Fano-resonant ultrathin film optical coatings.

Optical coatings are integral components of virtually every optical instrument. However, despite being a century-old technology, there are only a handful of optical coating types. Here, we introduce a type of optical coatings that exhibit photonic Fano resonance, or a Fano-resonant optical coating (FROC). We expand the coupled mechanical oscillator description of Fano resonance to thin-film nanocavities. Using FROCs with thicknesses in the order of 300 nm, we experimentally obtained narrowband reflection akin to low-index-contrast dielectric Bragg mirrors and achieved control over the reflection iridescence. We observed that semi-transparent FROCs can transmit and reflect the same colour as a beam splitter filter, a property that cannot be realized through conventional optical coatings. Finally, FROCs can spectrally and spatially separate the thermal and photovoltaic bands of the solar spectrum, presenting a possible solution to the dispatchability problem in photovoltaics, that is, the inability to dispatch solar energy on demand. Our solar thermal device exhibited power generation of up to 50% and low photovoltaic cell temperatures (~30 °C), which could lead to a six-fold increase in the photovoltaic cell lifetime.

Photothermal and Joule-Heating-Induced Negative-Photoconductivity-Based Ultraresponsive and Near-Zero-Biased Copper Selenide Photodetectors.

The development of a highly responsive, near-zero-biased broadband photo and thermal detector is required for self-powered night vision security, imaging, remote sensing, and space applications. Photothermal-effect-based photodetectors operate on the principle of photothermal heating and can sense radiation from the UV to IR spectral region for broadband photo and thermal detection. This type of photodetector is highly desirable, but few materials have been shown to meet the stringent requirements including broadband optical/thermal absorption with high absorption coefficients, low thermal conductivity, and a large Seebeck coefficient. Here, we demonstrate ultraresponsive, near-zero-biased photodetectors made of mass-producible Cu2±x Se nanomaterials. Our photodetectors are fabricated with powder pressing and operate on the principle of negative photoconductivity that utilizes the Seebeck effect under the combined effects of Joule and photothermal heating to detect extremely low levels of broadband optical radiation. We show that copper-deficient Cu1.8Se and selenium-deficient Cu2.5Se copper selenide materials have negative photoconductivity. However, stochiometric Cu2Se copper selenide shows positive photoconductivity. We demonstrate that a photodetector made from the Ag:n+-Cu1.8Se:p-Ag:n+ system has the best photoresponse and generates a 520 mA/mm negative photocurrent and a high responsivity of 621 A/W under low bias.

Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer.

BACKGROUND: A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes. METHODS: In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users), or elect to not use the test (non-users). RESULTS: The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73%) used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR) rate compared to non-users (38.1% vs 0%, p = 0.04) and a higher disease control (CR+PR+Stable) rate (81% vs 25%, p<0.01). Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01). CONCLUSIONS: The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay. TRIAL REGISTRATION: Clinicaltrials.gov NCT00901264.

Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia.

Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. A total of 109 patients with untreated AML had blood and/or bone marrow aspirate samples analyzed for anthracycline-induced apoptosis using the MiCK assay. The amount of apoptosis observed over 48 h was determined and expressed as kinetic units of apoptosis (KU). Complete remission (CR) was significantly higher (72%) in patients with high idarubicin-induced apoptosis >3 KU compared to patients with apoptosis ≤ 3 KU (p = 0.01). Multivariate analysis showed the only significant variables to be idarubicin-induced apoptosis and karyotype. Median overall survival of patients with idarubicin-induced apoptosis >3 KU was 16.1 months compared to 4.5 months in patients with apoptosis ≤ 3 KU (p = 0.004). Multivariate analysis showed the only significant variable to be idarubicin-induced apoptosis. Chemotherapy-induced apoptosis measured by the MiCK assay demonstrated significant correlation with outcomes and appears predictive of complete remission and overall survival for patients receiving standard induction chemotherapy.

The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care.

A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development.

Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response.

BACKGROUND: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. METHODS: A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay. RESULTS: Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03). CONCLUSION: The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

OBJECTIVE: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. METHODS: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. RESULTS: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. CONCLUSION: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

Non-linear random effects model for multivariate responses with missing data.

The use of random-effects models for the analysis of longitudinal data with missing responses has been discussed by several authors. In this paper, we extend the non-linear random-effects model for a single response to the case of multiple responses, allowing for arbitrary patterns of observed and missing data. Parameters for this model are estimated via the EM algorithm and by the first-order approximation available in SAS Proc NLMIXED. The set of equations for this estimation procedure is derived and these are appropriately modified to deal with missing data. The methodology is illustrated with an example using data coming from a study involving 161 pregnant women presenting to a private obstetrics clinic in Santiago, Chile.

Determination of the Thermal Death Time of Vibrio cholerae in Blue Crabs ( Callinectes sapidus ).

The D-values of Vibrio cholerae were determined in peptone water and in crab meat homogenate. In peptone water, the D-values in minutes were 1.70 at 49°C, 1.04 at 54°C, 0.63 at 60°C and 0.36 at 63°C. In crab meat homogenate, the D-values in minutes were 8.15 at 49°C, 5.02 at 54°C, 2.65 at 60°C, 1.60 at 66°C and 0.30 at 71°C. Whole crabs injected with 106 V. cholerae were cooked by boiling or steaming. No V. cholerae was recovered from crabs cooked in boiling water (100°C) for 15 min or in steam (100, 115.6 or 121.1°C) for 10 min when V. cholerae was injected into the crab's dorsal swim fin muscle. The rate of heat penetration during cooking of crabs was also determined.