Targeted Therapies for Ovarian Cancer

Epithelial ovarian cancer has the highest mortality rate of all gynaecological malignancies. Most women present with advanced disease and develop a recurrence after radical surgery and chemotherapy. Improving the results of first- or subsequent-line chemotherapy has been slow, and novel approaches to systemic treatment are needed. Ovarian cancer is a heterogeneous disease with complex molecular and genetic changes. Understanding these better will provide information on the mechanisms of resistance and opportunities to target therapy more rationally, exploiting specific changes in the tumour. Here we reviewed targeted approaches to therapy, focussing on targeting angiogenesis and inhibition of DNA repair, 2 areas that show promising activity. Additionally, we reviewed studies that are underway, targeting the cell cycle, signalling pathways and immunotherapeutic strategies. Many of these innovative approaches already demonstrate promising activity in ovarian cancer and have the potential to improve the outcome in women with ovarian cancer

Self-compassion and compassion towards one’s partner mediate the negative association between insecure attachment and relationship quality.

The quality of intimate relationships has been found to be a strong negative predictor for individuals’ mental and physical health problems. A significant predictor of relationship quality is adult attachment insecurity, but the mechanism by which attachment insecurity affects relationship quality needs further investigation. This study investigated whether self-compassion and compassion for one’s partner mediated this association. Three-hundred-forty-two individuals participated in an online survey assessing attachment anxiety and avoidance, compassionate and uncompassionate attitude towards self and one’s partner, as well as relationship quality and relationship satisfaction. The results showed that low self-compassionate attitude mediated the association between attachment anxiety and poor relationship quality. Further, low compassionate and high uncompassionate attitude towards one’s partner mediated the association between attachment avoidance and poor relationship quality. No mediating effect was found for relationship satisfaction. Implications for interventions are discussed

Agricultural Subsidies and the Doha Round: A Historic Breakthrough?

The international community witnessed a self-proclaimed \u27historical breakthrough\u27at the World Trade Organization (WTO) in late Summer 2004 as a framework was created to eliminate all export subsidies and reduce domestic subsidies and tariffs respectively. While many hailed this step as a major victory for developing nations, others have been cautious on the \u27success\u27of this agreement. This honor thesis evaluates the short- and long-term effects of this framework agreement on the agricultural sectors of the US, South Africa and Mali. The paper first undertakes a historical analysis of what led to this \u27victory\u27for developing nations at the WTO. The paper then focuses on two major crops, cotton and maize, in order to explore the impact of the agreement on poverty alleviation, food security and ecological and economic sustainability. Ultimately, the thesis proposes several policy considerations in order to harvest the \u27potential\u27 historical breakthrough in the longrun

Blinking statistics of a molecular beacon triggered by end-denaturation of DNA

We use a master equation approach based on the Poland-Scheraga free energy for DNA denaturation to investigate the (un)zipping dynamics of a denaturation wedge in a stretch of DNA, that is clamped at one end. In particular, we quantify the blinking dynamics of a fluorophore-quencher pair mounted within the denaturation wedge. We also study the behavioural changes in the presence of proteins, that selectively bind to single-stranded DNA. We show that such a setup could be well-suited as an easy-to-implement nanodevice for sensing environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat special issue on diffusio

Andreev scattering in the asymmetric ladder with preformed bosonic pairs

We discuss the phase coherence which emanates from the ladder-like proximity effect between a ``weak superconductor'' with preformed bosonic pairs (here, a single-chain Luther-Emery liquid with superconducting correlations that decay approximately as $x^{-1}$) and a Fermi gas with unpaired fermions. Carefully studying tunneling mechanism(s), we show that the boson-mediated Cooper pairing between remaining unpaired electrons results in a quasi long-range superconductivity: Superconducting correlations decay very slowly as $x^{-\eta}$ with $\eta\approx 1/2$. This process is reminiscent of the coupling of fermions to preformed bosonic pairs introduced in the context of high-Tc cuprates.Comment: 5 pages, final version (To appear in PRB Rapid Communication

Stepwise Projection: Toward Brane Setups for Generic Orbifold Singularities

The construction of brane setups for the exceptional series E6,E7,E8 of SU(2) orbifolds remains an ever-haunting conundrum. Motivated by techniques in some works by Muto on non-Abelian SU(3) orbifolds, we here provide an algorithmic outlook, a method which we call stepwise projection, that may shed some light on this puzzle. We exemplify this method, consisting of transformation rules for obtaining complex quivers and brane setups from more elementary ones, to the cases of the D-series and E6 finite subgroups of SU(2). Furthermore, we demonstrate the generality of the stepwise procedure by appealing to Frobenius' theory of Induced Representations. Our algorithm suggests the existence of generalisations of the orientifold plane in string theory.Comment: 22 pages, 3 figure

Outcome of patients with advanced ovarian cancer who do not undergo debulking surgery: A single institution retrospective review

OBJECTIVE: To assess the outcome of patients with advanced ovarian cancer (OC) who were treated without surgery, having received upfront chemotherapy and no interval debulking surgery (IDS). METHODS: Retrospective analysis of medical and chemotherapy records of consecutive patients with OC between 2005 and 2013 at UCL Hospitals London, UK who received neoadjuvant chemotherapy (NACT) was then found to be unsuitable for IDS following review by the multidisciplinary team. RESULTS: Eighty-three patients (18%) out of 467 receiving NACT did not undergo IDS. Median age was 70years (range 33-88); out of these 83 patients, 43 (51.8%) presented with stage IV disease. Forty-three of these 83 patients received carboplatin and paclitaxel (CP) (51.8%) and 37 received carboplatin alone (C) (44.6%); 3 patients (3.6%) received other platinum-based combinations. Reasons for not proceeding to surgery were: poor response to chemotherapy after 3-4 cycles of NACT (61/83, 73.5%); comorbidities (12/83, 14.5%); patient decision (4/83, 4.8%). Six patients (7.2%) received 2 lines of chemotherapy. In a univariate analysis CP, age <70years, and absence of comorbidities were factors influencing OS. In a multivariate analysis only having received CP remained independently associated with OS (HR 0.49, 95% CI 0.29-0.84). CONCLUSIONS: Chemotherapy alone can provide reasonable disease control in patients unsuitable for IDS and CP should be used if possible

Successive opening of the Fermi surface in doped N-leg Hubbard ladders

We study the effect of doping away from half-filling in weakly (but finitely) interacting N-leg Hubbard ladders using renormalization group and bosonization techniques. For a small on-site repulsion U, the N-leg Hubbard ladders are equivalent to a N-band model, where at half-filling the Fermi velocities are v_{1}=v_{N}<v_{2}=v_{N-1}<... We then obtain a hierarchy of energy-scales, where the band pairs (j,N+1-j) are successively frozen out. The low-energy Hamiltonian is then the sum of N/2 (or (N-1)/2 for N odd) two-leg ladder Hamiltonians without gapless excitations (plus a single chain for N odd with one gapless spin mode), similar to the N-leg Heisenberg spin-ladders. The energy-scales lead to a hierarchy of gaps. Upon doping away from half-filling, the holes enter first the band(s) with the smallest gap: For odd N, the holes enter first the nonbonding band (N+1)/2 and the phase is a Luttinger liquid, while for even N, the holes enter first the band pair (N/2,N/2+1) and the phase is a Luther-Emery liquid, similar to numerical treatments of the t-J model, i.e., at and close to half-filling, the phases of the Hubbard ladders for small and large U are the same. For increasing doping, hole-pairs subsequently enter at critical dopings the other band pairs (j,N+1-j) (accompanied by a diverging compressibility): The Fermi surface is successively opened by doping, starting near the wave vector (pi/2,pi/2). Explicit calculations are given for the cases N=3,4.Comment: 10 pages, 4 figures, to be published in Phys. Rev.

Inhomogeneously doped two-leg ladder systems

A chemical potential difference between the legs of a two-leg ladder is found to be harmful for Cooper pairing. The instability of superconductivity in such systems is analyzed by compairing results of various analytical and numerical methods. Within a strong coupling approach for the t-J model, supplemented by exact numerical diagonalization, hole binding is found unstable beyond a finite, critical chemical potential difference. The spinon-holon mean field theory for the t-J model shows a clear reduction of the the BCS gaps upon increasing the chemical potential difference leading to a breakdown of superconductivity. Based on a renormalization group approach and Abelian bosonization, the doping dependent phase diagram for the weakly interacting Hubbard model with different chemical potentials was determined.Comment: Revtex4, 11 pages, 7 figure