Ocular metastasis of primary gynecological malignancies, a rare but not insignificant entity: A systematic review.

The genital system remains one of the most common sites of carcinogenesis in women. Advances in surgery, radiation treatment, and chemotherapy have increased their efficacy and many patients survive for many years after their initial diagnosis. The eye is a rare site of metastasis from gynecological cancer due to its distant location from the genitalia. In this systematic review, we retrieved all case reports of patients with ocular metastasis from gynecological neoplasms. The demographic, clinical, and treatment characteristics were retrieved and analyzed. A total of 70 case reports were included. Forty-eight of these reports concerned patients with a known malignancy that recurred in the eye and in 22 patients' ocular symptomatology accompanied the initial diagnosis of the gynecologic malignancy. 73.9% of these patients exhibited concomitant metastasis to other organs. The mean disease-free interval was found at 25.7 months and mean survival time after the eye metastasis was 13.5 months. Refractory disease was identified as the most important risk factor associated with mortality. Because eye metastasis has such a dismal prognosis, all gynecologists who treat oncological patients should be highly suspicious for reported eye complaints.

Optimization of the facet structure of transition-metal catalysts applied to the oxygen reduction reaction.

Predicting the optimal structure for a catalytic material has been a long-standing goal, but typically an arbitrary active site on a uniform surface is modelled. Identification of the most-active facet structure for structure-sensitive chemistries, such as the oxygen reduction reaction, is lacking. Here we develop an approach to predict the optimal structure of a catalytic material by identifying the active site and identifying the density and spatial arrangement of such sites while minimizing the surface energy. We find that the theoretical peak performance predicted by linear scaling relations is unattainable because of the lack of suitable active sites on low-index planes, as well as geometric and stability constraints. A random array of vacancies results in a modest performance enhancement compared to ideal facets, whereas defect sites with a maximum density in disordered structures significantly increase the catalyst performance. We applied this methodology to the oxygen reduction reaction on defected Pt(111), Pt(100), Au(111) and Au(100) surfaces.

Acceleration and sensitivity analysis of lattice kinetic Monte Carlo simulations using parallel processing and rate constant rescaling.

Kinetic Monte Carlo (KMC) simulation provides insights into catalytic reactions unobtainable with either experiments or mean-field microkinetic models. Sensitivity analysis of KMC models assesses the robustness of the predictions to parametric perturbations and identifies rate determining steps in a chemical reaction network. Stiffness in the chemical reaction network, a ubiquitous feature, demands lengthy run times for KMC models and renders efficient sensitivity analysis based on the likelihood ratio method unusable. We address the challenge of efficiently conducting KMC simulations and performing accurate sensitivity analysis in systems with unknown time scales by employing two acceleration techniques: rate constant rescaling and parallel processing. We develop statistical criteria that ensure sufficient sampling of non-equilibrium steady state conditions. Our approach provides the twofold benefit of accelerating the simulation itself and enabling likelihood ratio sensitivity analysis, which provides further speedup relative to finite difference sensitivity analysis. As a result, the likelihood ratio method can be applied to real chemistry. We apply our methodology to the water-gas shift reaction on Pt(111).

Steady state likelihood ratio sensitivity analysis for stiff kinetic Monte Carlo simulations.

Kinetic Monte Carlo simulation is an integral tool in the study of complex physical phenomena present in applications ranging from heterogeneous catalysis to biological systems to crystal growth and atmospheric sciences. Sensitivity analysis is useful for identifying important parameters and rate-determining steps, but the finite-difference application of sensitivity analysis is computationally demanding. Techniques based on the likelihood ratio method reduce the computational cost of sensitivity analysis by obtaining all gradient information in a single run. However, we show that disparity in time scales of microscopic events, which is ubiquitous in real systems, introduces drastic statistical noise into derivative estimates for parameters affecting the fast events. In this work, the steady-state likelihood ratio sensitivity analysis is extended to singularly perturbed systems by invoking partial equilibration for fast reactions, that is, by working on the fast and slow manifolds of the chemistry. Derivatives on each time scale are computed independently and combined to the desired sensitivity coefficients to considerably reduce the noise in derivative estimates for stiff systems. The approach is demonstrated in an analytically solvable linear system.

Review of the various laparoscopic techniques used in the treatment of bowel endometriosis.

Colorectal infiltration by endometriotic implants accounts about 90% of all intestinal location and is difficult to be assessed preoperatively by means of history taking and clinical examination. During the last decade, a number of studies are trying to assess various minimally invasive procedures in order to establish a therapeutic plan that is efficacious and produces acceptable clinical outcomes, preventing the morbidity that results from open surgery. The study aims to review the efficacy of these procedures as therapeutic options of endometriosis infiltrating the bowel. Thirty five observational studies were finally included in the present review involving 3490 women. Intraoperative complications were observed in 4.3% of women and postoperative complications in 7.8%. Quality of life was statistically significantly improved, wherever recorded. Postoperative pain reduction and fertility scores were also improved among cases that received either segmental resection or less radical operations. The various techniques described seem to be efficacious, with acceptable intraoperative and postoperative complication rates. Laparoscopic disc shaving or disc resection in cases of minimal bowel involvement seem to be sufficient alternatives to segmental bowel resection, resulting in high rates of fertilization.

Teenage pregnancy antenatal and perinatal morbidity: results from a tertiary centre in Greece.

We present the experience of a tertiary referral hospital in Greece, evaluating obstetric and perinatal outcomes among teenage and average maternal age (AMA) women. We retrospectively assessed all singleton pregnancies during a twelve-month period (January-December 2012). A total of 1,704 cases were reviewed and divided into two groups: one of AMA mothers (20-34 years old) (1,460 women) and the other of teenage mothers (12-19 years old) (244 women). We observed significantly higher incidence rates of preterm births (p < 0.001), preterm premature rupture of the membranes (p < 0.001), gestational hypertension (p < 0.001), preeclampsia (p = 0.043) and Apgar scores < 7 at 5 min (p = 0.015) among teenage mothers. Antenatal surveillance was decreased among teenage mothers (p < 0.001), while rates of anaemia were higher (p < 0.001). Teenage pregnancy is accompanied by significant antenatal and perinatal complications that need specific obstetrical attention. Obstetricians should be aware of these complications in order to ameliorate the antenatal outcome of childbearing teenagers.

Lead growth on Si(111) surfaces reconstructed by indium.

We study the Pb growth on both √3 × âˆš3-In and 4 × 1-In reconstructed Si(111) surfaces at room and low temperature (160 K). The study takes place with complementary techniques, to investigate the role of the substrate reconstruction and temperature in determining the growth mode of Pb. Specifically, we focus on the correlation between the growth morphology and the electronic structure of the Pb films. The information is obtained by using Auger electron spectroscopy, low energy electron diffraction, soft x-ray photoelectron spectroscopy, scanning tunneling microscopy and spot profile analysis-low energy electron diffraction. The results show that, at low temperature and coverage ≤12 ML on the Si(111)√3 × âˆš3-In surface, Pb does not alter the initial semiconducting character of the substrate and three-dimensional Pb islands with poor crystallinity are grown on a wetting layer. On the other hand, for the same coverage range, Pb growth on the Si(111)4 × 1-In surface results in metallic Pb(111) crystalline islands after the completion of a double incomplete wetting layer. In addition, the bond arrangement of the adatoms is studied, confirming that In adatoms interact more strongly with the silicon substrate than the Pb ones. This promotes a stronger Pb-Pb interaction and enhances metallization. The onset of the metallization is correlated with the amount of pre-deposited In on the Si(111) surface. The decoupling of the Pb film from the 4 × 1-In interface can also explain the unusual thermal stability of the uniform height islands observed on this interface. The formation of these Pb islands is driven by quantum size effects. Finally, the different results of Pb growth on the two reconstructed surfaces confirm the importance of the interface, and also that the growth morphology, as well as the electronic structure of the Pb film can be tuned with the initial substrate reconstruction.

Waste biomass-to-energy supply chain management: a critical synthesis.

The development of renewable energy sources has clearly emerged as a promising policy towards enhancing the fragile global energy system with its limited fossil fuel resources, as well as for reducing the related environmental problems. In this context, waste biomass utilization has emerged as a viable alternative for energy production, encompassing a wide range of potential thermochemical, physicochemical and bio-chemical processes. Two significant bottlenecks that hinder the increased biomass utilization for energy production are the cost and complexity of its logistics operations. In this manuscript, we present a critical synthesis of the relative state-of-the-art literature as this applies to all stakeholders involved in the design and management of waste biomass supply chains (WBSCs). We begin by presenting the generic system components and then the unique characteristics of WBSCs that differentiate them from traditional supply chains. We proceed by discussing state-of-the-art energy conversion technologies along with the resulting classification of all relevant literature. We then recognize the natural hierarchy of the decision-making process for the design and planning of WBSCs and provide a taxonomy of all research efforts as these are mapped on the relevant strategic, tactical and operational levels of the hierarchy. Our critical synthesis demonstrates that biomass-to-energy production is a rapidly evolving research field focusing mainly on biomass-to-energy production technologies. However, very few studies address the critical supply chain management issues, and the ones that do that, focus mainly on (i) the assessment of the potential biomass and (ii) the allocation of biomass collection sites and energy production facilities. Our analysis further allows for the identification of gaps and overlaps in the existing literature, as well as of critical future research areas.

Stochastic simulations of ErbB homo and heterodimerisation: potential impacts of receptor conformational state and spatial segregation.

ErbB overexpression is linked to carcinogenesis. It is hypothesised that this is due to increased receptor density and receptor clustering, leading to increased receptor dimerisation and activation. Herein, spatial stochastic simulations have been performed to shed light receptor dimerisation processes. First, ligand-independent homodimerisation, is considered, based upon constitutive oligomerisation estimates (14%) in A431 cells that overexpress epidermal growth factor receptor (EGFR). When autocrine stimulation is blocked, ligand-independent EGFR activation is demonstrated by persistent, low levels of phosphorylation. The possibility that ligand-independent signalling is due to the fluctuation of EGFR conformation is considered. The agent-based model predicts the frequency (expressed as a probability) that uniformly distributed receptors would need to flux to the open conformation to reach 14% EGFR dimers at high receptor density. Simulations suggest that ligand-independent EGFR homodimerisation is highly density dependent, since collisions between 'open', dimerisation-competent receptors are a rare event at low receptor levels. Simulations that incorporate receptor clustering lower the threshold for homodimerisation of unoccupied receptors as well as the estimate of the probability for fluxing to the dimer-competent conformation. The impact of ErbB receptor clustering patterns on hetero and homodimerisation rates is also considered, using immunoelectron microscopy data derived from SKBR3 breast cancer cells that express ErbB2>>EGFR>ErbB3. Partial spatial segregation of ErbB receptors has a profound effect on simulated heterodimerisation rates. Despite the general assumption that ErbB2 is a preferred heterodimerising partner for other ErbBs, it is predicted that most ErbB2 will form homodimers. Overall, it is proposed that both receptor density and membrane spatial organisation contribute to the carcinogenesis process.

Temporal coarse-graining of microscopic-lattice kinetic Monte Carlo simulations via tau leaping.

A coarse-time-step method is presented that enables the execution of multiple events at each time increment of microscopic-lattice kinetic Monte Carlo simulations. The method employs the n-fold method to create groups of reactions in which the tau-leap algorithm of Gillespie, originally proposed for well-mixed systems, is applied. Creation of groups of reactions is an essential step to avoid violation of the leap condition that arises when the tau-leap algorithm is applied to a single site. The method is general, very easy to implement, and can result in substantial computational savings when global updating is employed. An illustrative example from crystal growth of a simple cubic lattice with the solid-on-solid approximation is presented.

Molecular dynamics study of the stabilization of the silica hexamer Si6O15(6-) in aqueous and methanolic solutions.

We use molecular dynamics simulations to study the stabilization of the hexameric, cagelike silicate with double three-ring structure in aqueous and methanolic solutions. We find that in purely aqueous environments its stabilization requires the presence of both tetramethylammonium and tetraethylammonium (TEA) cations and involves the formation of a stable TMA layer which leads to a water-silicate heteronetwork clathrate. We also find that TEA alone can facilely stabilize the hexamer when methanol cosolvent is added, in accordance with experiment. The mechanism of this stabilization, however, differs from that in purely aqueous environments. Because of the unique properties of water-methanol mixtures, the organosilicate complex does not participate in heteronetwork clathrates but resides in a large solvent cavity; that is, it is forced out of true solution.

Potential of mean force for tetramethylammonium binding to cagelike oligosilicates in aqueous solution.

We have carried out free energy calculations to compute the potential of mean force for the cagelike silicate polyion-TMA+ cation ion pair interaction in aqueous solution. We also have studied solvent reorganization-related entropic effects. We conclude that the organocations, as opposed to, for example, alkali-metal ions, play a pivotal role in reorganizing the solvent around the cagelike silicates in a manner conducive to the formation of heteronetwork clathrates that are stable both thermodynamically and kinetically. In the case of stable cagelike polysilicate anions, this solvent reorganization correlates with entropic losses. We also infer that transient cagelike polysilicate species, that may indeed form but participate in floppy clathrates, eventually have to give way to cagelike polysilicates that lead to more rigid structures.

The role of molecular interactions and interfaces in diffusion: transport diffusivity and evaluation of the Darken approximation.

Kinetic Monte Carlo (KMC) simulations are carried out to directly study diffusion of benzene through thin (37-100 nm) NaX zeolite membranes under a gradient in chemical potential. Nonlinearities in adsorbate loading near the membrane boundaries are shown to arise from the difference in adsorbate density between the zeolite and adjacent fluid phase. Direct extraction of the transport diffusivity from gradient KMC simulations enables testing of the Darken approximation. This rigorous approach reveals limitations of the Darken approximation and, for the first time, the potentially complex nonunique functionality and multiplicity of the transport diffusivity for strongly interacting adsorbates. In the companion paper we explore these nonlinear interfacial effects in the context of permeation through both single-crystal and polycrystalline membranes.

The role of molecular interactions and interfaces in diffusion: permeation through single-crystal and polycrystalline microporous membranes.

In this second paper of a two part series, we investigate the implications of the interfacial phenomenon, caused by adsorbate-adsorbate interactions coupled with the difference in adsorbate density between the zeolite and the gas phase, upon benzene permeation through single-crystal and polycrystalline microporous NaX membranes. The high flux predicted for thin single-crystal membranes reveals that substantially enhanced flux should be expected in submicron films. Simulations also indicate that the standard local equilibrium assumption made for larger scale membranes is inapplicable at the submicron scale associated with nanometer size grains of thin and/or polycrystalline membranes. Apparent activation energies predicted for benzene permeation through NaX membranes via kinetic Monte Carlo (KMC) simulations are in good agreement with laboratory experiments. The simulations also uncover temperature-dependent flux pathways leading to non-Arrhenius behavior observed experimentally. The failure of the Darken approximation, especially in the presence of the interfacial phenomenon, leads to a substantial overprediction of the flux. Simulations of polycrystalline membranes suggest that this same interfacial phenomenon leads to resistance that can reduce flux by an order of a magnitude with only moderate polycrystallinity.

Overcoming stiffness in stochastic simulation stemming from partial equilibrium: a multiscale Monte Carlo algorithm.

In this paper the problem of stiffness in stochastic simulation of singularly perturbed systems is discussed. Such stiffness arises often from partial equilibrium or quasi-steady-state type of conditions. A multiscale Monte Carlo method is discussed that first assesses whether partial equilibrium is established using a simple criterion. The exact stochastic simulation algorithm (SSA) is next employed to sample among fast reactions over short time intervals (microscopic time steps) in order to compute numerically the proper probability distribution function for sampling the slow reactions. Subsequently, the SSA is used to sample among slow reactions and advance the time by large (macroscopic) time steps. Numerical examples indicate that not only long times can be simulated but also fluctuations are properly captured and substantial computational savings result.

Molecular valves actuated by intermolecular forces.

Phase behavior in nanostructured thin films under a gradient in chemical potential is studied via kinetic Monte Carlo simulation. Switching between saturated, partially saturated, and unsaturated states drives precipitous changes in permeation. This phenomenon could render nanostructured thin films as molecular valves, where adsorbate-adsorbate forces actuate the flow of molecules.

Molecular sieve valves driven by adsorbate-adsorbate interactions: hysteresis in permeation of microporous membranes.

A recently derived mesoscopic framework describing activated micropore diffusion is employed to explore system criticality in microporous membranes under nonequilibrium conditions. Rapid exploration of parameter space, possible with this continuum framework, elucidates a novel temperature-induced ignition and extinction of the molecular flux under a macroscopic gradient in pressure (chemical potential). Deviation from equilibrium like phase behavior (i.e., shifting and narrowing of phase envelopes and double hysteresis) derives from asymmetry of the coupled boundaries of the nonequilibrium membrane. We confirm this new phase behavior, akin to "opening" and "closing" of a molecular valve, via gradient kinetic Monte Carlo simulations of thin one-dimensional and three-dimensional systems. The heat of adsorption, strength of adsorbate-adsorbate intermolecular forces, and chemical potential gradient are all shown to control 'valve' actuation, suggesting potential implications in chemical sensing and novel diffusion control.

Self-calibration techniques of underwater gamma ray spectrometers.

In situ continuous monitoring of radioactivity in the water environment has many advantages compared to sampling and analysis techniques but a few shortcomings as well. Apart from the problems encountered in the assembly of the carrying autonomous systems, continuous operation some times alters the response function of the detectors. For example, the continuous operation of a photomultiplier tube results in a shift in the measured spectrum towards lower energies, making thus necessary the re-calibration of the detector. In this work, it is proved, that when measuring radioactivity in seawater, a photo peak around 50 keV will be always present in the measured spectrum. This peak is stable, depends only on the scattering rates of photons in seawater and, when it is detectable, can be used in conjunction with other peaks (40K and/or 208Tl) as a reference peak for the continuous calibration of the detector.

Spatially adaptive grand canonical ensemble Monte Carlo simulations.

A spatially adaptive Monte Carlo method is introduced directly from the underlying microscopic mechanisms, which satisfies detailed balance, gives the correct noise, and describes accurately dynamic and equilibrium states for adsorption-desorption (grand canonical ensemble) processes. It enables simulations of large scales while capturing sharp gradients with molecular resolution at significantly reduced computational cost. A posteriori estimates, in the sense used in finite-elements methods, are developed for assessing errors (information loss) in coarse-graining and guiding mesh generation.

Molecular dynamics studies on the role of tetramethylammonium cations in the stability of the silica octamers Si8O20(8-) in solution.

The stability of silica octamers, Si(8) observed in tetramethylammonium (TMA) solutions by Kinrade et al. is investigated in connection with the TMA concentration by performing equilibrium molecular dynamics simulations of Si(8)-TMA-water mixture at two concentrations. At the experimental concentration at which the silica octamers have been observed spectroscopically, we find that, on the average, six TMA molecules surround the silica octamer, coordinated so that each cation occupies a face of the cubic octamer. We also find that upon TMA adsorption, water molecules associated with the siloxane oxygens leave the silica surface, whereas the hydrogen-bond network of the silanol oxygens with water molecules remains intact. No TMA adsorption is observed at the concentration at which the octamers have not been observed.