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Introduction Sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) in node-positive (N+) breast cancer patients at diagnosis remains a controversial issue, with no consensus on implementation or safety. Objectives We sought to assess the accuracy of SLNB after NAT in biopsy-proven N+ cases at diagnosis and the efficacy and accuracy of wire localization of the clipped node to improve results. Material and methods A cross-sectional diagnostic technique validation study in N+ patients following NAT was performed. The biopsy-proven affected lymph node was clipped at diagnosis. SLNB and axillary lymph node dissection (ALND) were performed in cases of clinical-radiological lymph node response after NAT. For the purposes of our study we added wire localization of the clipped node. Results 103 patients were included (mean age, 54.4 years [± 12.7]). Wire marking was performed in 28 cases. The overall identification rate (IR) of SLN was 81.6%. The median number of nodes removed was 2 (range 2). The overall false negative rate (FNR) was 6.1%. Sensitivity and overall accuracy were 93.9% and 95.2%, respectively (area under curve 0.97). In the double-marked (clip and wire) group the FNR decreased to 0% and accuracy was 100%. Axillary pathologic complete response was observed in 24.3% of cases. Conclusions SLNB is useful in node-positive patients at diagnosis who respond to NAT. Combining this with preoperative wire localization of the biopsied lymph node reduces the FNR without increasing the number of complications.

Proton exchange membrane (PEM) fuel cells have the potential to provide a clean and convenient source of power for applications such as vehicle transport. At their heart lies a platinum catalyst which is used to reduce oxygen to water. Although platinum is expensive it is the best elemental catalyst for the reaction. In order to make better use of the platinum and reduce production costs, nanoparticulate platinum is dispersed onto a carbon support. This results in a greater surface area per gram of platinum used. Efforts to improve the performance of fuel cells and make them cost effective have so far revolved around increasing the surface area. However in doing this the inter-particle spacing and diffusional characteristics of the catalyst have been ignored. In order to address this oversight, this thesis takes a novel bottom up approach to better understanding the oxygen reduction reaction on nanoparticulate platinum, supported on carbon. By using a model system and simulating the diffusional environment, this work reveals new insights into the oxygen reduction reaction. In Chapter 1 the fundamental electrochemical principles which underpin the subsequent work shall are examined. Chapter 2 begins with a look at the history of fuel cell development, before assessing the modern PEM fuel cell and the challenges faced in the present day to make it a viable power source. In Chapter 3 carbon electrode materials are assessed with a view towards their use as a substrate for platinum catalysts. The results gained from this prove useful in later chapters and are both novel and insightful for the selection of PEM fuel cell catalyst supports. In Chapters 4 and 5 voltammetry at nanomaterial modified electrodes are extensively analysed, using electrochemical simulation techniques. This reveals that diffusion can play a role in effects which are assumed to be purely kinetic. From this a major flaw is exposed in the currently accepted measures of oxygen reduction catalyst activity. Chapter 6 brings the information garnered from the previous chapters together. In this chapter nanoparticulate platinum dispersed onto a flat carbon substrate is used as a model system of a typical oxygen reduction catalyst. The resulting voltammetry from the model surfaces is then fitted effectively to results from electrochemical simulations, paying close attention to the diffusional environment around the nanoparticles. This approach leads to a key finding which had hitherto gone unrecognised.

The notion that some banks are “too big to fail” builds on the premise that governments will offer support to avoid the adverse consequences of disorderly bank failures. However, this promise of support comes at a cost: Large, complex, or interconnected banks might take on more risk if they expect future rescues. This article studies the effect of potential government support on banks’ appetite for risk. Using balance-sheet data for 224 banks in forty-five countries starting in March 2007, the authors find higher levels of impaired loans after an increase in government support. To measure support, they rely on Fitch Ratings’ support rating floors (SRFs), a new rating that isolates potential sovereign support from other sources of external support. A one-notch rise in the SRF is found to increase the impaired loan ratio by roughly 0.2—an 8 percent increase for the average bank. The authors obtain similar results when they assess the effect of increased support on net charge-offs and when they narrow their sample to U.S. banks only.

We present a dynamic over-the-counter model of the fed funds market, and use it to study the determination of the fed funds rate, the volume of loans traded, and the intraday evolution of the distribution of reserve balances across banks. We also investigate the implications of changes in the market structure, as well as the effects of central bank policy instruments such as open market operations, the Discount Window lending rate, and the interest rate on bank reserves.

We develop a model of the market for federal funds that explicitly accounts for its two distinctive features: banks have to search for a suitable counterparty, and once they have met, both parties negotiate the size of the loan and the repayment. The theory is used to answer a number of positive and normative questions: What are the determinants of the fed funds rate? How does the market reallocate funds? Is the market able to achieve an efficient reallocation of funds? We also use the model for theoretical and quantitative analyses of policy issues facing modern central banks.

We use minute-by-minute daily transaction-level payments data to document the cross-sectional and time-series behavior of the estimated prices and quantities negotiated by commercial banks in the fed funds market. We study the frequency and volume of trade, the size distribution of loans, the distribution of bilateral fed funds rates, and the intraday dynamics of the reserve balances held by commercial banks. We find evidence of the importance of the liquidity provision achieved by commercial banks that act as de facto intermediaries of fed funds.

Dynamic core-shell nanoparticles have received increasing attention in recent years. This paper presents a detailed study of Au-Hg nanoalloys, whose composing elements show a large difference in cohesive energy. A simple method to prepare Au@Hg particles with precise control over the composition up to 15 atom% mercury is introduced, based on reacting a citrate stabilized gold sol with elemental mercury. Transmission electron microscopy shows an increase of particle size with increasing mercury content and, together with X-ray powder diffraction, points towards the presence of a core-shell structure with a gold core surrounded by an Au-Hg solid solution layer. The amalgamation process is described by pseudo-zero-order reaction kinetics, which indicates slow dissolution of mercury in water as the rate determining step, followed by fast scavenging by nanoparticles in solution. Once adsorbed at the surface, slow diffusion of Hg into the particle lattice occurs, to a depth of ca. 3 nm, independent of Hg concentration. Discrete dipole approximation calculations relate the UV-vis spectra to the microscopic details of the nanoalloy structure. Segregation energies and metal distribution in the nanoalloys were modeled by density functional theory calculations. The results indicate slow metal interdiffusion at the nanoscale, which has important implications for synthetic methods aimed at core-shell particles.

This paper studies the relationship between the arrival of potential investors and market liquidity in a search-based model of asset trading. The entry of investors into a specific market causes two contradictory effects. First, it reduces trading costs, which then attracts new investors (the thick market externality effect). But second, as investors concentrate on one side of the market, the market becomes 'congested,' decreasing the returns to participating in this market and discouraging new investors from entering (what we call the congestion effect). The equilibrium level of market liquidity depends on which of the two effects dominates. When congestion is the leading effect, some interesting results arise. In particular, we find that diminishing trading costs in our market can impair liquidity and reduce welfare.

We study liquidity and systemic risk in high-value payment systems. Flows in high-value systems are characterized by high velocity, meaning that the total amount paid and received is high relative to the stock of reserves. In such systems, banks rely heavily on incoming funds to finance outgoing payments, necessitating a high degree of coordination and synchronization. We use lattice-theoretic methods to solve for the unique fixed point of an equilibrium mapping and conduct comparative statics analyses on changes to the environment. We find that banks attempting to conserve liquidity cause an increase in the demand for intraday credit and, ultimately, a disruption of payments. Additionally, we find that when a bank is identified as vulnerable to failure and other banks choose to cancel payments to that bank, there are systemic repercussions for the whole financial system.

We study liquidity and systemic risk in high-value payment systems. Flows in high-value systems are characterized by high velocity, meaning that the total amount paid and received is high relative to the stock of reserves. In such systems, banks rely heavily on incoming funds to finance outgoing payments, necessitating a high degree of coordination and synchronization. We use lattice-theoretic methods to solve for the unique fixed point of an equilibrium mapping and conduct comparative statics analyses on changes to the environment. We find that banks attempting to conserve liquidity cause an increase in the demand for intraday credit and, ultimately, a disruption of payments. Additionally, we find that when a bank is identified as vulnerable to failure and other banks choose to cancel payments to that bank, there are systemic repercussions for the whole financial system.

The addition of chemotherapy to radiation therapy has the potential to sterilize micrometastases and tumor foci adjacent and peripheral to the treatment field, so as to enhance local control of malignancy and improve primary and salvage therapy. Studies were done to investigate the effects of combining cisplatin (CP), the most active single agent in squamous-cell cancer of the cervix, with irradiation and the addition of a protein kinase C (PKC) inhibitor. This initial report of these studies describes our experience in exposing human cervical carcinoma (HeLa-S3) cells grown in culture as multicellular tumor spheroids to continuous CP combined with radiation in an attempt to mimic both clinically achievable serum concentrations of CP and a weekly fractionated-dose environment. Radiation-dose-dependent delays of spheroid growth were not significantly increased in the presence of the PKC inhibitor 7-OH-staurosporine (UCN-01) at 1.0 nM and 10.0 nM concentrations. When dose comparisons at 8 Gy alone (2 Gy x 4 fractions) were made for combined therapy with either CP alone (1.0 microgram/ml) or UCN-01 alone, absolute delays in spheroid growth at the highest concentrations used were comparable (range: 37-41 days). Although these data alone would not support minimal chemotherapeutic interaction, it appears that the overall effects observed for combination therapy were predominately radiation-dose dependent. The combination of UCN-01 plus CP (0.5 and 1.0 mu/ml, respectively) was effective in increasing the cytostatic and cytotoxic effects of irradiation at 4 Gy (2 Gy x 2 fractions). Observations made as early as day 4 and day 7 posttreatment were indicative ofor = 40% and 60%, respectively, of morphological damage. Spheroid growth was essentially static at these doses over the evaluation time of 60 days. Intracellular junctions were disorganized, and spheroid swelling was evident and contributed to the modest dimensional changes observed after treatment. No surviving fractions could be generated from spheroids that were mechanically disrupted, trypsinized, and plated at day 7 after the initiation of treatment. At 2 months, 88% (14/16) and 94% (15/16) of the multimodality treatment groups (4 Gy + UCN-01 + CP [0.5 and 1.0 mu/ml], respectively) had sterilized spheroids, indicating that the CP concentration dependence may not be a sole determinant of efficacy. Our therapeutic strategy for combining irradiation with CP was based on the contemporary use of CP as the most successful agent in producing high survival rates in gynecological malignancy. The combination of UCN-01 with CP and irradiation may, however, represent a more effective strategy for enhancing future cisplatin-based chemotherapy regimens.

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