Quality of care in surgery and methods to assess the volume-outcome relationship

This thesis outlines the proposed attributes of healthcare which can define its quality and reviews existing research in this area. Specifically, the limitations of existing research into the volume-outcome relationship within surgery are highlighted, thereby addressing the ‘health outcome’ dimension of quality of care. The principles and existing application of funnel plots within surgery are reviewed alongside their ability to overcome the limitations, risks and implications of contemporary ranking of surgical performance. Methods by which future research should be conducted are proposed as a conceptual model. This model, along with the proposed ‘quality’ attributes, identifies the research themes of the empirical studies. The application of a validated methodological scoring system formally explores the limitations of existing volume-outcome research within the uro-oncological field. A cross-sectional analysis of administrative data assesses the volume-outcome relationship for radical cystectomy in England, using an improved methodology that incorporates a multilevel model to account for the relationship and influence of both the surgeon and institution and adjustment for institutional structural and process of care confounders. Subsequently, risk-adjusted funnel plot methodology is applied to the dataset to further explore provider performance. A longitudinal analysis assesses compliance with healthcare policy for radical pelvic surgery in England by exploring the patterns of service provision, in response to the existing understanding of the volume-outcome relationship for uro-oncology. This thesis demonstrates the limitations with existing volume-outcome methodology and the need for improved methodology for both the interpretation and presentation of volume-outcome research. Appropriate handling of the data in volume-outcome analysis, which recognises the hierarchical nature, is important to adequately inform future service reconfiguration. Volume-outcome research is just one component of a quality framework that will help align healthcare with quality improvement programmes and must incorporate a multidimensional approach to measuring and presenting both the clinical and patient-orientated measures of quality of care

Developing a Substation Design Curriculum for Electronics Engineering Technology

Background: The latest technologies have created an increasing demand for the generation, transmission, and distribution of electricity. Substations are a crucial segment of our power grid. Substations are used to step-up voltages for the long-distance transmission of energy and to stepdown voltages for industrial and residential use. The demand for substation design curriculum was discussed at a meeting of the Industrial Advisory Committee (IAC) for EET. Members of the IAC consisted of professionals from Black & Veatch and other companies that work with power systems such as substations and switchgear. The curriculum was developed in close cooperation with Black & Veatch to shape the curriculum with a practical approach. Purpose: This paper describes the development of a substation design curriculum to be used in an Electronics Engineering Technology (EET) program at Pittsburg State University (PSU). Method: In 2019, a PSU faculty participated in a series of NSF sponsored workshops for facilitating the teaching of electric energy (Workshops for Facilitating Faculty to Teach Electric Energy Courses for Combating Climate Change, 2019) since the EET faculty did not have a strong background in power systems. In addition, a graduate assistant with a background in power systems was recruited to create the substation design curriculum. In the same year, a visit to Black & Veatch was conducted where the substation design process was presented to a PSU faculty and the graduate assistant. It was discussed what topics should be included in the curriculum. In 2020, the substation design curriculum was introduced into an existing Electric Power course. The substation curriculum included lectures on the basics of generation, transmission, and distribution; substation components; one-line diagrams; and circuit breaker topologies. The curriculum also consisted of two labs which used the PowerWorld software and an exam. A guest speaker from Black & Veatch concluded the substation curriculum with a presentation of substation design projects. The effectiveness of the substation design curriculum was assessed by analyzing student work on one of the labs and selected questions from the exam on substation design. Results: A rubric was applied to the lab and the average was 1.86 out of 3 points. The percentage of correct answers on selected questions in the exam was 95%.Conclusion: Assessment results for the labs and exam showed that students learned the material and the new curriculum was effective overall. Another benefit of the substation curriculum development was that the graduate student secured an internship at Black & Veatch where he worked in designing substations. In addition, Black & Veatch offered five full scholarships to PSU students in the EET program in 2020-21 academic year and the broadening of students’ knowledge in power systems

Prospectus, September 13, 2006

https://spark.parkland.edu/prospectus_2006/1019/thumbnail.jp

Prospectus, September 21, 2006

https://spark.parkland.edu/prospectus_2006/1020/thumbnail.jp

Current oscillations generated by precipitate formation in the mixing zone between two solutions inside a nanopore

Unlike biological protein pores in lipid membranes, nanopores fabricated in synthetic materials can withstand a wide range of environmental conditions including the presence of organic solvents. This capability expands the potential of synthetic nanopores to monitor chemical reactions occurring at the interface between solutions of organic and aqueous character. In this work, nanopores fabricated in borosilicate glass or silicon nitride connected a predominantly organic solvent to an aqueous solvent, thereby generating a mixing zone between these solutions inside the pore. This configuration was exploited to precipitate small organic molecules with low aqueous solubility inside the nanopores, and concomitantly, to monitor this precipitation by the decrease of the ionic conductance through the nanopores over time. Hence, this method provides a means to induce and investigate the formation of nanoprecipitates or nanoparticles. Interestingly, precipitates with a slight electric charge were cleared from the pore, causing the conductance of the pore to return to its original value. This process repeated, resulting in stable oscillations of the ionic current. Although such oscillations might be useful in fluidic logic circuits, few conditions capable of generating oscillations in ionic currents have been reported. The frequency and amplitude of oscillations could be tuned by changing the concentration of the precipitating molecule, the pH of the electrolyte, and the applied potential bias. In addition to generating oscillations, nanopores that separate two different solutions may be useful for monitoring and mediating chemical reactions in the mixing zone between two solutions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85433/1/cm10_45_454127.pd

Prospectus, October 4, 2006

https://spark.parkland.edu/prospectus_2006/1022/thumbnail.jp

Do standardised prognostic algorithms reflect local practice? Application of EORTC risk tables for non-muscle invasive (pTa/pT1) bladder cancer recurrence and progression in a local cohort.

A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC) and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1) transitional cell cancer (TCC) at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr) and progression (Ip-IVp), respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67%, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice

Downscaling an intense precipitation event in complex terrain: the importance of high grid resolution

Floods due to intense rainfall are a major hazard to both people and infrastructure in western Norway. Here steep orography enhances precipitation and the complex terrain channels the runoff into narrow valleys and small rivers. In this study we investigate a major rainfall and flooding event in October 2014. We compare high-resolution numerical simulations with measurements from rain gauges deployed in the impacted region. Our study has two objectives: (i) to understand the dynamical processes that drove the high rainfall and (ii) the importance of high grid resolution to resolve intense rainfall in complex terrain. This is of great interest for numerical weather prediction and hydrological modelling. Our approach is to dynamically downscale the ERA-Interim reanalysis with the Weather Research and Forecasting model (WRF). We find that WRF gives a substantially better representation of precipitation both in terms of absolute values as well as spatial and temporal distributions than a coarse resolution reanalysis. The largest improvement between the WRF simulations is found when we decrease the horizontal model grid spacing from 9 km to 3 km. Only minor additional improvements are obtained when downscaling further to 1 km. We believe that this is mainly related to the orography in the study area and its representation in the model. Realistic representations of gravity waves and the seeder–feeder effect seem to play crucial roles in reproducing the precipitation distribution correctly. An analysis of associated wavelengths shows the importance of the shortest resolvable length scales. On these scales our simulations also show differences in accumulated precipitation of up to 300 mm over four days, further emphasising the need for resolving short wavelengths. Therefore, our results clearly demonstrate the need for high-resolution dynamical downscaling for extreme weather impact studies in regions with complex terrain.publishedVersio

Role of Sprouty proteins as antagonists of RTK signaling

Krebszellen sind durch eine weitgehende Unabhängigkeit von Wachstumsfaktorstimuli und eine starke Überaktivierung von wachstums- und überlebens-promovierenden Signalübertragungssystemen gekennzeichnet. Auch die verminderte Expression der Sprouty (Spry) Proteine trägt nachweislich in malignen Tumoren verschiedener Gewebe zu diesem Phänotyp bei. In normalen Zellen fungieren die Spry Proteine, hauptsächlich über ihre hemmende Wirkung auf die Ras/Raf/MAPK Signalkaskade, als Modulatoren von Rezeptor-Tyrosin-Kinasen-aktivierten Signalwegen. In dieser Arbeit konnten wir zeigen, dass die Expression von Spry2, aber nicht von Spry1, im Nicht-kleinzelligen Lungenkarzinom (NSCLC) im Vergleich zum normalen adulten Lungenepithelium signifikant reduziert ist. Basierend auf dieser Erkenntnis, untersuchten wir den Einfluss der Spry2 Expression auf den malignen Phänotyp von NSCLC in Abhängigkeit von wildtyp (wt) und konstitutiv aktivem K-Ras. Während die verminderte Aktivität der MAPK Kaskade und die herabgesetzte Geschwindigkeit der Zellwanderung nach ektopischer Expression von Spry2 ausschließlich in K-Ras wt Zellen beobachtet wurde, war die Hemmung von Zellvermehrung und Tumorformation in der Maus bei der Re-expression von Spry2 unabhängig vom K-Ras Status. Die gewonnen Daten legen nahe, dass Spry2 neben der Ras/Raf/MAPK Kaskade eine zweite regulatorische Funktion wahrnimmt. Erhärtet wird diese Annahme durch Versuche mit einer Spry2 Mutante, die zwar nicht in der Lage war die Signalintensität der MAPK zu inhibieren, aber dennoch signifikant, wenn auch schwächer als Spry2 wt, die Zellvermehrung hemmte. Da alle Sprouty Proteine als Teil einer auto-regulatorischen Rückkoppelungsschleife beschrieben wurden, untersuchten wir in weiterer Folge die molekularen Grundlagen der Expressionsregulation verschiedener Spry Familienmitglieder. Erhöhte Spry2 und Spry4 Levels korrelierten signifikant mit der Expression von aktiviertem endogenen und ektopisch expremierten K-Ras in NSCLC-Zelllinien bzw. nicht-malignen Fibroblasten, während Spry1 nicht erhöht vorgefunden wurde und nicht direkt durch Ras-induzierte Signalwege reguliert wird. Durch die Verwendung verschiedener Wachstumsfaktoren und spezifischer Ras Mutationen konnten wir weiters zeigen, dass Spry2 hauptsächlich über aktivierende Ras/ Erk Signale reguliert wird, während bei Spry4 die Induktion der Spry4 Expression fast ausschließlich durch Serum angeregt und über mehrere Ras-aktivierte Signalwege beeinflusst wird. Bezüglich der Expressionsmuster während eines Zellzyklus zeigten alle untersuchten Spry Familienmitglieder phasenspezifisch fluktuierende und voneinander merklich unterschiedliche Expressionsprofile. Außerdem legen unsere Daten nahe, dass Spry1 und Spry2 über die Ebene der Transkription reguliert werden, da mRNA und Proteine übereinstimmend voneinander exprimiert vorliegen. Im Gegensatz dazu wird Spry4 eher durch post-translatorische Mechanismen stabilisiert. Über die exogene Expression von wildtyp und dominant negativem cCbl untersuchten wir den Einfluß von cCbl auf die Zellzyklusphase-abhängige Expression von Spry1, 2 und 4, v.a. zwischen später G1 und früher S Phase. Dabei konnten wir zeigen, dass die Herunterregulation von Spry2 während dieses Phasenfensters durch cCbl erfolgt, während Spry1 und Spry4 keine direkten Substrate von cCbl sind. Zusammenfassend, Spry2 wirkt der Erk Phosphorylierung entgegen und wird selbst durch Ras über den MAPK Signalweg induziert. Weiters inhibiert Spry2 die Zellproliferation über einen noch nicht beschriebenen Signalweg. Außerdem konnten wir zeigen, dass verschiedene Sprys über unterschiedliche Mechanismen in verschiedenen Zellzyklusphasen induziert werden. Auf Grund dieser Erkenntnisse liefern unsere Daten einen wichtigen Beitrag zum Verständnis der Rolle von Spry Proteinen, vor allem im Hinblick auf ihre Rolle in der Krebsentstehung und -progression.Self sufficiency of growth signals and desensitized signal transduction systems are hallmarks of human cancer. One group of proteins shown to be deregulated in malignant tumors of diverse tissues are members of the Sprouty (Spry) protein family. Sprys function as modulators of receptor tyrosine kinase (RTK) signaling mainly by interfering with the Ras/Raf/mitogen-activated protein kinase (MAPK) cascade as part of an auto-regulatory feedback loop. In this study, we show that Spry2, but not Spry1 expression, is consistently lowered and significantly reduced in non small cell lung cancer (NSCLC) compared to the normal adult lung epithelium. Based on this finding, we investigated the influence of Spry2 expression on the malignant phenotype of NSCLC cells in the background of wild type (wt) or constitutive active K-Ras. Ectopic expression of Spry2 antagonized extracellular-regulated kinase (Erk) activity and cell migration just in K-Ras wt cell lines. In contrast, inhibition of cell proliferation and tumor formation in mice in response to Spry2 re-expression was observed independently of the K-Ras status. In corroboration, a Spry2 mutant unable to inhibit MAPK phosphorylation still reduced cell proliferation significantly but less pronounced compared with the Spry2 wt protein. Since all Sprouty proteins had been suggested to be regulated as part of an auto-regulatory feedback loop, further experiments were designed to explore the precise requirements for induced expression of the Spry proteins. Increased Spry2 and Spry4 levels significantly correlated with the expression of activating endogenous and ectopic expressed K-Ras muations in NSCLC cells and non-malignant fibroblasts, whereas Spry1 was not found elevated and was not regulated directly via Ras-mediated signaling cacades. Using different growth factors and ectopic expression of Ras mutant forms, our data revealed that induction of Spry2 is exclusively dependent on Erk activation via Ras-dependent signaling, while induction of Spry4 expression was almost exclusively activated by serum and/or several Ras-influenced signaling cascades. Throughout the cell cycle all investigated Spry proteins showed clear and reproducible fluctuations, but interestingly their cell cycle-specific expression patterns differed markedly. Further, we demonstrate that Spry1 and Spry2 levels are mediated by transcriptional activation, since mRNA and protein levels were found coregulated, while Spry4 is stabilized by post-translatory modifications. Finally, we investigated the influence of ectopically expressed wildtype and dominant negative cCbl on the cell cycle-specific expression of Spry1, 2 and 4, especially between late G1 and early S phase. Our data indicate that Spry2 downregulation within this specific time-frame is mediated by cCbl, whereas Spry1 and Spry4 are not direct substrates of cCbl. Summarizing, Spry2 antagonizes Erk phosphorylation and is itself induced by Ras via MAPK activation. Furthermore, Spry2 inhibits cell proliferation by another yet unidentified pathway. In addition, we showed that Sprys are induced by different mechanisms, during different phases of the cell cycle and are independently deregulated in tumor cells. Therefore our data make an important contribution to understand the role of Spry proteins