bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration of GrassMaster II to estimate green and dry matter yield in Mediterranean pastures: effect of pasture moisture content
Authors: Serrano João , Shahidian Shakib , Marques da Silva José
Published: July 2016

Accurate assessment of standing pasture biomass in livestock production systems is a major factor for improving feed planning. Several tools are available to achieve this, including the GrassMaster II capacitance meter. This tool relies on an electrical signal, which is modified by the surrounding pasture. There is limited knowledge on how this capacitance meter performs in Mediterranean pastures. Therefore, we evaluated the GrassMaster II under Mediterranean conditions to determine (i) the effect of pasture moisture content (PMC) on the meter’s ability to estimate pasture green matter (GM) and dry matter (DM) yields, and (ii) the spatial variability and temporal stability of corrected meter readings (CMR) and DM in a bio-diverse pasture. Field tests were carried out with typical pastures of the southern region of Portugal (grasses, legumes, mixture and volunteer annual species) and at different phenological stages (and different PMC). There were significant positive linear relations between CMR and GM (r2 = 0.60, P < 0.01) and CMR and DM (r2 = 0.35, P < 0.05) for all locations (n = 347). Weak relationships were found for PMC (%) v. slope and coefficient of determination for both GM and DM. A significant linear relation existed for CMR v. GM and DM for PMC >80% (r2 = 0.57, P < 0.01, RMSE = 2856.7 kg ha–1, CVRMSE = 17.1% to GM; and r2 = 0.51, P < 0.01, RMSE = 353.7 kg ha–1, CVRMSE = 14.3% to DM). Therefore, under the conditions of this current study there exists an optimum PMC (%) for estimating both GM and DM with the GrassMaster II. Repeated-measurements taken at the same location on different dates and conditions in a bio-diverse pasture showed similar and stable patterns between CMR and DM (r2 = 0.67, P < 0.01, RMSE = 136.1 kg ha–1, CVRMSE = 6.5%). The results indicate that the GrassMaster II in-situ technique could play a crucial role in assessing pasture mass to improve feed planning under Mediterranean conditions.
Comparative evaluation of iron leach from different sources of fly ash under atmospherically relevant conditions
Authors: Borgatta Jaya , Paskavitz Amanda , Kim Deborah , Navea Juan G.
Published: July 2016

Environmental contextIron, a limiting nutrient of plankton in the ocean, is deposited to the sea from atmospheric aerosols. In particular, atmospheric acidic conditions promote dissolution of iron from fly ash, a by-product of coal-fired power plants. Here, we report that the iron leached from fly ash depends on its source region, and that the type of combustion process may influence the iron species mobilized. AbstractFly ash, an iron-containing by-product of coal-fired power plants, has been observed in atmospheric aerosol plumes. Under the acidic atmospheric conditions resulting from the uptake of atmospheric gases, iron leached from fly ash can impact global biogeochemical cycles. However, the fly ash source region, as well as its generating power plant, plays an important role in the amount, speciation and lability of iron. Yet no comparative studies have been made on iron leached from fly ash from different sources. This study reports the iron mobilisation by proton-promoted dissolution from well-characterised fly ash samples from three distinctive locations: the USA Midwest, north-east India and Europe. In addition, pH dependency was also investigated. Proton-promoted dissolution showed a variability between source regions with a relative iron leach in the order USA Midwestern>north-east Indian>European ash. In addition, the initial rate of iron leach suggests that source region is indeed a determining factor in the iron leaching capacity of fly ash, because dissolution from Midwestern fly ash is also faster than both European and Indian ash. Finally, the combustion process of fly ash proved to be significant for the iron speciation, given that well-combusted fly ash samples leached mostly Fe3+ rather than bioavailable Fe2+. The role of fly ash should therefore be taken into account in order to better understand the effects of combustion particles in atmospheric iron deposition.
Reducing the burden of sexually transmissible infections in Papua New Guinea requires strengthening of clinical services and engaging men
Authors: Hocking Jane S. , Vaughan Cathy , Lau Andrew , Machalek Dorothy A. , Graham Simon
Published: July 2016

In this edition of Sexual Health, Vallely et al. report the results of a cross-sectional prevalence survey of sexually transmissible infections (STIs) among women attending their first antenatal visit in three provinces of Papua New Guinea (PNG). This Editorial examines potential reasons for these high prevalence estimates and discusses strategies for addressing high STIs rates in PNG.
Influence of enhanced efficiency fertilisation techniques on nitrous oxide emissions and productivity response from urea in a temperate Australian ryegrass pasture
Authors: Suter H. C. , Sultana H. , Davies R. , Walker C. , Chen D.
Published: July 2016

The effect of a nitrification inhibitor on nitrous oxide (N2O) emissions across seasons, the effect of a urease inhibitor and a fine particle spray (both targeting ammonia (NH3) loss) on N2O emissions, and the potential for productivity benefits and efficiencies by using these enhanced efficiency fertilisers (EEFs) were investigated in temperate pastures. The study compared three treatments over an eight month period (April to December 2010): (1) urea (U), (2) urea with a nitrification inhibitor (3,4-dimethylpyrazole phosphate) (DMPP), and (3) urea with a urease inhibitor (N-(n-butyl) thiophosphoric triamide (NBTPT)) (GU). In autumn, when NH3 loss was predicted to be high, the effect of urea applied as a fine particle spray (containing urea, NBTPT and gibberellic acid (10g ha–1)) (FPA) on N2O emissions and productivity was determined.
N2O emissions from urea applied to pastures were low, and were larger in spring than autumn due to soil moisture and temperature. DMPP was an effective tool for mitigating N2O emissions, decreasing fertiliser-induced N2O emissions relative to urea by 76% over eight months. However, the urease inhibitor (NBTPT) (GU) increased N2O emissions from urea by 153% over eight months. FPA had no impact on N2O, but was only examined during periods of low emission (autumn). No significant biomass productivity, agronomic efficiency benefits, or improvements in apparent fertiliser recovery were observed with the DMPP and GU treatments. A significant biomass productivity benefit was observed with the FPA treatment 55 days after fertiliser was applied, most likely because of the gibberellic acid. The outcomes highlight that although DMPP effectively decreased N2O emissions it had no impact on biomass productivity compared with urea. The use of the GU increased N2O emissions by preserving NH3 in the soil. To avoid this a lower rate of N should be applied with the urease inhibitor.
The role of non-declining amphibian species as alternative hosts for Batrachochytrium dendrobatidis in an amphibian community
Authors: Stockwell Michelle P. , Bower Deborah S. , Clulow John , Mahony Michael J.
Published: July 2016

Context Pathogens with reservoir hosts have been responsible for most disease-induced wildlife extinctions because the decline of susceptible hosts does not cause the decline of the pathogen. The existence of reservoirs for Batrachochytrium dendrobatidis limits population recovery and conservation actions for threatened amphibians. As such, the effect of reservoirs on disease risk within host community assemblages needs to be considered, but rarely is. Aims In this study we aimed to determine if amphibian species co-occurring with the green and golden bell frog Litoria aurea, a declining species susceptible to B. dendrobatidis, act as alternate hosts. Methods We quantified B. dendrobatidis infection levels, sub-lethal effects on body condition and terminal signs of disease in amphibian communities on Kooragang Island and Sydney Olympic Park in New South Wales, Australia, where two of the largest remaining L. aurea populations persist. Key results We found L. aurea carried infections at a similar prevalence (6–38%) to alternate species. Infection loads ranged widely (0.01–11 107.3 zoospore equivalents) and L. aurea differed from only one alternate host species (higher median load in Litoria fallax) at one site. There were no terminal or sub-lethal signs of disease in any species co-occurring with L. aurea. Conclusion Our results suggest that co-occurring species are acting as alternate hosts to L. aurea and whether their presence dilutes or amplifies B. dendrobatidis in the community is a priority for future research. Implications For L. aurea and many other susceptible species, confirming the existence of reservoir hosts and understanding their role in community disease dynamics will be important for optimising the outcomes of threat mitigation and habitat creation initiatives for their long-term conservation.
Spontaneous wettability patterning via creasing instability
Authors: Chen Dayong , McKinley Gareth H. , Cohen Robert E.
Published: July 2016

Significance

Surfaces with patterned wettability contrast are important in many applications. Traditional fabrication methods rely on microfabrication technologies, which are generally not cost effective and are difficult to implement on curved surfaces. We show that wettability contrast can be patterned spontaneously on both flat and curved surfaces in a single step process by taking advantage of a reversible creasing instability. Moreover, the domain size, morphology, and wettability contrast can be controlled independently, yielding heterogeneous surfaces that show potential for generating high-throughput parallel microreactors and for harvesting water from humid air. This mechanical self-assembly approach can also lead to other functional materials beyond wettability patterning.
Spectral discrimination in color blind animals via chromatic aberration and pupil shape
Authors: Stubbs Alexander L. , Stubbs Christopher W.
Published: July 2016

Significance

We describe a means of obtaining spectral information using the principles of physical optics and an off-axis pupil shape without requiring spectrally distinct photoreceptor classes. The mechanism described here offers a possible solution to a long-standing puzzle in marine animals: cephalopods dramatically change color for both producing chromatically matched camouflage and signaling to conspecifics, despite having a single photoreceptor channel. The ability of these animals to achieve such excellent color matching to their surroundings, despite being “color blind” in the traditional sense, can be understood if they exploit chromatic aberration to deduce spectral information. The bizarre off-axis pupils of these animals can be understood as an adaptation that maximizes spectral information, even at the expense of image acuity.
Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and
Toxoplasma gondii
challenges with a single dose
Authors: Chahal Jasdave S. , Khan Omar F. , Cooper Christopher L. , McPartlan Justine S. , Tsosie Jonathan K. , Tilley Lucas D. , Sidik Saima M. , Lourido Sebastian , Langer Robert , Bavari Sina , Ploegh Hidde L. , Anderson Daniel G.
Published: July 2016

Significance

To respond better to evolving pathogens, sudden outbreaks, and individual patient needs, a flexible, safe, and efficient vaccine platform amenable to rapid production near the point of care is required. To this end, we created a fully synthetic, single-dose, adjuvant-free nanoparticle vaccine platform wherein modified dendrimer molecules nanoencapsulate antigen-expressing replicon mRNAs. Vaccines can be multiplexed and formed with multiple antigen-expressing replicons. After a single immunization, the rapid-production, contaminant-free vaccines elicit vital CD8
+
T-cell and antibody responses that fully protect against lethal exposures to several deadly pathogens, including Ebola virus, H1N1 influenza, and
Toxoplasma gondii
. We believe this technology may allow for rapid-response vaccines with broad efficacy that reduce the number and frequency of vaccinations, and healthcare worker burden.
Learning rational temporal eye movement strategies
Authors: Hoppe David , Rothkopf Constantin A.
Published: July 2016

Significance

In a dynamic world humans not only have to decide where to look but also when to direct their gaze to potentially informative locations in the visual scene. Little is known about how timing of eye movements is related to environmental regularities and how gaze strategies are learned. Here we present behavioral data establishing that humans learn to adjust their temporal eye movements efficiently. Our computational model shows how established properties of the visual system determine the timing of gaze. Surprisingly, a Bayesian learner only incorporating the scalar law of biological timing can fully explain the course of learning these strategies. Thus, humans use temporal regularities learned from observations to adjust the scheduling of eye movements in a nearly optimal way.
Measurements of extinct fission products in nuclear bomb debris: Determination of the yield of the Trinity nuclear test 70 y later
Authors: Hanson Susan K. , Pollington Anthony D. , Waidmann Christopher R. , Kinman William S. , Wende Allison M. , Miller Jeffrey L. , Berger Jennifer A. , Oldham Warren J. , Selby Hugh D.
Published: July 2016

Significance

This work describes an approach to postdetonation nuclear forensics involving isotopic measurements that allows for characterization of a nuclear detonation at any time. By performing high-precision measurements of stable isotope perturbations in nuclear bomb debris, it is possible to quantify short-lived fission products long after they have decayed below radiometric detection limits and become extinct. The extinct fission product concentrations can be used to reconstruct details of the nuclear device months to years after the detonation occurred. The approach is demonstrated by analysis of debris from the Trinity nuclear test and new estimates of the efficiency and yield of the historic test are presented.
Stochastic cycle selection in active flow networks
Authors: Woodhouse Francis G. , Forrow Aden , Fawcett Joanna B. , Dunkel Jörn
Published: July 2016

Significance

Nature often uses interlinked networks to transport matter or information. In many cases, the physical or virtual flows between network nodes are actively driven, consuming energy to achieve transport along different links. However, there are currently very few elementary principles known to predict the behavior of this broad class of nonequilibrium systems. Our work develops a generic foundational understanding of mass-conserving active flow networks. By merging previously disparate concepts from mathematical graph theory and physicochemical reaction rate theory, we relate the self-organizing behavior of actively driven flows to the fundamental topological symmetries of the underlying network, resulting in a class of predictive models with applicability across many biological scales.
A study of interstellar aldehydes and enols as tracers of a cosmic ray-driven nonequilibrium synthesis of complex organic molecules
Authors: Abplanalp Matthew J. , Gozem Samer , Krylov Anna I. , Shingledecker Christopher N. , Herbst Eric , Kaiser Ralf I.
Published: July 2016

Significance

Since the detection of the methylidyne radical (CH) in the interstellar medium nearly 80 y ago, about 200 molecules ranging from molecular hydrogen to fullerenes have been identified in interstellar and circumstellar environments, but the synthesis of complex organic molecules (COMs)––organics containing several atoms of carbon, hydrogen, nitrogen, and oxygen––has remained elusive to date. Here, we provide compelling evidence via laboratory experiments, computations, and modeling that the synthesis of COMs is driven by a cosmic-ray-triggered nonequilibrium chemistry within interstellar ices at temperatures as low as 10 K. These fundamental reaction mechanisms are of major significance to facilitate an understanding of the origin and evolution of the molecular universe.
Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis
Authors: Koopman Frieda A. , Chavan Sangeeta S. , Miljko Sanda , Grazio Simeon , Sokolovic Sekib , Schuurman P. Richard , Mehta Ashesh D. , Levine Yaakov A. , Faltys Michael , Zitnik Ralph , Tracey Kevin J. , Tak Paul P.
Published: July 2016

Significance

Rheumatoid arthritis (RA) is a chronic, prevalent, and disabling autoimmune disease that occurs when inflammation damages joints. Recent advances in neuroscience and immunology have mapped neural circuits that regulate the onset and resolution of inflammation. In one circuit, termed “the inflammatory reflex,” action potentials transmitted in the vagus nerve inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in RA. Although studied in animal models of arthritis and other inflammatory diseases, whether electrical stimulation of the vagus nerve can inhibit TNF production in humans has remained unknown. The positive mechanistic results reported here extend the preclinical data to the clinic and reveal that vagus nerve stimulation inhibits TNF and attenuates disease severity in RA patients.
Generalized nucleation and looping model for epigenetic memory of histone modifications
Authors: Erdel Fabian , Greene Eric C.
Published: July 2016

Significance

The genome-wide distribution of histone modifications influences cellular processes that involve access to the DNA. How cells establish and maintain these patterns is currently under debate. Understanding the underlying mechanisms is a prerequisite for predicting the cellular response to epigenetic drugs or programmed epigenetic editing. Here we simulated linear and looping-driven propagation mechanisms and compared the results to the spatiotemporal methylation profiles recently observed in fission yeast. We found that looping-driven spreading, which arises from productive collisions among nucleosomes and chromatin-bound histone modifiers, explains several key observations on engineered methylation domains. These findings point to important roles of chromatin-bound enzymes and chromatin dynamics in controlling modification patterns and epigenetic memory, which might not be restricted to repressive histone methylation.
DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
Authors: Presman Diego M. , Ganguly Sourav , Schiltz R. Louis , Johnson Thomas A. , Karpova Tatiana S. , Hager Gordon L.
Published: July 2016

Significance

The glucocorticoid receptor (GR) is a ligand-regulated transcription factor and one of the most targeted proteins in the pharmaceutical industry due to its powerful antiinflammatory actions. The search for side effects-free glucocorticoids relies exclusively on a model wherein the GR oligomerization state, whether a monomer or a dimer, dictates its transcriptional output. Here, we use an experimental approach where the GR–DNA interaction is observed in real time with a technique that allows the quantification of the oligomeric state of proteins in living cells. Unexpectedly, we find that DNA binding triggers tetramerization of the GR, which would be the truly activated form of the receptor. Our findings reveal a previously unidentified step in the glucocorticoid activation pathway.
Cytosine deamination and the precipitous decline of spontaneous mutation during Earth's history
Authors: Lewis Charles A. , Crayle Jesse , Zhou Shuntai , Swanstrom Ronald , Wolfenden Richard
Published: July 2016

Significance

Cytosine deamination appears to be largely responsible for spontaneous mutations in the modern world. Because of its sensitivity to temperature (Q
10
= 4), that reaction would have furnished a mechanism for rapid evolution on a warm earth. As the temperature fell from 100° to 25 °C, the rate of cytosine-based mutation would have fallen by a factor of more than 4,000, with a corresponding increase in the stability of genetic information. Other potentially mutagenic events are known to be even more sensitive to temperature, and would presumably have led to an even steeper decline in the rate of spontaneous mutation as the earth cooled.
Methylation interactions in
Arabidopsis
hybrids require RNA-directed DNA methylation and are influenced by genetic variation
Authors: Zhang Qingzhu , Wang Dong , Lang Zhaobo , He Li , Yang Lan , Zeng Liang , Li Yanqiang , Zhao Cheng , Huang Huan , Zhang Heng , Zhang Huiming , Zhu Jian-Kang
Published: July 2016

Significance

The epigenome influences gene regulation and genome evolution. The DNA methylomes of
Arabidopisis
hybrids are distinct from both parents; however, how the parental methylomes interact in hybrids is poorly understood. We discovered pervasive, nonadditive DNA methylation changes (“methylation interactions”) throughout the genome in hybrids of Col and C24
Arabidopsis
accessions. Methylation interactions correlated with high levels of small interfering RNAs, known components of the RNA-directed DNA methylation (RdDM) pathway. Indeed, abrogation of RdDM activity abolished methylation interactions in filial 1 (F1) hybrids. Methylation interactions have distinct polymorphism frequencies: Regions with increased methylation compared with the parents are highly conserved, whereas regions with decreased methylation are divergent. Our results show that RdDM is required for DNA methylation interactions in hybrids.
A Note on Popular Baby Names on the Social Security Website: An Important Onomastic Resource
Authors: Nuessel Frank
Published: July 2016

This note provides a road map for the use of the Social Security “Popular Baby Names” website. It gives information on how to navigate the site and utilize all of its features for research, decision making in the selection of a baby’s name, personal information, and many other possibilities.
Viking Mortuary Citations
Authors: Williams Howard
Published: July 2016

Introducing the European Journal of Archaeology's special issue ‘Mortuary Citations: Death and Memory in the Viking World’, this article outlines the justification and theoretical framework underpinning a new set of studies on Viking-age mortuary and commemorative practice as strategies of mortuary citation. The contributions to the collection are reviewed in relation to strengths and weaknesses in existing research and broader themes in mortuary archaeological research into memory work in past societies.
Citations in Stone: The Material World of Hogbacks
Authors: Williams Howard
Published: July 2016

This article explores a meshwork of citations to other material cultures and architectures created by the form and ornament of house-shaped early medieval recumbent stone monuments popularly known in Britain as ‘hogbacks’. In addition to citing the form and ornament of contemporary buildings, shrines, and tombs, this article suggests recumbent mortuary monuments referenced a far broader range of contemporary portable artefacts and architectures. The approach takes attention away from identifying any single source of origin for hogbacks. Instead, considering multi-scalar and multi-media references within the form and ornament of different carved stones provides the basis for revisiting their inherent variability and their commemorative efficacy by creating the sense of an inhabited mortuary space in which the dead are in dialogue with the living. By alluding to an entangled material world spanning Norse and Insular, ecclesiastical and secular spheres, hogbacks were versatile technologies of mortuary remembrance in the Viking Age.
‘Imbued with the Essence of the Owner’: Personhood and Possessions in the Reopening and Reworking of Viking-Age Burials
Authors: Klevnäs Alison Margaret
Published: July 2016

This article examines the wide range of grave disturbance practices seen in Viking-age burials across Scandinavia. It argues that the much-debated reopenings at high-profile sites, notably the Norwegian ‘royal’ mounds, should be seen against a background of widespread and varied evidence for burial reworking in Scandinavia throughout the first-millennium AD and into the Middle Ages. Interventions into Viking-age graves are interpreted as disruptive, intended to derail practices of memory-creation set in motion by funerary displays and monuments. However, the reopening and reworking of burials were also mnemonic citations in their own right, using a recurrent set of practices to make heroic, mythological, and genealogical allusions. The retrieval of portable artefacts was a key element in this repertoire, and in this article I use archaeological and written sources to explore the particular concepts of ownership which enabled certain possessions to work as material citations appropriating attributes of dead persons for living claimants.
SIFORM: shared informative factor models for integration of multi-platform bioinformatic data
Authors: An Xuebei , Hu Jianhua , Do Kim-Anh
Published: July 2016

Motivation: High-dimensional omic data derived from different technological platforms have been extensively used to facilitate comprehensive understanding of disease mechanisms and to determine personalized health treatments. Numerous studies have integrated multi-platform omic data; however, few have efficiently and simultaneously addressed the problems that arise from high dimensionality and complex correlations.

Results: We propose a statistical framework of shared informative factor models that can jointly analyze multi-platform omic data and explore their associations with a disease phenotype. The common disease-associated sample characteristics across different data types can be captured through the shared structure space, while the corresponding weights of genetic variables directly index the strengths of their association with the phenotype. Extensive simulation studies demonstrate the performance of the proposed method in terms of biomarker detection accuracy via comparisons with three popular regularized regression methods. We also apply the proposed method to The Cancer Genome Atlas lung adenocarcinoma dataset to jointly explore associations of mRNA expression and protein expression with smoking status. Many of the identified biomarkers belong to key pathways for lung tumorigenesis, some of which are known to show differential expression across smoking levels. We discover potential biomarkers that reveal different mechanisms of lung tumorigenesis between light smokers and heavy smokers.

Availability and Implementation: R code to implement the new method can be downloaded from http://odin.mdacc.tmc.edu/jhhu/

Contact:  jhu@mdanderson.org
Whole-pelvic radiotherapy with spot-scanning proton beams for uterine cervical cancer: a planning study
Authors: Hashimoto Shingo , Shibamoto Yuta , Iwata Hiromitsu , Ogino Hiroyuki , Shibata Hiroki , Toshito Toshiyuki , Sugie Chikao , Mizoe Jun-etsu
Published: July 2016

The aim of this study was to compare the dosimetric parameters of whole-pelvic radiotherapy (WPRT) for cervical cancer among plans involving 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or spot-scanning proton therapy (SSPT). The dose distributions of 3D-CRT-, IMRT-, and SSPT-based WPRT plans were compared in 10 patients with cervical cancer. All of the patients were treated with a prescribed dose of 50.4 Gy in 1.8-Gy daily fractions, and all of the plans involved the same planning target volume (PTV) constrictions. A 3D-CRT plan involving a four-field box, an IMRT plan involving seven coplanar fields, and an SSPT plan involving four fields were created. The median PTV D95% did not differ between the 3D-CRT, IMRT and SSPT plans. The median conformity index 95% and homogeneity index of the IMRT and SSPT were better than those of the 3D-CRT. The homogeneity index of the SSPT was better than that of the IMRT. SSPT resulted in lower median V20 values for the bladder wall, small intestine, colon, bilateral femoral heads, skin, and pelvic bone than IMRT. Comparing the Dmean values, SSPT spared the small intestine, colon, bilateral femoral heads, skin and pelvic bone to a greater extent than the other modalities. SSPT can reduce the irradiated volume of the organs at risk compared with 3D-CRT and IMRT, while maintaining excellent PTV coverage. Further investigations of SSPT are warranted to assess its role in the treatment of cervical cancer.
Spillovers in Local Banking Markets
Authors: Garmaise Mark J. , Natividad Gabriel
Published: July 2016

How are neighboring firms affected when a bank learns more about a given firm? We analyze exchange-rate-induced movements of Peruvian firms across a threshold that governs their regulatory treatment by banks. Firms that cross the threshold supply more information to their banks and experience a substantial increase in financing. We find positive spillover effects: the neighbors of the above-threshold firms also experience increased financing. These spillovers are confined to neighbors sharing a bank, and the performance of new loans to these neighbors improves, suggesting that the bank has become better informed about other local firms.

Received October 15, 2015; accepted May 16, 2016 by Editor Efraim Benmelech.
Pharmacokinetic Considerations in Designing Pediatric Studies of Proteins, Antibodies, and Plasma-Derived Products
Authors: Mahmood Iftekhar
Published: July 2016

Ignoring the principles of pediatric pharmacology can have serious consequences. Therefore, it is necessary to understand and recognize the impact of developmental processes in children. It is now well recognized that age and the disease state can alter the pharmacokinetics (PKs) of a drug, as a result adjustment in dosing regimen in children as compared with the adults is essential. This review emphasizes on the importance of PK studies in pediatric population for macromolecules. Macromolecules differ from small molecules in many respects, and it is necessary to have a thorough understanding of the behavior of macromolecules in the body across different age groups. The review highlights that like small molecules, the PKs of macromolecules in pediatric population also differ from adults, hence, a PK study is essential in pediatrics for appropriate dose selection in this population. The review also takes a critical look on the many extrapolation techniques to predict PK parameters in pediatrics from adult data.
Microglial Inhibition Influences XCL1/XCR1 Expression and Causes Analgesic Effects in a Mouse Model of Diabetic Neuropathy
Authors: Zychowska Magdalena , Rojewska Ewelina , Piotrowska Anna , Kreiner Grzegorz , Mika Joanna
Published: July 2016

Background

Recent studies indicated the involvement of some chemokines in the development of diabetic neuropathy; however, participation of the chemokine-C-motif ligand (XCL) subfamily remains unknown. The goal of this study was to examine how microglial inhibition by minocycline hydrochloride (MC) influences chemokine-C-motif ligand 1 (XCL1)–chemokine-C-motif receptor 1 (XCR1)/G protein–coupled receptor 5 expression and the development of allodynia/hyperalgesia in streptozotocin-induced diabetic neuropathy.

Methods

The studies were performed on streptozotocin (200 mg/kg, intraperitoneally)-induced mouse diabetic neuropathic pain model and primary glial cell cultures. The MC (30 mg/kg, intraperitoneally) was injected two times daily until day 21. XCL1 and its neutralizing antibody were injected intrathecally, and behavior was evaluated with von Frey and cold plate tests. Quantitative analysis of protein expression of glial markers, XCL1, and/or XCR1 was performed by Western blot and visualized by immunofluorescence.

Results

MC treatment diminished allodynia (0.9 ± 0.1 g; n = 7 vs. 3.8 ± 0.7 g; n = 7) and hyperalgesia (6.5 ± 0.6 s; n = 7 vs. 16.5 ± 1 s; n = 7) in the streptozotocin-induced diabetes. Repeated MC administration prevented microglial activation and inhibited the up-regulation of the XCL1/XCR1 levels. XCL1 administration (10 to 500 ng/5 μl; n = 9) in naive mice enhanced nociceptive transmission, and injections of neutralizing XCL1 (4 to 8 μg/5 μl; n = 10) antibody into the mice with diabetic neuropathic pain diminished allodynia/hyperalgesia. Microglia activation evoked in primary microglial cell cultures resulted in enhanced XCL1 release and XCR1 expression. Additionally, double immunofluorescence indicated the widespread coexpression of XCR1-expressing cells with spinal neurons.

Conclusions

In diabetic neuropathy, declining levels of XCL1 evoked by microglia inhibition result in the cause of analgesia. The putative mechanism corroborating this finding can be related to lower spinal expression of XCR1 together with the lack of stimulation of these XCR1 receptors, which are localized on neurons.
Duloxetine and Subacute Pain after Knee Arthroplasty when Added to a Multimodal Analgesic Regimen
Authors: YaDeau Jacques T. , Brummett Chad M. , Mayman David J. , Lin Yi , Goytizolo Enrique A. , Padgett Douglas E. , Alexiades Michael M. , Kahn Richard L. , Jules-Elysee Kethy M. , Fields Kara G. , Goon Amanda K. , Gadulov Yuliya , Westrich Geoffrey
Published: July 2016

Background

Duloxetine is effective for chronic musculoskeletal and neuropathic pain, but there are insufficient data to recommend the use of antidepressants for postoperative pain. The authors hypothesized that administration of duloxetine for 15 days would reduce pain with ambulation at 2 weeks after total knee arthroplasty.

Methods

In this triple-blinded, randomized, placebo-controlled trial, patients received either duloxetine or placebo for 15 days, starting from the day of surgery. Patients also received a comprehensive multimodal analgesic regimen including neuraxial anesthesia, epidural analgesia, an adductor canal block, meloxicam, and oxycodone/acetaminophen as needed. The primary outcome was the pain score (0 to 10 numeric rating scale) with ambulation on postoperative day 14.

Results

One hundred six patients were randomized and analyzed. On day 14, duloxetine had no effect on pain with ambulation; mean pain was 3.8 (SD, 2.3) for placebo versus 3.5 (SD, 2.1) for duloxetine (difference in means [95% CI], 0.4 [−0.5 to 1.2]; P = 0.386). Symptoms potentially attributable to duloxetine discontinuation at study drug completion (nausea, anxiety) occurred among nine patients (duloxetine) and five patients (placebo); this was not statistically significant (P = 0.247). Statistically significant secondary outcomes included opioid consumption (difference in mean milligram oral morphine equivalents [95% CI], 8.7 [3.3 to 14.1], P = 0.002 by generalized estimating equation) over the postoperative period and nausea on day 1 (P = 0.040). There was no difference in other side effects or in anxiety and depression scores.

Conclusions

When included as a part of a multimodal analgesic regimen for knee arthroplasty, duloxetine does not reduce subacute pain with ambulation.
Novel Approach of Treatment of Pilonidal Sinus Disease With Thrombin Gelatin Matrix as a Sealant
Authors: Elbanna Hosam G. , Emile Sameh Hany , Youssef Mohamed , Thabet Waleed , El-Hamed Tito M. Abd , Ghnnam Wagih M.
Published: July 2016

BACKGROUND:

Sacrococcygeal pilonidal sinus disease is a condition caused by insertion of fallen hair shafts into the skin. Different types of operations have been described for the management of pilonidal sinus, yet none of them have proven to be superior to the others. Recently, sealants like fibrin glue have been successfully used.

OBJECTIVE:

This study aimed to assess the efficacy of thrombin gelatin matrix as a new sealant for pilonidal sinus treatment.

DESIGN:

This was a prospective study conducted from March 2013 to March 2015.

SETTINGS:

The study was conducted in private hospitals in Mansoura City.

PATIENTS:

The study included 36 male patients (72%) and 14 female patients (28%), with a median age of 22 years.

INTERVENTIONS:

Fifty patients with pilonidal sinus were admitted and treated with thrombin gelatin matrix injection.

MAIN OUTCOME MEASURES:

Incidence and time of pilonidal sinus recurrence, postoperative pain and complications, duration of hospital stay, healing status, and time to return to work were recorded.

RESULTS:

The median duration of symptoms was 13 months, median operative time was 18 minutes, and median hospital stay was 6 hours. All of the procedures were conducted as day-case surgeries. Median follow-up duration was 24 months. Three patients (6%) had a breakdown of the sealant, and the wound was managed with daily dressings. Recurrence at 1 year was observed in 2 patients (4%). A total of 96% of patients were satisfied with the outcome of the procedure, and 92% of patients resumed their daily activities within 3 days.

LIMITATIONS:

Follow-up for a longer duration is required to ascertain the efficacy of this new technique. The cost of this treatment might be challenging for resource-limited communities.

CONCLUSIONS:

Management of pilonidal sinus using thrombin gelatin matrix, despite being expensive, is an effective, simple treatment that is easy to perform and associated with low recurrence rate, minimal morbidity, and rapid recovery.
Juvenile Polyps in Denmark From 1995 to 2014
Authors: Jelsig Anne Marie , Ousager Lilian Bomme , Brusgaard Klaus , Qvist Niels
Published: July 2016

BACKGROUND:

Juvenile polyps in the large bowel are rare but the most common type of polyp in children. The prevalence and incidence are unknown, and few studies exist on the occurrence in adults. They are considered not to harbor any malignant potential unless they are part of the hereditary juvenile polyposis syndrome.

OBJECTIVE:

We aimed to study the demographics of juvenile polyps in Denmark in a 20-year period from 1995 to 2015 in both adults and children. This is the first report on the occurrence, anatomic localization, and reoccurrence of these polyps in a whole population.

DESIGN:

Data from all of the patients who had been diagnosed with 1 or more juvenile polyp from January 1, 1995, until December 31, 2014, were obtained.

SETTINGS:

The study was conducted based on patients registered in the nationwide pathological register in Denmark, the Danish Pathology Data Bank.

PATIENTS:

We detected a total of 1772 patients who had 2108 juvenile polyps removed (male = 946; female = 826).

MAIN OUTCOME MEASURES:

We noted the sex, age, number, reoccurrence, and localization of polyps.

RESULTS:

Of the detected juvenile polyps ≈75% were detected in adults and ≈25% in children. Approximately 96% of the patients had a single juvenile polyp without reoccurrence, 1% fulfilled the diagnostic criteria for juvenile polyposis syndrome (more than 5 polyps), and 5% had multiple juvenile polyps (2–5 polyps). The incidence in the Danish population can be estimated to be between 1:45,000 and 1:65,000.

LIMITATIONS:

Miscoding or misclassification in the register cannot be ruled out. We only have data for the 20-year period, limiting the evaluation of reoccurrence, and no data for the endoscopic removal procedures.

CONCLUSIONS:

We conclude that juvenile polyps are rare, with the majority found in adults, and most often found as a single juvenile polyp. A subgroup of patients have juvenile polyposis syndrome, which requires follow-up.
A Nomogram to Predict Lymph Node Positivity Following Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer
Authors: Newton Andrew D. , Li Jiaqi , Jeganathan Arjun N. , Mahmoud Najjia N. , Epstein Andrew J. , Paulson E. Carter
Published: July 2016

BACKGROUND:

Patients with locally advanced rectal cancer typically receive neoadjuvant chemoradiation followed by total mesorectal excision. Other treatment approaches, including transanal techniques and close surveillance, are becoming increasingly common following positive responses to chemoradiation. Lack of pathologic lymph node staging is one major disadvantage of these novel strategies.

OBJECTIVE:

The purposes of this study were to determine clinicopathologic factors associated with positive lymph nodes following neoadjuvant chemoradiation for rectal cancer and to create a nomogram using these factors to predict rates of lymph node positivity.

DESIGN:

This is a retrospective cohort analysis.

SETTINGS:

This study used the National Cancer Database.

PATIENTS:

Patients aged 18 to 90 with clinical stage T3/T4, N0, M0 or Tany, N1-2, M0 adenocarcinoma of the rectum who underwent neoadjuvant chemoradiation before total mesorectal excision from 2010 to 2012 were identified.

MAIN OUTCOME MEASURES:

The primary outcome measure was lymph node positivity after neoadjuvant chemoradiation for locally advanced rectal cancer. Bivariate and multivariate analyses were used to determine the associations of clinicopathologic variables with lymph node positivity.

RESULTS:

Eight thousand nine hundred eighty-four patients were included. Young age, lower Charlson score, mucinous histology, poorly differentiated and undifferentiated tumors, the presence of lymphovascular invasion, elevated CEA level, and clinical lymph node positivity were significantly predictive of pathologic lymph node positivity following neoadjuvant chemoradiation. The predictive accuracy of the nomogram is 70.9%, with a c index of 0.71. There was minimal deviation between the predicted and observed outcomes.

LIMITATIONS:

This study is retrospective, and it cannot be determined when in the course of treatment the data were collected.

CONCLUSIONS:

We created a nomogram to predict lymph node positivity following neoadjuvant chemoradiation for locally advanced rectal cancer that can serve as a valuable complement to imaging to aid clinicians and patients in determining the best treatment strategy.
Fetal Heart Rate Response to Maternal Exercise
Authors: MONGA MANJU
Published: July 2016

Current guidelines regarding recommended exercise in pregnancy appear consistent with reported research regarding fetal heart changes in response to maternal exercise. Fetal heart rate increases during pregnancy, but maternal exercise appears well tolerated if performed in uncomplicated pregnancies and not in the supine position. Maximal levels of exercise that are well tolerated by the fetus have not yet been well defined; however, recent literature suggests that sustained exercise during pregnancy may have beneficial effects on autonomic control of fetal heart rate and variability that may lead to long-term health benefits.
The diagnostic accuracy of faecal calprotectin and small bowel capsule endoscopy and their correlation in suspected isolated small bowel Crohn’s disease
Authors: Hale Melissa F. , Drew Kaye , McAlindon Mark E. , Sidhu Reena
Published: July 2016

Introduction

Faecal calprotectin (FC) is less accurate at identifying inflammation in the small bowel than in the colon. Small bowel capsule endoscopy (SBCE) is a useful tool to detect small bowel inflammation. We investigated the diagnostic accuracy of FC and SBCE and their correlation in patients with suspected isolated small bowel Crohn’s disease.

Patients and methods

This was performed as a prospective single centre study including patients attending for SBCE with suspected small bowel Crohn’s disease. Patient demographics, symptoms, medications and blood parameters were collected. Capsule endoscopy findings were analysed against calprotectin values, final diagnosis and blood parameters.

Results

A total of 146 patients were included (99 females and 47 males) with a mean age of 38±14 years. FC of more than 50 mg/kg was not significantly associated with clinically relevant capsule endoscopy findings (P=0.25), correlation coefficient was 0.11. Sensitivity, specificity, positive and negative predictive values for FC at a cut-off of more than 50 mg/kg were 88.9% [95% confidence interval (CI): 65.3–98.6], 25.0% (95% CI: 17.8–33.4), 14.3 (95% CI: 8.4–22.2) and 94.1% (95% CI: 80.3–99.3), respectively. A raised FC was not significantly associated with an elevated C-reactive protein or the presence of anaemia (P=0.19 and 0.10, respectively).

Conclusion

FC performs modestly as a screening test to exclude small bowel inflammation. However, we recommend interpretation within the overall clinical context to avoid overlooking the infrequent patient with small bowel inflammation and a negative FC.
Molecular Analysis of Tumor Cell Components in Pilocytic Astrocytomas, Gangliogliomas, and Oligodendrogliomas
Authors: Mesturoux Laura , Durand Karine , Pommepuy Isabelle , Robert Sandrine , Caire François , Labrousse François
Published: July 2016

Gliomas and glioneuronal tumors are histologically polymorphous tumors. They can harbor a clear cell “oligodendroglial-like” component that can be difficult to distinguish from tumor cells of oligodendrogliomas or neurons, particularly on small samples. Thus, knowledge of the pattern of molecular markers in different tumor cell components is essential to ensure reliable diagnosis. Here, we screened 14 pilocytic astrocytomas (PA), 12 gangliogliomas, and 13 oligodendrogliomas for the KIAA1549-BRAF fusion gene, IDH1/2 mutations, and 1p19q losses in various areas of interest representative of the different tumor cell components. Molecular patterns were analyzed according to histologic type, tumor cell components, and clinical data. The KIAA1549-BRAF fusion gene was detected only in 8 out of 11 PAs (73%) and in 3 out of 9 gangliogliomas (33%) (P=0.003). Interestingly, all of the studied areas of interest within the same tumor exhibited the same KIAA1549-BRAF fusion gene status. IDH1-R132H and 1p19q loss were found only in 12 out of the 13 oligodendrogliomas (P<0.0001). Our study shows that cellular polymorphism in PAs and gangliogliomas does not affect the results of molecular analysis investigating the status of the KIAA1549-BRAF fusion gene. Thus, this molecular analysis can be reliably used even if the sample size is limited and the selection of different tumor areas is not possible.
Follistatin Expression in Human Invasive Breast Tumors: Pathologic and Clinical Associations
Authors: Couto Henrique L. , Dela Cruz Cynthia , Buzelin Marcelo A. , Toppa Nivaldo H. , Wainstein Alberto J. , Reis Fernando M.
Published: July 2016

Follistatin is a potent native activin antagonist that is expressed in the normal mammary gland and in different breast proliferative diseases. Despite experimental evidence that follistatin can modulate the breast cancer cell cycle, the clinical significance of follistatin expression in these tumors is unknown. The aim of this study was to correlate the intensity of follistatin expression in invasive breast cancer with some of its clinical and pathologic features, such as the disease stage and the hormonal receptor status. Paraffin blocks of tumor samples that had been fixed in buffered formalin were obtained from 154 women subjected to surgery for breast cancer between 2008 and 2012. Sections from all paraffin blocks were cut and processed together by immunohistochemistry using a commercial monoclonal antibody to human follistatin. The intensity of follistatin staining was unrelated to the menopausal status, the disease stage, the grade, progesterone receptor expression, and local or systemic recurrence. However, follistatin immunoreactivity was significantly stronger in estrogen receptor (ER)-negative tumors than in ER-positive tumors. These findings suggest that follistatin expression in invasive breast cancer is unrelated to the disease severity and the risk of recurrence, but is more intense in ER-negative tumors.