Statistical process control (SPC) is a toolbox to detect changes in the output of a process distribution. It can serve as a valuable resource to maintain high quality in a manufacturing process. This report is based on the work on evaluating and implementing methods for SPC in the process of chromatography instrument manufacturing at GE Healthcare, Umeå. To handle low volume and non-normally distributed process output data, non-parametric methods are considered. Eight control charts, three for for Phase I analysis, and five for Phase II analysis, are evaluated in this study. The usability of the charts are assessed based on ease of interpretation and the performance to detect distributional changes. The later is evaluated with simulations. The result of the project is the implementation of the RS/P-chart, suggested by Capizzi et al (2013), for Phase I analysis. Of the considered Phase I methods (and simulation scenarios), the RS/P-chart has the highest overall probability, of detecting a variety of distributional changes. Further, the RS/P-chart is easily interpreted, facilitating the analysis. For Phase II analysis, the use of two control charts, one based on the Mann-Whitney U statistic, suggested by Chakraborti et al (2008), and one on the Mood test statistic for dispersion, suggested by Ghute et al (2014), have been implemented. These are chosen mainly based on the ease of interpretation. To reduce the detection time for changes in the process distribution, the change-point chart based on the Cramer Von Mises statistic, suggested by Ross et al (2012), could be used instead. Using single observations, instead of larger samples, this chart is updated more frequently. However, this efficiently increases the false alarm rate and the chart is also considered much more difficult to interpret for the SPC practitioner. / Statistisk processkontroll (SPC) är en samling verktyg för att upptäcka förändringar, i fördelningen, hos utfallen i en process. Det kan fungera som en värdefull resurs för att upprätthålla en hög kvalitet i en tillverkningsprocess. Denna rapport är baserad på arbetet med att utvärdera och implementera metoder för SPC i en monteringsprocess av kromatografiinstrument på GE Healthcare, Umeå. Åtta styrdiagram, tre för för fas I analys, och fem för fas II analys, studeras i denna rapport. Användbarheten hos styrdiagrammen bedöms efter hur enkla de är att tolka och förmågan att upptäcka fördelningsförändringar. Den senare utvärderas med simuleringar. Resultatet av projektet är införandet av RS/P-metod, utvecklad av Capizzi et al (2013), för analysen i fas I. Av de utvärderade metoderna, (och simuleringsscenarier), har RS/P-diagrammet den högsta övergripande sannolikheten, för att upptäcka en mängd olika fördelningsförändringar. Vidare är metodens grafiska diagram lätt att tolka, vilket underlättar analysen. För fas II analys, har två styrdiagram, ett baserat på Mann-Whitney's U teststatistika, som föreslagits av Chakraborti et al (2008), och ett på Mood's teststatistika för spridning, som föreslagits av Ghute et al (2014), implementerats. Styrkan i dessa styrdiagram ligger främst i dess enkla tolkning. För snabbare identifiering av processförändringar kan styrdiagrammet baserat på Cramer von Mises teststatistika, som föreslagits av Ross et al (2012), användas. Baserat på enskilda observationer, istället för stickprov, har styrdiagrammet en högre uppdateringsfrekvens. Detta leder dock till ett ökat antal falska larm och styrdiagrammet anses dessutom vara avsevärt mycket svårare att tolka för SPC-utövaren.

The body of work presented here is a compendium of the multiple steps required for an investigator initiated trial of an existing medication (Valproic Acid- VPA) for a new indication (Retinitis Pigmentosa – RP). The chapters are listed in logical and chronological order of the process. In order to access patient records an expedited Institutional Review Board (IRB) application for retrospective chart review was submitted (Chapter 1). These records enabled the statistical analysis which not only laid the framework for the trial design, but also became the basis for two manuscripts (Chapter 2). Protocol development informed by the preliminary human studies (Chapter 3) was an instrumental part of the Investigational New Drug (IND) application (Chapter 3.5). This protocol along with the extensive case report forms that detail the intended data to be collected are included in the IND application. Because the Phase II clinical trial proposed attempting to identify the specific RP mutations of the subjects utilizing a National Eye Institute (NEI) study that enabled free genotyping services, two IRB applications were submitted (Chapter 3.6). The first was for approval of the NEI genotyping protocol, the second involved the VPA intervention. Two very different sources of funding for this trial were attempted (Chapter 4) – the NIH via the Challenge Grant mechanism and a private eye disease foundation (Foundation Fighting Blindness). In Chapter 5 I detail the alternate study designs that were considered and developed for this trial (and ultimately abandoned). Finally, in Chapter 6, I formally detail my suggestions to aid in the development of a comprehensive investigator initiated core facility at UMMMC. The goal of this project was two-fold. The first was to learn the entire process of trial and protocol design both from a Umass Institutional perspective as well as from the perspective of the FDA. The second goal was the very real prospect of helping patients with a blinding disease. This work was successful on both counts. IRB approval was received for all the submitted applications. The complexity and uniqueness of many aspects of these submissions culminated in a comprehensive learning experience. The process of working with the Umass Research Pharmacy as well as developing the industry contacts and know-how to develop a workable and financially feasible placebo were both particularly important learning experiences. FDA approval of the IND submission was also received, and the process of pre-communication and delving into the considerable and ever-changing rules and regulations resulted in an extensive and valuable knowledge base. While the practicality of funding has limited the ability of this trial to move forward at this point, given the extensive framework laid by this body of work, we are actively pursuing other opportunities. The third outcome of this work, while not as intentional, was the considerable process of determining the specific competencies and infrastructure that exist at UMMMC to enable investigator initiated drug intervention studies. While this institution is clearly moving rapidly in the direction of translational research, the many needs of these studies are often only clearly understood when the process is specifically undertaken. In completing the approval of this Phase II clinical trial, I was not only able to better understand and define the existing capabilities of UMMMC for this kind of research, I was able to add to that infrastructure when the existing knowledge or skill set was not available. In this manner, I was able to inform and guide many of the support personnel who guided me and have become a part of the strategic direction of UMMMC towards clinical translational research.

This thesis deals with phase II of IFRS 4 Insurance contracts. The aim of the standard is to establish the principles that an entity should apply to report useful information to users of its financial statements about the nature, amount, timing and uncertainty of cash flows from insurance contracts, so that the financial statements of the entity are comparable with financial statements of other entities. Therefore IASB introduced building blocks measurement model, where an insurance contract is measured based on the present value of expected fulfillment cash flows, risk margin and contractual service margin. The building blocks model is based on making extensive judgments when measuring the insurance contracts. To explain the judgments, the standard requires the entity to disclose details about the judgments in the footnotes to the financial statements. The building blocks model is used mainly for life insurance contracts. For contracts that last one year or less (usually non-life insurance contracts) the standard allows the entities to use a simplified approach for measuring insurance contracts that is similar as the current practice of measuring non-life insurance contracts. Revenues from insurance contracts should depict the transfer of promised services arising from the insurance contract in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those services (this approach is in line with the prepared IFRS 15 Revenue from Contracts with Customers).

No description available.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

A quantitative, exploratory, descriptive and contextual research study was conducted to establish the effect of reinforcement of information in phase II cardiac rehabilitation of myocardial infarction patients. Its aim was to determine the sufficiency of patient education during hospitalisation and the necessity for reinforcing information during follow-up sessions after the patient's discharge from hospital. Patients from two private hospitals in Gauteng were involved in the study. A quasi-experimental research design, namely the comparison group posttest-only design, was implemented with no random assignment of subjects to the experimental and control groups. A convenient non-probability sampling method was used and data was collected by means of questionnaires. The data analysis revealed that patients received sufficient education during hospitalisation, but that discharged patients still believed follow-up sessions to be a necessity. No significant difference was found in the knowledge levels of the experimental and control groups. / 'n Kwantitatiewe, verkennende, beskrywende en kontekstuele studie is uitgevoer om ondersoek in te stel na die effek van inligtingversterking in Fase II kardialerehabilitasie van miokardiale-infarksie-pasiente. Hiermee wou die navorser bepaal of pasientonderrig in die hospitaal voldoende was, en of die opvolging van pasiente na ontslag uit twee privaat hospitale in Gauteng noodsaaklik was om inligting te versterk. Vir die implementering van die studie is van 'n kwasi-eksperimentele navorsingsontwerp, naamlik die tweegroep-posttoets-ontwerp, gebruik gemaak. Respondente is nie ewekansig aan 'n eksperimentele en 'n kontrolegroep toegewys nie. 'n Nie-waarskynlike gerieflikheidsteekproeftrekking is gedoen, en data is ingesamel deur middel van die voltooiing van 'n vraelys. Die data-analise het getoon dat die pasientonderrig in die hospitaal voldoende was, maar dat pasiente steeds van mening was dat opvolging na ontslag noodsaaklik is. Geen beduidende verskil is gevind in die kennisvlakke van die eksperimentele en die kontrolegroep nie. / Health Sciences / M.A. (Nursing)

Infusões prolongadas de 5-fluorouracil são mais seguras e potencialmente mais efetivas no tratamento do câncer de cólon metastático do que infusões rápidas da mesma medicação. No entanto, infusões prolongadas requerem a disponibilidade de um acesso venoso central, bem como de bombas de infusão dispendiosas. O desenvolvimento de fluoropirimidinas orais permitiu que pacientes fossem expostos ao 5-fluorouracil por longo tempo, com maior conveniência. UFT e leucovorin administrados três vezes ao dia demonstraram previamente uma eficácia equivalente, com menor toxicidade, quando comparados a um regime convencional de infusão rápida de 5- fluorouracil e leucovorin. Este estudo com 98 pacientes foi desenhado e conduzido com objetivo de demonstrar equivalência no tempo de progressão com o uso de UFT e leucovorin administrados duas vezes ao dia, com o uso da mesma combinação administrada três vezes ao dia. Objetivos secundários incluíram análise de toxicidade, resposta objetiva e sobrevida global. O tempo mediano de progressão foi de 3,8 meses, comparado com 3,5 meses observados com o uso da medicação três vezes ao dia e a taxa de resposta foi de 11%, com uma sobrevida mediana de 12,8 meses, sendo comparável aos resultados de 12% e 12,4 meses obtidas com o uso da combinação três vezes ao dia. A incidência de diarréia com graus 3 e 4 foi de 30% no regime de administração duas vezes ao dia, e 21% no de três vezes ao dia. Esses resultados sugerem que o uso de UFT e leucovorin duas vezes ao dia tem eficácia e toxicidade similares àquelas obtidas com o uso da mesma medicação três vezes ao dia. / Prolonged infusions have been shown to be safer and potentially more effective than bolus regimens of 5- fluorouracil as treatment for advanced colorectal cancer. However, infusional 5- fluorouracil requires central venous access and costly infusion pumps. Development of oral fluoropyrimidines has allowed longer exposures to 5-fluorouracil with increased convenience. UFT and leucovorin given thrice daily showed improved safety and no significant difference in survival or response rate compared with bolus 5- fluorouracil and leucovorin. This study with 98 patients was conducted to evaluate whether UFT and leucovorin given twice daily provided comparable time to progression (TTP) to the same combination administered three times a day. Secondary objectives included evaluation of toxicity, overall tumor response rate, and survival. Median time to progression was 3.8 months, compared with 3.5 months observed with the thrice-daily regimen. The twice-daily regimen had a response rate of 11% and median survival of 12.8 months, comparable to the 12% and 12.4 months seen with the thrice-daily regimen. The incidence of grade 3-4 drug-related diarrhea was 30% on the twice-daily and 21% on the thrice-daily schedule. Results suggest that the twice-daily schedule has similar safety and efficacy to the thrice-daily schedule.

Thesis (M. En.)--Miami University, Institute of Environmental Sciences, 2005. / Title from first page of PDF document. Document formatted into pages; contains [1], v, 101 p. : ill. Includes bibliographical references (p. 63-64).

A quantitative, exploratory, descriptive and contextual research study was conducted to establish the effect of reinforcement of information in phase II cardiac rehabilitation of myocardial infarction patients. Its aim was to determine the sufficiency of patient education during hospitalisation and the necessity for reinforcing information during follow-up sessions after the patient's discharge from hospital. Patients from two private hospitals in Gauteng were involved in the study. A quasi-experimental research design, namely the comparison group posttest-only design, was implemented with no random assignment of subjects to the experimental and control groups. A convenient non-probability sampling method was used and data was collected by means of questionnaires. The data analysis revealed that patients received sufficient education during hospitalisation, but that discharged patients still believed follow-up sessions to be a necessity. No significant difference was found in the knowledge levels of the experimental and control groups. / 'n Kwantitatiewe, verkennende, beskrywende en kontekstuele studie is uitgevoer om ondersoek in te stel na die effek van inligtingversterking in Fase II kardialerehabilitasie van miokardiale-infarksie-pasiente. Hiermee wou die navorser bepaal of pasientonderrig in die hospitaal voldoende was, en of die opvolging van pasiente na ontslag uit twee privaat hospitale in Gauteng noodsaaklik was om inligting te versterk. Vir die implementering van die studie is van 'n kwasi-eksperimentele navorsingsontwerp, naamlik die tweegroep-posttoets-ontwerp, gebruik gemaak. Respondente is nie ewekansig aan 'n eksperimentele en 'n kontrolegroep toegewys nie. 'n Nie-waarskynlike gerieflikheidsteekproeftrekking is gedoen, en data is ingesamel deur middel van die voltooiing van 'n vraelys. Die data-analise het getoon dat die pasientonderrig in die hospitaal voldoende was, maar dat pasiente steeds van mening was dat opvolging na ontslag noodsaaklik is. Geen beduidende verskil is gevind in die kennisvlakke van die eksperimentele en die kontrolegroep nie. / Health Sciences / M.A. (Nursing)