bluuebunny/crossref_metadata_2025 huggingface dataset:
The intrinsic line width of the Fe K α line of AGN
Authors: Liu Jiren
Published: August 2016

X-ray fluorescent lines are unique features of the reflection spectrum of the cold torus when irradiated by the central AGN. Their intrinsic line widths can be used to probe the line-emitting region. The line widths of the Fe K α line measured from the first-order Chandra High Energy Grating (HEG) spectra are 3–5 times larger than those measured with the Si K α line for Circinus, Mrk 3, and NGC 1068. Because the observed Si K α and Fe K α lines are not necessarily coming from the same physical region, it is uncertain whether the line widths of the Fe K α line are overestimated or not. We measured the intrinsic line widths of the Fe K α line of several nearby bright AGN using the second- and third-order Chandra HEG spectra, whose spectral resolutions are better than the first-order data. We found the measured widths are all smaller than those from the first-order data. The results clearly show that the widths of the Fe K α line measured from the first-order HEG data are overestimated. It indicates that the Fe K α lines of the studied sources are originating from regions around the cold dusty torus.
The problematic growth of dust in high-redshift galaxies
Authors: Ferrara A. , Viti S. , Ceccarelli C.
Published: August 2016

Dust growth via accretion of gas species has been proposed as the dominant process to increase the amount of dust in galaxies. We show here that this hypothesis encounters severe difficulties that make it unfit to explain the observed UV and IR properties of such systems, particularly at high redshifts. Dust growth in the diffuse ISM phases is hampered by (a) too slow accretion rates, (b) too high dust temperatures, and (c) the Coulomb barrier that effectively blocks accretion. In molecular clouds these problems are largely alleviated. Grains are cold (but not colder than the CMB temperature, TCMB ≈ 20 K at redshift z = 6). However, in dense environments accreted materials form icy water mantles, perhaps with impurities. Mantles are immediately (≲1 yr) photo-desorbed as grains return to the diffuse ISM at the end of the cloud lifetime, thus erasing any memory of the growth. We conclude that dust attenuating stellar light at high-z must be ready-made stardust largely produced in supernova ejecta.
SXDF-ALMA 2 arcmin2 deep survey: Resolving and characterizing the infrared extragalactic background light down to 0.5 mJy
Authors: Yamaguchi Yuki , Tamura Yoichi , Kohno Kotaro , Aretxaga Itziar , Dunlop James S. , Hatsukade Bunyo , Hughes David , Ikarashi Soh , Ishii Shun , Ivison Rob J. , Izumi Takuma , Kawabe Ryohei , Kodama Tadayuki , Lee Minju , Makiya Ryu , Matsuda Yuichi , Nakanishi Kouichiro , Ohta Kouji , Rujopakarn Wiphu , Tadaki Ken-ichi , Umehata Hideki , Wang Wei-Hao , Wilson Grant W. , Yabe Kiyoto , Yun Min S.
Published: August 2016

We present a multiwavelength analysis of five submillimeter sources (S1.1mm = 0.54–2.02 mJy) that were detected during our 1.1 mm deep continuum survey in the Subaru/XMM-Newton Deep Survey Field (SXDF)-UDS-CANDELS field (2 arcmin2, 1σ = 0.055 mJy beam−1) using the Atacama Large Millimeter/submillimeter Array (ALMA). The two brightest sources correspond to a known single-dish (AzTEC) selected bright submillimeter galaxy (SMG), whereas the remaining three are faint SMGs newly uncovered by ALMA. If we exclude the two brightest sources, the contribution of the ALMA-detected faint SMGs to the infrared extragalactic background light is estimated to be $\sim 4.1^{+5.4}_{-3.0}\:$Jy deg−2, which corresponds to $\sim 16^{+22}_{-12}\%$ of the infrared extragalactic background light. This suggests that their contribution to the infrared extragalactic background light is as large as that of bright SMGs. We identified multiwavelength counterparts of the five ALMA sources. One of the sources (SXDF-ALMA3) is extremely faint in the optical to near-infrared region despite its infrared luminosity ($L_\mathrm{IR}\simeq 1\times 10^{12}\,L_{\odot}$ or SFR ≃ 100 M⊙ yr−1). By fitting the spectral energy distributions at the optical-to-near-infrared wavelengths of the remaining four ALMA sources, we obtained the photometric redshifts (zphoto) and stellar masses (M*): zphoto ≃ 1.3–2.5, M* ≃ (3.5–9.5) × 1010 M⊙. We also derived their star formation rates (SFRs) and specific SFRs as ≃30–200 M⊙ yr−1 and ≃0.8–2 Gyr−1, respectively. These values imply that they are main sequence star-forming galaxies.
Altered Morphology and Immunohistochemical Characteristics in Metastatic Malignant Melanoma After Therapy With Vemurafenib
Authors: Powell Matthew R. , Sheehan Daniel J. , Kleven Daniel T.
Published: August 2016

Metastatic melanoma is traditionally diagnosed using classic morphologic features in addition to immunohistochemical studies. The authors report a case of metastatic malignant melanoma where both morphology and immunohistochemistry were altered after treatment. This 51-year-old patient presented with metastatic melanoma to the brain and axilla. Initially, both metastases showed classic morphology and diffuse staining with the pan-melanoma antibody cocktail. This cocktail is a combination of 3 antibodies commonly used to diagnose melanocytic neoplasms: Melan-A (MART-1), tyrosinase, and HMB-45. In combination, the cocktail is highly sensitive for detecting melanocytic neoplasms and is commonly used to diagnose metastatic melanoma. Her tumor was positive for the BRAF 1799T>A (V600E) mutation, and she was treated with BRAF inhibitor therapy (vemurafenib). However, the axillary tumor recurred after treatment with vemurafenib. The recurrent tumor showed a markedly different morphology and complete loss of staining with the pan-melanoma antibody cocktail. This loss of staining accompanied by the change in morphology was an observation not previously documented after therapy with vemurafenib. This case demonstrates a potential pitfall in the diagnosis of metastatic or recurrent malignant melanoma.
Endodermal Cyst of the Third Nerve in a Child
Authors: Jiramongkolchai Kim , Bhatti Muhammed T. , Fuchs Herbert E. , Cummings Thomas E. , Jiramongkolchai Pawina , El-Dairi Mays A.
Published: August 2016

Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.
Reward-based training of recurrent neural networks for cognitive and value-based tasks
Authors: Song H. Francis , Yang Guangyu R. , Wang Xiao-Jing
Published: August 2016

Trained neural network models, which exhibit many features observed in neural recordings from behaving animals and whose activity and connectivity can be fully analyzed, may provide insights into neural mechanisms. In contrast to commonly used methods for supervised learning from graded error signals, however, animals learn from reward feedback on definite actions through reinforcement learning. Reward maximization is particularly relevant when the optimal behavior depends on an animal’s internal judgment of confidence or subjective preferences. Here, we describe reward-based training of recurrent neural networks in which a value network guides learning by using the selected actions and activity of the policy network to predict future reward. We show that such models capture both behavioral and electrophysiological findings from well-known experimental paradigms. Our results provide a unified framework for investigating diverse cognitive and value-based computations, including a role for value representation that is essential for learning, but not executing, a task.
Evolution of copper resistance in the kiwifruit pathogen Pseudomonas syringae pv. actinidiae through acquisition of integrative conjugative elements and plasmids
Authors: Colombi Elena , Straub Christina , Kunzel Sven , Templeton Matthew D , McCann Honour C , Rainey Paul B
Published: August 2016

Lateral gene transfer can precipitate rapid evolutionary change. In 2010 the global pandemic of kiwifruit canker disease caused by Pseudomonas syringae pv. actinidiae (Psa) reached New Zealand. At the time of introduction, the single clone responsible for the outbreak was sensitive to copper, however, analysis of a sample of isolates taken in 2015 and 2016 showed that a quarter were copper resistant. Genome sequences of seven strains showed that copper resistance (comprising czc/cusABC and copABCD systems) along with resistance to arsenic and cadmium, was acquired via uptake of integrative conjugative elements (ICEs), but also plasmids. Comparative analysis showed ICEs to have a mosaic structure, with one being a tripartite arrangement of two different ICEs and a plasmid that were isolated in 1921 (USA), 1968 (NZ) and 1988 (Japan), from P. syringae pathogens of millet, wheat and kiwifruit, respectively. Two of the Psa ICEs were nearly identical to two ICEs isolated from kiwifruit leaf colonists prior to the introduction of Psa into NZ. Additionally, we show ICE transfer in vitro and in planta, analyze fitness consequences of ICE carriage, capture the de novo formation of novel recombinant ICEs, and explore ICE host-range.
Assembly of Radically Recoded E. coli Genome Segments
Authors: Norville Julie E. , Gardner Cameron L. , Aponte Eduardo , Camplisson Conor K. , Gonzales Alexandra , Barclay David K. , Turner Katerina A. , Longe Victoria , Mincheva Maria , Teramoto Jun , Tominaga Kento , Sugimoto Ryota , DiCarlo James E. , Guell Marc , Hysolli Eriona , Aach John , Gregg Christopher J. , Wanner Barry L. , Church George M.
Published: August 2016

The large potential of radically recoded organisms (RROs) in medicine and industry depends on improved technologies for efficient assembly and testing of recoded genomes for biosafety and functionality. Here we describe a next generation platform for conjugative assembly genome engineering, termed CAGE 2.0, that enables the scarless integration of large synthetically recoded E. coli segments at isogenic and adjacent genomic loci. A stable tdk dual selective marker is employed to facilitate cyclical assembly and removal of attachment sites used for targeted segment delivery by sitespecific recombination. Bypassing the need for vector transformation harnesses the multi Mb capacity of CAGE, while minimizing artifacts associated with RecA-mediated homologous recombination. Our method expands the genome engineering toolkit for radical modification across many organisms and recombinase-mediated cassette exchange (RMCE).
Direct determination of diploid genome sequences
Authors: Weisenfeld Neil I. , Kumar Vijay , Shah Preyas , Church Deanna M. , Jaffe David B.
Published: August 2016

Determining the genome sequence of an organism is challenging, yet fundamental to understanding its biology. Over the past decade, thousands of human genomes have been sequenced, contributing deeply to biomedical research. In the vast majority of cases, these have been analyzed by aligning sequence reads to a single reference genome, biasing the resulting analyses and, in general, failing to capture sequences novel to a given genome.

Somede novoassemblies have been constructed, free of reference bias, but nearly all were constructed by merging homologous loci into single ‘consensus’ sequences, generally absent from nature. These assemblies do not correctly represent the diploid biology of an individual. In exactly two cases, true diploidde novoassemblies have been made, at great expense. One was generated using Sanger sequencing and one using thousands of clone pools.

Here we demonstrate a straightforward and low-cost method for creating true diploidde novoassemblies. We make a single library from ~1 ng of high molecular weight DNA, using the 10x Genomics microfluidic platform to partition the genome. We applied this technique to seven human samples, generating low-cost HiSeq X data, then assembled these using a new ‘pushbutton’ algorithm, Supernova. Each computation took two days on a single server. Each yielded contigs longer than 100 kb, phase blocks longer than 2.5 Mb, and scaffolds longer than 15 Mb. Our method provides a scalable capability for determining the actual diploid genome sequence in a sample, opening the door to new approaches in genomic biology and medicine.
Deep Learning and Association Rule Mining for Predicting Drug Response in Cancer. A Personalised Medicine Approach
Authors: Vougas Konstantinos , Krochmal Magdalena , Jackson Thomas , Polyzos Alexander , Aggelopoulos Archimides , Pateras Ioannis S. , Liontos Michael , Varvarigou Anastasia , Johnson Elizabeth O. , Georgoulias Vassilis , Vlahou Antonia , Townsend Paul , Thanos Dimitris , Bartek Jiri , Gorgoulis Vassilis G.
Published: August 2016

A major challenge in cancer treatment is predicting the clinical response to anti-cancer drugs for each individual patient. For complex diseases such as cancer, characterized by high inter-patient variance, the implementation of precision medicine approaches is dependent upon understanding the pathological processes at the molecular level. While the “omics” era provides unique opportunities to dissect the molecular features of diseases, the ability to utilize it in targeted therapeutic efforts is hindered by both the massive size and diverse nature of the “omics” data. Recent advances with Deep Learning Neural Networks (DLNNs), suggests that DLNN could be trained on large data sets to efficiently predict therapeutic responses in cancer treatment. We present the application of Association Rule Mining combined with DLNNs for the analysis of high-throughput molecular profiles of 1001 cancer cell lines, in order to extract cancer-specific signatures in the form of easily interpretable rules and use these rules as input to predict pharmacological responses to a large number of anti-cancer drugs. The proposed algorithm outperformed Random Forests (RF) and Bayesian Multitask Multiple Kernel Learning (BMMKL) classification which currently represent the state-of-the-art in drug-response prediction. Moreover, thein silicopipeline presented, introduces a novel strategy for identifying potential therapeutic targets, as well as possible drug combinations with high therapeutic potential. For the first time, we demonstrate that DLNNs trained on a large pharmacogenomics data-set can effectively predict the therapeutic response of specific drugs in different cancer types. These findings serve as a proof of concept for the application of DLNNs to predict therapeutic responsiveness, a milestone in precision medicine.
The ExAC Browser: Displaying reference data information from over 60,000 exomes
Authors: Karczewski Konrad J. , Weisburd Ben , Thomas Brett , Ruderfer Douglas M. , Kavanagh David , Hamamsy Tymor , Lek Monkol , Samocha Kaitlin E. , Cummings Beryl B. , Birnbaum Daniel ,   The Exome Aggregation Consortium, Daly Mark J. , MacArthur Daniel G.
Published: August 2016

Worldwide, hundreds of thousands of humans have had their genomes or exomes sequenced, and access to the resulting data sets can provide valuable information for variant interpretation and understanding gene function. Here, we present a lightweight, flexible browser framework to display large population datasets of genetic variation. We demonstrate its use for exome sequence data from 60,706 individuals in the Exome Aggregation Consortium (ExAC). The ExAC browser provides gene- and transcript-centric displays of variation, a critical view for clinical applications. Additionally, we provide a variant display, which includes population frequency and functional annotation data as well as short read support for the called variant. This browser is open-source, freely available, and has already been used extensively by clinical laboratories worldwide.
5‐Bromo‐2′‐deoxyuridine induced effluvium via p53‐mediated CD326‐positive keratinocyte apoptosis in C57BL/6 mice
Authors: Uh Kyung‐Jun , Hwang Woo‐Sung , Bae Ji‐Hyun , Jang Da‐Eun , Yeom Su‐Cheong
Published: August 2016

Anagen effluvium develops because of disturbances in the hair follicle cycle, leading to acute and severe hair loss in humans. The objective of this study was to establish a mouse model of anagen effluvium by 5‐bromo‐2′‐deoxyuridine (BrdU) treatment, and evaluate the pathological changes and underlying mechanisms. We treated 9–10‐day‐old pups and 3–7‐week‐old C57BL/6 mice with BrdU. After successfully inducing hair loss in the neonatal pups, microscopic, immunohistochemical and flow cytometry analyses were conducted. BrdU induced early onset alopecia in neonates and caused epidermal thickening and hair shaft breakage. BrdU appeared to incorporate the CD326‐positive keratinocyte layer and induced p53‐related apoptosis. Keratinocyte apoptosis caused immune cell infiltration in the dermal region; M2 macrophages and neutrophils were dominant. The BrdU‐induced hair loss was dose‐dependent, and alopecia was visible at a dose range of 25–200 μg/g bodyweight. The BrdU‐induced anagen effluvium mouse model is novel and easily established by administrating four simple BrdU injections to pups; these mice showed synchronized onset of alopecia symptoms with little individual variation. Moreover, this model showed an alopecia phenotype similar to that of human anagen effluvium with acute, severe and widespread hair loss.
Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis
Authors: Takahashi Toshifumi , Fujimoto Noriki , Kabuto Miho , Nakanishi Takeshi , Tanaka Toshihiro
Published: August 2016

Loss‐of‐function mutations of the IL36RN gene, encoding interleukin‐36 receptor antagonist (IL‐36Ra), have been reported as major pathogenic causes of generalized pustular psoriasis (GPP), especially in cases lacking previous histories of psoriasis vulgaris. Palmoplantar pustulosis (PPP), which is traditionally included among GPP‐related diseases, has a controversial association with IL36RN. While a negative view about the said association has been recently published from Europe, variations of the IL36RN gene show great ethnic differences. In this study, we performed mutation analysis of the IL36RN gene in 88 Japanese patients with PPP and identified three types of single base substitutions in four patients, namely, p.Pro82Leu in two patients, p.Asn47Ser in one and p.Thr123Met in another. All variations were heterozygous and different from previous European reports. We compared the immunohistochemical findings of IL‐36Ra on patients with and without variation of the IL36RN gene; however, no significant differences were observed. Our data and the previous European study suggest that PPP is not associated with mutations of the IL36RN gene.
Comparative morphology of sensilla on antenna, maxillary palp and labial palp of larvae of white‐spotted and yellow‐spotted Asian long‐horned beetle,Anoplophora glabripennisMotschulsky (Coleoptera: Cerambycidae)
Authors: Yang Yuchao , Xu Lili , Ren Lili , Xu Zhichun , Zong Shixiang
Published: August 2016

The Asian long‐horned beetle (ALB) is one of the most important wood‐boring insects worldwide that damages broad‐leaved trees, primarily poplar, willow, elm and maple. Based on the color of the spots on the elytra, the beetles are separated into white‐spotted (ALB‐W) and yellow‐spotted (ALB‐Y) Asian long‐horned beetles. In order to clarify the morphology of sensilla on antenna, maxillary palp and labial palp of ALB‐W and ALB‐Y larvae, we studied the typology, morphology, number and distribution of the sensilla by scanning electron microscopy. The results showed that: (i) the antennae of two biotypes had five types of sensilla, including three types of sensilla basiconica (b.) and two types of sensilla twig basiconica (s.tb); numbers of b.1, b.2, b.3 and s.tb1 on antenna were not significantly different (P > 0.05) between two biotypes, and the numbers of s.tb2 were significantly different (P < 0.05); (ii) the maxillary palp of two biotypes had four types of sensilla, including sensilla styloconica (st.), two types of s.tb and digitiform sensilla (ds.); the numbers of st. and ds. on the maxillary palp were not significantly different (P > 0.05) between two biotypes, and the numbers of s.tb1 and s.tb2 were significantly different (P < 0.05); (iii) the labial palp of two biotypes had four types of sensilla, including b., st. and two types of s.tb, and the numbers of b.3, st., s.tb1 and s.tb2 on the labial palp were not significantly different (P > 0.05) between two biotypes. We discuss the relationships between sensilla and damage caused by the larvae inside the host trees.
Chemical meat bait traps versus basic meat bait traps in collection of adult flies
Authors: Açikgöz Halide Nihal , Köse Serdal Kenan , Divrak Duygu
Published: August 2016

The aim of the present study is to compare the effectiveness of chemical meat bait traps and basic meat bait traps for collecting adult flies. Bait traps used to collect these species can be damaged by anthropogenic or environmental effects. In this study, chemical meat bait traps and basic meat bait traps were hung from trees in the garden of the Ankara University Forensic Sciences Institute. This activity was carried out on the first Monday of each month for nine months. During the study, 1894 specimens were collected. Of all these species, 1787 (94.35%) were obtained from chemical meat bait traps (CMBTs), while 107 (5.65%) were obtained from basic meat bait traps (BMBTs). To determine the diversity of species in CMBT and BMBT sample groups in our study, Shannon Wiener and Simpson diversity and dominance indices were used. Shannon Evenness Index was calculated to determine the relationship between species community‐density. Cluster analysis provided a summary of the similarity in species composition of different regions. The CMBT and BMBT trap groups similarity/dissimilarity feature was checked using Bray–Curtis cluster analysis. The number of species collected from CMBTs was considerably higher than in BMBTs. The results of this study will help researchers to save time. In addition, it should be kept in mind that thiamethoxam is harmful to the environment when it contaminates sources of water.
Neighborhood‐Level Drinking Norms and Alcohol Intervention Outcomes in HIV Patients Who Are Heavy Drinkers
Authors: Elliott Jennifer C. , Delker Erin , Wall Melanie M. , Feng Tianshu , Aharonovich Efrat , Tracy Melissa , Galea Sandro , Ahern Jennifer , Sarvet Aaron L. , Hasin Deborah S.
Published: August 2016

Background

Heavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV‐infected patients. Therefore, we investigated whether neighborhood‐level drinking norms modified response to alcohol intervention among HIV‐infected heavy drinkers.

Methods

Heavily‐drinking HIV comprehensive care patients (n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood‐level drinking norms were obtained from a separate general population study.

Results

Patients’ reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients’ reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity).

Conclusions

Neighborhood‐level drinking norms help explain differential response to an alcohol MI intervention among HIV‐infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions.
Neovascular age‐related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population‐based study
Authors: Hu Chao‐Chien , Lin Herng‐Ching , Sheu Jau‐Jiuan , Kao Li‐Ting
Published: August 2016

Purpose

This case–control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age‐related macular degeneration (AMD) using a population‐based data set in Taiwan.

Methods

We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age‐ and sex‐matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls.

Results

Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04–1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91–1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15–1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05–1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32–1.65) were significantly associated with AMD.

Conclusions

This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population.
Mode of perfusion influences infarct size, coronary flow and stress kinases in the isolated mouse heart
Authors: Bliksøen M. , Rutkovskiy A. , Vaage J. , Stensløkken K.‐O.
Published: August 2016

Aim

The isolated, retrogradely perfused heart (modified Langendorff model) is a widely used method in experimental heart research. The presence of an intraventricular balloon is necessary to get functional measurements. We have previously shown that the balloon induces phosphorylation of some suggested cardioprotective mitogen‐activated protein kinases (MAPK): P38‐MAPK, ERK 1/2 and JNK. We hypothesized that the balloon could influence cardioprotection, protect against ischaemia reperfusion injury and interfere with coronary flow.

Methods and Results

Isolated mouse hearts were perfused for 5, 10, 20, 40 and 60 min with a balloon in the left ventricle. We found a wavelike phosphorylation of all MAPK while AKT displayed a gradual dephosphorylation when compared to non‐perfused hearts. Hearts were subjected to 20 min of stabilization with or without the balloon, followed by 35 min of ischaemia and 120 min of reperfusion. Although the MAPK were phosphorylated, the infarcts were larger in the balloon group. When the balloon was present during the entire protocol, compared to removal at the end of ischaemia, the infarct size was also larger, especially in the endocardial layer. The balloon reduced post‐ischaemic endocardial coronary flow, despite a higher average flow, indicating a hyperperfused epicard. Blocking the balloon‐induced ERK 1/2 phosphorylation during stabilization did not affect infarct size. The effect of post‐conditioning was influenced by the balloon, showing reduced infarct size when the balloon was present.

Conclusion

The balloon used for pressure measurements may contributes to cell death possibly by reducing endocardial coronary flow.
Eosinophilic drug reactions detected by a prospective pharmacovigilance programme in a tertiary hospital
Authors: Ramírez Elena , Medrano‐Casique Nicolás , Tong Hoi Y. , Bellón Teresa , Cabañas Rosario , Fiandor Ana , González‐Ramos Jessica , Herranz Pedro , Trigo Elena , Muñoz Mario , Borobia Alberto M. , Carcas Antonio J. , Frías Jesús
Published: August 2016

Aim

We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors.

Methods

All peripheral eosinophilia >700 × 106 cells l−1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed.

Results

The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90–25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug‐induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13–35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28–22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01–1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human‐herpesvirus 6 was subsequently detected.

Conclusions

Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.
Gene‐specific DNA methylation may mediate atypical antipsychotic‐induced insulin resistance
Authors: Burghardt Kyle J , Goodrich Jacyln M , Dolinoy Dana C , Ellingrod Vicki L
Published: August 2016

Objectives

Atypical antipsychotics (AAPs) carry a significant risk of cardiometabolic side effects, including insulin resistance. It is thought that the insulin resistance resulting from the use of AAPs may be associated with changes in DNA methylation. We aimed to identify and validate a candidate gene associated with AAP‐induced insulin resistance by using a multi‐step approach that included an epigenome‐wide association study (EWAS) and validation with site‐specific methylation and metabolomics data.

Methods

Subjects with bipolar disorder treated with AAPs or lithium monotherapy were recruited for a cross‐sectional visit to analyze peripheral blood DNA methylation and insulin resistance. Epigenome‐wide DNA methylation was analyzed in a discovery sample (n = 48) using the Illumina 450K BeadChip. Validation analyses of the epigenome‐wide findings occurred in a separate sample (n = 72) using site‐specific methylation with pyrosequencing and untargeted metabolomics data. Regression analyses were conducted controlling for known confounders in all analyses and a mediation analysis was performed to investigate if AAP‐induced insulin resistance occurs through changes in DNA methylation.

Results

A differentially methylated probe associated with insulin resistance was discovered and validated in the fatty acyl CoA reductase 2 (FAR2) gene of chromosome 12. Functional associations of this DNA methylation site with untargeted phospholipid‐related metabolites were also detected. Our results identified a mediating effect of this FAR2 methylation site on AAP‐induced insulin resistance.

Conclusions

Going forward, prospective, longitudinal studies assessing comprehensive changes in FAR2 DNA methylation, expression, and lipid metabolism before and after AAP treatment are required to assess its potential role in the development of insulin resistance.
Understanding ironic criticism and empathic praise: The role of emotive communication
Authors: Agostino Alba , Im‐Bolter Nancie , Stefanatos Arianna K. , Dennis Maureen
Published: August 2016

Ironic criticism and empathic praise are forms of social communication that influence the affective states of others in a negative or positive way. In a sample of 76 typically developing children and adolescents (mean age = 11 years; 4 months; SD: 2 years; 8 months), we studied how understanding of emotional expression (facial expression of emotion) and emotive communication (affective theory of mind) was related to the ability to understand negatively valenced ironic criticism and positively valenced empathic praise. We modelled comprehension of irony and empathy in school‐aged children in relation to age and understanding of emotional expression and emotive communication. As expected, children showed significantly better understanding of emotional expression than emotive communication, which requires understanding why someone might mask their inner emotions. Meditational analyses showed that emotive communication partially mediated the relation between age and understanding ironic criticism and empathic praise. These findings suggest that the development of understanding irony and empathy over the school‐age years is associated with affective attributions or affective theory of mind.

Statement of contribution

What is already known on this subject?

Theory of mind has been found to be related to the developmental understanding of social communication.

Correct interpretation of facial emotional cues is also important for interpreting social communication.

What does this study add?

Affective components (i.e., affective theory of mind) also contribute to the development of social communication.

Emotive communication, the ability to modulate one's emotional expression according to social display rules may be predictive of social communication competency.
Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents
Authors: Gu Hong‐shun , Chen Xi , Zhang Jian‐wei , Zhang Lan , Li Lin
Published: August 2016

In this study, a series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities of the target compounds were evaluated in vitro and in vivo. The results showed that synthesized compounds 7a–7g decreased the activity of dopamine D2 receptors in HEK293 cells co‐transfected with D2 receptor/G protein α16a, with IC50 values of 0.051–0.35 μm. Compounds 7a–7g inhibited the over‐production of nitric oxide stimulated by lipopolysaccharide/interferon‐γ in BV‐2 microglial cells. In mice, intragastric administration of 7d, 7e, and 7g reversed the increase in locomotor activity induced by MK‐801 (an antagonist of NMDA receptors) and decreased the hyperactivity of climbing behavior induced by apomorphine (a dopamine receptor agonist). These results suggest that some of the novel flavanone derivatives have potential antipsychotic effects and may be useful in the treatment of schizophrenia.
Elevation of Vδ1 T cells in peripheral blood and livers of patients with primary biliary cholangitis
Authors: Hua F , Wang L , Rong X , Hu Y , Zhang J M , He W , Zhang F C
Published: August 2016

Primary biliary cholangitis (PBC), hitherto called primary biliary cirrhosis, is a cholestatic liver disease of unclear aetiology with autoimmune features. Accumulating evidence revealed that γδ T cells were involved in the development of autoimmune diseases. As one of γδ T cells subsets, however, the role of Vδ1 T cells in the immunopathogenesis of PBC is poorly understood. We analysed peripheral blood Vδ1 T cells in PBC patients in active stage (ASP, n = 18), adequate responders (AR, n = 10) and inadequate responders (IAR, n = 4) to ursodeoxycholic acid (UDCA) and an age-matched healthy control group (n = 16) by flow cytometric analysis. The ASP group exhibited a significantly higher proportion and absolute number of Vδ1 T cells, which were also observed in immunofluorescence staining of liver biopsy specimens of PBC patients. Moreover, these Vδ1 T cells expressed a series of activation markers and intracellular cytokines, which may contribute to the immunopathogenesis of PBC. Our study will help to clarify the role of Vδ1 T cells in the development of PBC.
Validation of the Airway–Dyspnoea–Voice–Swallow (ADVS) scale and Patient‐Reported Outcome Measure (PROM) as disease‐specific instruments in paediatric laryngotracheal stenosis
Authors: Nouraei S.A.R. , Makmur E. , Dias A. , Butler C.R. , Nandi R. , Elliott M.J. , Hewitt R.
Published: August 2016

Objective

To validate the Airway–Dyspnoea–Voice–Swallow (ADVS) instrument as a disease‐specific Patient‐Reported Outcome Measure in paediatric laryngotracheal stenosis.

Design

Prospective observational study.

Setting

A quaternary referral centre for complex airway disease.

Participants

Forty‐eight patients (30 males) with a mean age of 49 ± 49 months who underwent laryngotracheal surgery or microlaryngoscopy and bronchoscopy (MLB) following laryngotracheal surgery.

Main outcome measures

Airway–Dyspnoea–Voice–Swallow summary scale and Patient‐Reported Outcome Measure (PROM), Paediatric Quality of Life (PedsQL) scale, Paediatric Voice Handicap Index (pVHI) and Lansky performance scale were administered to patients before and 6–8 weeks following airway examination/surgery.

Results

Most patients (73%) had intubation‐related subglottic stenosis, and 60% of patients had prior airway treatments. The majority of patients (77%) had more than one major chronic morbidity, and the commonest procedures were diagnostic MLB (49%), followed by airway dilation (29%). Cronbach‐α value for the ADVS PROM was 0.71 overall and 0.85, 0.86 and 0.64 for the dyspnoea, voice and swallow domains, respectively. Rank correlations between Dyspnoea, Voice and Swallow summary scale and PROM scores were 0.83, 0.71 and 0.81, respectively (P < 0.0001). For those patients undergoing diagnostic MLB, pre‐ and post‐examination scores were highly correlated (intraclass correlations >0.75). There was a significant rank correlation between ADVS PROM score and Lansky performance score (r = −0.68; P < 0.0001). There were significant correlations between PROM score and PedsQL (r = −0.57; P < 0.0001) and between voice domain of the PROM and pVHI (r = 0.78; P < 0.0001). There were strong correlations between Myer–Cotton stenosis severity and dyspnoea scale and PROM score (r = 0.68; P < 0.0001). There were significant differences in voice and swallow ADVS scales and PROM scores between patients with and without concomitant laryngeal/oesophageal pathology. Patient age and presence of high dyspnoea and swallowing PROM scores were independently associated with poorer quality of life and performance status.

Conclusions

These series of observations validate the ADVS instrument as a disease‐specific outcome measure for paediatric laryngotracheal stenosis. Dyspnoea and swallowing dysfunction appear to have the greatest impact on quality of life. More widespread adoption of the ADVS instrument could help create a shared language for outcomes communication and benchmarking for children with this complex condition.
A national analysis of trends, outcomes and volume–outcome relationships in thyroid surgery
Authors: Nouraei S.A.R. , Virk J.S. , Middleton S.E. , Aylin P. , Mace A. , Vaz F. , Kaddour H. , Darzi A. , Tolley N.S.
Published: August 2016

Objectives

Thyroid conditions are common, and their incidence is increasing. Surgery is the mainstay treatment for many thyroid conditions, and understanding its utilisation trends and morbidity is central to improving patient care.

Design

An N = near‐all analysis of the English administrative dataset to identify trends in thyroid surgery specialisation, volume–outcome relationships, and the incidence and risk factors for short‐ and long‐term morbidity.

Main outcome measures

Between 2004 and 2012, 72 594 patients underwent elective thyroidectomy in England. Information about age, sex, morbidities, nature of thyroid disease and surgery, adjuvant treatments and complications including hypocalcaemia and vocal palsy was recorded.

Results

Mean age at surgery was 49 ± 30, and a female predominance (82%) was observed. Most patients underwent hemithyroidectomy (51%) or total thyroidectomy (32%). Patients underwent surgery for benign (52.5%), benign inflammatory (21%) and malignant (17%) thyroid diseases. Thyroid surgery grew by 2.9% a year and increased in specialisation. Increased surgeon volume significantly reduced lengths of stay: the proportion of length of stay outliers fell from 11.8% for patients of occasional thyroidectomists (<5 per year) to 2.8% for patients of high‐volume surgeons (>50 thyroidectomies a year). Post‐discharge vocal palsy and hypocalcaemia occurred in 1.87% and 1.58% of cases, respectively. High‐volume surgeons had a reduced incidence of vocal palsy, and volumes >30 were consistently protective.

Conclusions

Thyroid surgery is increasingly specialised. High‐volume surgeons, that is patients who perform 50 or more thyroidectomies per year, achieve lower complications and shorter lengths of stay.
Baseline swallowing measures predict recovery at 6 weeks after transoral robotic surgery for head and neck cancer
Authors: Owen S. , Puvanendran M. , Meikle D. , Bowe I. , O'Hara J. , Patterson J. , Paleri V.
Published: August 2016

Objectives

To explore whether pre‐treatment swallowing measures predict swallowing recovery at 6 weeks after transoral robotic surgery (TORS).

Design

Prospective cohort study.

Setting

Tertiary care cancer centre in the United Kingdom.

Participants

Fifty‐one consecutive patients undergoing TORS for head and neck cancer, between April 2013 and February 2015.

Main outcome measures

Swallowing function assessed by Performance Status Scale (PSS) Normalcy of Diet, timed water swallow test capacity scores (WST) and duration of tube feeding.

Results

The primary site distribution was as follows: 21 oropharynx, 8 larynx, 6 mucosectomy and 6 hypopharynx. T stages included 7 staged Tx, 21 T1–T2 tumours and 1 T3 tumour. Moderate‐to‐severe comorbidity was found in 45/51 patients. Mean PSS score was 83 (sd 27.54); mean WST score was 11.14 (sd 7.97). Most patients (73%) required tube feeding post‐operatively, with mean tube feed duration of 18.08 days (sd 17.91); 76% resumed oral intake by 6 weeks. Pre‐treatment swallow tests showed moderate negative correlation with tube feeding duration: PSS (rho 0–.430, P = .003); WST (rho 0–.503, P = 0.002).

Conclusions

The majority of TORS patients resume oral intake by 6 weeks. This study shows that impaired swallowing prior to surgery correlates with post‐operative duration of tube feeding and strengthens the evidence for the utility of these measures in this clinical setting.
Prediction, prevention, and management of delayed graft function: where are we now?
Authors: Nashan Björn , Abbud‐Filho Mario , Citterio Franco
Published: August 2016

Delayed graft function (DGF) remains a major barrier to improved outcomes after kidney transplantation. High‐risk transplant recipients can be identified, but no definitive prediction model exists. Novel biomarkers to predict DGF in the first hours post‐transplant, such as neutrophil gelatinase‐associated lipocalin (NGAL), are under investigation. Donor management to minimize the profound physiological consequences of brain death is highly complex. A hormonal resuscitation package to manage the catecholamine “storm” that follows brain death is recommended. Donor pretreatment with dopamine prior to procurement lowers the rate of DGF. Hypothermic machine perfusion may offer a significant reduction in the rate of DGF vs simple cold storage, but costs need to be evaluated. Surgically, reducing warm ischemia time may be advantageous. Research into recipient preconditioning options has so far not generated clinically helpful interventions. Diagnostic criteria for DGF vary, but requirement for dialysis and/or persistent high serum creatinine is likely to remain key to diagnosis until current work on early biomarkers has progressed further. Management centers on close monitoring of graft (non)function and physiological parameters. With so many unanswered questions, substantial reductions in the toll of DGF in the near future seem unlikely but concentrated research on many levels offers long‐term promise.
Bayley‐III motor scale and neurological examination at 2 years do not predict motor skills at 4.5 years
Authors: Burakevych Nataliia , Mckinlay Christopher Joel Dorman , Alsweiler Jane Marie , Wouldes Trecia Ann , Harding Jane Elizabeth ,   the Chyld Study Team
Published: August 2016

Aim

To determine whether Bayley Scales of Infant and Toddler Development (3rd edition) (Bayley‐III) motor scores and neurological examination at 2 years corrected age predict motor difficulties at 4.5 years corrected age.

Method

A prospective cohort study of children born at risk of neonatal hypoglycaemia in Waikato Hospital, Hamilton, New Zealand. Assessment at 2 years was performed using the Bayley‐III motor scale and neurological examination, and at 4.5 years using the Movement Assessment Battery for Children (2nd edition) (MABC‐2).

Results

Of 333 children, 8 (2%) had Bayley‐III motor scores below 85, and 50 (15%) had minor deficits on neurological assessment at 2 years; 89 (27%) scored less than or equal to the 15th centile, and 54 (16%) less than or equal to the 5th centile on MABC‐2 at 4.5 years. Motor score, fine and gross motor subtest scores, and neurological assessments at 2 years were poorly predictive of motor difficulties at 4.5 years, explaining 0 to 7% of variance in MABC‐2 scores. A Bayley‐III motor score below 85 predicted MABC‐2 scores less than or equal to the 15th centile with a positive predictive value of 30% and a negative predictive value of 74% (7% sensitivity and 94% specificity).

Interpretation

Bayley‐III motor scale and neurological examination at 2 years were poorly predictive of motor difficulties at 4.5 years.
Right ventricular global longitudinal strain in repaired tetralogy of Fallot
Authors: Toro Kamill Del , Soriano Brian D. , Buddhe Sujatha
Published: August 2016

Background

Echocardiogram has limitations in effectively assessing right ventricular (RV) function in children post tetralogy of Fallot (TOF) repair. We evaluated the utility of speckle tracking echocardiography (STE)‐based RV global longitudinal strain (GLS) for the assessment of RV systolic function.

Methods

All patients with repaired TOF who had both echocardiograms and cardiac MRI (CMR) within a 6‐month interval were included. RV volumes and ejection fraction (EF) were obtained by CMRs. Traditional echocardiographic function parameters and RV GLS were compared to CMR‐derived RV EF. Subjects were divided into two groups based on CMR RV EF (group I: RV EF ≥45%; and group II: RV EF <45%).

Results

A total of 57 subjects were included. Mean age was 13.0±3.6 years and 58% were males. Group I had 39 subjects and group II had 18. Only six of the 18 patients (33%) in group II were identified as having at least mild RV dysfunction by echocardiogram. The mean RV GLS was significantly abnormal in group II (−15.3±3.8%) compared to group I (−20.9±3.3%; P<.001). By ROC analysis, an RV GLS cutoff value of −18% had 78% sensitivity and 77% specificity in identifying RV EF <45% (area under curve .87, P<.001). Intra‐ and inter‐observer reproducibility of RV GLS were good.

Conclusion

RV GLS is a simple and effective tool for the assessment of RV systolic function in patients post TOF repair. This technique would help further refine patient selection for timing of CMR and management.