INVASIVE BLADDER CANCER - Aspects on staging and prognosis

Background: The difficulty of determining the prognosis for the individual patient with invasive bladder cancer is a major clinical problem. Currently, decisions regarding therapy are mainly based on tumour stage and grade, the first of which is notoriously demanding to ascertain. New molecular markers are however proposed to be of prognostic value. At present, there is considerable debate regarding the effects of delay on prognosis, lymph node staging and detection and staging of transitional cell carcinoma (TCC) involving the prostatic urethra and prostate in males. This thesis is based on investigations of the impact of diagnostic and treatment delay on prognosis in invasive bladder cancer (Papers I and II). Intra-operative sentinel node (SN) detection for lymph node staging is evaluated prospectively in Paper III, as are the incidence of TCC in the prostatic urethra and prostate and the preoperative detection of such tumour growth in Paper IV. The prognostic values of expression profiling and tissue microarray (TMA) in high-risk bladder cancer are investigated in Papers V and VI. Results and conclusions: 1) Diagnostic delay in patients with T1 tumours might have an adverse effect on the prognosis. 2) Treatment delay in patients with invasive bladder cancer submitted to radical cystectomy did not influence disease-specific survival or stage progression in the present study. 3) Intraoperative SN detection is feasible during radical cystectomy and improves nodal staging. 4) Preoperative biopsies from the prostatic urethra identified 66% of patients with TCC in the prostatic urethra and/or prostate in a prospective study investigating the prostate and bladder neck with sagittal whole-mount technique. 5) Preoperative investigation with cold cup mapping biopsies has a low sensitivity for detection of CIS (23%) and is probably of little clinical value for identifying patients at risk of TCC in the prostatic urethra/prostate in the cystoprostatectomy specimen. 6) Expression profiling identified a 50 gene signature predicting lymph node metastasis and survival in patients submitted to radical cystectomy. 7) TMA-based analysis of prognostic markers in invasive bladder cancer seems to be of limited value

The Future of Generic Biologics: Should the United States “Follow-On” the European Pathway?

The United States is embarking on a biotechnology drug revolution. In the last few decades, biotech drugs have saved millions of lives, and the market for these miracle cures continues to grow at an astronomical rate. Unfortunately, as the market for biotech drugs is skyrocketing, drug prices are following suit. As Congress strives to make these new drugs more affordable, it must not ignore significant safety concerns unique to these revolutionary therapies. Congress should follow the lead of the European Union to create an accessible pathway for generic forms of biotech drugs that includes strict regulatory measures to ensure drug safety and efficacy

Benefits and challenges with coordinated inventory control at Volvo Parts

Coordinated inventory control is a concept within inventory management where decisions are based on stock and demand situations throughout a whole system of interconnected warehouses and inventories, and where control parameters are simultaneously determined and set at all installations. This thesis is a part of a larger research collaboration project in coordinated inventory control where NGiL (Next Generation Innovative Logistics), a Lund based research institute, and Volvo Parts AB in Gothenburg participate. Volvo Parts handles the aftermarket distribution, sales and related services for the Volvo Group companies and has centrally controlled complex multi-level warehouse structures and routines. These warehouse structures are well suited for a coordinated inventory control approach. A new multi-level inventory control model has been developed by NGiL especially for the Volvo Parts supply chain in Europe. The model utilizes advanced mathematical concepts to mimic Volvo Parts inventory systems consisting of several dealers and warehouses on a market. The model optimizes the reorder points at all locations with the aim of minimizing the total costs of the system while still maintaining or increasing today’s service to end customers. The purpose of this thesis is to prepare for this pilot study by analyzing the information systems, processes, structures and routines at Volvo Parts, design methods for extraction and calculation of the necessary parameters, select an appropriate market and to perform a selection of suitable spare parts and accessories to be included in the pilot study. A suitable market for the pilot study and a method to select and classify 100 parts with all necessary parameters are the main results of the thesis. The study is performed as an action research project, meaning that the authors are stationed at Volvo Parts headquarters in Gothenburg and observe the daily work, perform the necessary data extractions from the IT systems themselves and conduct interviews on a daily basis. The gathered data is a combination of primary and secondary quantitative data from the IT systems and calculations, as well as a lot of primary qualitative data from interviews and observations. The authors also function as mediators between NGiL researchers and Volvo Parts personnel. The developed model is concluded to be a good representation of the reality of Volvo Parts’ supply chain on the selected market Spain, and the authors do not see any large obstacles in a generalization to other Volvo Parts markets with the same structure or even other companies. The one major discrepancy between the NGiL model and current Volvo Parts control methods is how service levels are measured and how goals on these service levels are achieved. We have also performed a simulation study for some of the selected parts and found that the potential for cost reductions is significant and that the optimized solution fulfills target service levels in almost all cases. We also found out that there are no clear correlations or patterns between the cost reduction and any of the part characteristics that were studied, implying that a larger simulation study or a real life pilot study is necessary in order to further investigate the full potential of the NGiL model

New methods for the preparation of (bio)sensor surfaces : Molecular gradients and mixed monolayers containing oligo(ethylene glycols)

Alkanethiols form very close-packed and well ordered self-assembled monolayers on gold surfaces. The simple preparation of the organo-metal interface and the possibility to tailor the ƒç-functional group of the thiol individually for each target makes it attractive for a variety of applications. In the recent years many biosensors, for example affinity sensors, DNA chips and array systems, have been developed, which include a thiol sublayer for the covalent binding of receptor molecules. One important problem that must be avoided in biosensor design is non-specific adsorption of (bio)molecules on the sensing surface. Therefore, creating an optimal surface or basis layer is a major goal in biosensor applications. Two main directions for the preparation of thiol basis layers are described in this paper: 1) mixed monolayers and 2) molecular gradients. Oligo(ethylene glycol) terminated thiols (Eg4, Eg6 = HS-(CH2)15-CONH-(CH2)2-O)4,6-H), mercaptooctadecane (MOD), 16-mercaptohexadecan-1-ol (MHD), 16-mercaptohexadecanoic acid (MHA) and 16-mercaptohexadecan-1-amine (MDA) were chosen as model thiols for the investigations. All gold surfaces were cleaned using the TL1 procedure (NH3:H2O2:H2O 1:1:5 at 80¢XC). FT-IR spectroscopy, ellipsometry, impedance and contact angle measurements were used to characterize the monolayers. The combination of optical and electrochemical methods allows detailed statements about quality, structure and stability of the organic layer. The infrared reflection-absorption spectra were recorded at room temperature on a Bruker IFS 66, system equipped with a grazing angle (85o) infrared reflection accessory and a liquid-nitrogen-cooled MCT detector. The measurement chamber was continuously purged with nitrogen gas during the measurements. The acquisition time was around 10 min at 2 cm-1 resolution. A spectrum of a deuterated hexadecanthiolate (HS-(CD2)15-CD3) was used as reference

Islandshästens energiförbrukning i tölt i förhållande till galopp

Denna studie är en undersökning vad gäller islandshästens energiförbrukning i tölt och galopp. Studien ska ge en bättre bild av hur vi anstränger våra hästar vid tävling och vid avelsbedömning. Studien ska också försöka kartlägga andningsfrekvensen i förhållande till stegcykeln i tölt. Med hjälp av hjärtfrekvensen kan man räkna ut mängden syre som krävs vid ett visst arbete. Energiförbrukningen mäts i mängden syre förbrukad under en viss sträcka. Idag vet man att energiförbrukningen sker enligt en U-formad kurva för gångarterna skritt, trav och galopp. Man vet också att det finns en koppling mellan andningsfrekvensen och stegcykeln i galopp men inte lika tydliga kopplingar i övriga gångarter. I försöket användes fyra hästar som reds i fyra olika tempon i tölt och galopp, en minut för varje tempo med en stegring av hastigheten. Hjärtfrekvensen användes för att räkna ut energiförbrukningen vid de olika hastigheterna och gångarterna. Energiförbrukningen verkar öka kurvlinjärt i tölt. Tölten verkar ligga högre i energiförbrukning i jämförelse med galopp. Mjölksyra mättes även i slutet av försöket och visar värden över mjölksyratröskeln, högre efter galoppen än tölten men galoppen reds också i högre tempo. Utefter resultaten kan man dra paralleller till tävling i tölt och avelsbedömningar. En töltfinal rids under ca 9 minuter effektiv ridning. Efter de mjölksyravärden man fått under de fyra minuter vid den här studien kan man förvänta sig högre efter en hel töltfinal. Då det lägsta och högsta tempot som rids under tävling verkar vara de mest energikrävande kan det vara bra att ha detta i åtanke vid utfodring och träning av tävlingshästar. Att galoppen ligger lägre i energiförbrukning verkar rimligt då galopp är en gångart som hästarna väljer mer naturligt än tölt. Energiförbrukningen i tölt verkar ske enligt en U-formad kurva och verkar ligga högre i energiförbrukning jämfört med galopp. Säkrare studier krävs med fler hästar för att få ett ännu tydligare resultat. Andningen kunde inte tydligt kopplas till stegfrekvensen i tölt men de verkar ta fler steg per andetag i ett högre tempo. Vidare studier krävs

On Molecular Classification of Bladder Cancer: Out of One, Many.

Comparative analysis showed that bladder cancer classification systems identify overlapping subtypes but at different levels. Muscle-invasive bladder cancer shows remarkable heterogeneity, and six subtypes were identified that differ in transcriptional networks, marker profiles, and expression of actionable targets

Numerical analyses of an experimental excavation supported by panels of lime-cement columns

The influence of ground improvement with panels of overlapping lime-cement columns on the behavior of a braced excavation loaded to failure has been investigated using 3D numerical analyses and the results are compared with an experimental full-scale failure test. The analyses reveal that stress-induced strength anisotropy of lime-cement improved clay needs to be considered when the stress path for the actual field conditions differs from that in conventional laboratory testing. In addition to strength parameters, the modulus of deformation that is consistent with the actual encountered stress path is also needed for reasonable predictions

Photonic bandgap plasmonic waveguides

A novel type of a plasmonic waveguide has been proposed featuring an "open" design that is easy to manufacture, simple to excite and that offers a convenient access to a plasmonic mode. Optical properties of photonic bandgap (PBG) plasmonic waveguides are investigated experimentally by leakage radiation microscopy and numerically using the finite element method confirming photonic bandgap guidance in a broad spectral range. Propagation and localization characteristics of a PBG plasmonic waveguide have been discussed as a function of the wavelength of operation, waveguide core size and the number of ridges in the periodic reflector for fundamental and higher order plasmonic modes of the waveguide

An integral equation based numerical solution for nanoparticles illuminated with collimated and focused light

To address the large number of parameters involved in nanooptical problems, a more efficient computational method is necessary. An integral equation based numerical solution is developed when the particles are illuminated with collimated and focused incident beams. The solution procedure uses the method of weighted residuals, in which the integral equation is reduced to a matrix equation and then solved for the unknown electric field distribution. In the solution procedure, the effects of the surrounding medium and boundaries are taken into account using a Green’s function formulation. Therefore, there is no additional error due to artificial boundary conditions unlike differential equation based techniques, such as finite difference time domain and finite element method. In this formulation, only the scattering nano-particle is discretized. Such an approach results in a lesser number of unknowns in the resulting matrix equation. The results are compared to the analytical Mie series solution for spherical particles, as well as to the finite element method for rectangular metallic particles. The Richards-Wolf vector field equations are combined with the integral equation based formulation to model the interaction of nanoparticles with linearly and radially polarized incident focused beams