bluuebunny/crossref_metadata_2025 huggingface dataset:
Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients
Authors: Nové‐Josserand Raphaële , Grard Soazic , Auzou Lila , Reix Philippe , Murris‐Espin Marlène , Brémont François , Mammar Benyebka , Mely Laurent , Hubert Dominique , Durieu Isabelle , Burgel Pierre‐Régis
Published: October 2016

Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first‐line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti‐IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab‐related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow‐up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid‐sparing therapy in CF patients with ABPA. A randomized‐controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost‐effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190–197. © 2016 Wiley Periodicals, Inc.
Antenatal smoking and substance‐misuse, infant and newborn response to hypoxia
Authors: Ali Kamal , Rosser Thomas , Bhat Ravindra , Wolff Kim , Hannam Simon , Rafferty Gerrard F. , Greenough Anne
Published: October 2016

Objectives

To determine at the peak age for sudden infant death syndrome (SIDS) the ventilatory response to hypoxia of infants whose mothers substance misused in pregnancy (SM infants), or smoked during pregnancy (S mothers) and controls whose mothers neither substance misused or smoked. In addition, we compared the ventilatory response to hypoxia during the neonatal period and peak age of SIDS.

Working hypothesis

Infants of S or SM mothers compared to control infants would have a poorer ventilatory response to hypoxia at the peak age of SIDS.

Study Design

Prospective, observational study.

Patient‐subject selection

Twelve S; 12 SM and 11 control infants were assessed at 6–12 weeks of age and in the neonatal period.

Methodology

Changes in minute volume, oxygen saturation, heart rate, and end tidal carbon dioxide levels on switching from breathing room air to 15% oxygen were assessed. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines.

Results

The S and SM infants had a greater decline in minute volume (P = 0.037, P = 0.016, respectively) and oxygen saturation (P = 0.031) compared to controls. In all groups, the magnitude of decline in minute volume in response to hypoxia was higher in the neonatal period compared to at 6–12 weeks (P < 0.001).

Conclusions

Both maternal substance misuse and smoking were associated with an impaired response to a hypoxic challenge at the peak age for SIDS. The hypoxic ventilatory decline was more marked in the neonatal period compared to the peak age for SIDS indicating a maturational effect. Pediatr Pulmonol. 2017;52:650–655. © 2016 Wiley Periodicals, Inc.
Perchlorate Residues Emitted during the Use and Demilitarization of Simulators
Authors: Brochu Sylvie , Turcotte‐Savard Marc‐Olivier
Published: October 2016

This study assessed the dispersion of perchlorate and dioxins and furans (PCDD/PCDF) residues following the use or demilitarization by blow‐in‐place of the Groundburst Simulator (GB) C1A1 and the Thunderflash (TF) C1A1 commonly used in the Canadian Armed Forces (CAF). The amount of unburned perchlorate residues per pyrotechnic device reached 0.8 and 43 mg for the regular use of TF and the GB, respectively. Their demilitarization by blow‐in‐place operations led to higher dispersion of unburned perchlorate residues, up to 6 and 2300 mg per TF and GB, respectively. Very high deposition rates were obtained for water‐soaked items: up to 460 mg per TF and up to 6600 mg for the GB. Dioxins and furans reached a maximum of 1 pg of Toxic Equivalent (TEQ) for the regular use, and 9 pg TEQ for the BIP operations. Based on these results, it is recommended to find alternate ways to demilitarize malfunctioning and weathered items found in military ranges and training areas.
Germinal‐center kinase‐like kinase co‐crystal structure reveals a swapped activation loop and C‐terminal extension
Authors: Marcotte Douglas , Rushe Mia , M. Arduini Robert , Lukacs Christine , Atkins Kateri , Sun Xin , Little Kevin , Cullivan Michael , Paramasivam Murugan , Patterson Thomas A. , Hesson Thomas , D. McKee Timothy , May‐Dracka Tricia L. , Xin Zhili , Bertolotti‐Ciarlet Andrea , Bhisetti Govinda R. , Lyssikatos Joseph P. , Silvian Laura F.
Published: October 2016

Germinal‐center kinase‐like kinase (GLK, Map4k3), a GCK‐I family kinase, plays multiple roles in regulating apoptosis, amino acid sensing, and immune signaling. We describe here the crystal structure of an activation loop mutant of GLK kinase domain bound to an inhibitor. The structure reveals a weakly associated, activation‐loop swapped dimer with more than 20 amino acids of ordered density at the carboxy‐terminus. This C‐terminal PEST region binds intermolecularly to the hydrophobic groove of the N‐terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an “active” kinase, including the salt bridge between the C‐helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P‐loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.
Effect of fuel concentration and force on collective transport by a team of dynein motors
Authors: Takshak Anjneya , Roy Tanushree , Tandaiya Parag , Kunwar Ambarish
Published: October 2016

Motor proteins are essential components of intracellular transport inside eukaryotic cells. These protein molecules use chemical energy obtained from hydrolysis of ATP to produce mechanical forces required for transporting cargos inside cells, from one location to another, in a directed manner. Of these motors, cytoplasmic dynein is structurally more complex than other motor proteins involved in intracellular transport, as it shows force and fuel (ATP) concentration dependent step‐size. Cytoplasmic dynein motors are known to work in a team during cargo transport and force generation. Here, we use a complete Monte‐Carlo model of single dynein constrained by in vitro experiments, which includes the effect of both force and ATP on stepping as well as detachment of motors under force. We then use our complete Monte‐Carlo model of single dynein motor to understand collective cargo transport by a team of dynein motors, such as dependence of cargo travel distance and velocity on applied force and fuel concentration. In our model, cargos pulled by a team of dynein motors do not detach rapidly under higher forces, confirming the experimental observation of longer persistence time of dynein team on microtubule under higher forces.
The prognostic value of stromal FK506‐binding protein 1 and androgen receptor in prostate cancer outcome
Authors: Leach Damien A. , Trotta Andrew P. , Need Eleanor F. , Risbridger Gail P. , Taylor Renea A. , Buchanan Grant
Published: October 2016

BACKGROUND

Improving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer‐specific survival, and that stromal AR reduces metastasis. For this paper, we tested the hypothesis that the AR‐regulated gene FKBP51 could be used as a marker of AR activity to better predict outcome.

METHODS

Using immunohistochemistry on a cohort of 64 patient‐matched benign and malignant prostate tissues, we assessed patient outcome by FKBP51 and AR levels. Immunoblot and RT‐qPCR were used to demonstrate androgen regulation of FKBP51 in primary and primary human prostatic fibroblasts and fibroblast cell‐lines. RESULTS. As predicted by FKBP51 level, high AR activity in cancer stroma was associated with longer median survival (1,306 days) compared with high AR alone (699 days), whereas those with low AR and/or low FKBP51 did poorly (384 and 338 days, respectively). Survival could not be predicted on the basis cancer epithelial AR levels or activity, and was not associated with immunoreactivity in patient matched benign tissues.

CONCLUSION

FKBP51 improves the ability of stromal AR to predict prostate cancer‐specific mortality. By adding additional immunological assessment, similar to what is already in place in a number of other cancers, we could better serve patients with prostate cancer in prognosis and informed treatment choices. Prostate 77:185–195, 2017. © 2016 Wiley Periodicals, Inc.
Detecting pyrethroid resistance in predatory mites inhabiting soil and litter: an in vitro test
Authors: El Adouzi Marine , Bonato Olivier , Roy Lise
Published: October 2016

BACKGROUND

While resistance against insecticides is widely known in pest arthropods, it remains poorly known in non‐target arthropods of the same agrosystems. This may be of crucial importance in the context of organic pest management or integrated pest management. First, stopping of pesticide pressure during farm conversion may lead to important rearrangements of non‐target communities due to fitness cost of resistance in populations of some species. Second, resistant biological agents may be useful to farms with low synthetic pesticide use. Communities of mesostigmatid mites, encompassing numerous predatory species, are supposed to be involved in important ecological processes in both crop soils and animal litter/manure.

RESULTS

Here we provide a tarsal contact method for assessing resistance in different populations from various species of mesostigmatid mites. Analyses of data from repeated tests on three populations from different mesostigmatid families proved the method to be robust and able to generate consistent and reliable mortality percentages according to insecticide concentration.

CONCLUSION

Our bioassay system allows for both one‐shot estimate of pyrethroid sensitivity in mite populations and estimation of how it changes over time, making possible survival analyses and assessment of recovery from knockdown. The rating system retained makes it possible to score response to insecticides in a consistent and standard way in species from different mesostigmatid families. © 2016 Society of Chemical Industry
Diagnosis, assessment and management of headache
Authors: Fontebasso Manuela
Published: October 2016

Headache is a common presentation in primary care, but assessment and treatment can be complex. This article provides an overview of the current guidelines on diagnosis and management of headache and migraine, with an emphasis on a patient‐centred approach.
Anticipatory prescribing for end of life care
Authors: Ogden Joy
Published: October 2016

In patients receiving end of life care at home, anticipatory prescribing can provide a back‐up for when urgent symptom control is needed. This article discusses the practicalities surrounding anticipatory prescribing, including the use of ‘just in case’ boxes, the role of family members and how to handle difficult conversations with patients.
Management of type 1 and type 2 diabetes requiring insulin
Authors: Abiola Dorothy , Sathyapalan Thozhukat , Hepburn David
Published: October 2016

Insulin is a required therapy for people with type 1 diabetes, and its use in the treatment of type 2 diabetes has been increasing in recent years. This article discusses the main types of insulin currently available, their properties and their role in the management of both type 1 and type 2 diabetes.
Immune activation with peptide assemblies carrying Lewis y tumor‐associated carbohydrate antigen
Authors: Yamazaki Yuji , Watabe Naoki , Obata Hiroaki , Hara Eri , Ohmae Masashi , Kimura Shunsaku
Published: October 2016

Molecular assemblies varying morphologies in a wide range from spherical micelle, nanosheet, curved sheet, nanotube and vesicle were prepared and loaded with Lewis y (Ley) tumor‐associated carbohydrate antigen on the assembly surface. The molecular assemblies were composed of poly(sarcosine)m‐block‐poly(L‐lactic acid)30 (m = 15 or 50, Lactosome), poly(sarcosine)m‐block‐(D/L‐Leu‐Aib)n (m = 22 or 30, n = 6 or 8) and their combinations. The molecular assemblies carrying Ley on the surface were administered in BALB/c nu/nu mice. The major epitopes of the molecular assemblies are commonly Ley and poly(sarcosine). IgM productions upon administrations of the molecular assemblies were assayed by ELISA, showing that anti‐poly(sarcosine) IgM was highly produced by Lactosome of spherical micelle but with a negligible amount of anti‐Ley IgM. On the other hand, the nanosheet of the interdigitated monolayer triggered the production of anti‐Ley IgM but with less anti‐poly(sarcosine) IgM production. Taken together, IgM specificity differs according to the molecular environment of the epitopes in the molecular assemblies. The antigenicity of poly(sarcosine) was augmented in polymeric micelle providing loose environment for B cells to penetrate in, whereas a high density of Ley on the molecular assembly was required for anti‐Ley IgM production. The antigenicity of Ley is therefore dependent on the molecular assemblies on which Ley is displayed on the surface. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Structural and electric properties of AgGaTe2 layers prepared using mixed source of Ag2Te and Ga2Te3
Authors: Uruno Aya , Kobayashi Masakazu
Published: October 2016

AgGaTe2 layers were prepared on Si substrates by a closed space sublimation method using a mixed powder source of Ag2Te and Ga2Te3. Ag2Te buffer layer deposition was introduced to eliminate melt‐back etching. The effect of the molar ratio of Ag2Te and Ga2Te3 in the mixed source on the crystallinity of the AgGaTe2 layer was investigated. The composition and the phase of the layer was found to change depending on the molar ratio in the deposits, which could be controlled by the source molar ratio along with the Ag2Te buffer layer thickness. It was confirmed that (112) oriented uniform AgGaTe2 layer with an abrupt interface between AgGaTe2 and Si was formed after those parameters were tuned. The obtained layer exhibited the acceptor concentration of around 2.5 × 1016 cm−3. A solar cell was fabricated using the p‐AgGaTe2/n‐Si heterojunction, and exhibited a conversion efficiency of 1.15%.
Tunable ultrasensitive terahertz sensing based on surface plasmon polariton of doped monolayer graphene
Authors: Huang Yi , Zhong Shuncong , Yao Haizi , Cui Daxiang
Published: October 2016

We reported the surface plasmon resonance (SPR) on doped monolayer graphene (MLG) for terahertz (THz) sensing of refractive index of testing samples using a prism‐coupling attenuated total reflection configuration. The theoretical detection range and sensitivity of the THz plasmonic sensor were investigated. The sensor performance in terms of variation of detection accuracy with different refractive index was explored. It was demonstrated that the Fermi level energy of MLG and also the gap distance between the prism base and the MLG had great effects on the performance of THz sensing. The gap distance not only caused the coupling resonance frequency shift in the reflection spectrum, but also affected the full width at half maxima (FWHM) of the SPR curve. The incident angle of THz radiation was also the key impact factor of the detection accuracy of the sensor. The effective SPR frequency could be tuned by controlling the incident angle or the Fermi level energy. The results revealed the maximum sensitivity of the THz plasmonic sensor up to 6.65 THz RIU−1 with a figure of merit (FOM) of 1187 RIU−1 for Fermi level energy ranges from 0.4 to 1.2 eV, making the sensor potential for ultra‐sensitive SPR sensing in the terahertz regime.
Photovoltaic properties of low temperature solution processed earth abundant CuO nanocrystal‐based hybrid solar cells
Authors: Ganga B. G. , Seetharaman S. M. , Varma P. C. R. , Namboothiry M. A. G. , Santhosh P. N.
Published: October 2016

p‐type copper oxide (CuO) nanocrystals were prepared by a wet chemical method and are used to make thin films by spin casting. CuO nanocrystals were characterised using XRD, Raman, TEM and XPS. Low temperature solution processed thin films of CuO crystals showed a hole mobility of 4.57 × 10−4 cm2 V−1 s−1 perpendicular to the plane of the film and is measured using space charge limited current method. Due to the difficulty in making solution processed homo p–n junction and n‐doping of CuO, a planar hybrid heterojunction solar cell is fabricated using solution processed CuO and a n‐type organic material, [6,6]‐phenyl‐C70 butyric acid methyl ester (PCBM). A power conversion efficiency of 0.23% is obtained for hybrid solar cell comprising CuO as active layer where all the device fabrications were carried out at temperature ≤100 °C. Analysis of the current density–voltage (J–V) characteristics at different light intensities is carried out to unravel the recombination mechanism occurring at the interface. Further, effect of annealing the active layer on the photovoltaic performance is investigated.
Fabrication of hydrophilic graphene film by molecular functionalization
Authors: Taniguchi Yoshiaki , Miki Tsubasa , Mitsuno Takanori , Ohno Yasuhide , Nagase Masao , Minagawa Keiji , Yasuzawa Mikito
Published: October 2016

We demonstrated the fabrication of a hydrophilic graphene film by functionalization using a phosphorylcholine group. Since the phosphorylcholine group retains water molecules, it is expected that a hydrophilic graphene film can be realized from the initial hydrophobic characteristic. To evaluate the molecular functionalization, the contact angle and four‐terminal resistivity were measured after every 1 min of phosphorylcholine group functionalization. The contact angle showed a sudden decrease of approximately 20° after 3 min. On the other hand, the resistivity gradually increased in accordance with the Langmuir adsorption isotherm. These results indicate that the phosphorylcholine group successfully modified the surface of graphene, and a hydrophilic graphene film was obtained without significant degradation of the electrical characteristics.

Time dependence of the net contact angle change and resistivity change. The insets show the photographs of the contact angle measurement for the initial hydrophobic film and for the hydrophilic film obtained by functionalization.
Triterpenoids‐Enriched Extract from the Aerial Parts of Salvia miltiorrhiza Regulates Macrophage Polarization and Ameliorates Insulin Resistance in High‐Fat Fed Mice
Authors: Leng Jing , Chen Mei‐Hong , Zhou Zhi‐Hui , Lu Ya‐Wen , Wen Xiao‐Dong , Yang Jie
Published: October 2016

Adipose tissue inflammation and macrophage polarization are tightly associated with the development of obesity‐associated insulin resistance. Our previous studies have demonstrated the triterpenoids‐enriched extract from the aerial parts of Salvia miltiorrhiza (TTE) could significantly improve atherosclerosis in LDLR−/− mice. However, its molecular mechanisms of TTE ameliorating insulin resistance remain unclear. In the present study, obesity model with insulin resistance induced by feeding high‐fat diet (HFD) was established. Dietary TTE attenuated hyperlipidemia, improved glucose intolerance in mice and mediated the activation of IRS‐1/PI3K/Akt insulin signaling pathway. Meanwhile, dietary TTE also attenuated macrophage infiltrations into adipose tissue and modified the phenotype ratio of M1/M2 macrophages. Furthermore, our results showed that TTE regulated the polarization of macrophages partly via adenosine monophosphate‐activated kinase (AMPK). Taken together, these findings suggested that TTE has a potential clinical utility in improving insulin resistance. Its mechanisms might be contributed to its beneficial effects on macrophage polarization via AMPK. Copyright © 2016 John Wiley & Sons, Ltd.
Bilberry: Chemical Profiling, in Vitro and in Vivo Antioxidant Activity and Nephroprotective Effect against Gentamicin Toxicity in Rats
Authors: Veljković Milica , Pavlović Dragana R. , Stojiljković Nenad , Ilić Sonja , Jovanović Ivan , Poklar Ulrih Nataša , Rakić Violeta , Veličković Ljubinka , Sokolović Dušan
Published: October 2016

We assessed possible protective effect of bilberry diet in rat model of nephrotoxicity. In vivo and in vitro antioxidant activity and chemical profiling of this functional food was performed. With aid of HPLC‐DAD and spectrophotometric method, 15 individual anthocyanins were quantified alongside total tannin, phenylpropanoid, and anthocyanin content. The study was conducted on four groups of rats: control, treated with only gentamicin, treated with only bilberry, and treated with both gentamicin and bilberry. Kidney function was evaluated by tracking urea and creatinine. Morphology of renal tissue and its changes were recorded pathohistologically and quantified morphometrically. Bilberry (100 mg/kg daily) showed strong nephroprotective effect against gentamicin toxicity in rats (as shown through MDA, AOPP, and catalase levels). In conclusion, the demonstrated protective activity of bilberry extract matched well with the assessed in vivo and in vitro antioxidant activity as well as with its polyphenolic content, particularly with high anthocyanin levels. Copyright © 2016 John Wiley & Sons, Ltd.
Online learning with the Continuous Ranked Probability Score for ensemble forecasting
Authors: Thorey J. , Mallet V. , Baudin P.
Published: October 2016

Ensemble forecasting resorts to multiple individual forecasts to produce a discrete probability distribution that represents the uncertainties accurately. Before every forecast, a weighted empirical distribution function is derived from the ensemble, so as to minimize the Continuous Ranked Probability Score (CRPS). We apply online learning techniques that have previously been used for deterministic forecasting and adapt them for the minimization of the CRPS. The proposed method guarantees theoretically that the aggregated forecast competes, in terms of CRPS, against the best weighted empirical distribution function with weights constant in time. This is illustrated on synthetic data. Additionally, our study improves knowledge of the CRPS expectation for model mixtures. We generalize results about the bias of the CRPS computed with ensemble forecasts and propose a new scheme to achieve fair CRPS minimization, without any assumption about the distribution.
Mechanism for odd‐electron anion generation of dihydroxybenzoic acid isomers in matrix‐assisted laser desorption/ionization mass spectrometry with density functional theory calculations
Authors: Yamagaki Tohru , Takeuchi Michika , Watanabe Takehiro , Sugahara Kohtaro , Takeuchi Takae
Published: October 2016

Rationale

Proton and radical are transferred between matrices and matrix and analyte in matrix‐assisted laser desorption/ionization (MALDI) and these transfers drive ionization of analytes. The odd‐electron anion [M–2H]•– was generated in dihydroxybenzoic acids (DHBs) and the ion abundance of the 2,5‐DHB was the highest among six DHB isomers. We were interested in the mechanism of the ion generation of the odd‐electron anion.

Methods

The observed [M–2H]•– and [M–3H]− ions, which were generated with the hydrogen radical removed from the phenolic hydroxyl groups (OH) in DHB isomers, were analyzed using negative‐ion MALDI‐MS. The enthalpy for ion generation and their stable structures were calculated using the density functional theory (DFT) calculation program Gaussian 09 with the B3LYP functional and the 6–31+G(d) basis set.

Results

The number of observed [M–2H]•– and [M–3H]− ions of the DHB isomers was dependent on the positions of the phenolic OH groups in the DHB isomers because the carboxy group interacts with the ortho OH group due to neighboring group participation, as confirmed from the stable structures of the [M–2H]•– anions calculated with the Gaussian 09 program. The DHB isomers were placed into three categories according to the number of the ions.

Conclusions

Odd‐electron anions ([M–2H]•–) and [M–2H•–H]− ([M–3H]−) ions were generated from DHB isomers due to removal of the hydrogen radical from the phenolic groups. The enthalpy for ion generation revealed that ion formation proceeds via a two‐step pathway through the [M–M]− ion as an intermediate. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.
Summer‐type hypersensitivity pneumonitis in a patient with rheumatoid arthritis on methotrexate and tacrolimus
Authors: Ohkubo Hirotsugu , Okayama Minami , Fukumitsu Kensuke , Niimi Akio
Published: October 2016

A 59‐year‐old woman receiving methotrexate and tacrolimus for rheumatoid arthritis (RA) was referred to our hospital following bilateral ground‐glass opacity observed in her chest X‐ray and elevated serum KL‐6. After methotrexate and tacrolimus cessation, shortness of breath developed and ground‐glass opacity observed in the chest computed tomography rapidly worsened. Bronchoalveolar lavage showed increased lymphocytes, and trans‐bronchial lung biopsy confirmed lymphocytic alveolitis. In addition, the patient had serum antibodies against Trichosporon asahii, a fungal pathogen. The mildew in her bathroom and washing machine which were the source of the fungus were removed, which resulted in no further relapse of the condition. In this patient's case, methotrexate and tacrolimus may have masked and suppressed summer‐type hypersensitivity pneumonitis.
Comparisons of risk prediction methods using nested case‐control data
Authors: Salim Agus , Delcoigne Bénédicte , Villaflores Krystyn , Koh Woon‐Puay , Yuan Jian‐Min , van Dam Rob M. , Reilly Marie
Published: October 2016

Using both simulated and real datasets, we compared two approaches for estimating absolute risk from nested case‐control (NCC) data and demonstrated the feasibility of using the NCC design for estimating absolute risk. In contrast to previously published results, we successfully demonstrated not only that data from a matched NCC study can be used to unbiasedly estimate absolute risk but also that matched studies give better statistical efficiency and classify subjects into more appropriate risk categories. Our result has implications for studies that aim to develop or validate risk prediction models. In addition to the traditional full cohort study and case‐cohort study, researchers designing these studies now have the option of performing a NCC study with huge potential savings in cost and resources. Detailed explanations on how to obtain the absolute risk estimates under the proposed approach are given. Copyright © 2016 John Wiley & Sons, Ltd.
Understanding the effects of conditional dependence in research studies involving imperfect diagnostic tests
Authors: Wang Zhuoyu , Dendukuri Nandini , Joseph Lawrence
Published: October 2016

When two imperfect diagnostic tests are carried out on the same subject, their results may be correlated even after conditioning on the true disease status. While past work has focused on the consequences of ignoring conditional dependence, the degree to which conditional dependence can be induced has not been systematically studied. We examine this issue in detail by introducing a hypothetical missing covariate that affects the sensitivities of two imperfect dichotomous tests. We consider four forms for this covariate, normal, uniform, dichotomous and trichotomous. In the case of a dichotomous covariate, we derive an expression showing that the conditional covariance is a function of the product of the changes in test sensitivities (or specificities) between the subgroups defined by the covariate. The maximum possible covariance is induced by a dichotomous covariate with a very strong effect on both tests. Through simulations, we evaluate the extent to which fitting a latent class model ignoring each type of covariate but including a general covariance term can adjust for the correlation induced by the covariate. We compare the results to when the conditional dependence is ignored. We find that the bias because of ignoring conditional dependence is generally small even for moderate covariate effects, and when bias is present, a model including a covariance term works well. We illustrate our methods by analyzing data from a childhood tuberculosis study. Copyright © 2016 John Wiley & Sons, Ltd.
Work stressors, sleep quality, and alcohol‐related problems across deployment: A parallel process latent growth modeling approach among Navy members
Authors: Bravo Adrian J. , Kelley Michelle L. , Hollis Brittany F.
Published: October 2016

This study examined how work stressors were associated with sleep quality and alcohol‐related problems among U.S. Navy members over the course of deployment. Participants were 101 U.S. Navy members assigned to an Arleigh Burke‐class destroyer who experienced an 8‐month deployment after Operational Enduring Freedom/Operation Iraqi Freedom. Approximately 6 weeks prior to deployment, 6 weeks after deployment, and 6 months reintegration, participants completed measures that assessed work stressors, sleep quality, and alcohol‐related problems. A piecewise latent growth model was conducted in which the structural paths assessed if work stressors influenced sleep quality or its growth over time, and in turn if sleep quality influenced alcohol‐related problems intercepts or growth over time. A significant indirect effect was found such that increases in work stressors from pre‐ to postdeployment predicted decreases in sleep quality, which in turn were associated with increases in alcohol‐related problems from pre‐ to postdeployment. These effects were maintained from postdeployment through the 6‐month reintegration. Findings suggest that work stressors may have important implications for sleep quality and alcohol‐related problems. Positive methods of addressing stress and techniques to improve sleep quality are needed as both may be associated with alcohol‐related problems among current Navy members.
Adipose Stromal Vascular Fraction-Mediated Improvements at Late-Stage Disease in a Murine Model of Multiple Sclerosis
Authors: Bowles Annie C. , Strong Amy L. , Wise Rachel M. , Thomas Robert C. , Gerstein Brittany Y. , Dutreil Maria F. , Hunter Ryan S. , Gimble Jeffrey M. , Bunnell Bruce A.
Published: October 2016

Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes. The SVF can be culture expanded to generate ASC lines. Clinical trials continue to demonstrate the safety and efficacy of ASC therapies for treating several diseases. However, little is known about the effectiveness of the SVF for neurodegenerative diseases, such as MS. At late-stage disease, EAE mice show severe motor impairment. The goal for these studies was to test the effectiveness of SVF cells and ASC in EAE mice after the onset of neuropathology. The clinical scoring, behavior, motor function, and histopathologic analyses revealed significant improvements in EAE mice treated with the SVF or ASC. Moreover, SVF treatment mediated more robust improvements to CNS pathology than ASC treatment based on significant modulations of inflammatory factors. The most pronounced changes following SVF treatment were the high levels of interleukin-10 in the peripheral blood, lymphoid and CNS tissues along with the induction of regulatory T cells in the lymph nodes which indicate potent immunomodulatory effects. The data indicate SVF cells effectively ameliorated the EAE immunopathogenesis and supports the potential use of SVF for treating MS.
Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations
Authors: Oliveira Vitor Antunes , Favero Gaia , Stacchiotti Alessandra , Giugno Lorena , Buffoli Barbara , de Oliveira Claudia Sirlene , Lavazza Antonio , Albanese Massimo , Rodella Luigi Fabrizio , Pereira Maria Ester , Rezzani Rita
Published: October 2016

This work investigated the effects of mercury chloride (HgCl2) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18th gestation day) and lactating (7th lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2‐exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500–1512, 2017.
Wireless resource virtualization: opportunities, challenges, and solutions
Authors: Kalil M. , Youssef M. , Shami A. , Al‐Dweik A. , Ali S.
Published: October 2016

Wireless resource virtualization (WRV) is currently emerging as a key technology to overcome the major challenges facing the mobile network operators (MNOs) such as reducing the capital, minimizing the operating expenses, improving the quality of service, and satisfying the growing demand for mobile services. Achieving such conflicting objectives simultaneously requires a highly efficient utilization of the available resources including the network infrastructure and the reserved spectrum. In this paper, the most dominant WRV frameworks are discussed where different levels of network infrastructure and spectrum resources are shared between multiple MNOs. Moreover, we summarize the major benefits and most pressing business challenges of deploying WRV. We further highlight the technical challenges and requirements for abstraction and sharing of spectrum resources in next generation networks. In addition, we provide guidelines for implementing comprehensive solutions that are able to abstract and share the spectrum resources in next generation network. The paper also presents an efficient algorithm for base station virtualization in long‐term evolution (LTE) networks to share the wireless resources between MNOs who apply different scheduling polices. The proposed algorithm maintains a high‐level of isolation and offers throughput performance gain. Copyright © 2016 John Wiley & Sons, Ltd.
Cover Image, Volume 7, Issue 6
Authors: Petitto L. A. , Langdon C. , Stone A. , Andriola D. , Kartheiser G. , Cochran C.
Published: October 2016

The cover image, created by Laura‐Ann Petitto, is based on the article Visual Sign Phonology: Insights into Human Reading and Language from a Natural Soundless Phonology, DOI: 10.1002/wcs.1404. Design Credit: Laura‐Ann Petitto, Graphic Artist Yiqiao Wang, and Tara Congdon.

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Employment and Social Trends by Region
Authors:   Research Department
Published: October 2016

Labour market and social conditions vary considerably across regions. In terms of unemployment, the short‐term outlook shows that Europe and Central Asia and Northern America will do relatively well in comparison to other regions, including Latin America and the Caribbean, the Arab States, Asia, and Sub‐Saharan Africa. However, unemployment levels and rates do not often capture well the extent of the labour market and social challenges. This is particularly the case in the emerging and developing economies, where the persistence of vulnerable employment, informal employment and working poverty is of key concern (ILO, 2015i). Even in Europe and Central Asia and Northern America, where unemployment is expected to decline, long‐term unemployment and youth unemployment remain significant labour market and social challenges. In this respect, all countries and regions of the world are confronting the challenge of creating sufficient quality employment.

With that in mind, this chapter will assess both across and within regions (i) recent economic and labour market developments; (ii) short‐term employment and social prospects; and (iii) major deficits and challenges to achieving success in terms of the SDGs.
Cover Image, Volume 8, Issue 6
Authors: Cardozo Timothy , Gupta Priyanka , Ni Eric , Young Lauren M. , Tivon Doreen , Felsovalyi Klara
Published: October 2016

The cover image, by Timothy Cardozo et al., is based on the Advanced Review Data sources for in vivo molecular profiling of human phenotypes, DOI: 10.1002/wsbm.1354.

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A five-year retrospective evaluation of a faculty research fellowship programme at the medical college of Georgia
Authors: Wyatt Tasha R. , Braun Kelli , Evans Lance , Rossi Alexis , Wallach Paul M. , Stepleman Lara M.
Published: October 2016

Introduction In institutional assessments of faculty, scholarly activity is often cited as a deficiency. Faculty lack the training and resources needed to produce peer-reviewed, quality scholarship. Although a variety of formats have been suggested and used to fill this void, fellowships are a commonly used format to foster educational leaders within institutions. In 2010, the Educational Innovation Institute at the Medical College of Georgia created an educational research fellowship to address this need.

Methods To assess the success of our programme, we compared all graduating fellows’ current curriculum vitae (CVs) with the version submitted at the time of their application, looking for educational scholarship produced during and after their participation in the fellowship. Qualitative data sources, such as article reflections, mid-fellowship surveys, and exit surveys were analyzed to identify the mechanisms that contributed to their success. The constant comparative method was used to identify themes and patterns.

Results A comparison of CVs collected at the time of application with a current CV indicate the 11 participants produced: 60 presentations at regional or national meetings, 16 peer reviewed publications, received funding for 7 grants supporting educational research, and won 7 national research awards. Our qualitative analysis identified three major mechanisms: 1) dedicated time to conducting educational research, 2) opportunities to engage with others, and 3 ) understanding the differences between educational and clinical research.

Discussion Previous criticisms of fellowships include faculty not producing educational scholarship after completing their programme.
High-Volume Repeaters of Self-Harm
Authors: Ness Jennifer , Hawton Keith , Bergen Helen , Waters Keith , Kapur Navneet , Cooper Jayne , Steeg Sarah , Clarke Martin
Published: October 2016

Abstract. Background: Repetition of self-harm is common and is strongly associated with suicide. Despite this, there is limited research on high-volume repetition. Aim: To investigate individuals with high-volume repeat self-harm attendances to the emergency department (ED), including their patterns of attendance and mortality. Method: Data from the Multicentre Study of Self-Harm in England were used. High-volume repetition was defined as ⩾15 attendances within 4 years. An attendance timeline was constructed for each high-volume repeater (HVR) and the different patterns of attendance were explored using an executive sorting task and hierarchical cluster analysis. Results: A small proportion of self-harm patients are HVRs (0.6%) but they account for a large percentage of self-harm attendances (10%). In this study, the new methodological approach resulted in three types of attendance patterns. All of the HVRs had clusters of attendance and a greater proportion died from external causes compared with non-HVRs. Conclusion: The approach used in this study offers a new method for investigating this problem that could have both clinical and research benefits. The need for early intervention is highlighted by the large number of self-harm episodes per patient, the clustered nature of attendances, and the higher prevalence of death from external causes.
Paola Receives 2016 G. K. Gilbert Award
Authors:   AGU
Published: October 2016

Christopher Paola will receive the 2016 G. K. Gilbert Award at the 2016 American Geophysical Union Fall Meeting, to be held 12–16 December in San Francisco, Calif. The award recognizes "a scientist who has either made a single significant advance or sustained significant contributions to the field of Earth and planetary surface processes, and who has in addition promoted an environment of unselfish cooperation in research and the inclusion of young scientists into the field."
The Role of Pediatric Psychologists in Solid Organ Transplant Candidacy Decisions: Ethical Considerations
Authors: Kelly Sarah L. , Morris Nneka , Mee Laura , Brosig Cheryl , Self Mariella M.
Published: October 2016

The donor shortage in pediatric solid organ transplantation raises ethical considerations for transplant providers who must balance ethical responsibilities to the patient, the donor, and the general pool of transplant candidates. The United Network for Organ Sharing (UNOS) requires transplant centers to incorporate a psychosocial evaluation into a multidisciplinary transplant evaluation, but individual transplant centers differ in their approach to considering how psychosocial factors contribute to ethical decision making in candidacy decisions. Through psychosocial transplant evaluations and interventions to optimize a patient’s candidacy, pediatric psychologists offer unique expertise to transplant teams. However, they must actively balance professional ethics, bioethics, and legal mandates that often contribute to challenging transplant candidacy decisions. An adolescent case example is discussed to illustrate ethical problem solving in the pediatric transplant context.
Loss of Rictor with aging in osteoblasts promotes age-related bone loss
Authors: Lai Pinling , Song Qiancheng , Yang Cheng , Li Zhen , Liu Sichi , Liu Bin , Li Mangmang , Deng Hongwen , Cai Daozhang , Jin Dadi , Liu Anling , Bai Xiaochun
Published: October 2016

Osteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment.
MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis
Authors: Zhou Qingxin , Zhu Yuekun , Wei Xiaoli , Zhou Jianhua , Chang Liang , Sui Hong , Han Yu , Piao Daxun , Sha Ruihua , Bai Yuxian
Published: October 2016

Altered expression of microRNA-590-5p (miR-590-5p) is involved in tumorigenesis, however, its role in colorectal cancer (CRC) remains to be determined. In this study, we focused on examining the effects of different expression levels of miR-590-5p in cancer cells and normal cells. Results showed that there are lower expression levels of miR-590-5p in human CRC cells and tissues than in normal control cells and tissues. Similarly, in our xenograft mouse model, knockdown of miR-590-5p promoted the progression of CRC. However, an overexpression of miR-590-5p in the mice inhibited angiogenesis, tumor growth, and lung metastasis. Nuclear factor 90 (NF90), a positive regulator of vascular endothelial growth factor (VEGF) mRNA stability and protein synthesis, was shown to be a direct target of miR-590-5p. The overexpression of NF90 restored VEGFA expression and rescued the loss of tumor angiogenesis caused by miR-590-5p. Conversely, the NF90-shRNA attenuated the increased tumor progression caused by the miR-590-5p inhibitor. Clinically, the levels of miR-590-5p were inversely correlated with those of NF90 and VEGFA in CRC tissues. Furthermore, knockdown of NF90 lead to a reduction of pri-miR-590 and an increase of mature miR-590-5p, suggesting a negative feedback loop between miR-590-5p and NF90. Collectively, these data establish miR-590-5p as an anti-onco-miR that inhibits CRC angiogenesis and metastasis through a new mechanism involving NF90/VEGFA signaling axis, highlighting the potential of miR-590-5p as a target for human CRC therapy.