bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of 0.05 % Cyclosporine Ophthalmic Microemulsion for the treatment of Moderate to Severe Dry Eye Disease – an Indian Experience
Authors: Goel Upsham , Desai Dipan , Lavingia Bharti , Gokhale Nikhil , Jadhav Sonali , Gogtay Jaideep
Published: April 2015

Background :

Dry eye disease is a multi-factorial disease with a significant immunological component. The purpose of this study was to assess the efficacy, safety and tolerability of cyclosporine 0.05% ophthalmic microemulsion, in patients with moderate to severe dry eye disease.

Materials and Methods:

This was a prospective, open label, non-comparative, multicentre study of 37 patients with moderate to severe dry eye, treated with cyclosporine 0.05 % ophthalmic micro-emulsion, for a period of 4 weeks. The primary efficacy endpoint was mean change in Schirmer tear test score (mm), at week 4 from baseline. The secondary efficacy endpoints included mean change in Ocular Surface Disease Index (OSDI) and ocular discomfort scores, use of artificial tears, and global evaluation of the treatment. The incidence and nature of adverse events were recorded.

Results:

A total of 34 patients (23 women) completed the study. After 4 weeks, Schirmer tear test score improved by 4.95 mm (95%, CI 3.47 to 6.41; p=0.000). There was significant reduction in mean OSDI and ocular discomfort score, by -0.93 (p=0.000) and -8.71 (p=0.000), respectively at week 4. According to clinician's global evaluations, a majority of the patients (58.1%) experienced at least a 75% to 90% improvement in symptoms from baseline. During the 4 week treatment period, 3 (8.82%) patients reported adverse events of mild to moderate intensity.

Conclusion:

Our findings indicate that cyclosporine 0.05% is an effective, safe and well tolerated treatment in Indian patients with moderate to severe dry eye disease.
Femtosecond Laser Assisted Cataract Surgery in White Cataract
Authors: Titiyal Jeewan Singh , Arora Tarun
Published: April 2015

Aim:

To demonstrate application of femtosecond laser technology in patients with white cataract.

Methods:

Video-based description of successful management of intumescent white cataract with femtosecond laser technology.

Results:

We performed femtosecond laser assisted cataract surgery in multiple patients with different morphologies of white cataract. Successful completion of capsulotomy along with intraocular lens implantation in the bag was achieved in all the cases. No case had extension of capsulotomy upto the periphery.

Conclusion:

Femtosecond laser technology has revolutionized the management of difficult cataract case scenarios especially intumescent white cataract. Intraocular lens implantation in the bag with ideal capsular margin overlap can be achieved with ease in most cases.
Management of Astigmatism in Cataract
Authors: Taneja Mukesh
Published: April 2015

Over the past few years, cataract surgery has, become quite akin to refractive surgery allowing greater control over the patients' refractive and visual outcome. Now the patients expect perfect vision after the cataract surgery and surgeons strive hard to deliver the same. In this respect a residual astigmatism after the cataract surgery is viewed as an undesirable outcome both by the patients and surgeons. Various approaches have been advocated for tackling the pre-existing astigmatism in patients having cataract surgery. These include on-axis corneal incision (OCI), limbal relaxing incisions (LRI), paired opposite clear corneal incisions (OCCI), Toric IOLs and finally bioptics, where one exploits the advanced technology and exquisite accuracy of excimer laser. A number of popular nomograms are currently available for making accurate correction in the astigmatism during cataract surgery among which, the nomograms by Nichamin and Donnenfeld are more popular for LRIs and commonly used. The online availability of these nomograms as well as that of Toric IOLs calculators have made the pre-op planning for the astigmatism corrections much easier than before. Based on the effective results of all these techniques, one can consider the simple stepladder approach to guide astigmatism management at the time of cataract management. A surgeon may become more comfortable with one particular technique as compared to another and should, therefore, choose an approach which works best in his or her hands.
Update on Ocular Oncology
Authors: Shanmugam Mahesh P , Ramanjulu Rajesh , Dwivedi Shyamal
Published: April 2015

Medicine is an ever-changing subject. With the current developments, diagnosing and treating of patients has reached newer heights. This article describes the newer developments in ocular oncology particularly retinoblastoma (most common intra-ocular tumor in children, melanoma (most common intra-ocular tumor) and haemangioma (a common tumor presenting from young to adult).
Topical Fluoroquinolones: Current Perspectives
Authors: Pradhan Sayali , Prajna N Venkatesh
Published: April 2015

Fluoroquinolone class of antibiotics has become popular by the virtue of its properties like broad spectrum bactericidal activity, better intraocular concentration, minimal side effects and resistance. Over the years serial modifications in the parent molecule have given rise to a range of fluoroquinolone molecules with augmented antibacterial coverage and less resistance. They act by inhibition of bacterial DNA synthesis. Topical fluoroquinolones are being used in various ocular bacterial infections and in antibacterial prophylaxis. These provide a convenient and an effective option to the traditional fortified antibiotic combinations in the treatment of bacterial keratitis. Fluoroquinolone resistance has been encountered especially among Staphylococci, Pseudomonas and Serratia. The newer 8-methoxyfluoroquinolones due to their structural properties are less likely to develop resistance and have emerged as a new promising antibacterial therapy.
Strain localization driven by thermal decomposition during seismic shear
Authors: Platt John D. , Brantut Nicolas , Rice James R.
Published: April 2015

Field and laboratory observations show that shear deformation is often extremely localized at seismic slip rates, with a typical deforming zone width on the order of a few tens of microns. This extreme localization can be understood in terms of thermally driven weakening mechanisms. A zone of initially high strain rate will experience more shear heating and thus weaken faster, making it more likely to accommodate subsequent deformation. Fault zones often contain thermally unstable minerals such as clays or carbonates, which devolatilize at the high temperatures attained during seismic slip. In this paper, we investigate how these thermal decomposition reactions drive strain localization when coupled to a model for thermal pressurization of in situ groundwater. Building on Rice et al. (2014), we use a linear stability analysis to predict a localized zone thickness that depends on a combination of hydraulic, frictional, and thermochemical properties of the deforming fault rock. Numerical simulations show that the onset of thermal decomposition drives additional strain localization when compared with thermal pressurization alone and predict localized zone thicknesses of ∼7 and ∼13 μm for lizardite and calcite, respectively. Finally we show how thermal diffusion and the endothermic reaction combine to limit the peak temperature of the fault and that the pore fluid released by the reaction provides additional weakening of ∼20–40% of the initial strength.
Crust beneath the northwestern Deccan Volcanic Province, India: Evidence for uplift and magmatic underplating
Authors: Rao K. Madhusudhan , Kumar M. Ravi , Rastogi B. K.
Published: April 2015

The northwestern Deccan Volcanic Province of India and its pericratonic rift basins were reactivated during different stages after the breakup of India from the Gondwanaland and collision with the Asian plate. In this study, we present results of crustal thickness and average crustal Vp/Vs ratios beneath this plume‐affected region using common conversion point imaging and H‐k stacking analysis of 6893 receiver functions using data from a network comprising 58 broadband seismic stations sited on diverse tectonic terrains. We find large variations in crustal thickness, with the Moho depths varying from 28 to 43 km in the Kachchh rift, 28 to 38 km in the Cambay rift, 39.5–41.5 km in the north and eastern parts of the Cambay rift, and 29 to 39 km in the Saurashtra region and South Gujarat. A Moho upwarp of 6 to 7 km in the Saurashtra region can be attributed to positive buoyancy and uplift due to thermal influx affected by the Reunion plume. High crustal Vp/Vs ratios beneath the Kachchh rift (1.8 to 2.05), coastal areas of Saurashtra (1.75 to 2.06), and North Gujarat (1.81 to 1.85) indicate dominance of a mafic/ultramafic crust. High regional heat flow, high electrical conductivity, large intracrustal S wave velocity reduction, and high average crustal Poisson's ratios are consistent with partial melt related to the process of magmatic underplating in the lower crust. At other stations, the crust appears to be felsic with Vp/Vs ratios in the range of 1.57 to 1.76.
Waving in the rain
Authors: Cavaleri Luigi , Bertotti Luciana , Bidlot Jean‐Raymond
Published: April 2015

We consider the effect of rain on wind wave generation and dissipation. Rain falling on a wavy surface may have a marked tendency to dampen the shorter waves in the tail of the spectrum, the related range increasing with the rain rate. Historical and sailors’ reports suggest that this leads to calmer wave conditions, certainly so for the action of breakers. We have explored this situation using a fully coupled meteorological‐wave model system, adding an artificial rain rate‐dependent damping of the tail. Contrarily to direct marine experience, the experimental results show higher wind speeds and wave heights. A solid indication of the truth is achieved with the direct comparison between operational model (where rain effect is ignored) and measured data. These strongly support the sailors’ claims of less severe wave conditions under heavy rain. This leads to a keen analysis of the overall process, in particular on the role of the tail of the spectrum in modulating the wind input and the white‐capping, and how this is presently modeled in operational activity. We suggest that some revision is due and that the relationship between white‐capping and generation by wind is deeper and more implicative than presently generally assumed.
Geochemical variations in Japan Sea back‐arc basin basalts formed by high‐temperature adiabatic melting of mantle metasomatized by sediment subduction components
Authors: Hirahara Yuka , Kimura Jun‐Ichi , Senda Ryoko , Miyazaki Takashi , Kawabata Hiroshi , Takahashi Toshiro , Chang Qing , Vaglarov Bogdan S. , Sato Takeshi , Kodaira Shuichi
Published: April 2015

The Yamato Basin in the Japan Sea is a back‐arc basin characterized by basaltic oceanic crust that is twice as thick as typical oceanic crust. Two types of ocean floor basalts, formed during the opening of the Japan Sea in the Middle Miocene, were recovered from the Yamato Basin during Ocean Drilling Program Legs 127/128. These can be considered as depleted (D‐type) and enriched (E‐type) basalts based on their incompatible trace element and Sr‐Nd‐Pb‐Hf isotopic compositions. Both types of basalts plot along a common mixing array drawn between depleted mantle and slab sediment represented by a sand‐rich turbidite on the Pacific Plate in the NE Japan fore arc. The depleted nature of the D‐type basalts suggests that the slab sediment component is nil to minor relative to the dominant mantle component, whereas the enrichment of all incompatible elements in the E‐type basalts was likely caused by a large contribution of bulk slab sediment in the source. The results of forward model calculations using adiabatic melting of a hydrous mantle with sediment flux indicate that the melting conditions of the source mantle for the D‐type basalts are deeper and hotter than those for the E‐type basalts, which appear to have formed under conditions hotter than those of normal mid‐oceanic ridge basalts (MORB). These results suggest that the thicker oceanic crust was formed by greater degrees of melting of a hydrous metasomatized mantle source at unusually high mantle potential temperature during the opening of the Japan Sea.
Seasonal variability and fluxes of nitrate in the surface waters over the Arctic shelf slope
Authors: Randelhoff Achim , Sundfjord Arild , Reigstad Marit
Published: April 2015

Understanding the present state and possible future scenarios of Arctic Ocean primary productivity has been hampered by the scarcity of year‐round nutrient measurements. Here the first yearlong moored time series of near‐surface nitrate concentrations in the Eastern Arctic, together with hydrography, currents, and chlorophyll a fluorescence, is reported from the shelf slope northeast of Svalbard. Variability was dominated by the inflow of Atlantic Water (AW). Nitrate was near depleted during July–September and reached a maximum concentration of 10 μM in March. Vertical nitrate gradients were eroded by mid‐December, demonstrating the importance of the AW in breaking down upper ocean stratification during fall. Upward nitrate fluxes through the nitracline in the AW inflow region during fall were 2.5 ± 0.5 mmol m−2 d−1. The spring bloom triggered extensive nitrate drawdown from June, from which an annual new production of 31 g C m−2 was estimated.
Microstructural evolution in bitaxial crack‐seal veins: A phase‐field study
Authors: Ankit Kumar , Urai Janos L. , Nestler Britta
Published: April 2015

Bitaxial crack sealing by epitaxial crystal growth is the most common vein‐forming process in Earth's crust, but the details of the microstructural processes in these are not well understood. Here we model the evolution of bitaxial crack‐seal quartz veins in two and three dimensions, using the phase‐field method. Our numerical simulations show the influence of different parameters, such as the obliquity of crack opening and crack location, grain size, and orientations on the evolving vein microstructure. We examine the underlying growth competition observed during epitaxial growth of quartz. Results show many similarities with natural microstructures such as stretched crystals and compare well with the previous numerical findings. As the ratio of crack aperture and matrix grain size for the present studies is chosen to be sufficiently large for growth competition to occur before complete sealing, it leads to the formation of crystal fragments along the crack‐opening trajectory. We explain how such fragment trails act as potential indicators of the opening of crack‐seal veins, if they are confirmed to be common in natural microstructures. Finally, we highlight the importance of accounting for the third dimension in the numerical simulations by analyzing the evolution of fluid connectivity in 2‐D and 3‐D during the sealing process.
Immune Complexes
Authors: Eggleton Paul , Javed Moazzam , Pulavar David , Sheldon Gemma
Published: April 2015

Antigen–antibody complexes are formed when the body's immune system raises antibodies against antigenic determinants of host or foreign substances that recognise and bind to the antigen molecules. Normally, insoluble immune complexes that are formed are cleared by the phagocytic cells of the immune system, but when an excess of antigen–antibody are present, the immune complexes are often deposited in tissues, where they can elicit complement activation, localised inflammation resulting in the generation of tissue lesions in a variety of autoimmune diseases, exacerbating disease pathology. Conversely, exogenous antigen–antibody complexes can trigger specific cell‐mediated immunity when taken up, processed and presented with MHC class I molecules by dendritic cells. This results in direct priming of CD8+ cytotoxic T cells, by a process termed ‘cross‐presentation’. This can be of benefit in the induction of tumour protection and immunity against viral infections. Therefore, the generation of immune complexes can initiate both autoimmunity and protection against tumours and infectious agents.

Key Concepts

IgG and IgM are the two major classes of antibodies involved in immune complex formation.

The Fab region of antibodies can bind to many antigens comprising proteins, carbohydrates, nucleic acids or lipids.

In the blood circulation, small antigen–antibody complexes form soluble lattices when either antibody or antigen is present in excess.

When antigens and specific antibody are present in equivalent concentrations, large insoluble complexes can form, initiating an inflammatory reaction.

Insoluble immune complexes often deposit in joints and filtration organs (e.g. kidneys), leading to recruitment and activation of complement proteins and phagocytes.

The Fc portion of antibodies can bind to Fc receptors (FcRs) on cells and C1q, activating immune responses.

Tumour antigen–antibody complexes can activate dendritic cell maturation and promote the development of long‐lasting CD8 memory T cells against tumour antigens.

Viral antigens presented to T cells by dendritic cells results in rapid cellular immunity, while antigen–antibody complexes sustain the T‐cell effector memory.
M
ohl,
H
ugo von
Authors: Dröscher Ariane
Published: April 2015

Hugo von Mohl (1805–1872) – German botanist and microscopist – was one of the central figures in the emerging fields of plant anatomy and physiology. His most famous contributions concerned the plant cell, in particular the cell wall and cell division, and the origin of plant vessels from cells. These studies paved the way for cell theory. Moreover, he greatly engaged in the transformation of botany into an inductive science and promoted its institutional autonomy from medicine as well as from philosophy, co‐founding in Tübingen Germany's first faculty of natural sciences.
Philosophy of Selection (Natural, Sexual and Drift)
Authors: Pievani Telmo
Published: April 2015

Four main ingredients are necessary for the recipe of natural selection: a common demanding and competitive environment; individual, spontaneous variation; inheritance of part of this variation and a sufficient time frame. The result is a differential survival and reproduction of varying individuals, multiplied over generations: self‐reproducing lineages of organisms change over time. As a statistical process with probabilistic outcomes, natural selection can be explained without using misleading terms such as “adaptation” and “chance”. The selective process is an experienced fact in nature and an explanatory pattern that could be generalised in different forms (such as sexual selection, kin selection and so on). Despite its strong explanatory power, natural selection is a constrained process and is not self‐sufficient: it is the pivot within a plurality of complementary and alternative explanatory patterns, the most important of which is the genetic drift.

Key Concepts

Natural selection cannot be reduced to easy metaphors such as “survival of the fittest” or “survival of the strongest”.

As differential survival and reproduction over generations, natural selection can be described without references to slippery words such as “adaptation” and “chance”.

Natural selection has been the first scientific explanation able to replace the “argument from design” of natural theology.

Saying that we are products of natural selection does not mean that we are children of purely fortuitous chains of events.

It is a mistake to assign to natural selection the old (intentional) attributes of a “designer”.

Natural selection needs two additional demanding requirements to occur: a continuously emerging variation and a perceived individual advantage.

Survival and reproduction are two faces of the same coin, inseparable.

Natural selection can be generalised into “selective processes”.

Genetic drift is another probabilistic sampling process, but with nonselective outcomes.

Selective processes do not work in a
vacuum
, but find case by case trade‐offs with structural constraints and constraints to variation.
Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends
Authors: Buch‐Månson Nina , Bonde Sara , Bolinsson Jessica , Berthing Trine , Nygård Jesper , Martinez Karen L.
Published: April 2015

Vertical arrays of nanostructures (NSs) are emerging as promising platforms for probing and manipulating live mammalian cells. The broad range of applications requires different types of interfaces, but cell settling on NS arrays is not yet fully controlled and understood. Cells are both seen to deform completely into NS arrays and to stay suspended like tiny fakirs, which have hitherto been explained with differences in NS spacing or density. Here, a better understanding of this phenomenon is provided by using a model that takes into account the extreme membrane deformation needed for a cell to settle into a NS array. It is shown that, in addition to the NS density, cell settling depends strongly on the dimensions of the single NS, and that the settling can be predicted for a given NS array geometry. The predictive power of the model is confirmed by experiments and good agreement with cases from the literature. Furthermore, the influence of cell‐related parameters is evaluated theoretically and a generic method of tuning cell settling through surface coating is demonstrated experimentally. These findings allow a more rational design of NS arrays for the numerous exciting biological applications where the mode of cell settling is crucial.
Micropatterned P(VDF‐TrFE) Film‐Based Piezoelectric Nanogenerators for Highly Sensitive Self‐Powered Pressure Sensors
Authors: Lee Ju‐Hyuck , Yoon Hong‐Joon , Kim Tae Yun , Gupta Manoj Kumar , Lee Jeong Hwan , Seung Wanchul , Ryu Hanjun , Kim Sang‐Woo
Published: April 2015

Here micropatterned poly(vinylidenefluoride‐co‐trifluoroethylene) (P(VDF‐TrFE)) films‐based piezoelectric nanogenerators (PNGs) with high power‐generating performance for highly sensitive self‐powered pressure sensors are demonstrated. The microstructured P(VDF‐TrFE)‐based PNGs reveal nearly five times larger power output compared to a flat film‐based PNG. The micropatterning of P(VDF‐TrFE) polymer makes itself ultrasensitive in response to mechanical deformation. The application is demonstrated successfully as self‐powered pressure sensors in which mechanical energy comes from water droplet and wind. The mechanism of the high performance is intensively discussed and illustrated in terms of strain developed in the flat and micropatterned P(VDF‐TrFE) films. The impact derived from the patterning on the output performance is studied in term of effective pressure using COMSOL multiphysics software.
A Combination of Spin Diffusion Methods for the Determination of Protein–Ligand Complex Structural Ensembles
Authors: Pilger Jens , Mazur Adam , Monecke Peter , Schreuder Herman , Elshorst Bettina , Bartoschek Stefan , Langer Thomas , Schiffer Alexander , Krimm Isabelle , Wegstroth Melanie , Lee Donghan , Hessler Gerhard , Wendt K.‐Ulrich , Becker Stefan , Griesinger Christian
Published: April 2015

Structure‐based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin‐diffusion‐based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein–ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X‐ray analysis.
Molecular Structure and Dynamics of Water at the Water–Air Interface Studied with Surface‐Specific Vibrational Spectroscopy
Authors: Bonn Mischa , Nagata Yuki , Backus Ellen H. G.
Published: April 2015

Water interfaces provide the platform for many important biological, chemical, and physical processes. The water–air interface is the most common and simple aqueous interface and serves as a model system for water at a hydrophobic surface. Unveiling the microscopic (<1 nm) structure and dynamics of interfacial water at the water–vapor interface is essential for understanding the processes occurring on the water surface. At the water interface the network of very strong intermolecular interactions, hydrogen‐bonds, is interrupted and the density of water is reduced. A central question regarding water at interfaces is the extent to which the structure and dynamics of water molecules are influenced by the interruption of the hydrogen‐bonded network and thus differ from those of bulk water. Herein, we discuss recent advances in the study of interfacial water at the water–air interface using laser‐based surface‐specific vibrational spectroscopy.
Controllable Scission and Seamless Stitching of Metal–Organic Clusters by STM Manipulation
Authors: Kong Huihui , Wang Likun , Sun Qiang , Zhang Chi , Tan Qinggang , Xu Wei
Published: April 2015

Scanning tunneling microscopy (STM) manipulation techniques have proven to be a powerful method for advanced nanofabrication of artificial molecular architectures on surfaces. With increasing complexity of the studied systems, STM manipulations are then extended to more complicated structural motifs. Previously, the dissociation and construction of various motifs have been achieved, but only in a single direction. In this report, the controllable scission and seamless stitching of metal–organic clusters have been successfully achieved through STM manipulations. The system presented here includes two sorts of hierarchical interactions where coordination bonds hold the metal–organic elementary motifs while hydrogen bonds among elementary motifs are directly involved in bond breakage and re‐formation. The key to making this reversible switching successful is the hydrogen bonding, which is comparatively facile to be broken for controllable scission, and, on the other hand, the directional characteristic of hydrogen bonding makes precise stitching feasible.
The effect of mechanical recycling on the microstructure and properties of PA66 composites reinforced with carbon fibers
Authors: Colucci Giovanna , Ostrovskaya Oxana , Frache Alberto , Martorana Brunetto , Badini Claudio
Published: April 2015

This article aims to prepare by injection molding recycled polymeric composites based on PA66 reinforced with short carbon fibers after artificial aging for applications in the automotive field. The aging cycles involves the combined action of UV radiation, moisture, and temperature in order to simulate the common outdoor conditions. The 100% recycled composites are obtained by the regranulation of the aged specimens followed by the remelting and re‐injection molding. The study is focused on the comparison between the mechanical behavior and the microstructure of the composites before and after mechanical recycling. The results of mechanical, thermal, and morphological investigations reveal that the recycling process had no significant effect on the final properties and microstructure of the recycled composites. Therefore the recycled PA66CF30 composites could be successfully used for structural or semi‐structural automotive applications guaranteeing good final performances and advantages from the environmental point of view. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42275.
Capacity Constraints and Public Financial Management in SmallPacific Island Countries
Authors: Haque Tobias Akhtar , Knight David , Jayasuriya Dinuk
Published: April 2015

Sound public financial management is a key concern of Pacific island country governments and their development partners. Public Expenditure and Financial Accountability assessments have become a ubiquitous tool for assessing public financial management performance in the region. This paper summarizes Pacific island country performance using global data and identifies a relationship between small population size and lower scores in Public Expenditure and Financial Accountability assessments. This relationship reflects capacity constraints to successful implementation of capacity‐intensive public financial management functions measured in such assessments. The analysis suggests that high scores may be an unrealistic and inappropriate goal for Pacific governments and development partners. Greater account should be taken of population‐related capacity constraints when designing and implementing public financial management reforms. Scarce capacity should be prioritized towards binding constraints to service delivery and macroeconomic management, rather than dispersed in attempts to improve assessment scores through adopting capacity‐intensive ‘best‐practice’ systems.
Epidural analgesia and perioperative kidney function after major liver resection
Authors: Kambakamba P , Slankamenac K , Tschuor C , Kron P , Wirsching A , Maurer K , Petrowsky H , Clavien P A , Lesurtel M
Published: April 2015

Background

Epidural analgesia (EDA) is a common analgesia regimen in liver resection, and is accompanied by sympathicolysis, peripheral vasodilatation and hypotension in the context of deliberate intraoperative low central venous pressure. This associated fall in mean arterial pressure may compromise renal blood pressure autoregulation and lead to acute kidney injury (AKI). This study investigated whether EDA is a risk factor for postoperative AKI after liver surgery.

Methods

The incidence of AKI was investigated retrospectively in patients who underwent liver resection with or without EDA between 2002 and 2012. Univariable and multivariable analyses were performed including recognized preoperative and intraoperative predictors of posthepatectomy renal failure.

Results

A series of 1153 patients was investigated. AKI occurred in 8·2 per cent of patients and was associated with increased morbidity (71 versus 47·3 per cent; P = 0·003) and mortality (21 versus 0·3 per cent; P < 0·001) rates. The incidence of AKI was significantly higher in the EDA group (10·1 versus 3·7 per cent; P = 0·003). Although there was no significant difference in the incidence of AKI between patients undergoing minor hepatectomy with or without EDA (5·2 versus 2·7 per cent; P = 0·421), a substantial difference in AKI rates occurred in patients undergoing major hepatectomy (13·8 versus 5·0 per cent; P = 0·025). In multivariable analysis, EDA remained an independent risk factor for AKI after hepatectomy (P = 0·040).

Conclusion

EDA may be a risk factor for postoperative AKI after major hepatectomy.
Ba3V2S4O3: A Mott Insulating Frustrated Quasi‐One‐Dimensional S=1 Magnet
Authors: Hopkins Emily J. , Prots Yurii , Burkhardt Ulrich , Watier Yves , Hu Zhiwei , Kuo Chang‐Yang , Chiang Jen‐Che , Pi Tun‐Wen , Tanaka Arata , Tjeng Liu Hao , Valldor Martin
Published: April 2015

Through a solid‐state reaction, a practically phase pure powder of Ba3V2S4O3 was obtained. The crystal structure was confirmed by X‐ray single‐crystal and synchrotron X‐ray powder diffraction (P63, a=10.1620(2), c=5.93212(1) Å). X‐ray absorption spectroscopy, in conjunction with multiplet calculations, clearly describes the vanadium in charge‐disproportionated VIIIS6 and VVSO3 coordinations. The compound is shown to be a strongly correlated Mott insulator, which contradicts previous predictions. Magnetic and specific heat measurements suggest dominant antiferromagnetic spin interactions concomitant with a weak residual ferromagnetic component, and that intrinsic geometric frustration prevents long‐range order from evolving.
Evolution of a Short Route to Strychnine by Using the Samarium‐Diiodide‐Induced Cascade Cyclization as a Key Step
Authors: Beemelmanns Christine , Reissig Hans‐Ulrich
Published: April 2015

This comprehensive report accounts the development of a highly diastereoselective samarium diiodide‐induced cascade reaction of substituted indolyl ketones. The complexity‐generating transformation with SmI2 allows the diastereoselective generation of three stereogenic centers including one quaternary center in one step. The obtained tetra‐ or pentacyclic dihydroindole derivatives are structural motifs of many monoterpene indole alkaloids, and their subsequent transformations gave way to one of the shortest approaches towards strychnine (14 % overall yield in ten steps, or 10 % overall yield in eight steps). During the course of this report we discuss the influence of substituents on the cyclization step, plausible mechanistic scenarios for the SmI2‐induced cascade reaction, diastereoselective reductive amination, and regioselective dehydratization protocols towards the pentacyclic core structure of strychnos alkaloids.
Autoinduced Catalysis and Inverse Equilibrium Isotope Effect in the Frustrated Lewis Pair Catalyzed Hydrogenation of Imines
Authors: Tussing Sebastian , Greb Lutz , Tamke Sergej , Schirmer Birgitta , Muhle‐Goll Claudia , Luy Burkhard , Paradies Jan
Published: April 2015

The frustrated Lewis pair (FLP)‐catalyzed hydrogenation and deuteration of N‐benzylidene‐tert‐butylamine (2) was kinetically investigated by using the three boranes B(C6F5)3 (1), B(2,4,6‐F3‐C6H2)3 (4), and B(2,6‐F2‐C6H3)3 (5) and the free activation energies for the H2 activation by FLP were determined. Reactions catalyzed by the weaker Lewis acids 4 and 5 displayed autoinductive catalysis arising from a higher free activation energy (2 kcal mol−1) for the H2 activation by the imine compared to the amine. Surprisingly, the imine reduction using D2 proceeded with higher rates. This phenomenon is unprecedented for FLP and resulted from a primary inverse equilibrium isotope effect.
Optimal DNA Templates for Rolling Circle Amplification Revealed by In Vitro Selection
Authors: Mao Yu , Liu Meng , Tram Kha , Gu Jimmy , Salena Bruno J. , Jiang Yuyang , Li Yingfu
Published: April 2015

Rolling circle amplification (RCA) has been widely used as an isothermal DNA amplification technique for diagnostic and bioanalytical applications. Because RCA involves repeated copying of the same circular DNA template by a DNA polymerase thousands of times, we hypothesized there exist DNA sequences that can function as optimal templates and produce more DNA amplicons within an allocated time. Herein we describe an in vitro selection effort conducted to search from a random sequence DNA pool for such templates for phi29 DNA polymerase, a frequently used polymerase for RCA. Diverse DNA molecules were isolated and they were characterized by richness in adenosine (A) and cytidine (C) nucleotides. The top ranked sequences exhibit superior RCA efficiency and the use of these templates for RCA results in significantly improved detection sensitivity. AC‐rich sequences are expected to find useful applications for setting up effective RCA assays for biological sensing.
Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo
Authors: Grosskopf Stefanie , Eckert Chris , Arkona Christoph , Radetzki Silke , Böhm Kerstin , Heinemann Udo , Wolber Gerhard , von Kries Jens‐Peter , Birchmeier Walter , Rademann Jörg
Published: April 2015

Selective inhibitors of the protein tyrosine phosphatase SHP2 (src homology region 2 domain phosphatase; PTPN11), an enzyme that is deregulated in numerous human tumors, were generated through a combination of chemical synthesis and structure‐based rational design. Seventy pyridazolon‐4‐ylidenehydrazinyl benzenesulfonates were prepared and evaluated in enzyme assays. The binding modes of active inhibitors were simulated in silico using a newly generated crystal structure of SHP2. The most powerful compound, GS‐493 (4‐{(2Z)‐2‐[1,3‐bis(4‐nitrophenyl)‐5‐oxo‐1,5‐dihydro‐4H‐pyrazol‐4‐yliden]hydrazino}benzenesulfonic acid; 25) inhibited SHP2 with an IC50 value of 71±15 nM in the enzyme assay and was 29‐ and 45‐fold more active toward SHP2 than against related SHP1 and PTP1B. In cell culture experiments compound 25 was found to block hepatocyte growth factor (HGF)‐stimulated epithelial–mesenchymal transition of human pancreatic adenocarcinoma (HPAF) cells, as indicated by a decrease in the minimum neighbor distances of cells. Moreover, 25 inhibited cell colony formation in the non‐small‐cell lung cancer cell line LXFA 526L in soft agar. Finally, 25 was observed to inhibit tumor growth in a murine xenograft model. Therefore, the novel specific compound 25 strengthens the hypothesis that SHP2 is a relevant protein target for the inhibition of mobility and invasiveness of cancer cells.
Effects of a clinician referral and exercise program for men who have completed active treatment for prostate cancer: A multicenter cluster randomized controlled trial (ENGAGE)
Authors: Livingston Patricia M. , Craike Melinda J. , Salmon Jo , Courneya Kerry S. , Gaskin Cadeyrn J. , Fraser Steve F. , Mohebbi Mohammadreza , Broadbent Suzanne , Botti Mari , Kent Bridie ,   the ENGAGE Uro‐Oncology Clinicians' Group
Published: April 2015

BACKGROUND

The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer.

METHODS

This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12‐week exercise program comprising 2 supervised gym sessions and 1 home‐based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self‐reported physical activity; the secondary outcomes were quality of life, anxiety, and symptoms of depression.

RESULTS

A significant intervention effect was observed for vigorous‐intensity exercise (effect size: Cohen's d, 0.46; 95% confidence interval [CI], 0.09‐0.82; P = .010) but not for combined moderate and vigorous exercise levels (effect size: d, 0.08; 95% CI, −0.28 to 0.45; P = .48). Significant intervention effects were also observed for meeting exercise guidelines (≥150 min/wk; odds ratio, 3.9; 95% CI, 1.9‐7.8; P = .002); positive intervention effects were observed in the intervention group for cognitive functioning (effect size: d, 0.34; 95% CI, −0.02 to 0.70; P = .06) and depression symptoms (effect size: d, −0.35; 95% CI, −0.71 to 0.02; P = .06). Eighty percent of participants reported that the clinician's referral influenced their decision to participate in the exercise program.

CONCLUSIONS

The clinician referral and 12‐week exercise program significantly improved vigorous exercise levels and had a positive impact on mental health outcomes for men living with prostate cancer. Further research is needed to determine the sustainability of the exercise program and its generalizability to other cancer populations. Cancer 2015;121:2646–2654. © 2015 American Cancer Society.
Delay of treatment change after objective progression on first‐line erlotinib in epidermal growth factor receptor‐mutant lung cancer
Authors: Lo Peter C. , Dahlberg Suzanne E. , Nishino Mizuki , Johnson Bruce E. , Sequist Lecia V. , Jackman David M. , Jänne Pasi A. , Oxnard Geoffrey R.
Published: April 2015

BACKGROUND

Erlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first‐line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date.

METHODS

Patients who had Response Evaluation Criteria In Solid Tumors‐defined PD who were participating in 3 prospective trials of first‐line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR‐sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan.

RESULTS

In total, 92 eligible patients were studied, including 42 with and 50 without an EGFR‐sensitizing mutation. The EGFR‐mutant cohort had a slower rate of progression (P = .003) and a longer TTC (P < .001). Among the patients with EGFR‐mutant cancers, 28 (66%) continued single‐agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR‐mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC.

CONCLUSIONS

A change in systemic therapy commonly can be delayed in patients with EGFR‐mutant lung cancer who objectively progress on first‐line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases. Cancer 2015;121:2570–2577. © 2015 American Cancer Society.
Immunologic evidence of a strong association between non‐Hodgkin lymphoma and simian virus 40
Authors: Tognon Mauro , Luppi Mario , Corallini Alfredo , Taronna Angelo , Barozzi Patrizia , Rotondo John Charles , Comar Manola , Casali Maria Vittoria , Bovenzi Massimo , D'Agostino Antonio , Vinante Fabrizio , Rigo Antonella , Ferrarini Isacco , Barbanti‐Brodano Giuseppe , Martini Fernanda , Mazzoni Elisa
Published: April 2015

BACKGROUND

Non‐Hodgkin lymphoma (NHL), the most common cancer of the lymphatic system, is of unknown etiology. The identification of etiologic factors in the onset of NHL is a key event that could facilitate the prevention and cure of this malignancy. Simian virus 40 (SV40) has been considered an oncogenic agent in the onset/progression of NHL.

METHODS

In this study, an indirect enzyme‐linked immunosorbent assay with 2 synthetic peptides that mimic SV40 antigens of viral capsid proteins 1 to 3 was employed to detect specific antibodies against SV40. Serum samples were taken from 2 distinct cohorts of NHL‐affected patients (NHL1 [n = 89] and NHL2 [n = 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n = 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n = 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n = 130], HS2 [n = 83], and HS3 [n = 87]).

RESULTS

Immunologic data indicated that in serum samples from NHL patients, antibodies against SV40 mimotopes were detectable with a prevalence of 40% in NHL1 patients and with a prevalence of 43% in NHL2 patients. In HSs of the same median age as NHL patients, the prevalence was 16% for the HS1 group (57 years) and 14% for the HS2 group (65 years). The difference was statistically significant (P < .0001 and P < .001). Interestingly, the difference between NHL1/NHL2 patients and BC patients (40%/43% vs 15%, P < .001) and between NHL1/NHL2 patients and UNPC patients (40%/43% vs 25%, P < .05) was significant.

CONCLUSIONS

Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy. Cancer 2015;121:2618–2626. © 2015 American Cancer Society.
PSkel: A stencil programming framework for CPU‐GPU systems
Authors: Pereira Alyson D. , Ramos Luiz , Góes Luís F. W.
Published: April 2015

The use of Graphics Processing Units (GPUs) for high‐performance computing has gained growing momentum in recent years. Unfortunately, GPU‐programming platforms like Compute Unified Device Architecture (CUDA) are complex, user unfriendly, and increase the complexity of developing high‐performance parallel applications. In addition, runtime systems that execute those applications often fail to fully utilize the parallelism of modern CPU‐GPU systems. Typically, parallel kernels run entirely on the most powerful device available, leaving other devices idle. These observations sparked research in two directions: (1) high‐level approaches to software development for GPUs, which strike a balance between performance and ease of programming; and (2) task partitioning to fully utilize the available devices. In this paper, we propose a framework, called PSkel, that provides a single high‐level abstraction for stencil programming on heterogeneous CPU‐GPU systems, while allowing the programmer to partition and assign data and computation to both CPU and GPU. Our current implementation uses parallel skeletons to transparently leverage Intel Threading Building Blocks (Intel Corporation, Santa Clara, CA, USA) and NVIDIA CUDA (Nvidia Corporation, Santa Clara, CA, USA). In our experiments, we observed that parallel applications with task partitioning can improve average performance by up to 76% and 28% compared with CPU‐only and GPU‐only parallel applications, respectively. Copyright © 2015 John Wiley & Sons, Ltd.
Feedback control for noise‐aided parallel micromanipulation of several particles using dielectrophoresis
Authors: Zemánek Jiří , Michálek Tomáš , Hurák Zdeněk
Published: April 2015

The paper describes a novel control strategy for simultaneous manipulation of several microscale particles over a planar microelectrode array using dielectrophoresis. The approach is based on a combination of numerical nonlinear optimization, which gives a systematic computational procedure for finding the voltages applied to the individual electrodes, and exploitation of the intrinsic noise, which compensates for the loss of controllability when two identical particles are exposed to identical forces. Although interesting on its own, the proposed functionality can also be seen as a preliminary achievement in a quest for a technique for separation of two particles. The approach is tested experimentally with polystyrene beads (50 microns in diameter) immersed in deionized water on a flat microelectrode array with parallel electrodes. A digital camera and computer vision algorithm are used to measure the positions. Two distinguishing features of the proposed control strategy are that the range of motion is not limited to interelectrode gaps and that independent manipulation of several particles simultaneously is feasible even on a simple microelectrode array.
Quantitation of sunitinib, an oral multitarget tyrosine kinase inhibitor, and its metabolite in urine samples by nonaqueous capillary electrophoresis time of flight mass spectrometry
Authors: Rodríguez Juana , Castañeda Gregorio , Muñoz Lorena , Villa Jose C.
Published: April 2015

A rapid, sensitive, and specific method was developed and validated using a nonaqueous‐capillary electrophoresis method with TOF‐MS for determination of sunitinib and N‐desethyl sunitinib in human urine. In order to avoid ionic suppression a urine samples dilution with methanol 1:10 previous step was used. This was the only treatment step to urine samples before the injection. Despite this dilution of the urine, the detection limit was as low as 0.07 mg/L for sunitinib and 0.15 mg/L for N‐desethyl sunitinib. Separation of compounds was achieved with a mixture of 5 mM ammonium formate in methanol. The calibration curves were linear over the range of 0.5–50.0 mg/L for the two analyzed compounds. The within‐run and between‐run precisions were within 5%, while the accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical practice to monitor sunitinib and N‐desethyl sunitinib drugs in the urine of cancer patients treated with once daily administration.