bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential treatment of actinic keratosis with cryotherapy and ingenol mebutate: reflectance confocal microscopy monitoring of efficacy and local skin reaction
Authors: Pasquali Paola , Segurado‐Miravalles Gonzalo , González Salvador
Published: August 2018

Background

Sequential treatment of actinic keratosis (AK) and cancerization field with cryotherapy and ingenol mebutate (IM) is widely used in clinical practice, however, the order of application of sequential treatment has not been examined yet.

Objective

To compare different sequential treatments of IM and cryotherapy in AK and to monitor cure rates and local skin reactions (LSR) through reflectance confocal microscopy (RCM).

Methods

Patients with AK were treated with IM and cryotherapy. Group A received treatment with IM before cryotherapy, and group B patients were firstly treated with cryotherapy and secondly IM. RCM evaluation of epidermal dysplasia and LSR was performed prior to the first treatment (Week 0), before the second treatment (Week 2), and one month and two months after initial assessment.

Results

The study included 26 patients – 14 patients in group A and 12 patients in group B. In both groups, significant improvement in epidermal dysplasia RCM parameters between the first and last visit was observed. Regarding LSR parameters, group A presented fewer LSR parameters than group B on the second visit. This difference was present even if comparison was made between the third visit of group A and the second visit of group B.

Conclusions

Both sequences of treatment are effective, but IM treatment before cryotherapy is recommended because of the lower LSR. This probably decreases patient discomfort and improves compliance.
Flavobacteria as secondary pathogens in carp suffering from koi sleepy disease
Authors: Adamek Mikolaj , Teitge Felix , Jung‐Schroers Verena , Heling Max , Gela David , Piackova Veronika , Kocour Martin , Steinhagen Dieter
Published: August 2018

Koi sleepy disease (KSD) is a disease with increasing importance in global common carp aquaculture. Despite the fact that carp edema virus (CEV) is most likely the causative agent of KSD, the disease often presents itself as multifactorial with several parasites and bacteria species present on gills, skin or in internal organs. Therefore, in this study, we analysed and presented initial results on an interaction of flavobacteria and CEV in the development of clinical KSD in carp suffering from proliferative gill disease. We examined selected field samples from Germany and Hungary and confirmed the presence of CEV and flavobacteria co‐infections in subset of the samples. In several infection experiments, we studied the transfer and dynamics of both infections. Furthermore, we analysed which Flavobacterium species could be isolated from KSD‐affected fish and concluded that Flavobacterium branchiophilum is a possible copathogen. Antibiotic treatment experiments showed that CEV seems to be the primary pathogen causing an insult to the gills of carp and by these enabling other pathogens, including F. branchiophilum, to establish co‐infections. Despite the fact that F. branchiophilum co‐infection is not required for the development of clinical KSD, it could contribute to the pathological changes recorded during the outbreaks.
Early stages of infection of three‐spined stickleback (Gasterosteus aculeatus) with the cestode Schistocephalus solidus
Authors: Wohlleben Anika Marie , Franke Frederik , Hamley Madeleine , Kurtz Joachim , Scharsack Jörn Peter
Published: August 2018

Parasitic helminths have evolved strategies to evade their host's immune systems. Particularly, the early time of interactions between helminths and their hosts might be decisive for their infection success. We used the cestode Schistocephalus solidus, and its highly specific second intermediate host, the three‐spined stickleback (Gasterosteus aculeatus) to investigate parasite infection and host cellular immune responses starting 1 day postexposure (dpe). We recovered live parasites from stickleback body cavities already 24 hr after exposure. Infection rates increased up to 50% and did not change from 4 dpe onwards. Thus, not all parasites had reached the body cavity at the early time points and clearance of the parasite at later time points did not occur. Stickleback head kidney leucocytes (HKLs) did not show distinct signs of activation and lymphocyte proliferation, granulocyte‐to‐lymphocyte ratios and respiratory burst activity of infected sticklebacks did not deviate from controls significantly. The immune system was activated only late, as indicated by an increase in the total count of HKL relative to stickleback weight (HKL per mg fish), which was significantly elevated in infected fish 32 dpe. S. solidus seems to evade leucocyte activity early during infection facilitating its establishment in the hosts’ body cavity.
Evidence for the primacy of living root inputs, not root or shoot litter, in forming soil organic carbon
Authors: Sokol Noah W. , Kuebbing Sara. E. , Karlsen‐Ayala Elena , Bradford Mark A.
Published: August 2018

Soil organic carbon (SOC) is primarily formed from plant inputs, but the relative carbon (C) contributions from living root inputs (i.e. rhizodeposits) vs litter inputs (i.e. root + shoot litter) are poorly understood. Recent theory suggests that living root inputs exert a disproportionate influence on SOC formation, but few field studies have explicitly tested this by separately tracking living root vs litter inputs as they move through the soil food web and into distinct SOC pools.

We used a manipulative field experiment with an annual C4 grass in a forest understory to differentially track its living root vs litter inputs into the soil and to assess net SOC formation over multiple years.

We show that living root inputs are 2–13 times more efficient than litter inputs in forming both slow‐cycling, mineral‐associated SOC as well as fast‐cycling, particulate organic C. Furthermore, we demonstrate that living root inputs are more efficiently anabolized by the soil microbial community en route to the mineral‐associated SOC pool (dubbed ‘the in vivo microbial turnover pathway’).

Overall, our findings provide support for the primacy of living root inputs in forming SOC. However, we also highlight the possibility of nonadditive effects of living root and litter inputs, which may deplete SOC pools despite greater SOC formation rates.
Reactive Oxygen Species‐mediated Degradation of Antidiabetic Compounds: Cytotoxic Implications of Their Photodegradation Products
Authors: Challier Cecilia , Laurella Sergio , Allegretti Patricia , Sabini Carola , Sabini Liliana , García Norman A. , Biasutti Alicia , Criado Susana
Published: August 2018

Reactive oxygen species (ROS) have been described in their double physiological function, helping in the maintenance of health as well as contributing to oxidative stress. Diabetes mellitus is a chronical disease nearly related to oxidative stress, whose treatment (in type II variant) consists in the administration of antidiabetic compounds (Andb) such as Gliclazide (Gli) and Glipizide (Glip). In this context, as Andb may be exposed to high ROS concentrations in diabetic patients, we have studied the potential ROS‐mediated degradation of Gli and Glip through photosensitized processes, in the presence of Riboflavin (Rf) vitamin. We found that singlet oxygen (O2(1∆g)) participated in the Rf‐sensitized photodegradation of both Andb, and also superoxide radical anion in the case of Gli. Two principal products derived from O2(1∆g)‐mediated degradation of Gli were identified and their chemical structures characterized, through HPLC mass spectrometry. O2(1∆g)‐mediated degradation products and their toxicity was assayed on Vero cell line. These studies demonstrated that neither Gli nor its photoproducts caused cytotoxic effect under the experimental conditions assayed. Our results show strong evidences of ROS‐mediated Andb degradation, which may involve the reduction or loss of their therapeutic action, as well as potential cytotoxicity derived from their oxidation products.
Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3‐dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase‐negative staphylococci
Authors: Bochniarz Mariola , Kocki Tomasz , Dąbrowski Roman , Szczubiał Marek , Wawron Władysław , Turski Waldemar A.
Published: August 2018

Contents

The aim of the study was to investigate serum and milk concentrations of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and indoleamine 2,3‐dioxygenase (IDO) activity in cows suffering from subclinical mastitis caused by coagulase‐negative staphylococci (MSCNS). TRP and kynurenines were determined by high‐performance liquid chromatography (HPLC), and IDO activity was calculated as the KYN/TRP ratio. The blood and milk samples were collected from 40 midlactation Holstein‐Fresian cows from two herds in the Lublin region in Poland. In the milk samples from 20 cows with subclinical mastitis, coagulase‐negative staphylococci were isolated and in the milk obtained from healthy cows growth of microorganisms was not detected. TRP, KYN and KYNA concentrations were significantly lower in milk of cows with MSCNS compared to control animals (4.47 vs. 7.24 µM, 0.14 vs. 0.21 µM, 1.58 vs. 2.18 nM, respectively). There was no statistically significant difference in TRP and KYNA concentrations in serum between the studied animal groups (32.97 vs. 39.29 µM, 31.3 vs. 26.5 nM, respectively). In turn, the level of KYN was lower in the serum (0.81 vs. 1.13 µM) of cows with mastitis compared to healthy ones. No statistically significant differences in IDO activity, both in serum and in milk (25.24 and 27.55, 28.56 and 27.17, respectively) was revealed between the studied groups. These findings may have potential implications for diagnosis of mastitis in cows because reduction of these parameters in milk might be a marker predicting the occurrence of the disease.
TREATMENT OF HYPERBILIRUBINEMIA: VARIOUS TECHNOLOGIES AND CHALLENGES
Authors: Salimi Esmaeil , Ghaee Azadeh , Ismail Ahmad Fauzi , Othman Mohd Hafiz Dzarfan
Published: August 2018

Bilirubin removal from blood and curing patients suffering from hyperbilirubinemia by surgery, medication or interventional therapies was common, previously. Alternative bilirubin separation techniques such as plasma exchange, affinity chromatography and etc., are efficient in reducing high levels of bilirubin with fewer side effects. However, due to the various causes and complications associated with hyperbilirubinemia, different strategies are needed for the treatment. This article offers a historical overview on these strategies, challenges and also outlines the technological advantages and disadvantages associated with various bilirubin removal techniques.
APPLICATION OF ELECTRICAL RESISTIVITY TOMOGRAPHY (ERT) FOR SLOPE FAILURE INVESTIGATION: A CASE STUDY FROM KUALA LUMPUR
Authors: Ismail Nurul Iffah , Wan Yaacob Wan Zuhairi
Published: August 2018

Electrical Resistivity Tomography (ERT) is a commonly used tool in near surface geophysical surveys to investigate numerous geological, environmental, and engineering problems including landslides. In this study, an electrical resistivity survey was conducted at a landslide area, located in Bukit Setiawangsa, Kuala Lumpur, Malaysia. On 29th December 2012, a luxury hilltop bungalow was split into two when a 43m retaining wall was collapsed after a continuous heavy downpour. 2-D electrical resistivity survey have been acquired along two (2) profiles on the adjacent slope in an effort to mitigate the risks of instability, especially during the rectification work of the failed slope using a Schlumberger Array. It produced useful information about the geometry and characteristics of the study area. In addition, the 2-D resistivity method was performed to determine the behaviour of electrical resistivity underlying the slope areas and estimate the location of the failure surface. Four (4) boreholes were also drilled to obtain engineering properties of the study area such as soil classification, moisture content, soil hardness and SPT N-value.  In order to develop the relationship between resistivity and engineering properties, a comparison between soil hardness and the resistivity value was made. Results from the ERT indicated the presence of zones with low resistivity values identified as percolated water in permeable loose soil, which was believed to be the potential slip surface. The findings of this study also showed that the electrical resistivity imaging coupled with borehole drillings were useful tools for the characterisation of slope failure via subsurface profiles and engineering properties of soil.
EFFECT OF HYBRID FIBER ON THE MECHANICAL PROPERTIES OF RECYCLED AGGREGATE CONCRETE
Authors: Ismail Sallehan , Ramli Mahyuddin
Published: August 2018

This study investigates the effect of inclusion of polyolefin and polypropylene fibers at various volume fractions in single and hybrid forms on the mechanical properties of recycled aggregate concrete (RAC) mix that consists of treated coarse recycled concrete aggregate (RCA). Testing parameters, such as compressive strength, flexural strength, static modulus of elasticity, and impact load resistance, are utilized to evaluate the mechanical strength of specimens. The various properties of the modified RAC are also analyzed and compared with those of normal concrete and unmodified RAC specimens. Findings indicate that the mechanical strength properties of RAC mixture using treated RCA were significantly enhanced by adding fibers. The overall optimized mechanical strength results could be obtained in RAC mixtures with fiber in hybrid form, where their compressive strength at long-term curing age, can be significantly improved by 7% upto 11% higher than normal concrete. In addition, RAC mix with hybrid fibers produced the highest flexural strength and impact load resistance by an increase of 5% and 175%, respectively as compared with the control concrete.
The Short and Long Run Effects of Selected Variables on Tax Revenue - A Case Study
Authors: Siami-Namini Sima , Muhammad Daniel , Fahimullah Fahad
Published: August 2018

The main objective of this article is to empirically examine the short and long-run relationship between real tax revenue and real local government expenditure as well as investigate the relationship between real sales tax revenue and real individual tax revenue and selective variables in Washington, D.C. for the period ranging from 1984-2015. The study uses the Johansen co-integration techniques as well as the bivariate and multivariate vector error correction model (VECM). The results indicate that there is a unidirectional and one-way causality running from real local government expenditure to the real DC’s tax revenue in the short and long-run, but not vice versa. The finding indicates that DC’s tax revenue changes local government expenditure. As a result, budget deficits can be avoided by implementing policies that stimulate DC’s tax revenue. The Granger-causality test shows that DC resident employment does affect real individual tax in the short and long-run, simultaneously. The Granger-causality test shows that DC resident employment, household’s population and stock of housing does affect real sales tax revenue in the short and long-run simultaneously. Furthermore, the results of the impulse response function (IRF) indicate that household’s population and stock of housing are the major short-run effect on the real individual income tax and real sales tax revenue.
Conocimientos y actitudes de enfermería sobre promoción de la salud: una mirada de región
Authors: Loboa Rodriguez Nelly Johanna , León Saavedra Patricia Elizabeth
Published: August 2018

Introducción: la promoción de la salud se congura como un medio para conseguir la salud, concepto que involucra la articulación de conocimientos, actitudes, infraestructura, servicios, recursos y habilidades Objetivo: describir los conocimientos y actitudes sobre promoción de la salud que tienen las enfermeras en programas de atención integral al niño sano en instituciones prestadoras de servicios en el departamento del Meta, durante el 2013. Material y método: estudio cualitativo exploratorio-descriptivo con muestreo intencional opinático. Se realizó un análisis de contenido a partir de la información obtenida de entrevistas semiestructuradas grabadas, transcritas y validadas. Resultados: se trabajó con tres categorías de análisis: 1) impacto de la promoción de la salud, 2) herramientas para proporcionar cuidado de enfermería en la promoción de la salud y 3) dispositivos que inciden en el desarrollo de la promoción de la salud. Conclusiones: la promoción de la salud es un proceso encaminado a realizar, en conjunto, acciones destinadas a mejorar las condiciones y calidad de vida, implementando actitudes positivas y coherentes al quehacer de las enfermeras. Ello es de amplia importancia en la atención a la población infantil que aporta a la rentabilidad social del país.
Intervenciones de enfermería en neonatos con presión positiva continua
Authors: García Reza Cleotilde , Mejía-Flores María Andrea , Guadarrama Pérez Liliana , Gómez Martínez Vicenta
Published: August 2018

Objetivo: describir las intervenciones de enfermería en neonatos con presión positiva continua con prongs, hospitalizados en una unidad neonatal mexicana. Métodos: corte transversal en una muestra no aleatoria por conveniencia, conformada por veinticinco enfermeras que tenían bajo sus cuidados a recién nacidos con sistema de presión positiva con prongs. La recolección de datos fue realizada con un cuestionario autoplicado. El análisis fue descriptivo, y se obtuvieron medidas de tendencia central de las variables cuantitativas que mostraron una distribución normal. Las variables cualitativas se describen con valores relativos. Se respetaron aspectos éticos según la reglamentación vigente mexicana. Resultados: participaron veinticinco enfermeras con grado académico: el 88% con licenciatura y solo el 24% especialistas neonatólogas. Los neonatos usan la presión positiva continua: el 52% de 3 a 5 días; el 20% de 6 a 7 días y el 28% de 8 a 12 días. El nivel de lesión nasal y los resultados con prongs, mediante el cuidado constante de la enfermera sobre la aparición de estas, evidenciaron que el 60% de los neonatos presentó lesión leve; el 36%, moderada, y el 4%, severa. Conclusiones: las intervenciones de cuidado del neonato deben dirigirse a minimizar las lesiones de piel y tabique nasal para contribuir con las normas internacionales de seguridad del neonato.
Identificación y análisis comparativo de las tendencias jurisprudenciales de la Superintendencia Financiera de Colombia y la Corte Suprema de Justicia relativas al contrato de seguro
Authors: Durán Roncancio Natalia Alejandra , Hernández Ordoñez Joan Sebastián , Muñoz Salas Danilo Andrés , Parada Vargas David , Rodríguez Plazas Stefania , Tejeiro Carrillo David Augusto , Jiménez Vélez Manuela
Published: August 2018

Transcurridos los primeros cinco años desde la creación de la Delegatura para Funciones Jurisdiccionales de la Superintendencia Financiera de Colombia, y dado que a la fecha esta entidad ha emitido más de 7533 providencias en ejercicio de las funciones judiciales que le fueron conferidas por el Artículo 57 de la Ley 1480 de 2011, consideramos pertinente efectuar un análisis descriptivo y crítico en torno a los pronunciamientos más destacados de la Delegatura en torno a las controversias más frecuentes en torno al Contrato de Seguro, en comparación con la línea jurisprudencial de la Sala Civil de la Corte Suprema de Justicia.

A través de este escrito ofrecemos a la comunidad académica un espacio de reflexión en torno a las perspectivas de protección al Consumidor de Seguros y la imperiosa necesidad de tutela de los intereses de quienes fungen como parte en la relación asegurativa, identificando así los puntos de convergencia y desencuentro.

Con tal fin, la presente investigación se ha delimitado en torno a las controversias asociadas a la nulidad relativa del contrato de seguro por declaraciones inexactas o reticentes a cargo de la parte asegurada, a la terminación ‘automática’ por impago de la prima, a las divergencias interpretativas, a la delimitación del riesgo mediante exclusiones y a conflictos derivados de la legitimación en la causa por activa de los herederos y cónyuge en el seno de los seguros de vida grupo deudores.
Perception of relative pitch of sentence-length utterances
Authors: Davidson Lisa
Published: August 2018

Differences in relative pitch have several linguistic uses, such as tone and dynamic intonational patterns. In addition, listeners are also sensitive to average pitch differences both within and across male and female speakers. While much research uses isolated syllables to investigate how well listeners can distinguish differences in pitch, this study focuses on listeners' ability to identify relative pitch differences across whole utterances. Listeners are presented with 28 items of the same sentence spoken by female politicians and are asked to rate how low or high the pitch of the utterance is on a 5-point scale. Results indicate that listeners use all steps of the scale to categorize the mean F0 of the stimuli (range: 130–250 Hz) and not a “high/medium/low” system or one in which only the extremes are categorized as high or low.
Long-term outcome of treat and extend intravitreal ziv-aflibercept therapy
Authors: Mansour Ahmad M , Charbaji Abdulrazzak , Farah Michel Eid , Mansour Hana A , Chhablani Jay
Published: August 2018

Aim

To assess the 30-month outcome of treat and extend (TAE) intravitreal ziv-aflibercept therapy in eyes with macular diseases.

Methods

In this prospective study, consecutive subjects received intravitreal 0.05 mL ziv-aflibercept (1.25 mg) injections for various macular diseases. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) and central macular thickness (CMT) on spectral domain optical coherence tomography. Paired comparison was done using Wilcoxon signed-rank test calculator.

Results

Fifty-three eyes of 48 subjects (33 naïve eyes) received intravitreal ziv-aflibercept and were followed between 12 and 30 months following TAE included neovascular age-related macular degeneration (nAMD) (35 eyes) and diabetic macular oedema (DMO) (18 eyes). In eyes with nAMD, CMT decreased by 107.8 µm at the 30-month follow-up (p=0.012) with BCVA gain of 0.52 (p=0.001). In eyes with DMO, CMT decreased by 224.3 µm at the 30-month follow-up (p=0.027) with BCVA gain of 0.46 (p=0.042). Combining all disease categories, the mean number of injections was 9.2 at month 12, 2.5 between 12 and 18 months, 1.6 between 18 and 24 months and 1.0 between 24 and 30 months.

Conclusions

Using TAE regimen, intravitreal ziv-aflibercept appeared efficacious at managing retinal disease through month 30 using the TAE regimen.
Peter Robinson
Authors: Rossdale Peter , Hunt Michael , Peace Colin , Ricketts Sidney , Digby Nicholas Wingfield , Greet Timothy , Steven Neil , Pilsworth Robert , McGladdery Andrew , Carson Deidre , Barrelet Frederic , Shepherd Michael , Payne Richard , Ramzan Peter , Bathe Andrew
Published: August 2018

A vet with extraordinary compassion – his care about patients’ wellbeing, and the consideration he had for concerned farmers or upset pet owners was second to none.
COMPLEX BIOLOGICAL IMMUNE SYSTEM THROUGH THE EYES OF DUAL-PHASE EVOLUTION
Authors: SHINDE SNEHAL B. , KURHEKAR MANISH P.
Published: August 2018

Dual-phase evolution (DPE) and the network theory help to analyze prominent properties of the complex adaptive systems (CASs) such as emergence and self-organization that are caused due to the phase transitions. These transitions are observed because of the increase and decrease in the number of system components and their interactions. The immune system, which is one of the CASs, provides an adaptive response to the foreign molecules. Prior to this response, the immune system is present in the circulation state and during the response, it moves into the growth state, where the number of immune cells and their cell–cell contacts increase rapidly. The phase transitions from the circulation state to the growth state and then back to the circulation state cause the emergence and self-organization of the immune system, respectively. There is a need to understand these complex cellular dynamics during the immune response. In this paper, we have proposed an integrated model of DPE, network theory, and the immune system that has helped to understand and analyze the phases and properties of the immune system. Analysis of the growth phase network is provided and it is concluded that this network exhibits scale-free nature following power law for the degree distribution of nodes.
The Connection of Life with Respiration: Edmund Goodwyn’s unexplored treasure of cardiopulmonary physiology
Authors: Vega Jose L.
Published: August 2018

The advent of artificial ventilation was largely sparked by the popular belief that drowning and other causes of asphyxia could induce death-like states known as suspended animation. While the mystical nature of such states befuddled some physicians into the early 1900s, an English medical student by the name of Edmund Goodwyn (1756–1829) published a thesis in 1786, which demonstrated that suspended animation was simply the physical manifestation of extreme hypoxia. Goodwynʼs work advanced one of the earliest arguments in favor of artificial ventilation for the treatment of asphyxia over alternative resuscitation measures like heat and exsanguination. In addition, Goodwyn’s remarkable dissertation contains the first account of a reflex known as diving bradycardia, and possibly the first vehement refutation of claims by his contemporaries that pulmonary circulation stopped during exhalation. While miscellaneous aspects of his thesis have occasionally been mentioned by a few medical historians, the overall visionary nature of his work has yet to be recognized. This article attempts to accomplish this goal and to provide a first biographical glimpse of a man whose scientific career appears to have ended prematurely, perhaps because of his profound aversion to controversy.
Nonlinear Electromagnetic Inverse Scattering Imaging Based on IN-LSQR
Authors: Zhou Huilin , Liu Youwen , Wang Yuhao , Chen Liangbing , Duan Rongxing
Published: August 2018

A nonlinear inversion scheme is proposed for electromagnetic inverse scattering imaging. It exploits inexact Newton (IN) and least square QR factorization (LSQR) methods to tackle the nonlinearity and ill-posedness of the electromagnetic inverse scattering problem. A nonlinear model of the inverse scattering in functional form is developed. At every IN iteration, the sparse storage method is adopted to solve the storage and computational bottleneck of Fréchet derivative matrix, a large-scale sparse Jacobian matrix. Moreover, to address the slow convergence problem encountered in the inexact Newton solution via Landweber iterations, an LSQR algorithm is proposed for obtaining a better solution of the internal large-scale sparse linear equations in the IN step. Numerical results demonstrate the applicability of the proposed IN-LSQR method to quantitative inversion of scatterer electric performance parameters. Moreover, compared with the inexact Newton method based on Landweber iterations, the proposed method significantly improves the convergence rate with less computational and storage cost.
Economic Evaluation of Letrozole for Early Breast Cancer in a Health Resource-Limited Setting
Authors: Ye Ming , Lu Jingsong , Yang Fan , Wu Bin
Published: August 2018

Objective. Long-term aromatase inhibitor (AI) therapy is expected to improve the health outcomes with high health resource consumption in early breast cancer. The aim of the study was to assess the cost-effectiveness of letrozole for postmenopausal women with estrogen receptor positive early breast cancer in a health resource-limited setting. Methods. A Markov model was developed to project the lifetime outcomes based on the clinical course of early breast cancer. The clinical and utility data were derived from reported results. Costs were estimated from the perspective of Chinese health care. The quality-adjusted life-year (QALY) and incremental cost-effective ratio (ICER) were measured. Probabilistic sensitivity and one-way analyses were conducted. Results. Compared to 5 years of tamoxifen therapy, 5 years of AI treatment with letrozole improved the QALYs (10.44 versus 10.84) and increased the lifetime costs (CNY ¥13,613 versus CNY ¥28,797), resulting in an ICER of CNY ¥38,092 /QALY. The ICER of 5 years of letrozole versus 2–3 years of tamoxifen and then letrozole was CNY ¥68,233 /QALY. Sensitivity analyses showed that the age of initiating adjuvant endocrine therapy was the most influential parameter. Conclusions. In health resource-limited settings, adjuvant endocrine therapy with letrozole is a cost-effective strategy compared to tamoxifen in women with early breast cancer.
A Polysome-Based microRNA Screen Identifies miR-24-3p as a Novel Promigratory miRNA in Mesothelioma
Authors: Oliveto Stefania , Alfieri Roberta , Miluzio Annarita , Scagliola Alessandra , Secli Raissa S. , Gasparini Pierluigi , Grosso Stefano , Cascione Luciano , Mutti Luciano , Biffo Stefano
Published: August 2018

The expression of miRNAs in cancer has been widely studied and has allowed the definition of oncomirs and oncosuppressors. We note that it is often underestimated that many mRNAs are expressed, but translationally silent. In spite of this, systematic identification of miRNAs in equilibrium with their target mRNAs on polysomes has not been widely exploited. To identify biologically active oncomirs, we performed a screen for miRNAs acting on the polysomes of malignant mesothelioma (MPM) cells. Only a small percentage of expressed miRNAs physically associated with polysomes. On polysomes, we identified miRNAs already characterized in MPM, as well as novel ones like miR-24-3p, which acted as a promigratory miRNA in all cancer cells tested. miR-24-3p positively regulated Rho-GTP activity, and inhibition of miR-24-3p reduced growth in MPM cells. Analysis of miR-24-3p common targets, in two mesothelioma cell lines, identified a common subset of downregulated genes. These same genes were downregulated during the progression of multiple cancer types. Among the specific targets of miR-24-3p was cingulin, a tight junction protein that inhibits Rho-GTP activity. Overexpression of miR-24-3p only partially abrogated cingulin mRNA, but completely abrogated cingulin protein, confirming its action via translational repression. We suggest that miR-24-3p is an oncomir and speculate that identification of polysome-associated miRNAs efficiently sorts out biologically active miRNAs from inactive ones.

Significance: Subcellular localization of miRNAs may predict their role in cancer and identify novel oncogenic miRNAs involved in cancer progression.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5741/F1.large.jpg. Cancer Res; 78(20); 5741–53. ©2018 AACR.
Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non–Small Cell Lung Cancer
Authors: Bahcall Magda , Awad Mark M. , Sholl Lynette M. , Wilson Frederick H. , Xu Man , Wang Stephen , Palakurthi Sangeetha , Choi Jihyun , Ivanova Elena V. , Leonardi Giulia C. , Ulrich Bryan C. , Paweletz Cloud P. , Kirschmeier Paul T. , Watanabe Masayuki , Baba Hideo , Nishino Mizuki , Nagy Rebecca J. , Lanman Richard B. , Capelletti Marzia , Chambers Emily S. , Redig Amanda J. , VanderLaan Paul A. , Costa Daniel B. , Imamura Yu , Jänne Pasi A.
Published: August 2018

Purpose:

MET inhibitors can be effective therapies in patients with MET exon 14 (METex14) mutant non–small cell lung cancer (NSCLC). However, long-term efficacy is limited by the development of drug resistance. In this study, we characterize acquired amplification of wild-type (WT) KRAS as a molecular mechanism behind crizotinib resistance in three cases of METex14-mutant NSCLC and propose a combination therapy to target it.

Experimental Design:

The patient-derived cell line and xenograft (PDX) DFCI358 were established from a crizotinib-resistant METex14-mutant patient tumor with massive focal amplification of WT KRAS. To characterize the mechanism of KRAS-mediated resistance, molecular signaling was analyzed in the parental cell line and its KRAS siRNA-transfected derivative. Sensitivity of the cell line to ligand stimulation was assessed and KRAS-dependent expression of EGFR ligands was quantified. Drug combinations were screened for efficacy in vivo and in vitro using viability and apoptotic assays.

Results:

KRAS amplification is a recurrent genetic event in crizotinib-resistant METex14-mutant NSCLC. The key characteristics of this genetic signature include uncoupling MET from downstream effectors, relative insensitivity to dual MET/MEK inhibition due to compensatory induction of PI3K signaling, KRAS-induced expression of EGFR ligands and hypersensitivity to ligand-dependent and independent activation, and reliance on PI3K signaling upon MET inhibition.

Conclusions:

Using patient-derived cell line and xenografts, we characterize the mechanism of crizotinib resistance mediated by KRAS amplification in METex14-mutant NSCLC and demonstrate the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism.
Bonhoeffer and Reformation Ecclesiology
Authors: Garcia Javier
Published: August 2018

This article offers a threefold engagement with Dietrich Bonhoeffer’s ecumenically oriented ecclesiology. First, it proposes a new avenue of understanding Bonhoeffer’s ecclesiology in relation to the Reformed tradition by comparing him with John Calvin instead of with Karl Barth, which is the common route of Bonhoeffer scholarship. Second, it identifies points of convergence between Bonhoeffer and Calvin that have been neglected in the literature, notably in the areas of ecclesial participation and sanctification. Third, it calls for a return to Bonhoeffer’s primary goal in ecumenism—to discern God’s concrete commandment to the churches in history—in the Trump era.
Do the Different Sensory Areas Within the Cat Anterior Ectosylvian Sulcal Cortex Collectively Represent a Network Multisensory Hub?
Authors: Meredith M. Alex , Wallace Mark T. , Clemo H. Ruth
Published: August 2018

Current theory supports that the numerous functional areas of the cerebral cortex are organized and function as a network. Using connectional databases and computational approaches, the cerebral network has been demonstrated to exhibit a hierarchical structure composed of areas, clusters and, ultimately, hubs. Hubs are highly connected, higher-order regions that also facilitate communication between different sensory modalities. One computationally identified network hub is the visual area of the Anterior Ectosylvian Sulcal cortex (AESc) of the cat. The Anterior Ectosylvian Visual area (AEV) is but one component of the AESc since the latter also includes the auditory (Field of the Anterior Ectosylvian Sulcus — FAES) and somatosensory (Fourth somatosensory representation — SIV) areas. To better understand the nature of cortical network hubs, the present report reviews the biological features of the AESc. Within the AESc, each area has extensive external cortical connections as well as among one another. Each of these core representations is separated by a transition zone characterized by bimodal neurons that share sensory properties of both adjoining core areas. Finally, core and transition zones are underlain by a continuous sheet of layer 5 neurons that project to common output structures. Altogether, these shared properties suggest that the collective AESc region represents a multiple sensory/multisensory cortical network hub. Ultimately, such an interconnected, composite structure adds complexity and biological detail to the understanding of cortical network hubs and their function in cortical processing.
Revisiting the diversity of Ludioctenus Fairmaire (Elateridae: Agrypninae), with description of a new species from Afghanistan, and discussion on the systematic position of Tetrigusina
Authors: KUNDRATA ROBIN , SORMOVA ELISKA , PROSVIROV ALEXANDER S.
Published: August 2018

The genus Ludioctenus Fairmaire, 1893 hitherto included only L. cyprius (Baudi di Selve, 1871) from the eastern Mediterranean and L. pakistanicus Schimmel & Tarnawski, 2012 from Pakistan. Here, we describe L. afghanicus sp. nov. from the Nuristan Province in eastern Afghanistan. The distribution and morphological diversity of Ludioctenus is discussed, main diagnostic characters for all species are figured, and an identification key to the species of this genus is provided. Female pregenital segments and genitalia are figured for the first time for Ludioctenus, and the systematic position of this genus and its relatives is discussed.
The millipede Craspedosoma raulinsii Leach, 1814 (Chordeumatida: Craspedosomatidae) in North America with comments on the derivation of its binomial name
Authors: McALPINE DONALD F. , SHEAR WILLIAM A.
Published: August 2018

The millipede Craspedosoma raulinsii (Craspedosomatidae) is widespread in Central Europe from Belarus and southern Scandinavia west to Britain and Ireland. Although the species is often not common and rarely encountered (Blower 1985, Hoffman 1999, Lee 2006), Kime (2004) reports C. raulinsii as the third most widespread millipede in Belgium. Shelley (1990) reported C. raulinsii (as C. rawlinsii) for the first time from North America (from Gatineau Park, Quebec, Canada) and noted the occurrence is the first introduction of a representative of the order Chordeumatida in the New World. Here we report new records that suggest widespread occurrence of this introduced millipede in eastern Canada and comment on the commonly-applied spelling of the specific epithet of the species. Vouchers have been deposited in the collections of the New Brunswick Museum (NBM).
A new subspecies of Xixuthrus from Papua New Guinea (Coleoptera: Cerambycidae, Prioninae)
Authors: MISSORI PAOLO , ERCOLI LUCIA
Published: August 2018

The prionine genus Xixuthrus consists of species among the largest cerambycids in the world, attaining sizes more than 150 mm. The genus occurs in the Australo–Indo–Pacific regions with 18 species, six of which are found in New Guinea (Xixuthrus arfakianus, granulipennis, helleri, lameerei, microcerus axis, thomsoni). Their habitat is limited to primeval rainforests, and in many areas, it is under threat because of logging and human deforestation. The life cycle of these beetles is unknown, and they remain elusive and mysterious because of the limited accessibility to specimens living in dense rainforest of middle–high volcanic regions with inaccessible steep slopes affected by high humidity, fog, and heavy rainfall. The new subspecies described here was collected in the centre of Papua New Guinea, where many beetles are to date undescribed.
Erythropoietin response to anaemia in heart failure
Authors: Montero David , Haider Thomas , Flammer Andreas J
Published: August 2018

Background

Despite multiple factors correlating with the high prevalence of anaemia in heart failure, the prevailing mechanisms have yet to be established. The purpose of this study is to systematically review the literature and determine whether low circulating haemoglobin is primarily underlain by erythropoietin resistance or defective production in heart failure.

Design and methods

We conducted a systematic search of MEDLINE since its inception until May 2017 for articles reporting erythropoietin and haemoglobin concentrations in heart failure patients not treated with erythropoietin-stimulating agents. The primary outcome was the mean difference in observed/predicted (O/P) erythropoietin ratio between heart failure patients and normal reference values. Meta-regression analyses assessed the influence of potential moderating factors.

Results

Forty-one studies were included after systematic review, comprising a total of 3137 stable heart failure patients with mean age and left ventricular ejection fraction ranging from 52 years to 80 years and 21% to 59%. The O/P erythropoietin ratio was below reference values in 24 of 25 studies in anaemic heart failure patients ( n = 1094, range = 0.49–1.05), whereas only one out of 16 studies in non-anaemic heart failure patients presented a low O/P erythropoietin ratio ( n = 2043, range = 0.91–1.97). In studies comparing anaemic versus non-anaemic heart failure patients ( n = 1531), the mean O/P erythropoietin ratio was consistently reduced in anaemic heart failure patients (mean difference = –0.68, 95% confidence interval = −0.78, −0.57; p < 0.001). In meta-regression, the O/P erythropoietin ratio was negatively associated with age, female sex, left ventricular ejection fraction, inflammation and disease severity.

Conclusion

Anaemia in heart failure is overwhelmingly characterized by impaired erythropoietin production, which is exacerbated with age, female sex, left ventricular ejection fraction, inflammation and disease severity.
Pay for Delay Agreements: Antitrust Watch Intensifies
Authors: Chawla Twinkle , Verma Ruchi
Published: August 2018

The pharmaceutical sector has constantly endeavoured to balance its dual objectives of promoting state-of-art innovation and achieving affordable healthcare for all. The contrasting aims are also germane to the inevitable conflict between the competition law and the patent law with respect to this sector. Reverse payment settlement is one such concept that lies at the cross-section of these two legislations and strangely offers an uncanny mechanism where extreme partisans (i.e., innovator and generics) become comrades, thereby prodding genuine concerns and exposing legal vulnerabilities of such agreements.

Against this backdrop, this article seeks to examine the growing undercurrent re reverse payment settlement agreements from a competition law perspective. In an attempt to harmonize the conflicting policy objectives, it will study the interplay between patent law and competition law by placing reliance on the approach followed by other jurisdictions. Further, this article will also assess whether reverse payment settlement agreements fall within the statutory construct of the Competition Act, 2002 and whether the Competition Commission of India (“CCI”) can assert its jurisdiction over such agreements. An attempt is also made to outline the approach which the CCI could adopt, bearing in mind the importance of ensuring exclusivity as an incentive for innovation.
Nivolumab-induced cold agglutinin syndrome successfully treated with rituximab
Authors: Hasanov Merve , Konoplev Sergej N. , Hernandez Cristhiam M. Rojas
Published: August 2018

Key Points

Cold agglutinin syndrome is one of the rare immune-related adverse events of nivolumab. Rituximab should be considered for treatment of nivolumab-induced cold agglutinin syndrome.
The effect of religiosity during childhood and adolescence on drug consumption patterns in adults addicted to crack cocaine
Authors: Rezende-Pinto Alexandre , Moreira-Almeida Alexander , Ribeiro Marcelo , Laranjeira Ronaldo , Vallada Homero
Published: August 2018

Background

Although many studies suggest that religiosity is a protective factor against drug use, there is little information on its effect on drug consumption patterns of those who do use drugs.

Aims

We aimed to examine if there is any relationship between religiosity during childhood and adolescence, and drug consumption in adult crack users.

Method

We performed a cross-sectional study of adults addicted to crack cocaine. Logistic regression analysis was used to estimate the odds ratio for the association between religious history in the age groups 8–11, 12–14 and 15–17 years and outcome variables.

Results

From a total of 531 respondents, religious involvement during childhood and adolescence was correlated to less frequent onset of drug consumption before 18 years (odds ratio 0.95, 95% CI 0.92–0.98) and less craving (odds ratio 0.95, 95% CI 0.91–0.99), mainly between the ages of 15 and 17 years.

Conclusions

Religiosity provides some protection against drug consumption patterns in crack cocaine addicts.

Declaration of interest

None.
Use of Helium/Oxygen Mixture in Noninvasive Ventilation During Urgent Tracheotomy for Upper Airway Compression: A Case Report
Authors: Mathais Quentin , Goutorbe Philippe , Vatin Loraine , Morvan Jean Baptiste , Meaudre Eric
Published: August 2018

Ventilation or oxygenation can be difficult or even impossible in cases of upper airway obstruction. In this case report, we used a helium/oxygen mixture administered via noninvasive positive-pressure ventilation to perform an urgent tracheotomy under local anesthesia on a patient presenting upper airway compression. It improved his comfort and his stridor, facilitating supine positioning. This case describes another potential indication of the helium/oxygen mixture in noninvasive ventilation.
Impact of detecting potentially serious incidental findings during multi-modal imaging
Authors: Gibson Lorna M , Littlejohns Thomas J , Adamska Ligia , Garratt Steve , Doherty Nicola ,   UK Biobank Imaging Working Group, Wardlaw Joanna M , Maskell Giles , Parker Michael , Brownsword Roger , Matthews Paul M , Collins Rory , Allen Naomi E , Sellors Jonathan , Sudlow Cathie LM
Published: August 2018

Background: There are limited data on the impact of feedback of incidental findings (IFs) from research imaging.  We evaluated the impact of UK Biobank’s protocol for handling potentially serious IFs in a multi-modal imaging study of 100,000 participants (radiographer ‘flagging’ with radiologist confirmation of potentially serious IFs) compared with systematic radiologist review of all images.

Methods: Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry scans from the first 1000 imaged UK Biobank participants were independently assessed for potentially serious IFs using both protocols. We surveyed participants with potentially serious IFs and their GPs up to six months after imaging to determine subsequent clinical assessments, final diagnoses, emotional, financial and work or activity impacts.

Results: Compared to systematic radiologist review, radiographer flagging resulted in substantially fewer participants with potentially serious IFs (179/1000 [17.9%] versus 18/1000 [1.8%]) and a higher proportion with serious final diagnoses (21/179 [11.7%] versus 5/18 [27.8%]). Radiographer flagging missed 16/21 serious final diagnoses (i.e., false negatives), while systematic radiologist review generated large numbers of non-serious final diagnoses (158/179) (i.e., false positives). Almost all (90%) participants had further clinical assessment (including invasive procedures in similar numbers with serious and non-serious final diagnoses [11 and 12 respectively]), with additional impact on emotional wellbeing (16.9%), finances (8.9%), and work or activities (5.6%).

Conclusions: Compared with systematic radiologist review, radiographer flagging missed some serious diagnoses, but avoided adverse impacts for many participants with non-serious diagnoses. While systematic radiologist review may benefit some participants, UK Biobank’s responsibility to avoid both unnecessary harm to larger numbers of participants and burdening of publicly-funded health services suggests that radiographer flagging is a justifiable approach in the UK Biobank imaging study. The potential scale of non-serious final diagnoses raises questions relating to handling IFs in other settings, such as commercial and public health screening.