bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of concomitant chemoradiation on survival for patients with T1‐2N1 head and neck cancer
Authors: Zumsteg Zachary S. , Kim Sungjin , David John M. , Yoshida Emi J. , Tighiouart Mourad , Shiao Stephen L. , Scher Kevin , Mita Alain , Sherman Eric J. , Lee Nancy Y. , Ho Allen S.
Published: December 2016

BACKGROUND

Single‐modality radiotherapy is considered a standard‐of‐care option for certain stage III, T1‐2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population.

METHODS

This study analyzed patients in the National Cancer Data Base with cT1‐2N1M0 invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx who were diagnosed between 2004 and 2012 and were undergoing definitive radiation. Patients who were undergoing surgery before radiation with unknown follow‐up or for whom either the receipt or timing of chemotherapy was unknown were excluded.

RESULTS

In all, 5030 patients with T1‐2N1 oropharyngeal, laryngeal, or hypopharyngeal cancer were included. The median follow‐up was 56.8 months (95% confidence interval [CI], 55.7‐58.6 months). Overall, 68% of the patients received concomitant chemoradiation (CCRT). The use of CCRT significantly increased during the time period of this study from 53% in 2004 to 78% in 2012 (P < .001). CCRT was associated with improved overall survival (OS) in comparison with radiation alone in a multivariate analysis (hazard ratio [HR], 0.80; 95% CI, 0.72‐0.88; P < .001). In propensity score–adjusted analyses, CCRT remained significantly associated with improved OS, with 5‐year OS rates of 63.5% (95% CI, 60.7%‐66.2%) and 55.6% (95% CI, 52.7%‐58.4%; P < .001) with CCRT and radiation alone, respectively. Subgroup analyses showed a benefit across the majority of subgroups, including patients with oropharyngeal cancer (HR, 0.74; 95% CI, 0.65‐0.85; P < .001).

CONCLUSIONS

Concomitant chemoradiation is associated with improved survival for patients with T1‐2N1 HNSCC. Prospective trials in this population should be pursued. Cancer 2017;123:1555–1565. © 2017 American Cancer Society.
Predictors of multidomain decline in health‐related quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer
Authors: Dess Robert T. , Jackson William C. , Suy Simeng , Soni Payal D. , Lee Jae Y. , Abugharib Ahmed E. , Zumsteg Zachary S. , Feng Felix Y. , Hamstra Daniel A. , Collins Sean P. , Spratt Daniel E.
Published: December 2016

BACKGROUND

Stereotactic body radiation therapy (SBRT) for localized prostate cancer involves high‐dose‐per‐fraction radiation treatments. Its use is increasing, but concerns remain about treatment‐related toxicity. The authors assessed the incidence and predictors of a global decline in health‐related quality of life (HRQOL) after prostate SBRT.

METHODS

From 2008 to 2014, 713 consecutive men with localized prostate cancer received treatment with SBRT according to a prospective institutional protocol. Expanded Prostate Cancer Index Composite (EPIC‐26) HRQOL data were collected at baseline and longitudinally for 5 years. EPIC‐26 is comprised of 5 domains. The primary endpoint was defined as a decline exceeding the clinically detectable threshold in ≥4 EPIC‐26 domains, termed multidomain decline.

RESULTS

The median age was 69 years, 46% of patients had unfavorable intermediate‐risk or high‐risk disease, and 20% received androgen‐deprivation therapy. During 1 to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had multidomain declines, respectively. On multivariable analysis, lower baseline bowel HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2‐2.7; P < .01) and baseline depression (odds ratio, 5.7; 95% confidence interval, 1.3‐24.3; P = .02) independently predicted for multidomain decline. Only 3% to 4% of patients had long‐term multidomain declines exceeding twice the clinical threshold, and 30% of such declines appeared to be related to prostate cancer treatment or progression of disease.

CONCLUSIONS

Prostate SBRT has minimal long‐term impact on multidomain decline, and the majority of more significant multidomain declines appear to be unrelated to treatment. This emphasizes the importance of focusing not only on the side effects of prostate cancer treatment but also on other comorbid illnesses that contribute to overall HRQOL. Cancer 2017;123:1635–1642. © 2017 American Cancer Society.
Precipitation and Crystallization Kinetics in Silica Gardens
Authors: Glaab Fabian , Rieder Julian , Klein Regina , Choquesillo‐Lazarte Duane , Melero‐Garcia Emilio , García‐Ruiz Juan‐Manuel , Kunz Werner , Kellermeier Matthias
Published: December 2016

Silica gardens are extraordinary plant‐like structures resulting from the complex interplay of relatively simple inorganic components. Recent work has highlighted that macroscopic self‐assembly is accompanied by the spontaneous formation of considerable chemical gradients, which induce a cascade of coupled dissolution, diffusion, and precipitation processes occurring over timescales as long as several days. In the present study, this dynamic behavior was investigated for silica gardens based on iron and cobalt chloride by means of two synchrotron‐based techniques, which allow the determination of concentration profiles and time‐resolved monitoring of diffraction patterns, thus giving direct insight into the progress of dissolution and crystallization phenomena in the system. On the basis of the collected data, a kinetic model is proposed to describe the relevant reactions on a fundamental physicochemical level. The results show that the choice of the metal cations (as well as their counterions) is crucial for the development of silica gardens in both the short and long term (i.e. during tube formation and upon subsequent slow equilibration), and provide important clues for understanding the properties of related structures in geochemical and industrial environments.
Doxapram‐mediated Increase in Cardiac Output Reduces Opioid Plasma Concentrations: A Pharmacokinetic/Pharmacodynamic–Pharmacokinetic/Pharmacodynamic Modeling Study in Healthy Volunteers
Authors: Roozekrans M , Olofsen E , van der Schrier R , Boom M , Mooren R , Dahan A
Published: December 2016

Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is the blockade of background K+‐channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1,000–3,500 ng/mL) on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the potent opioid alfentanil (Cp 100–200 ng/mL). Population PK‐PD analyses were performed on the doxapram PK‐CO data and the alfentanil PK‐antinociception data. The analyses showed that the doxapram‐induced increase in CO explained the increase in alfentanil distribution and elimination clearances causing a significant reduction in plasma alfentanil Cp and antinociception. This novel approach in which one PK‐PD model effectively drives another PK‐PD model highlights the importance of physiological influences on PK and PD of a potent opioid with rapid onset of effect and low clinical margin of safety.
Interactions Between Therapeutic Proteins and Small Molecules: The Shared Role of Perpetrators and Victims
Authors: Cavaco M , Goncalves J
Published: December 2016

Therapeutic proteins (TPs) are becoming increasingly important as therapeutic agents. A consequence of expanding their clinical indications is coadministration with well‐established small‐molecule drugs (sMDs), which could lead to unpredictable effects. According to the existing regulatory guidance, the development of an sMD includes the evaluation of potential drug‐drug interactions (DDIs). For TPs, only a few drug interaction studies have been published. Limited clinically relevant models, long half‐lives, and complex elimination pathways are among the associated difficulties.
Develop strategies to lead through changing budgetary options
Authors: Hope Joan
Published: December 2016

Over the past eight years, community colleges have enjoyed a renaissance, said Rufus Glasper, president and chief executive officer for the League for Innovation in the Community College and chancellor emeritus of the Maricopa Community Colleges in Arizona. They have gotten support at the federal level, and funding has been made available to help with completion initiatives.
Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α–CXCR4 and TP53–TPM1 proteins
Authors: Chen Chien‐Cheng , Hsia Ching‐Wu , Ho Cheng‐Wen , Liang Chang‐Min , Chen Chieh‐Min , Huang Kun‐Lun , Kang Bor‐Hwang , Chen Yi‐Hui
Published: December 2016

Background: Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self‐renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions. Results: We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia‐inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4‐specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin‐1), and increased nuclear‐to‐cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N‐acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs. Conclusions: Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α–CXCR4 pathway and hyperoxia via the TP53–TPM1 pathway. Developmental Dynamics 246:162–185, 2017. © 2016 Wiley Periodicals, Inc.
Evaluating canopy transpiration and water use of two typical planted tree species in the dryland Loess Plateau of China
Authors: Zhang Handan , Wei Wei , Chen Liding , Yang Lei
Published: December 2016

Large‐scale vegetation restoration has been conducted in China's Loess Plateau over the past several decades to control soil and water loss. However, these efforts have not followed any specific guidelines to select plant species that balance the twin goals of vegetation restoration and water demand. In the present study, we measured canopy transpiration characteristics of oriental arborvitae (Platycladus orientalis) and Chinese pine (Pinus tabulaeformis), two species that are commonly planted in restoration efforts, and recorded water input and output for these two species during the growing season. P. tabulaeformis had a higher tolerance than P. orientalis to warmer and drier environments and used water over a wider time span. Canopy transpiration significantly increased when rainfall exceeded 15 mm and was negatively correlated with net change of soil water content. Meanwhile, rainless intervals also affected canopy transpiration recovery. Canopy transpiration of P. tabulaeformis was 25.4% higher than that of P. orientalis. Soil water content under P. orientalis declined by 28.4% after the growing season, while it slightly increased under P. tabulaeformis (0.7%). Our results suggested that although P. tabulaeformis plantation had higher canopy transpiration, this water use did not drastically reduce soil water content, mainly due to the lower evaporation caused by the dense canopy cover. However, the low soil water content also implied that a better management, such as a mixed plantation of these two species and other supplemental water‐conservation techniques, should be considered to better use water in this semiarid region.
Plant size affects mutualistic and antagonistic interactions and reproductive success across 21 Brassicaceae species
Authors: Schlinkert Hella , Westphal Catrin , Clough Yann , Grass Ingo , Helmerichs Juliane , Tscharntke Teja
Published: December 2016

Plant size has been hypothesized to be a major driver of biotic interactions. However, it is little understood how plant size affects plant mutualists vs. antagonists and the plant's resulting reproductive success. We established a common garden experiment covering an interspecific plant size gradient (from 10 to 130 cm height) across 21 annual Brassicaceae species, thereby standardizing features of habitat and surrounding landscape. We assessed flower‐visiting pollinators and florivores (pollen beetle adults and larvae) and the resulting effects of all these flower‐visiting insects on plant reproductive success. Besides flower characteristics (size, abundance, color), plant size had a generally positive effect on abundance and species richness of pollinators as well as on abundance of pollen beetle adults and larvae. Pollen beetles reduced seed number as well as thousand‐seed weight, whereas pollinators increased seed number only. Overall, increasing plant size led to less thousand‐seed weight but had no effect on seed number, indicating counterbalancing effects of herbivory and pollination. In conclusion, seed number of large plant species should benefit from locations with many pollinators and few herbivores and small plant species' seed number from locations with few pollinators and many herbivores.
Evaluating the influence of anthropogenic landscape change on wolf distribution: implications for woodland caribou
Authors: Ehlers Libby P. W. , Johnson Chris J. , Seip Dale R.
Published: December 2016

Across much of the range of woodland caribou (Rangifer tarandus caribou), predator–prey dynamics have changed as a result of large‐scale industrial development. Land clearing and associated early‐successional forests have resulted in a greater density and distribution of moose (Alces alces), deer (Odocoileusspp.), and their associated predators. This process of apparent competition has resulted in increased predation on woodland caribou. We employed a combination of field and statistical methods to better understand the distribution and interactions of wolves (Canis lupus) and caribou across a region with high levels of industrial development. We used count models to investigate the frequency of wolf occurrence relative to landcover types, disturbance features, and caribou habitat. As predicted, the co‐occurrence between caribou and wolves was rare. Similarly, the remains of caribou were identified at a small proportion of the sites where wolves killed large prey. Caribou occurred at low densities across the study area, and thus, wolves likely pursued other more abundant deer species. Encounters between wolves and caribou habitat was most likely to occur in the low‐elevation boreal forest and areas closer to and with higher densities of forestry cutblocks. Our results highlight the importance of understanding the spatial dynamics of multi‐species interactions when developing recovery strategies for threatened and endangered species.
Can functional traits predict plant community response to global change?
Authors: Kimball Sarah , Funk Jennifer L. , Spasojevic Marko J. , Suding Katharine N. , Parker Scot , Goulden Michael L.
Published: December 2016

One primary goal at the intersection of community ecology and global change biology is to identify functional traits that are useful for predicting plant community response to global change. We used observations of community composition from a long‐term field experiment in two adjacent plant communities (grassland and coastal sage shrub) to investigate how nine key plant functional traits were related to altered water and nitrogen availability following fire. We asked whether the functional responses of species found in more than one community type were context dependent and whether community‐weighted mean and functional diversity were significantly altered by water and nitrogen input. Our results suggest varying degrees of context dependency. We found that plants with high leaf nitrogen concentration (specifically nitrogen fixers), shallow roots, and low leaf mass per unit area and plant‐level transpiration were similarly negatively influenced by added nitrogen across community types. In contrast, responses to water manipulations exhibited greater context dependency; plants with high water‐use efficiency, lower plant‐level transpiration rates, and shallower roots were negatively impacted by simulated drought in the shrub‐dominated community, but there was no significant relationship between these traits and changes in water inputs in the grassland community. Similarly, we found context dependency in community‐wide trait responses to global change. Functional diversity tended to be higher in plots with reduced water as compared to those with added water in grassland, while the opposite trend was observed in coastal sage scrub. Our results indicate that some traits are strong predictors of species and community response to altered water and nitrogen availability, but the magnitude and direction of the response may be modulated by the abiotic and biotic context.
Heart failure in haemoglobinopathies: pathophysiology, clinical phenotypes, and management
Authors: Farmakis Dimitrios , Triposkiadis Filippos , Lekakis John , Parissis John
Published: December 2016

Hereditary haemoglobinopathies, mainly beta‐thalassemia and sickle cell disease, constitute the most common monogenic disorders in humans, and although once geographically confined, they are currently globally distributed. They are demanding clinical entities that require multidisciplinary medical management. Despite their genotypic and phenotypic heterogeneity, the haemoglobinopathies share several similarities in pathophysiology, clinical manifestations, therapeutic requirements, and complications, among which heart failure (HF) represents a leading cause of mortality and morbidity. However, haemoglobinopathies have generally been addressed in a rather fragmentary manner. A unifying approach focusing on the underlying similarities of HF attributes in the two main entities might contribute to their better understanding, characterization, and management. In the present review, we attempt such an approach to the pathophysiology, clinical phenotypes, and management of HF in haemoglobinopathies.
Structure and Bonding of High‐Spin Nitrosyl–Iron(II) Compounds with Mixed N,O‐Chelators and Aqua Ligands
Authors: Wolf Markus , Klüfers Peter
Published: December 2016

High‐spin nitrosyl–iron centres of the Enemark–Feltham {FeNO}7 type exist in aqueous solution. Examples include the tentative “brown‐ring” species [Fe(H2O)5(NO)]2+ and a tentative FeII/edta/NO species formed in the processes for scrubbing NO from flue‐gas streams. Inert‐gas bubbling through the solutions subdivides the ferrous nitrosyl complexes in a less stable subclass – a prominent member being the brown‐ring complex – and a more stable subclass to which the edta species belongs. The structural chemistry of the less stable subclass of {FeNO}7‐type complexes from aqueous media is presented here. They contain aminecarboxylato co‐ligands of limited denticity and aqua ligands that complete an OC‐6 environment of the Fe atom. Crystalline compounds for single‐crystal structure analysis were obtained for various co‐ligands: [Fe(H2O)2(ida)(NO)] (2a), [Fe(H2O)(heida)(NO)] (2b), [Fe(H2O)2(NO)(oda)] (2c), [Fe(H2O)2(NO)(phida)]·H2O (2d), [Fe(bnida)(H2O)2(NO)] (2e), [Fe(brbnida)(H2O)2(NO)] (2f) and [Fe(dipic)(H2O)2(NO)] (2g) (ida = iminodiacetate, heida = hydroxyethyliminodiacetate, oda = oxodiacetate, phida = N‐phenyliminodiacetate, bnida = N‐benzyliminodiacetate, brbnida = N‐4‐bromobenzyliminodiacetate, dipic = dipicolinate). The Fe–NO interaction was studied by DFT and CASSCF methods. Due to mostly covalent Fe–NO π bonds, the charge distribution in the less stable subclass is close to FeII(NO) with a small FeIII(NO–) contribution.
Rump and shoulder muscles from grass and linseed fed cattle as important sources of n‐3 fatty acids for beef consumers
Authors: Kronberg Scott L. , Scholljegerdes Eric J. , Maddock Robert J. , Barceló‐Coblijn Gwendolyn , Murphy Eric J.
Published: December 2016

Ground beef has potential to be a relatively inexpensive and sustainable source of n‐3 fatty acids (FA) for people who frequently consume it, but don't consume n‐3 containing fish. To enhance n‐3 FA content in ground beef, we evaluated FA content in pertinent muscles from grass‐fed cattle that were supplemented with flaxseed for 75 days before slaughter and compared them with loin muscle from these cattle. Lipids from rump (m. biceps femoris), shoulder (m. triceps brachii), and loin (m. longissimus dorsi) were separated into neutral and phospholipids and FA mass determined using gas liquid chromatography. In phospholipids, concentration of α‐linolenic acid (ALA; 18:3n‐3), eicosapentaenoic acid (EPA; 20:5n‐3), docosapentaenoic acid (DPA; 22:5n‐3), and docosahexaenoic acid (DHA; 22:6n‐3) were higher in shoulder and rump compared to loin (p < 0.0001). Compared to shoulder, FA concentration was higher in the rump (p < 0.0001) except for DPA (p = 0.53). ALA, EPA, DPA, and DHA were increased between 1.5‐ and 1.8‐fold in the rump and 1.3‐ and 1.5‐fold in the shoulder compared to loin, respectively. Lean ground beef made with rump and shoulder muscles from grass‐fed cattle supplemented with flaxseed has potential to be a source of dietary n‐3 FA for many people.

Practical applications: Frequently consumed foods containing n‐3 FA may help reduce chronic inflammation, atherosclerosis, and cardiovascular disease when consumed early in life. Given that many people do not consume recommended amounts of n‐3 containing fish, foods they do consume frequently, such as ground beef, should be evaluated as potential useful sources of n‐3 FA. Muscles from the rump and shoulder of cattle that are raised on a grass‐based diet with flaxseed supplementation have potential to provide more n‐3 FA to ground beef consumers than is generally appreciated.

Compared to bovine loin muscle, bovine shoulder and rump muscles tend to have higher concentrations of alpha‐linolenic acid (ALA; 18:3n‐3) and the long‐chain omega‐3 fatty acids eicosapentaenoic acid (EPA; 20:5n‐3), docosapentaenoic acid (DPA; 22:5n‐3), and docosahexaenoic acid (DHA; 22:6n‐3). This is healthful for many people in that shoulder and rump muscles are less expensive beef which is eaten by millions of people as ground/minced beef in foods such as hamburgers, tacos, and empanadas; thus, providing a practical source of omega‐3 fatty acids for people who seldom eat expensive sources such as salmon and tuna.
Metal‐Free Photocatalytic Reductive Dehalogenation Using Visible‐Light: A Time‐Resolved Mechanistic Study
Authors: Martinez‐Haya Rebeca , Miranda Miguel A. , Marin M. Luisa
Published: December 2016

The reductive dehalogenation of organic bromides has been achieved in the presence of riboflavin (RF) as photocatalyst under visible‐light irradiation. Specifically, benzyl bromide (2) and α‐bromoacetophenone (3) were quantitatively converted into toluene and acetophenone, respectively, by using amines as electron donors and iPrOH as hydrogen donor, whereas bromobenzene (1) did not react. The thermodynamics of the reduction of the radical anion of RF were evaluated by using the redox potentials of the species involved: The reaction was found to be thermodynamically exergonic for 2 and 3, but not expected to occur for bromobenzene (1). The viability of the different competing processes on the timescales of the corresponding singlet and triplet RF excited states (1RF* and 3RF*) was analyzed by time‐resolved techniques. The quenching of 1RF* by amines was very efficient, and comparison of the transient absorption spectra recorded in the absence and presence of amines additionally confirmed the efficient redox process between 1RF* and the amines. Moreover, RF·– was quenched by bromides 2 and 3, but not by 1. Thus, a deeper understanding of the overall mechanism of the photocatalytic reductive reaction has been achieved, and the key role of the radical anion of the photocatalyst has been demonstrated.
Competency‐based degrees: Another way to grow the enrollment pie?
Authors: Dennis Marguerite J.
Published: December 2016

The majority of colleges and universities in the United States award credit based on the Carnegie Unit, which has been in place for more than a century. Currently, only 29 percent of students enrolled in colleges and universities are “traditional” 18–22‐year‐olds, enrolling directly after high school. And a quarter of all college students in the United States are over the age of 30. For this older, working, nontraditional population, sitting in a classroom for four, five, or six years is just not a viable option.
Carbon Dioxide Absorption using Solid Sorbents Incorporating Purified Components of Tetraethylenepentamine
Authors: Numaguchi Ryohei , Chowdhury Firoz A. , Yamada Hidetaka , Yogo Katsunori
Published: December 2016

Tetraethylenepentamine (TEPA) components are separated by fractional distillation, and the structure of each fraction is established using spectroscopic methods. Then, solid sorbents incorporating these components are prepared, and the capacities and rates of CO2 absorption of the sorbents are evaluated to elucidate how the molecular structure affects the absorption performance.
Experimental study of deformable connection consisting of buckling‐restrained brace and rubber bearings to connect floor system to lateral force resisting system
Authors: Tsampras Georgios , Sause Richard , Fleischman Robert B. , Restrepo Jose I.
Published: December 2016

This paper presents experimental and numerical studies of a full‐scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake‐resistant building. The purpose of the deformable connection is to limit the earthquake‐induced horizontal inertia force transferred from the floor system to the LFRS and, thereby, to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a buckling‐restrained brace (BRB) and steel‐reinforced laminated low‐damping rubber bearings (RB).

The test results show that the force–deformation responses of the connection are stable, and the dynamic force responses are larger than the quasi‐static force responses. The BRB+RB force–deformation response depends mainly on the BRB response. A detailed discussion of the BRB experimental force–deformation response is presented. The experimental results show that the maximum plastic deformation range controls the isotropic hardening of the BRB. The hardened BRB force–deformation responses are used to calculate the overstrength adjustment factors. Details and limitations of a validated, accurate model for the connection force–deformation response are presented. Numerical simulation results for a 12‐story reinforced concrete wall building with deformable connections show the effects of including the RB in the deformable connection and the effect of modeling the BRB isotropic hardening on the building seismic response. Copyright © 2016 John Wiley & Sons, Ltd.
Multi‐method (14C, 36Cl, 234U/230Th) age bracketing of the Tschirgant rock avalanche (Eastern Alps): implications for absolute dating of catastrophic mass‐wasting
Authors: Ostermann Marc , Ivy‐Ochs Susan , Sanders Diethard , Prager Christoph
Published: December 2016

Correct and precise age determination of prehistorical catastrophic rock‐slope failures prerequisites any hypotheses relating this type of mass wasting to past climatic regimes or palaeo‐seismic records. Despite good exposure, easy accessibility and a long tradition of absolute dating, the age of the 230 million m3 carbonate‐lithic Tschirgant rock avalanche event of the Eastern Alps (Austria) still is relatively poorly constrained. We herein review the age of mass‐wasting based on a total of 17 absolute ages produced with three different methods (14C, 36Cl, 234U/230Th). Chlorine‐36 (36Cl) cosmogenic surface exposure dating of five boulders of the rock avalanche deposit indicates a mean event age of 3.06 ± 0.62 ka. Uranium‐234/thorium‐230 (234U/230Th) dating of soda‐straw stalactites formed in microcaves beneath boulders indicate mean precipitation ages of three individual soda straws at 3.20 ± 0.26 ka, 3.04 ± 0.10 ka and 2.81 ± 0.15 ka; notwithstanding potential internal errors, these ages provide an ‘older‐than’ (ante quam) proxy for mass‐wasting.

Based on radiocarbon ages (nine sites) only, it was previously suggested that the present rock avalanche deposit represents two successive failures (3.75 ± 0.19 ka bp, 3.15 ± 0.19 ka bp). There is, however, no evidence for two events neither in surface outcrops nor in LiDAR derived imagery and drill logs. The temporal distribution of all absolute ages (14C, 36Cl, 234U/230Th) also does not necessarily indicate two successive events but suggest that a single catastrophic mass‐wasting took place between 3.4 and 2.4 ka bp. Taking into account the maximum age boundary given by reinterpreted radiocarbon datings and the minimum U/Th‐ages of calcite precipitations within the rock avalanche deposits, a most probable event age of 3.01 ± 0.10 ka bp can be proposed. Our results underscore the difficulty to accurately date catastrophic rock slope failures, but also the potential to increase the accuracy of age determination by combining methods. Copyright © 2016 John Wiley & Sons, Ltd.
Test method for characterising the thermal protective performance of fabrics exposed to flammable liquid fires
Authors: Kemp S.E. , Annaheim S. , Rossi R.M. , Camenzind M.A.
Published: December 2016

People, such as emergency service and military personnel, require protection from fires involving flammable liquids and liquefiable solids (Class B fires) in a number of situations. Fires involving flammable liquids typically reach higher temperatures sooner when compared to other types of fuel, yet there appears to be little literature that specifically investigates the protective performance of fabrics against such fires. Therefore, a new method was developed to enable the characterisation of the protective performance of fabrics when exposed to flammable liquid fires. Fabric samples were mounted on a sample plate inclined to three different angles of incidence. Known volumes of hydrocarbon fuel were pipetted into a fuel reservoir, ignited, then tipped onto fabric samples. Ten thermocouples embedded in the sample plate measured the resultant change in temperature at the technical rear of the fabric samples throughout the exposure. Significant differences were observed between fabrics for maximum temperature, time to maximum temperature, maximum heat flux, transferred energy and estimated burn risk. Therefore, this new methodology enabled discrimination among fabrics based on the protection they provide. Differences were also observed when the volume of fuel and the angle of incidence varied and, therefore, these device settings must be controlled for repeatable results. Copyright © 2016 John Wiley & Sons, Ltd.
Order Aggressiveness, Trading Patience, and Trader Types in a Limit Order Market
Authors: Chiu Junmao , Chung Huimin , Wang George H. K.
Published: December 2016

This study examines the order aggressiveness and trading patience of foreign institutional traders, futures proprietary firm traders, individual day and non‐day traders in the Taiwan index futures market. We consider order choice given a completely transparent limit order book. Our empirical results show that individual (foreign institutional) traders use a more aggressive (patient) order submission strategy than the other trader types. We find significant differences among trader types in the timing of order aggressiveness and trading patience over the intraday time period. Both top and rest‐of‐the‐order‐book activities affect traders’ order submission decisions. © 2016 Wiley Periodicals, Inc. Jrl Fut Mark 37:1094–1123, 2017
Update on pharmacotherapies for cholestatic liver disease
Authors: Ali Ahmad H. , Tabibian James H. , Lindor Keith D.
Published: December 2016

Cholestatic liver diseases are conditions with impaired bile formation and/or flow due to genetic, immunologic, environmental, or other causes. Unless successfully treated, this can lead to chronic liver injury and end‐stage liver disease. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) embody the most prominent adult cholestatic liver diseases with regard to incidence, morbidity, and mortality. A considerable proportion of patients with PBC and PSC experience progressive liver disease and ultimately liver‐related death due to a paucity of effective pharmacotherapy; however, novel pharmacologic developments offer substantial promise in this regard. Here, we provide a brief review and update on current and emerging pharmacotherapies for PBC and PSC. (Hepatology Communications 2017;1:7–17)
Biomimetic calcium phosphate/polyelectrolyte multilayer coatings for sequential delivery of multiple biological factors
Authors: Jacobs E. E. , Gronowicz G. , Hurley M. M. , Kuhn L.T.
Published: December 2016

Combinations of growth factors synergistically enhance tissue regeneration, but typically require sequential, rather than co‐delivery from biomaterials for maximum efficacy. Polyelectrolyte multilayer (PEM) coatings can deliver multiple factors without loss of activity; however, sequential delivery from PEM has been limited due to interlayer diffusion that results in co‐delivery of the factors. This study shows that addition of a biomimetic calcium phosphate (bCaP) barrier layer to a PEM coating effectively prevents interlayer diffusion and enables sequential delivery of two different biomolecules via direct cell access. A simulated body fluid method was used to deposit a layer of bCaP followed by 30 bilayers of PEM made with poly‐l‐Lysine (+) and poly l‐Glutamic acid (−) (bCaP‐PEM). Measurements of MC3T3‐E1 proliferation and viability over time on bCaP‐PEM were used to demonstrate the sequential delivery kinetics of a proliferative factor [fibroblast growth factor‐2 (FGF‐2)] followed by a cytotoxic factor (antimycin A, AntiA). FGF‐2 and AntiA both retained their bioactivity within bCaP‐PEM, yet no release of FGF‐2 or AntiA from bCaP‐PEM was observed when cells were absent indicating a cell‐mediated, local delivery process. This coating technique is useful for a variety of applications that would benefit from highly localized, sequential delivery of multiple biomolecules governed by cell initiated degradation that avoids off‐target effects associated with diffusion‐based release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1500–1509, 2017.
IL‐7 and procalcitonin are useful biomarkers in the comprehensive evaluation of the severity of acute cholangitis
Authors: Suwa Yusuke , Matsuyama Ryusei , Goto Koki , Kadokura Toshiaki , Sato Mari , Mori Ryutaro , Kumamoto Takafumi , Taguri Masataka , Miyasho Taku , Endo Itaru
Published: December 2016

Background

The incidence of biliary tract infection (BTI), especially healthcare‐associated cholangitis, is increasing. However, there are few reports concerning biomarkers of acute cholangitis. We therefore performed an exhaustive investigation of several biomarkers.

Methods

We retrospectively measured 11 cytokines, six chemokines and procalcitonin (PCT), and endotoxin activity assay (EAA) values (IRB: 110512019) of 61 samples with acute cholangitis.

Result

The 28‐day mortality rate was 9.8%. The levels of most cytokines and chemokines were significantly correlated with each other. A low IL‐7 level was found to predict blood culture positivity. Low IL‐7 level was also found to predict disseminated intravascular coagulation. Low IL‐7 levels and a high PCT level were found to be predictors of severe cholangitis. The 28‐day mortality in the group of patients with an IL‐7 level of ≤6.0 and a PCT level of >0.5 was 18.2%. It was significantly higher than in the other group.

Conclusion

The combined use of IL‐7 and PCT may be useful for evaluating severe acute cholangitis; these results may suggest that severe acute cholangitis is affected by immunosuppressive changes.
Spatial downscaling of TRMM‐based precipitation data using vegetative response in Xinjiang, China
Authors: Zhang Qiang , Shi Peijun , Singh Vijay P. , Fan Keke , Huang Jiajun
Published: December 2016

Station‐based observed precipitation data are available in a limited way and only at low spatial resolution. High‐resolution satellite rainfall products can help to monitor precipitation changes over large areas. The Tropical Rainfall Measuring Mission 3B43 (TRMM 3B43) precipitation data with coarse spatial resolution and low data accuracy are capable of depicting the spatial variability of precipitation, but fail to estimate the accurate magnitude. These data available in Xinjiang, China, need to be evaluated, especially because Xinjiang has a complex terrain and application of such data becomes a challenging task. Based on the relation between precipitation and normalized difference vegetation index (NDVI), a proxy for vegetation, a new statistical downscaling algorithm is proposed in this study. The calibration was based on geographical difference analysis (GDA) and the monthly fractions derived from the un‐calibrated TRMM data can be used to disaggregate high‐resolution annual precipitation to high‐resolution monthly precipitation. The accuracy of downscaled TRMM precipitation was evaluated based on station‐based observed precipitation for a period of 1998–2010. Results indicated that: (1) optimal relations shown by R2 between TRMM precipitation and NDVI at different temporal and spatial scales were different: the largest R2 value was 0.69 for the period of 1998–2010 at a spatial resolution of 1.00° × 1.00°, was 0.70 for the dry year (2001 in this study) at a spatial resolution of 0.75° × 0.75°, and was 0.67 for the wet year (2010 in this study) at a spatial resolution of 1.25° × 1.25°; (2) the downscaled TRMM precipitation data obtained using NDVI described spatial patterns of precipitation reasonably well at a spatial resolution of 8 km × 8 km with more detailed information when compared to the raw TRMM precipitation at a spatial resolution of 0.25° × 0.25°; (3) the downscaled TRMM precipitation with GDA calibration, PDSGDA, can exclude the regions with irrigation‐ and/or ground water‐induced vegetation coverage. Therefore, PDSGDA obtained in this study can be regarded as estimated alternative precipitation data across Xinjiang for management of water resources and agricultural irrigation activities.
Thiol/disulfide homeostasis as a novel indicator of oxidative stress in obstructive sleep apnea patients
Authors: Dinc Mehmet Emre , Ozdemir Cengiz , Ayan Nilhan Nurlu , Bozan Nazım , Ulusoy Seckin , Koca Cemile , Erel Ozcan
Published: December 2016

Objectives

The aim of the present study was to assess thiol/disulfide (SS) homeostasis as a novel indicator of oxidative stress in patients with obstructive sleep apnea (OSA) and to investigate the effect of continuous positive airway pressure (CPAP) therapy on oxidative parameters.

Study Design

Prospective clinical study.

Methods

A total of 104 subjects, 44 in an OSA group and 60 in two control groups (control simple snoring group, control OSA group) were included. The levels of parameters were measured using the Erel and Neselioglu method in patients with moderate or severe OSA before and after CPAP therapy.

Results

The serum native thiol (SH) and total SH levels as well as the %SH/total SH ratio were significantly lower (P < 0.05) in OSA patients compared to controls, and the SS level and %SS/SH and %SS/total SH ratios were significantly higher (P < 0.05). After CPAP therapy, the native SH level and %SH/total SH ratio were significantly higher (P < 0.05) than before CPAP therapy, and the SS level and %SS/SH and %SS/total SH ratios were significantly lower (P < 0.05). Significant negative correlations were evident between the apnea/hypopnea index (AHI) and the native SH level and %SH/total SH ratio (P < 0.05) before CPAP therapy; and significant positive correlations were seen between the AHI and the %SS/SH and %SS/total SH ratios but not with the SS level.

Conclusion

We found that oxidative stress was increased and CPAP therapy had a positive effect in patients with moderate or severe OSA.

Level of Evidence

3b. Laryngoscope, 127:E244–E250, 2017
Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation
Authors: Sendra Gisbert Luis , Miguel Matas Antonio , Sabater Ortí Luis , Herrero María José , Sabater Olivas Laura , Montalvá Orón Eva María , Frasson Matteo , Abargues López Rafael , López‐Andújar Rafael , García‐Granero Ximénez Eduardo , Aliño Pellicer Salvador Francisco
Published: December 2016

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50–62 2017 AASLD.
A Robust and Efficient Feature Selection Algorithm for Microarray Data
Authors: Bari Mehrab Ghanat , Salekin Sirajul , Zhang Jianqiu (Michelle)
Published: December 2016

In the past decades, a few synergistic feature selection algorithms have been published, which includes Cooperative Index (CI) and K‐Top Scoring Pair (k‐TSP). These algorithms consider the synergistic behavior of features when they are included in a feature panel. Although promising results have been shown for these algorithms, there is lack of a comprehensive and fair comparison with other feature selection algorithms across a large number of microarray datasets in terms of classification accuracy and computational complexity. There is a need in evaluating their performance and reducing the complexity of such algorithms. We compared the performance of synergistic feature selection algorithms with 11 other commonly used algorithms based on 22 microarray gene expression binary class datasets. The evaluation confirms that synergistic algorithms such as CI and k‐TSP will gradually increase the classification performance as more features are used in the classifiers. Also, in order to cut down computational cost, we proposed a new feature selection ranking score called Positive Synergy Index (PSI). Testing results show that features selected using PSI as well as synergistic feature selection algorithms provide better performance compared to with all other methods, while PSI has a computational complexity significantly lower than that of other synergistic algorithms.
Identification of CLK1 Inhibitors by a Fragment–linking Based Virtual Screening
Authors: Walter Anne , Chaikuad Apirat , Loaëc Nadège , Preu Lutz , Knapp Stefan , Meijer Laurent , Kunick Conrad , Koch Oliver
Published: December 2016

Alternative splicing plays an important role in the regulation of protein biosynthesis. CDC2‐like kinases (CLKs) phosphorylate splicing factors rendering them a potential target for treating diseases caused by splicing dysregulation. As selective and potent inhibitors of CLK1 are still lacking, a fragment‐linking based virtual screening campaign was successfully applied to identify new inhibitors showing activity on CLK1. These inhibitors exhibit a novel 2,4‐substituted 1,3‐thiazole scaffold that is suitable for further modification. A subsequently performed docking and protein structure based analysis revealed first hints for inhibitors showing preferred binding activity for CLK1 and DYRK2 over other splicing kinases.
Adipocyte lipopolysaccharide binding protein (LBP) is linked to a specific lipidomic signature
Authors: Moreno‐Navarrete José María , Jové Mariona , Padró Teresa , Boada Jordi , Ortega Francisco , Ricart Wifredo , Pamplona Reinald , Badimón Lina , Portero‐Otín Manuel , Fernández‐Real José Manuel
Published: December 2016

Objective

Lipopolysaccharide binding protein (LBP) is part of a family of structurally and functionally related lipid transfer proteins. This study aimed to investigate the associations of LBP with the lipid composition of human adipose tissue.

Methods

Lipidomic analysis was performed in whole adipose tissue. To validate the associations found, LBP was knocked down (KD) in 3T3‐L1 adipocytes, and lipidomic profile was evaluated by nontargeted lipidomics.

Results

LBP gene expression was negatively associated with phosphatidylcholine, phosphatidylserine, and sphingomyelin relative abundance in vivo. LBP expression was also decreased in those samples with the highest docosahexanoic content, implicated in the resolution of inflammation. The KD of LBP (by ∼70%) led to sharp changes in the lipidome of adipocytes. Of note, specific plasmalogen species PE(O‐16:0/22:5), PE(38:2), odd chain glycerolipids, and cholesteryl linoleate were upregulated by LBP KD. In contrast, GM3 gangliosides, several ceramides, a triacylglycerol potentially containing arachidonate, and cholesteryl palmitate were downregulated by LBP KD.

Conclusions

LBP seems to play a role in the regulation of lipid composition of adipose tissue linked to resilience to inflammation.