activities - influence the R&D performance analysis problems, such as the need for more systematic, objective, balanced and multi-dimensional approaches for R&D measure selection, as well as the incompatibility of R&D measurement systems to other corporate measurement systems and vice versa. Secondly, the above-mentioned characteristics and challenges bring forth the significance of the influencing factors and dimensions that need to be recognized in order to derive the selection criteria for measures and choose the right R&D metrics, which is the most crucial step in the measurement system development process. The main purpose of this study is to support the management and control of the research and development activities of organizations by increasing the understanding of R&D performance analysis, clarifying the main factors related to the selection of R&D measures and by providing novel types of approaches and methods for systematizing the whole strategy- and business-based selection and development process of R&D indicators.The final aim of the research is to support the management in their decision making of R&D with suitable, systematically chosen measures or evaluation methods of R&D performance. Thus, the emphasis in most sub-areas of the present research has been on the promotion of the selection and development process of R&D indicators with the help of the different tools and decision support systems, i.e. the research has normative features through providing guidelines by novel types of approaches. The gathering of data and conducting case studies in metal and electronic industry companies, in the information and communications technology (ICT) sector, and in non-profit organizations helped us to formulate a comprehensive picture of the main challenges of R&D performance analysis in different organizations, which is essential, as recognition of the most importantproblem areas is a very crucial element in the constructive research approach utilized in this study. Multiple practical benefits regarding the defined problemareas could be found in the various constructed approaches presented in this dissertation: 1) the selection of R&D measures became more systematic when compared to the empirical analysis, as it was common that there were no systematic approaches utilized in the studied organizations earlier; 2) the evaluation methods or measures of R&D chosen with the help of the developed approaches can be more directly utilized in the decision-making, because of the thorough consideration of the purpose of measurement, as well as other dimensions of measurement; 3) more balance to the set of R&D measures was desired and gained throughthe holistic approaches to the selection processes; and 4) more objectivity wasgained through organizing the selection processes, as the earlier systems were considered subjective in many organizations. Scientifically, this dissertation aims to make a contribution to the present body of knowledge of R&D performance analysis by facilitating dealing with the versatility and challenges of R&D performance analysis, as well as the factors and dimensions influencing the selection of R&D performance measures, and by integrating these aspects to the developed novel types of approaches, methods and tools in the selection processes of R&D measures, applied in real-world organizations. In the whole research, facilitation of dealing with the versatility and challenges in R&D performance analysis, as well as the factors and dimensions influencing the R&D performance measure selection are strongly integrated with the constructed approaches. Thus, the research meets the above-mentioned purposes and objectives of the dissertation from the scientific as well as from the practical point of view.

Sliding Mode Control for Switched Mode Power Supplies

Control applications of switched mode power supplies have been widely investigated. The main objective ofresearch and development (R&D) in this field is always to find the most suitable control method to be implemented in various DC/DC converter topologies. Inother words, the goal is to select a control method capable of improving the efficiency of the converter, reducing the effect of disturbances (line and load variation), lessening the effect of EMI (electro magnetic interference), and beingless effected by component variation. The main objective of this research work is to study different control methods implemented in switched mode power supplies namely (PID control, hysteresis control, adaptive control, current programmed control, variable structure control (VSC), and sliding mode control (SMC). The advantages and drawbacks of each control method are given. Two control methods, the PID and the SMC are selected and their effects on DC/DC (Buck, Boost, and Buck-Boost) converters are examined. Matlab/SimulinkTM is used to implement PID control method in DC/DC Buck converter and SMC in DC/DC (Buck, and Buck Boost) converters. For the prototype, operational amplifiers (op-amps) are used to implement PID control in DC/DC Buck converter. For SMC op-amps are implemented in DC/DC Buck converter and dSPACETM is used to control the DC/DC Buck-Boost converter. The SMC can be applied to the DC/DC (Buck, Boost, and Buck-Boost) converters. A comparison of the effects of the PID control and the SMC on the DC/DC Buck converter response in steady state, under line variations, load variations, and different component variations is performed. Also the Conducted RF-Emissions between the PID and SMC DC/DC Buck Converter are compared. The thesis shows that, in comparison with the PID control, the SMC provides better steady-state response, better dynamic response, less EMI, inherent order reduction, robustness against system uncertainty disturbances, and an implicit stability proof. Giving a better steady-state and dynamic response, the SMC is implemented in a DC/DC resonant converter. The half-wave zero current switching (HWZCS) DC/DC Buck converter is selected as a converter topology. A general guideline to select the tank component values, needed for the designing of a HWZCS DC/DC Buck, is obtained. The implementation of the SMC to a HWZCS DC/DC Buck converter is analysed. The converter response is investigated in the steady-state region and in the dynamic region.

Involvement of family physicians in structured programs for chronic diseases or multi-morbidity in Switzerland.

The increasing prevalence of chronic diseases and multi-morbidity represents challenges for health systems worldwide. In that perspective, the current organization of healthcare delivery, fragmentation of care, limited use of evidence-based guidelines and patients'insufficient empowerment are some reasons explaining the current limited effectiveness of the management of chronically ill patients. Based on theoretical models such as the Chronic Care Model (CCM), initiatives targeting improvements in the care of patients with chronic diseases have been implemented worldwide since more than a decade. Their development in Switzerland, a health system where more than half of practices are still single handed [6], is only recent and infrequent. Structured programs for patients with chronic diseases or multimorbidity usually propose patient-centered interventions and consider an integrative multidisciplinary approach. Currently, little is known on the existence of such programs and on the role of family physicians (FPs)within these programs, in Switzerland. The objective of this study was to identify and describe current structured programs targeting chronic diseases or multi-morbidity in Switzerland. This may help in examining innovative approaches that are only developed locally but would deserve wider interest for further implementation. We conducted a telephone-based survey between June and November 2013 and contacted systematically key institutions, informants and stakeholders nationwide and in the 26 cantons...

Protocolo para la zonificación intraparcelaria de la viña para vendimia selectiva a partir de imágenes multiespectratrales

En este trabajo se presenta un protocolo para la zonificación intraparcelaria de la viña con la finalidad de vendimia selectiva. Se basa en la adquisición de una imagen multiespectral detallada en el momento del envero, a partir de la cual se obtiene el índice de vegetación de la diferencia normalizada (NDVI). Este índice se clasifica en áreas de vigor alto y bajo mediante un proceso de clasificación no supervisada (algoritmo ISODATA). Las zonas resultantes se generalizan y se transfieren al monitor de cosecha de una máquina vendimiadora para realizar la recolección selectiva. La uva recolectada según este protocolo en parcelas control ha mostrado diferenciación en cuanto a parámetros de calidad como el pH, la acidez total, el contenido de polifenoles y el color. La imagen multiespectral utilizada fue adquirida por el satélite Quickbird-2. Los datos de calidad de la uva fueron muestreados según una malla regular de 5 filas por 10 cepas, procediendo a un test estadístico de rangos múltiples para analizar la separación de medias de las variables analizadas en cada zona de NDVI.

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

Sheeting efficiency improvement through production planning and control development.

Arkitus on kartongin jatkojalostusmuoto, jonka tehokkuus muodostuu monen tekijän vaikutuksesta. Tämän työn tavoitteena oli parantaa arkitustehokkuutta tutkitussa kahden folioleikkurin arkittamossa tuotannonsuunnittelun ja tuotannonohjauksen kehittämisellä. Kartonkitehtaan sisäisessä jalostusketjussa arkitus on viimeinen vaihe, mikä tekee siitä pitkälti riippuvaisen edeltävistä konevaiheista, eli kartonkikoneista ja PE-päällystyskoneista. Pelkkä arkituksen tuotannonsuunnittelun huomiointi ei siis vielä takaa hyvää lopputulosta arkitustehokkuuden kannalta. Folioarkitustoiminta on hyvin asiakassuuntautunutta. Arkkikoot määräytyvät asiakkaiden omien tarpeiden perusteella, jolloin eri arkkikokojen kokonaismäärä kasvaa huomattavan suureksi. Viime vuosien trendinä on ollut tilauseräkokojen pieneneminen. Näiden tekijöiden yhteisvaikutuksena arkituksen tuotantoprosessille on ominaista erilaisten asetusten aiheuttama katkonaisuus. Lisäksi pelkästään yhden millimetrin muutos arkin leveydessä voi usein vaikuttaa arkitustehokkuuteen hyvinkin merkittävästi. Näistä syistä arkituksen tuotannonsuunnittelun apuvälineeksi tarvitaan tarkkuuteen ja joustavuuteen kykenevää tietojärjestelmää. Tehokkaan tuotannonohjauksen tueksi tarvitaan lisäksi erilaisia leikkuri- ja kartonkilaatukohtaisia raportteja. Työn teoriaosassa käsitellään tarkemmin arkitustoiminnan ominaisuuksia ja sen tehokkuuteen vaikuttavia tekijöitä. Lisäksi käsitellään tuotannonsuunnittelun ja tuotannonohjauksen periaatteita ja toimintoja.

Kartonkikoneen tuotannonsuunnittelu jalostuslähtöisesti

Työn tarkoituksena oli selvittää monipope-menetelmän taustaa, menetelmän karkea tekninen toteutus, sovellettavuus kartonkikone KA1:n tuotantoon ja menetelmän mukanaan tuomat edut ja haitat, sekä ratkaisumallit mahdollisten tuotannollisten häiriötilanteiden ratkaisemista varten. Työssä selvitettiin myös tuotannon, tuotannon-suunnittelun, varastoinnin, asiakaspalvelun ja tuottavuuden tehostamista monipope-menetelmän avulla, sekä tuotannonsuunnittelun jalostuslähtöisyyden korostamista. Työn kirjallisuusosassa käsitellään lyhyesti toiminnanohjauksen, tuotannonsuunnittelun ja materiaalinhallinnan perusteiden lisäksi tuotannon-suunnittelussa hyödynnettävän tietojärjestelmän toimintaa ja kartonkitehtaan tuotantoprosessi kartonkikoneiden ja muovipäällystyskoneiden osalta. Kokeellisessa osassa perehdyttiin tuotannon ja tuotannonsuunnittelun tämän hetkiseen tilaan, selvitettiin monipope-menetelmän idea ja sen karkea tekninen toteutus ja tutkittiin monipopemenetelmän sovellettavuutta pohjautuen toteutuneeseen tuotantoon ja nykyisiin tuotannon rajoitteisiin. Välivarastointikapasiteetin rajoittaminen johti päällystyskapasiteetin uudelleen organisoimisen ja nykyisen kapasiteetin riittävyyden selvittämiseen koetrimmitysten avulla. Lisäksi selvitettiin uuden menetelmän avulla saavutettavaa tuotannon nousua erityisesti jatkojalostuksen osalta. Monipope-menetelmän sovellettavuustutkimuksissa havaittiin uuden menetelmän tuovan mukanaan lukuisia etuja ja säästöjä muun muassa materiaalikulujen alentumisen ja vähentyneiden työvaiheiden kautta. Kartonkikone KA1:n tuotteiden jatkojalostuksen tuotannon nousuksi määritettiin noin 2 %:ia ja tämän lisäksi uusi menetelmä yksinkertaistaisi ja helpottaisi koko kartonkitehtaan rullaliikennettä ja varastojen hallintaa. Menetelmä toisi uusia toimintamalleja KA1:n tuotannon häiriötilanteiden varalle, lisäisi tuotannonsuunnittelun joustavuutta ja helpottaisi myös asiakaspalvelun ja laaduntarkkailun kehittämistä. Tutkimuksen tuloksena voidaan todeta, että monipope-menetelmän tuomat edut ovat kiistattomat. Menetelmän soveltamisen mahdollisuuksia tulisikin miettiä jatkossa investointeja suunnitellessa, jotta menetelmän toteuttaminen kohtuullisin investointikustannuksin nykyisten tuotantoedellytysten lisäksi olisi mahdollista.

Production Control Principles in Printed Wiring Board Fabrication

Työn tavoitteena oli kuvata piirilevyvalmistaja Aspocomp Oy:n Espoon tehtaan tämän hetkinen tuotannonohjausperiaate ja tunnistaa siinä esiintyvät puutteet sekä kehittää vaihtoehtoinen tuotannonohjausperiaate piirilevyvalmistukseen. Vaihtoehtoisen ohjausperiaatteen lähtökohtana oli tuotannonohjauksen sopeuttaminen vaativaan ja jatkuvasti muuttuvaan liiketoimintaympäristöön. Työn teoreettinen osa keskittyi tuotannonohjauksen eri lähestymistapoihin. Kirjallisuuskatsauksessa esitetään eri tuotannonohjausperiaatteiden keskeiset sisällöt, jotka muodostavat rungon toimivalle tuotannonohjauskäytännölle. Työn kokeellinen osa keskittyi Espoon piirilevytehtaan tuotannonohjausperiaatteen selvittämiseen. Espoon piirilevytehtaan nykyisessä tuotannonohjausperiaatteessa havaittujen ongelmakohtien ja liiketoimintaympäristön vaatimusten perusteella kehitettiin vaihtoehtoinen tuotannonohjaustapa. Vaihtoehtoisen tuotannonohjaustavan päämääränä oli läpimenoajan lyhentäminen sekä tuotannon parempi hallittavuus. Vaihtoehtoinen toimintamalli tavoitteiden saavuttamiseksi perustuu pullonkaulateoriaan, jossa keskeisin muutos nykyiseen toimintamalliin oli puolivalmisteiden varastointi toimitusajan lyhentämiseksi sekä tuotantovolyymin heilahdusten vaikutusten vähentämiseksi. Työn kokeellisessa osassa ilmeni, että kysynnän muutokset ja kapasiteetin suunnittelun puute aiheuttivat ongelmia piirilevytehtaan tuotannonohjauksessa.

Variaciones dimensionales en piezas plásticas de inyección y análisis de los medios de control

En la industria de la automoción, así como en todas las que se dedican a fabricar piezas, ya sean plásticas o de otros materiales, es tan importante la Producción como la Calidad. No sirve de nada fabricar mucho si no son piezas de una calidad adecuada, y del mismo modo no es rentable fabricar muy poco volumen por mucho que tenga una calidad excelente. Por ello hay que buscar siempre el equilibrio entre ambos conceptos. La finalidad es tener procesos lo más robustos posibles que nos permitan fabricar cantidad con una buena calidad. La finalidad de este trabajo es buscar los parámetros que más afectan en un proceso de inyección, es decir, saber cuáles son los que debemos tener bajo control para lograr una calidad de piezas buena y un proceso estable y controlado. Para ver si el proceso es capaz de lograr ese objetivo utilizamos gráficos basados en la teoría de 6- sigma que nos calculan el coeficiente de capacidad del proceso (Cpk). A su vez analizaremos los sistemas de medida que utilizamos en cada una de las piezas analizadas para evaluar si son los correctos y nos permiten discriminar piezas buenas de malas en el proceso productivo. La conclusión del trabajo es que hay que prestar especial atención en controlar aquellos aspectos de un proceso que nos aportan variación, y no invertir tiempo ni dinero en aquellos otros que no nos aportan valor añadido y que no afectan sustancialmente al proceso. Este análisis por supuesto lleva su coste, que he analizado y plasmado en las conclusiones para saber lo que le cuesta aproximadamente a una empresa realizarlo.

Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy.

OBJECTIVE: Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP). METHODS: Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR. RESULTS: Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047). CONCLUSION: We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.