Scanning apertureless microscopy below the diffraction limit: Comparisons between theory and experiment

The exact nature of the signal in scanning apertureless microscopy techniques is the subject of much debate. We have sought to resolve this controversy by carrying out simulations and experiments on the same structures. Simulations of a model of tip–sample coupling are shown to exhibit features that are in agreement with experimental observations at dimensions below the diffraction limit. The simulation of the optical imaging process is carried out using atomic force microscope data as a topographical template and a tip–sample dipole coupling model as the source of optical signal. The simulations show a number of key fingerprints including a dependence on the polarization of the external laser source, the size of the tip, and index of refraction of the sample being imaged. The experimental results are found to be in agreement with many of the features of the simulations. We conclude that the results of the dipole coupling theory agree qualitatively with experimental data and that apertureless microscopy measures optical properties, not just topography

Electron-nuclei spin relaxation through phonon-assisted hyperfine interaction in a quantum dot

We investigate the inelastic spin-flip rate for electrons in a quantum dot due to their contact hyperfine interaction with lattice nuclei. In contrast to other works, we obtain a spin-phonon coupling term from this interaction by taking directly into account the motion of nuclei in the vibrating lattice. In the calculation of the transition rate the interference of first and second orders of perturbation theory turns out to be essential. It leads to a suppression of relaxation at long phonon wavelengths, when the confining potential moves together with the nuclei embedded in the lattice. At higher frequencies (or for a fixed confining potential), the zero-temperature rate is proportional to the frequency of the emitted phonon. We address both the transition between Zeeman sublevels of a single electron ground state as well as the triplet-singlet transition, and we provide numerical estimates for realistic system parameters. The mechanism turns out to be less efficient than electron-nuclei spin relaxation involving piezoelectric electron-phonon coupling in a GaAs quantum dot.Comment: 8 pages, 1 figur

The equity of school facilities funding: Examples from Kentucky.

While there is an extensive literature analyzing the relative equity of state funding systems for current operating revenues, there is a dearth of research on capital funding systems. This article presents an analysis of the school capital funding system in Kentucky since 1990, using the operating-revenue analysis concepts of horizontal equity, vertical equity, and fiscal neutrality. In general one could tentatively conclude that Kentucky’s capital-funding system was reasonably equitable until an expansion of district options in 2003–04 was followed by greater measures of inequity. This analysis points to specific methods for Kentucky to restore equity to its school capital funding structure as well as a model for analysis of other capital funding systems

Pemphigus foliaceus in a patient with gastrointestinal stromal tumor treated with adjuvant imatinib mesylate

Pemphigus is an autoimmune bullous disease with a number of described associations, including medications, which have been grouped into three structural categories - thiol drugs, phenol drugs, and drugs with neither functional group [1]. Discontinuation of the offending medication is considered a mainstay of therapy. We report a patient in whom the onset of pemphigus foliaceus was associated with initiation of imatinib mesylate adjuvant therapy in a patient with resected gastrointestinal stromal tumor (GIST). Imatinib was continued because of the survival benefit to the patient with a resected, high risk GIST. Treatment with rituximab resulted in near resolution of his blistering rash and follow up enzyme-linked immunosorbent assay (ELISA) demonstrated reference range immunoreactivity for both desmoglein 1 and desmoglein 3. After dose increase of imatinib therapy owing to tumor growth, the patient subsequently again developed a similar eruption. Re-biopsy and ELISA were consistent with recurrence of pemphigus. In conclusion, although the patient's pemphigus was cleared with a single cycle of rituximab infusions while continuing imatinib therapy, the disease returned after imatinib dose was increased a year later, suggesting a dose-response relationship

Outcomes of percutaneous endovascular intervention for type II endoleak with aneurysm expansion

ObjectiveType II endoleak (T2EL) with aneurysm expansion is believed to place patients at risk for aneurysm-related mortality (ARM). Treatment with glue and/or coil embolization of the aneurysm sac, inferior mesenteric artery (IMA), and lumbar branches via translumbar or transarterial approaches has been utilized to ablate such endoleaks, and thus decrease ARM. We evaluated the midterm results of percutaneous endovascular treatment of T2EL with aneurysm expansion.MethodsSingle-institution, 5-year (January 2003 to August 2008) retrospective study of all endovascular interventions for T2EL with sac expansion. Blinded, independent review of all available pre- and post-T2EL intervention computed tomography (CT) scans was performed. Aneurysm sac maximal transverse diameters and aneurysm sac growth rates prior to and following T2EL intervention were analyzed.ResultsForty-two patients (34 male, eight female; mean age, 75) underwent T2EL intervention at 26 ± 20 months after endovascular aneurysm repair (EVAR) and were subsequently followed for 23 ± 20 months. Seven out of 42 patients (17%) underwent repeat T2EL intervention. Interventions included 44 translumbar sac embolizations, and transcatheter embolizations of nine IMAs and seven lumbar/hypogastric arteries. Aneurysm diameter was 6.1 ± 1.6 cm at EVAR, 6.6 ± 1.5 cm at initial T2EL treatment, and 6.9 ± 1.7 cm at last follow-up. There were no significant differences in the rates of aneurysm sac growth pre- and post-T2EL treatment. At last follow-up imaging, recurrent or persistent T2EL was noted in 72% of patients. Of 42 patients, nine (21%) received operative endoluminal correction of occult type I or type III endoleaks that were diagnosed during the T2EL angiographic intervention. There were no aneurysm ruptures or ARMs during follow-up; overall mortality for the 5-year study period was 24%.ConclusionsIn this series, percutaneous endovascular intervention for type II endoleak with aneurysm sac growth does not appear to alter the rate of aneurysm sac growth, and the majority of patients display persistent/recurrent endoleak. However, diagnostic angiographic evaluation may reveal unexpected type I and III endoleaks and is therefore recommended for all patients with T2EL and sac growth. While coil and glue embolization of aneurysm sac and selected branch vessels does not appear to yield benefit in our series, the diagnosis and subsequent definitive treatment of previously occult type I and III endoleaks may explain the absence of delayed rupture and ARM in our series

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study

Purpose A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. Methods GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. Results Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). Conclusion The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin

A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: Results from Cancer and Leukemia Group B Study 90006

The use of docetaxel prolongs survival for patients with castrate resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the anti-tumor effect of docetaxel and estramustine in patients with CRPC

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P \u3c .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned

Pharmacodynamic and Clinical Results from a Phase I/II Study of the HSP90 Inhibitor Onalespib in Combination with Abiraterone Acetate in Prostate Cancer.

PURPOSE:Onalespib is a potent, fragment-derived second-generation HSP90 inhibitor with preclinical activity in castration-resistant prostate cancer (CPRC) models. This phase I/II trial evaluated onalespib in combination with abiraterone acetate (AA) and either prednisone or prednisolone (P) in men with CRPC progressing on AA/P. PATIENTS AND METHODS:Patients with progressing CRPC were randomly assigned to receive 1 of 2 regimens of onalespib combined with AA/P. Onalespib was administered as intravenous infusion starting at 220 mg/m2 once weekly for 3 of 4 weeks (regimen 1); or at 120 mg/m2 on day 1 and day 2 weekly for 3 of 4 weeks (regimen 2). Primary endpoints were response rate and safety. Secondary endpoints included evaluation of androgen receptor (AR) depletion in circulating tumor cells (CTC) and in fresh tumor tissue biopsies. RESULTS:Forty-eight patients were treated with onalespib in combination with AA/P. The most common ≥grade 3 toxicities related to onalespib included diarrhea (21%) and fatigue (13%). Diarrhea was dose limiting at 260 and 160 mg/m2 for regimens 1 and 2, respectively. Transient decreases in CTC counts and AR expression in CTC were observed in both regimens. HSP72 was significantly upregulated following onalespib treatment, but only a modest decrease in AR and GR was shown in paired pre- and posttreatment tumor biopsy samples. No patients showed an objective or PSA response. CONCLUSIONS:Onalespib in combination with AA/P showed mild evidence of some biological effect; however, this effect did not translate into clinical activity, hence further exploration of this combination was not justified