Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

94 ß-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.

The ß-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of ß-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.

Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues.

Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD↓ are cleaved only twofold faster than DEVE↓, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase-7, can cleave peptides containing DEVpS↓ at only threefold slower rate than DEVD↓, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity.

Highly spectrum-selective ultraviolet photodetector based on p-NiO/n-IGZO thin film heterojunction structure.

Ultraviolet photodetector with p-n heterojunction is fabricated by magnetron sputtering deposition of n-type indium gallium zinc oxide (n-IGZO) and p-type nickel oxide (p-NiO) thin films on ITO glass. The performance of the photodetector is largely affected by the conductivity of the p-NiO thin film, which can be controlled by varying the oxygen partial pressure during the deposition of the p-NiO thin film. A highly spectrum-selective ultraviolet photodetector has been achieved with the p-NiO layer with a high conductivity. The results can be explained in terms of the "optically-filtering" function of the NiO layer.

DNA metabarcoding of insects and allies: an evaluation of primers and pipelines.

Metabarcoding, the coupling of DNA-based species identification and high-throughput sequencing, offers enormous promise for arthropod biodiversity studies but factors such as cost, speed and ease-of-use of bioinformatic pipelines, crucial for making the leapt from demonstration studies to a real-world application, have not yet been adequately addressed. Here, four published and one newly designed primer sets were tested across a diverse set of 80 arthropod species, representing 11 orders, to establish optimal protocols for Illumina-based metabarcoding of tropical Malaise trap samples. Two primer sets which showed the highest amplification success with individual specimen polymerase chain reaction (PCR, 98%) were used for bulk PCR and Illumina MiSeq sequencing. The sequencing outputs were subjected to both manual and simple metagenomics quality control and filtering pipelines. We obtained acceptable detection rates after bulk PCR and high-throughput sequencing (80-90% of input species) but analyses were complicated by putative heteroplasmic sequences and contamination. The manual pipeline produced similar or better outputs to the simple metagenomics pipeline (1.4 compared with 0.5 expected:unexpected Operational Taxonomic Units). Our study suggests that metabarcoding is slowly becoming as cheap, fast and easy as conventional DNA barcoding, and that Malaise trap metabarcoding may soon fulfill its potential, providing a thermometer for biodiversity.

Breast milk DHA levels in Sri Lankan mothers vary significantly in three locations that have different access to dietary fish.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFA) notably docosahexaenoeic acid (DHA) and arachidonic acid (ARA) are important for the optimum growth and development of the infant. DHA and ARA levels in breast-milk are thought to be influenced both by direct nutritional intake, and by the genetic variation of the FA desaturase enzymes. OBJECTIVES: To assess the fatty acid distribution in mothers' milk and their babies' blood, in three areas of Sri Lanka, with different access to sea-fish, and to see how the availability of dietary fish would affect fatty acid levels. METHODS: 6-12 week-old mother-baby pairs were recruited and mother's dietary intake assessed. Packed RBC from infants and breast milk (BM) from mothers were transported on dry ice to the Nutrition Laboratory, University of Otago, New Zealand for fatty acids extraction and quantification. RESULTS: We studied 136 mothers in three locations in Sri Lanka - Matara, Colombo, and Kandy. The breastmilk DHA levels were high in all three locations (0.79%, 0.53% and 0.37% respectively), and correlated with fish consumption. ARA levels did not vary significantly. In the 119 mother-infant pairs studied, infant erythrocyte DHA levels did not correlate significantly with BM DHA. CONCLUSIONS: Even the modest access to sea fish in the most inland site, resulted in BM-DHA levels higher than those found in any infant formula. Higher BM-DHA levels in the two other sites with greater access to fish did not lead to further increase in infant RBC-DHA levels. Where access to sea fish is limited, mothers should be encouraged to actively increase their fish intake as this would improve their DHA status, and also that of their breast milk.

Droplet spreading on a two-dimensional wicking surface.

The dynamics of droplet spreading on two-dimensional wicking surfaces were studied using square arrays of Si nanopillars. It was observed that the wicking film always precedes the droplet edge during the spreading process causing the droplet to effectively spread on a Cassie-Baxter surface composed of solid and liquid phases. Unlike the continual spreading of the wicking film, however, the droplet will eventually reach a shape where further spreading becomes energetically unfavorable. In addition, we found that the displacement-time relationship for droplet spreading follows a power law that is different from that of the wicking film. A quantitative model was put forth to derive this displacement-time relationship and predict the contact angle at which the droplet will stop spreading. The predictions of our model were validated with experimental data and results published in the literature.

Effect of thermal annealing on the efficiency of heterojunction photovoltaic cells fabricated using poly(3-hexylthiophene) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester.

The effects of thermal annealing on the efficiency of heterojunction photovoltaic (PV) cells that were fabricated using poly(3-hexylthiophene) (P3HT) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester (PCBM) were investigated. The absorption spectra showed that the absorption intensity of the P3HT:PCBM layer that was annealed for 5 min had the highest value among the several samples with different annealing temperatures. The atomic force microscopy image showed that the P3HT:PCBM layer that was annealed for 5 min had the best surface morphology. The X-ray photoelectron spectroscopy demonstrated that the P3HT:PCBM layer that was annealed at 140 degrees C for 10 min enhanced the PCBM aggregation on the surface Al layer that was covered by the P3HT:PCBM layer. The efficiencies of the PV cells that were annealed at 3, 5, and 10 min were approximately 2.7, 4.2, and 3.5%, respectively. Based on the experiment results, the variations in the efficiency of the PV cells due their thermal treatment were described.

Dynamics of wicking in silicon nanopillars fabricated with interference lithography and metal-assisted chemical etching.

The capillary rise of liquid on a surface, or "wicking", has potential applications in biological and industrial processes such as drug delivery, oil recovery, and integrated circuit chip cooling. This paper presents a theoretical study on the dynamics of wicking on silicon nanopillars based on a balance between the driving capillary forces and viscous dissipation forces. Our model predicts that the invasion of the liquid front follows a diffusion process and strongly depends on the structural geometry. The model is validated against experimental observations of wicking in silicon nanopillars with different heights synthesized by interference lithography and metal-assisted chemical etching techniques. Excellent agreement between theoretical and experimental results, from both our samples and data published in the literature, was achieved.

Covalent assembly of gold nanoparticles for nonvolatile memory applications.

This work reports a versatile approach for enhancing the stability of nonvolatile memory devices through covalent assembly of functionalized gold nanoparticles. 11-mercapto-1-undecanol functionalized gold nanoparticles (AuNPs) with a narrow size distribution and particle size of about 5 nm were synthesized. Then, the AuNPs were immobilized on a SiO(2) substrate using a functionalized polymer as a surface modifier. Microscopic and spectroscopic techniques were used to characterize the AuNPs and their morphology before and after immobilization. Finally, a metal-insulator-semiconductor (MIS) type memory device with such covalently anchored AuNPs as a charge trapping layer was fabricated. The MIS structure showed well-defined counterclockwise C-V hysteresis curves indicating a good memory effect. The flat band voltage shift was 1.64 V at a swapping voltage between ±7 V. Furthermore, the MIS structure showed a good retention characteristic up to 20,000 s. The present synthetic route to covalently immobilize gold nanoparticles system will be a step towards realization for the nanoparticle-based electronic devices and related applications.

Prophylactic laser peripheral iridotomy and cataract progression.

PURPOSE: To determine whether prophylactic laser peripheral iridotomy (LPI) for primary angle closure (PAC) is associated with cataract progression. METHODS: In 1999, Mongolian volunteers aged>or=50 years were invited to participate in a longitudinal study. Glaucoma was excluded in all participants and 712 of them were selected to undergo a full ophthalmic examination as part of the study protocol. Lenses were graded and PAC diagnosed using international classification systems. In 2005, all traced participants underwent a similar dilated examination. Diagnosis of cataract progression was based on the inter-observer variation +2 standard deviations. The association between LPI at baseline and cataract progression was assessed using chi2-test and logistic regression. RESULTS: Of 712 participants, 158 were diagnosed with occludable angles and treated with LPI. In 2005, 137 participants (19.2%) had died, 315 (315/575=54.8%) were traced, and dilated examination was performed on 276 (48%) of them. Progression of nuclear opacity (NO), cortical, and posterior subcapsular (PSC) opacities were evident in 40 (14.5%, 95% confidence interval (CI)=10.6-19.2%), 89 (32.2%, 95% CI=26.8-38.1%), and 11 participants (4.0%, 95% CI=2.0-7.0%), respectively. Although NO was more likely to progress in those with LPI in a crude analysis (odds ratio (OR)=2.02, 95% CI=1.00-4.11, P=0.05), no evidence of an independent association was detected in multivariate analysis adjusting for age, sex, and baseline Schaffer grading (adjusted OR=1.24, 0.41-3.75, P=0.7). There was no evidence of an association between LPI and progression of PSC or cortical opacities. CONCLUSIONS: There is no evidence that prophylactic LPI is independently associated with cataract progression in this study.

Electronic health record goes personal world-wide.

OBJECTIVE: Increasing patient demand for convenient access to their own healthcare data has led to more personal use of the Electronic Health Record (EHR). With "consumer empowerment" being an important issue of EHR, we are seeing a more "patient-centric" approach of EHR from countries around the world. Researchers have reported on issues in EHR sharing including concerns on privacy and security, consumer empowerment, competition among providers, and content standards. This study attempts to analyze prior research and to synthesize comprehensive, empirically-based conceptual models of EHR for personal use. METHODS: We use "B2C(2B) " to represent this new behavior of EHR sharing and exchange, with "consumer" in the center stage. RESULTS: Based on different information sharing mechanisms, we summarized the "B2C(2B) " behavior into three models, namely, the Inexpensive data media model, the Internet patient portal model and the Personal portable device model. Models each have their own strengths and weaknesses in their ways to share patient data and to address privacy and security concerns. CONCLUSION: Personal use of EHR under the B2C(2B) model does look promising based on our study. We started to observe a trend that governments around the world are embarking on related projects. With multiple stake-holders involved, we are only beginning to understand the complexity of such undertakings.

Radiofrequency ablation for 110 malignant liver tumours: preliminary results on percutaneous and surgical approaches.

BACKGROUND: Radiofrequency ablation (RFA) has been widely applied for the treatment of hepatocellular carcinoma and liver metastases. The reported mortality and morbidity rates are low. The aim of this study is to evaluate the safety and efficacy of RFA, and compare the results performed percutaneously versus surgically. PATIENTS AND METHODS: From 2003 to 2006, 79 patients with hepatic malignancies (59 hepatocellular carcinoma, 20 liver metastases) with a total of 110 lesions underwent RFA in our centre. Postablation assessment by CT scan was performed in all patients at 1-, 3- and 6-month intervals. Post-procedural complications, recurrence and survival were analysed. RESULTS: The patients' mean age was 60.0 years. In 46.8% of cases, we used a percutaneous approach; in 53.2% of cases, a surgical approach (8.9% laparoscopic; 44.3% open) was used if percutaneous approach was not feasible. The mean tumour size was 2.4 cm. Within the surgical group, 69% of patients received concomitant operative procedures such as cholecystectomy and hepatectomy. No treatment-related mortality was observed. Immediate complications occurred in five patients (6.3%), including gastric serosal burn (n = 1), ground pad superficial skin burn (n = 1), intra-abdominal bleeding (n = 2) and pleural effusion (n = 1). All patients except one attended subsequent follow-up, with a mean period of 16 months. Ablation was considered complete in 82.3% of patients (percutaneous approach 81.1%, surgical approach 83.3%, p = 0.72). Intrahepatic recurrence was observed in 52.3%, the majority of them located away from the RFA site. Extrahepatic recurrences were observed in 16.9% (percutaneous approach 16.7%, surgical approach 17.1%, p = 0.76). The overall one- and two-year survival rate was 93.7% and 74.4% respectively, and no statistically significant difference was observed between the two approaches. CONCLUSION: RFA is a safe and effective procedure for treating patients with malignant liver tumours. No difference in short term outcomes was observed between percutaneous and surgical approaches. A more prolonged follow-up study is required to assess longer-term outcomes.

Dendrimer-encapsulated Pt nanoparticles in supercritical medium: synthesis, characterization, and application to device fabrication.

In this work we describe a general method for formation of Pt nanoparticles within an ultrathin film matrix and its application for non-volatile memory (NVM). Our approach involves the formation of Pt nanoparticles within ultrathin film matrix formed by covalent layer-by-layer (LbL) assembly of pyromellitic dianhydride (PMDA) and second generation of polyamidoamine (PAMAM) dendrimer in supercritical carbon dioxide (SCCO(2)). The hyperbranched component in the film structure serves to confine nanoparticle size and improve distribution. The memory effect and retention capability is demonstrated by means of a metal-insulator semiconductor (MIS) device fabricated using the nanoparticle-laden thin film as the insulating layer.

Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys.

Her-2/neu is a well-characterized tumor-associated antigen, the overexpression of which in human carcinomas correlates with a poor prognosis. Here, we evaluated Her-2/neu-specific humoral and cellular immune responses in immunized monkeys after immunization with nonreplicating adenovirus (AdHM) expressing the extracellular and transmembrane domain of human Her-2/neu (HM) and/or naked DNA vaccine (pHM-hGM-CSF) expressing human granulocyte-macrophage colony-stimulating factor together with HM. Priming of monkeys with AdHM generated Her-2/neu-specific long-lasting antibody production. Furthermore, these Her-2/neu-specific antibodies produced by AdHM immunization, some of which shared epitope specificity with Herceptin, were able to induce antibody-dependent cellular cytotoxicity against Her-2-expressing target cells. Cellular immune responses were elicited in all monkeys immunized with Her-2/neu-expressing vaccine; interferon-gamma was secreted when these splenocytes were restimulated with Her-2/neu-expressing autologous cells, and immunization with AdHM induced Her-2/neu-specific lymphoproliferative responses. Further, immunization with pHM-hGM-CSF before AdHM immunization noticeably enhanced cytotoxic T-lymphocyte activity. In addition, we observed no abnormalities that would indicate that the genetic vaccines had toxic effects in the immunized monkeys. Thus, we can conclude that our genetic vaccines efficiently elicited Her-2/neu-specific humoral and cellular immune responses without causing severe adverse effects in nonhuman primates and that as such they warrant further clinical investigation.