bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of inclusions on the high‐temperature low‐cycle fatigue performance of cast MarBN: Experimental characterisation and computational modelling
Authors: O'Hara E.M. , Harrison N.M. , Polomski B.K. , Barrett R.A. , Leen S.B.
Published: June 2018

The presence of inclusions is a known source of crack initiation and component failure in cast materials. In this work, the role of inclusions is investigated via a combined program of high‐temperature low‐cycle fatigue testing and computational modelling of a tempered martensitic steel, MarBN. Microstructural analysis has shown that manufacturing‐induced oxide inclusions are a key source of fatigue crack initiation. A fully coupled, critical plane life prediction and damage model is implemented in a unified cyclic viscoplastic user‐material subroutine and applied to predict damage and micro‐crack initiation for inclusions. It is deduced that more careful control of the development of inclusions in the manufacturing process will provide enhanced material and component performance for highly flexible and ultrasupercritical plant conditions.
Unraveling salt stress signaling in plants
Authors: Yang Yongqing , Guo Yan
Published: June 2018

Salt stress is a major environmental factor limiting plant growth and productivity. A better understanding of the mechanisms mediating salt resistance will help researchers design ways to improve crop performance under adverse environmental conditions. Salt stress can lead to ionic stress, osmotic stress and secondary stresses, particularly oxidative stress, in plants. Therefore, to adapt to salt stress, plants rely on signals and pathways that re‐establish cellular ionic, osmotic, and reactive oxygen species (ROS) homeostasis. Over the past two decades, genetic and biochemical analyses have revealed several core stress signaling pathways that participate in salt resistance. The Salt Overly Sensitive signaling pathway plays a key role in maintaining ionic homeostasis, via extruding sodium ions into the apoplast. Mitogen‐activated protein kinase cascades mediate ionic, osmotic, and ROS homeostasis. SnRK2 (sucrose nonfermenting 1‐related protein kinase 2) proteins are involved in maintaining osmotic homeostasis. In this review, we discuss recent progress in identifying the components and pathways involved in the plant's response to salt stress and their regulatory mechanisms. We also review progress in identifying sensors involved in salt‐induced stress signaling in plants.
I‐123 DaTscan SPECT Brain Imaging in Parkinsonian Syndromes: Utility of the Putamen‐to‐Caudate Ratio
Authors: Matesan Manuela , Gaddikeri Santhosh , Longfellow Katelan , Miyaoka Robert , Elojeimy Saeed , Elman Shana , Hu Shu‐Ching , Minoshima Satoshi , Lewis David
Published: June 2018

BACKGROUND AND PURPOSE

Computer‐based analysis of Dopamine transporter imaging (DaTscan) can aid in image interpretation. In this study, we examined the distribution of putamen‐to‐caudate ratios (PCRs) obtained by using a clinically available semiquantification method.

METHODS

Medical records of 32 patients (M:16) with a diagnosis of Parkinson's disease (PD) (n = 22) or Parkinson's plus syndromes (PPS) (n = 10) based on clinical follow‐up, were retrospectively reviewed. Single photon emission tomography (SPECT) imaging was performed 4 hours after intravenous injection of 3–5 mCi [I‐123]‐ioflupane. Semiquantitative evaluation using DaTQUANT software was performed. Utility of PCR with a cutoff of .7 and .8 in the diagnosis of nigrostriatal degeneration was assessed. PD and PPS groups based on clinical assessment and caudate‐to‐background ratio (CBR) were assessed separately.

RESULTS

Minimum PCR for both hemispheres was .74 ± .09 (Mean ± SD, range: .58‐.89), with 65.63% patients (21/32) having PCR > .7. Mean PCR in mild nigrostriatal degeneration was .77 ± .08 (range: .62‐.89) and in advanced nigrostriatal degeneration was .73 ± .09 (range: .58‐.89). Mean PCR in PD group was .73 ± .09 (range: .58‐.89) and in PPS group was .75 ± .10 (range: .61‐.88).

CONCLUSIONS

Although PCR can intrinsically be a useful indication of disease, this ratio obtained in our analysis by using one of the clinically available automatic semiquantitative methods has large variability and might not be a reliable numeric marker in interpretation of [I‐123]ioflupane studies. This may be due to difficulty in separating caudate from putamen on SPECT images, as well as the nonuniform decreased Ioflupane uptake in both putamen and caudate.
Job burnout: The contribution of emotional stability and emotional self‐efficacy beliefs
Authors: Alessandri Guido , Perinelli Enrico , De Longis Evelina , Schaufeli Wilmar B. , Theodorou Annalisa , Borgogni Laura , Caprara Gian Vittorio , Cinque Luigi
Published: June 2018

Consistent with insights from both trait and social cognitive theories, this study presents a theoretical model positing emotional self‐efficacy beliefs in managing negative emotions at work as a key mechanism that contributes to mediate the negative relationship between emotional stability – a trait highly associated with positive affect and mental health – and job burnout. To test this assertion, a two‐wave study using a representative sample of 416 new military cadets of an Italian military academy was designed. Military cadets were involved in the study 2 months after their entrance into the academy and then again, a year later. Results from structural equation modelling supported the hypothesized model. As predicted, self‐efficacy beliefs in managing negative emotions at work significantly mediated the longitudinal relation between emotional stability and job burnout, even after controlling for the effect of the other Big Five traits, education, previous experience in military contexts, gender, and age. Practical implications and directions for future research are discussed. In conclusion, our study demonstrates that self‐efficacy in managing negative emotions at work represents an important mechanism linking emotional stability level to burnout symptoms.

Practitioner points

Self‐efficacy in managing negative emotions at work proved to be an important resource for workers in managing job‐related stress: practitioners interested in reducing burnout symptoms in stressful working environments should take into account this variable.

Self‐efficacy beliefs in managing negative emotions at work are cognitive structures malleable to change. Literature on social cognitive theory offers several suggestions on how to promote individuals’ positive beliefs on managing negative emotions and dysphoric affect. Hence, findings and literature reported in this study may be useful for practitioners aiming at strengthen workers’ self‐efficacy in managing negative emotions at work, through the development and application of coaching and training programmes.
PETROLEUM CHARGE AND MIGRATION IN THE BLACK SEA: INSIGHTS FROM OIL AND SOURCE ROCK GEOCHEMISTRY
Authors: Mayer J. , Sachsenhofer R.F. , Ungureanu C. , Bechtel A. , Gratzer R. , Sweda M. , Tari G.
Published: June 2018

Although a number of significant oil and gas discoveries have been made within the Western Black Sea and the surrounding area, only sparse data about migration mechanisms are available. In this paper, biomarker and isotope data from five oilfields and one oil show located offshore Bulgaria and Romania (in the western Black Sea), and from one field onshore Georgia (at the margin of the eastern Black Sea), were compared with geochemical data from potential source rock intervals from borehole samples. The source rock data came from offshore Bulgaria and outcrop samples from onshore Georgia. The biomarker data indicates that all the oils analysed were generated by source rocks of Late Cretaceous or Cenozoic age. In the Western Black Sea sub‐basin, the most likely source rocks are Oligocene to Lower Miocene shales of the Maikop Group. Compound‐specific isotope data indicate that Lower Oligocene source rocks are the most significant although a contribution by Lower Miocene diatom‐rich source rocks cannot be excluded. For an oil sample from the Shromisubani field onshore Georgia, isotope data from individual n‐alkanes together with biomarker data indicates that the oil contains a mixture of hydrocarbons generated from the Middle Eocene Kuma Formation and the Oligocene part of the Maikop Group.

Oligocene and Miocene source rocks are immature at the shelfal locations where the oil samples were recovered. Charge for these hydrocarbon accumulations is interpreted to have been provided by long‐distance lateral migration from source kitchens in more central parts of the Black Sea basin, where Oligocene and (some) Miocene source rocks are within the oil and gas window. The results of this study highlight the prospectivity of recently‐discovered deep‐water plays, and significantly de‐risk future deep‐water projects within the Black Sea area.
Examining Family Quality of Life Within the Context of a Participant‐Directed ASD Funding Program in British Columbia, Canada
Authors: Gardiner Emily , Iarocci Grace
Published: June 2018

Individuals with autism spectrum disorder (ASD) will access significant supports across their lifespan, often within multiple service systems (e.g., medical, education, mental health, and social). The responsibility for service coordination most often falls to the family, and frustrations with systemic and practical barriers have significant implications for family functioning, and specifically for family quality of life (FQOL). This mixed‐methods study examined caregivers' perceptions of service access within British Columbia, a province that utilizes a participant‐directed model. Families described how their interactions with the service system impacted their FQOL, and differences across families representative of both the high and low ends of the FQOL satisfaction continuum were examined. Caregivers (N = 118) of individuals with ASD (aged 6–18 years) reported on their satisfaction with support and FQOL, and described their service navigation experiences. Fifteen caregivers also participated in follow‐up interviews, in which they elaborated on their perceptions of service delivery, highlighting the associated strengths and challenges. Overall, only approximately one‐quarter of participants were “satisfied” or “very satisfied” with the resources and funds available to their family, and the average satisfaction rating was low. Caregivers shared their concerns about the British Columbia service context, describing the system as inflexible, complicated, and inaccessible. Participants shared how burdensome they found funding and service coordination to be, and highlighted the strain associated with the lack of available guidance. This suggests that it is not enough to simply make families responsible for service coordination if they are not also armed with the necessary knowledge and supports. The implications for policy and practice are reviewed.
Multiple Matrix Gaussian Graphs Estimation
Authors: Zhu Yunzhang , Li Lexin
Published: June 2018

Matrix-valued data, where the sampling unit is a matrix consisting of rows and columns of measurements, are emerging in numerous scientific and business applications. Matrix Gaussian graphical models are a useful tool to characterize the conditional dependence structure of rows and columns. We employ non-convex penalization to tackle the estimation of multiple graphs from matrix-valued data under a matrix normal distribution. We propose a highly efficient non-convex optimization algorithm that can scale up for graphs with hundreds of nodes. We establish the asymptotic properties of the estimator, which requires less stringent conditions and has a sharper probability error bound than existing results. We demonstrate the efficacy of our proposed method through both simulations and real functional magnetic resonance imaging analyses.
Atmospheric pressure plasma jet: A facile method to modify the intimal surface of polymeric tubular conduits
Authors: Tucker Bernabe S. , Baker Paul A. , Xu Kunning G. , Vohra Yogesh K. , Thomas Vinoy
Published: June 2018

Atmospheric pressure plasma jet (APPJ) based modification as a facile method to modify the intimal surface of small caliber nanofibrous tubular tissue scaffolds for potential use as vascular-graft or spinal-cord conduit is reported here. Polycaprolactone, a biomaterial used in the US Food and Drug Administration approved scaffolds for various tissue regeneration and bioabsorbable suture applications, was electrospun into thin nano/microfibers to form seamless three-dimensional (3D) conduits of 4 mm intimal diameter. The 3D conduits were subjected to treatment with an APPJ produced by dielectric barrier discharge using controlled gas flow into ambient atmosphere. He/air or He/air/NH3 gas mixtures combined with 8.5 kV pulsed direct current signal proved effective in creating a sustained and reactive cold plasma jet to modify the intimal surface of tubular scaffolds without affecting its biomechanical properties. The treatment resulted in surface chemistry modification as indicated by enrichment of oxygenated functional groups. Surface chemistry was determined via x-ray photoelectron spectroscopy. Scanning electron microscopy and glycerol contact angle measurements were used to determine the surface morphology and surface wettability. The data support the conclusion that APPJ is as an effective, facile, and robust approach to modify the intimal surface of small-caliber (<4 mm) tubular conduits (successfully accomplished and initially reported here) for potential applications in vascular and neural tissue engineering.
Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in
mcr
-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-
H
30Rx and Non-x
Authors: Sato Toyotaka , Shiraishi Tsukasa , Hiyama Yoshiki , Honda Hiroyuki , Shinagawa Masaaki , Usui Masaru , Kuronuma Koji , Masumori Naoya , Takahashi Satoshi , Tamura Yutaka , Yokota Shin-ichi
Published: June 2018

Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (
mcr
) gene-negative colistin-resistant
Escherichia coli
clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-
H
30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter).
Dementia and advance directives: some empirical and normative concerns
Authors: Jongsma Karin R , Kars Marijke C , van Delden Johannes J M
Published: June 2018

The authors of the paper ‘Advance euthanasia directives: a controversial case and its ethical implications’ articulate concerns and reasons with regard to the conduct of euthanasia in persons with dementia based on advance directives. While we agree on the conclusion that there needs to be more attention for such directives in the preparation phase, we disagree with the reasons provided by the authors to support their conclusions. We will outline two concerns with their reasoning by drawing on empirical research and by providing reasons that contradict their assumptions about competence of people with dementia and the (un)importance of happiness in reasoning about advance directives of people with dementia. We will draw attention to the important normative questions that have been overstepped in their paper, and we will outline why further research is required.
Ventilation inhomogeneity in infants with recurrent wheezing
Authors: Lu Zihang , Foong Rachel E , Kowalik Krzysztof , Moraes Theo J , Boyce Ayanna , Dubeau Aimee , Balkovec Susan , Gustafsson Per Magnus , Becker Allan B , Mandhane Piush J , Turvey Stuart E , Lou Wendy , Ratjen Felix , Sears Malcolm , Subbarao Padmaja
Published: June 2018

Background

The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing.

Objective

To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls.

Methods

This is a case–control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography.

Results

LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (−0.11 to 0.63) vs −0.58 (−0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05).

Conclusions

Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.
Novel role of PKR in palmitate-induced Sirt1 inactivation and endothelial cell senescence
Authors: Li Yapei , Peng Zhouyangfan , Wang Chunle , Li Le , Leng Yiping , Chen Ruifang , Yuan Hong , Zhou Shenghua , Zhang Zhen , Chen Alex F.
Published: June 2018

Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases. Elevated palmitate (PA) is an independent risk factor of cardiovascular diseases, but its role in endothelial cell senescence is currently unknown. During the course of studying the prosenescent role of PA, we discovered a key role of dsRNA-dependent protein kinase [protein kinase R (PKR)] in endothelial senescence. Exposure of human umbilical vein endothelial cells (HUVECs) to PA-induced cell senescence is characterized by increased levels of senescence-associated β-galactose glucosidase activity, excessive production of reactive oxygen species production, impaired cellular proliferation, and G1 phase arrest. This phenomenon is associated with an increase of PKR autophosphorylation and decreased activity of sirtuin 1 (Sirt1), a pivotal antisenescent factor. PKR inactivation by PKR siRNA or its phosphorylation inhibitor 2-aminopurine significantly attenuated PA-induced HUVEC senescence by reversing Sirt1 activity and its downstream signaling. Moreover, to study the regulatory mechanism between PKR and Sirt1, we found that PKR promotes JNK activation to inhibit Sirt1 activity and that this effect could be reversed by the JNK inhibitor SP600125. These findings provide evidence that PKR mediates PA-induced HUVEC senescence by inhibiting Sirt1 signaling. Our study provides novel insights into the actions and mechanisms of PKR in endothelial senescence.

NEW & NOTEWORTHY This study first provides a novel observation that dsRNA-dependent protein kinase (PKR) mediates palmitate-induced sirtuin 1 inactivation and subsequent human umbilical vein endothelial cell senescence. Most importantly, these new findings will provide a potential therapeutic strategy to improve free fatty acid-induced endothelial senescence by targeting PKR in cardiovascular diseases.
Blood pressure predicts endothelial function and the effects of ethinyl estradiol exposure in young women
Authors: Adler Tessa E. , Usselman Charlotte W. , Takamata Akira , Stachenfeld Nina S.
Published: June 2018

Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18–35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78–91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95–113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18–31%, n = 8; obese: 38–59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not.

NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.
New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis
Authors: Kimura Dai , Saravia Jordy , Jaligama Sridhar , McNamara Isabella , Vu Luan D. , Sullivan Ryan D. , Mancarella Salvatore , You Dahui , Cormier Stephania A.
Published: June 2018

Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of the present study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age and then reinfected 4 wk later. Serum-free medium was administered to age-matched mice as a control. Echocardiography and right ventricular systolic pressure (RVSP) measurements via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation monitoring did not indicate hypoxia at 2–4 days post-RSV infection, before reinfection, and at 2–7 days after reinfection. RSV-infected mice had significantly higher RVSP than control mice. Pulsed-wave Doppler recording of the pulmonary blood flow by echocardiogram demonstrated a significantly shortened pulmonary artery acceleration time and decreased pulmonary artery acceleration time-to-ejection time ratio in RSV-infected mice. Morphometry showed that RSV-infected mice exhibited a significantly higher pulmonary artery medial wall thickness and had an increased number of muscularized pulmonary arteries compared with control mice. These findings, confirmed by RVSP measurements, demonstrate the development of PH in the lungs of mice infected with RSV as neonates. This animal model can be used to study the pathogenesis of PH secondary to RSV bronchiolitis and to assess the effect of treatment interventions.

NEW & NOTEWORTHY This is the first mouse model of respiratory syncytial virus-induced pulmonary hypertension, to our knowledge. This model will allow us to decipher molecular mechanisms responsible for the pathogenesis of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis with the use of knockout and/or transgenic animals and to monitor therapeutic effects with echocardiography.
EWS/ETS-Driven Ewing Sarcoma Requires BET Bromodomain Proteins
Authors: Gollavilli Paradesi Naidu , Pawar Aishwarya , Wilder-Romans Kari , Natesan Ramakrishnan , Engelke Carl G. , Dommeti Vijaya L. , Krishnamurthy Pranathi M. , Nallasivam Archana , Apel Ingrid J. , Xu Tianlei , Qin Zhaohui S. , Feng Felix Y. , Asangani Irfan A.
Published: June 2018

The EWS/ETS fusion transcription factors drive Ewing sarcoma (EWS) by orchestrating an oncogenic transcription program. Therapeutic targeting of EWS/ETS has been unsuccessful; however, identifying mediators of the EWS/ETS function could offer new therapeutic options. Here, we describe the dependency of EWS/ETS-driven transcription upon chromatin reader BET bromdomain proteins and investigate the potential of BET inhibitors in treating EWS. EWS/FLI1 and EWS/ERG were found in a transcriptional complex with BRD4, and knockdown of BRD2/3/4 significantly impaired the oncogenic phenotype of EWS cells. RNA-seq analysis following BRD4 knockdown or inhibition with JQ1 revealed an attenuated EWS/ETS transcriptional signature. In contrast to previous reports, JQ1 reduced proliferation and induced apoptosis through MYC-independent mechanisms without affecting EWS/ETS protein levels; this was confirmed by depleting BET proteins using PROTAC-BET degrader (BETd). Polycomb repressive complex 2 (PRC2)-associated factor PHF19 was downregulated by JQ1/BETd or BRD4 knockdown in multiple EWS lines. EWS/FLI1 bound a distal regulatory element of PHF19, and EWS/FLI1 knockdown resulted in downregulation of PHF19 expression. Deletion of PHF19 via CRISPR-Cas9 resulted in a decreased tumorigenic phenotype, a transcriptional signature that overlapped with JQ1 treatment, and increased sensitivity to JQ1. PHF19 expression was also associated with worse prognosis in patients with EWS. In vivo, JQ1 demonstrated antitumor efficacy in multiple mouse xenograft models of EWS. Together these results indicate that EWS/ETS requires BET epigenetic reader proteins for its transcriptional program and can be mitigated by BET inhibitors. This study provides a clear rationale for the clinical utility of BET inhibitors in treating EWS.

Significance:

These findings reveal the dependency of EWS/ETS transcription factors on BET epigenetic reader proteins and demonstrate the potential of BET inhibitors for the treatment of EWS. Cancer Res; 78(16); 4760–73. ©2018 AACR.
Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer
Authors: Kim Tae Won , Peeters Marc , Thomas Anne , Gibbs Peter , Hool Kristina , Zhang Jianqi , Ang Agnes Lee , Bach Bruce Allen , Price Timothy
Published: June 2018

Purpose: The accumulation of emergent RAS mutations during anti-EGFR therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status.

Experimental Design: This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the PlasmaSelect-R 64-gene panel at 0.1% sensitivity.

Results: Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS. Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval, 11.5–15.4) and 7.9 months (6.4–9.6), respectively (P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations.

Conclusions: Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Clin Cancer Res; 24(22); 5602–9. ©2018 AACR.
Elective Nodal Irradiation Attenuates the Combinatorial Efficacy of Stereotactic Radiation Therapy and Immunotherapy
Authors: Marciscano Ariel E. , Ghasemzadeh Ali , Nirschl Thomas R. , Theodros Debebe , Kochel Christina M. , Francica Brian J. , Muroyama Yuki , Anders Robert A. , Sharabi Andrew B. , Velarde Esteban , Mao Wendy , Chaudhary Kunal R. , Chaimowitz Matthew G. , Wong John , Selby Mark J. , Thudium Kent B. , Korman Alan J. , Ulmert David , Thorek Daniel L.J. , DeWeese Theodore L. , Drake Charles G.
Published: June 2018

Purpose: In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of radiotherapy with immune checkpoint blockade (ICB).

Experimental Design: We developed a preclinical model to compare stereotactic radiotherapy (Tumor RT) with or without ENI to examine immunologic differences between radiotherapy techniques that spare or irradiate the DLN.

Results: Tumor RT was associated with upregulation of an intratumoral T-cell chemoattractant chemokine signature (CXCR3, CCR5-related) that resulted in robust infiltration of antigen-specific CD8+ effector T cells as well as FoxP3+ regulatory T cells (Tregs). The addition of ENI attenuated chemokine expression, restrained immune infiltration, and adversely affected survival when combined with ICB, especially with anti-CLTA4 therapy. The combination of stereotactic radiotherapy and ICB led to long-term survival in a subset of mice and was associated with favorable CD8 effector-to-Treg ratios and increased intratumoral density of antigen-specific CD8+ T cells. Although radiotherapy technique (Tumor RT vs. ENI) affected initial tumor control and survival, the ability to reject tumor upon rechallenge was partially dependent upon the mechanism of action of ICB; as radiotherapy/anti-CTLA4 was superior to radiotherapy/anti-PD-1.

Conclusions: Our results highlight that irradiation of the DLN restrains adaptive immune responses through altered chemokine expression and CD8+ T-cell trafficking. These data have implications for combining radiotherapy and ICB, long-term survival, and induction of immunologic memory. Clinically, the immunomodulatory effect of the radiotherapy strategy should be considered when combining stereotactic radiotherapy with immunotherapy. Clin Cancer Res; 24(20); 5058–71. ©2018 AACR.
Familial Forms of Cushing Syndrome in Primary Pigmented Nodular Adrenocortical Disease Presenting with Short Stature and Insidious Symptoms: A Clinical Series
Authors: Navarro Moreno Constanza , Delestienne Amaury , Marbaix Etienne , Aydin Selda , Hörtnagel Konstanze , Lechner Sarah , Sznajer Yves , Beauloye Véronique , Maiter Dominique , Lysy Philippe A.
Published: June 2018

Cushing syndrome (CS) is a rare disease in children, frequently associated with subtle or periodic symptoms that may delay its diagnosis. Weight gain and growth failure, the hallmarks of hypercortisolism in pediatrics, may be inconsistent, especially in ACTH-independent forms of CS. Primary pigmented nodular adrenocortical disease (PPNAD) is the rarest form of ACTH-independent CS, and can be associated with endocrine and nonendocrine tumors, forming the Carney complex (CNC). Recently, phenotype/genotype correlations have been described with particular forms of CNC where PPNAD is isolated or associated only with skin lesions. We present four familial series of CS due to isolated PPNAD, and compare them to available data from the literature. We discuss the clinical and molecular findings, and underline challenges in diagnosing PPNAD in childhood.
ПРОБЛЕМА ВІЛ-АСОЦІЙОВАНОГО ТУБЕРКУЛЬОЗУ В УКРАЇНІ
Authors: Moskaliuk V. D. , Kolotylo T. R.
Published: June 2018

Мета роботи – оцінити епідемічну небезпеку теперішньої ситуації з ВІЛ-інфекції та туберкульозу (ТБ) в Україні.Охарактеризовано показники захворюваності на ВІЛ-інфекцію і туберкульоз у різних регіонах України. Відзначено, що основна причина погіршення епідеміологічної ситуації полягає в зміні біологічних властивостей мікобактерій туберкульозу з розвитком полі- та мультирезистентності штамів збудника до антимікобактерійних препаратів. Проаналізовано істотні недоліки контролю за туберкульозом. Подібним чином характеризується ситуація з ВІЛ-інфекції, епідемія якої також контролюється не повною мірою. Винятково несприятливий прогноз відносно комбінованої патології ВІЛ-інфекції з туберкульозом (ВІЛ/ТБ) для України. Досі ТБ залишається основною ко-інфекцією та причиною смерті хворих на ВІЛ-інфекцію. Вказано на недоліки протиепідемічної роботи стосовно ВІЛ/ТБ.
Desafios na redução da mortalidade materna no Município de São Paulo
Authors: Vega Carlos Eduardo Pereira
Published: June 2018

Desde 1993 as causas da mortalidade materna vem sendo estudadas pelo Comitê de Mortalidade Materna do Município de São Paulo. Até o ano de 2016 acumulamos 3505 mortes maternas, sendo 2389 óbitos devidos a causas diretas ou indiretas. A principal causa da mortalidade materna é a hipertensão arterial, com 538 (22,5%) óbitos, seguida pelas complicações hemorrágicas de terceiro trimestre e puerpério com 330 (13,8%) ocorrências. As outras três causas responsáveis pelo óbito materno são as doenças cardiovasculares, complicações de aborto (incluindo os abortos inseguros) e a infecção puerperal. São feitas considerações sobre as cinco principais causas de morte materna e são disponibilizadas sugestões elaboradas pelo Comitê de Mortalidade Materna do Município de São Paulo para a redução desses eventos. As demais causas em menor número, mas não menos importantes, não serão objeto desse estudo.
Frantz’s tumor in a female patient with diarrhea: case report of a rare pancreatic neoplasm
Authors: Farias Luis Arthur Brasil Gadelha , Maciel Danielle Souza Carvalho , De Araujo Mariana Silton Pinheiro , Da Silva Angélica Maria Holanda Pascoal , Cairutas Rebeca Viana Brígido de Moura , Leite Débora Praciano Correia Férrer , Carmo Gardênia Costa do , Pessoa Francisco Sérgio Rangel de Paula
Published: June 2018

O tumor pseudopapilar sólido, também conhecido como tumor de Frantz, é um tumor raro do pâncreas. Relatamos o caso de uma paciente de 25 anos com dor abdominal, febre, diarréia e perda de peso.TC de abdome com contraste revelou pâncreas alargado com lesão hipodensa de aparência nodular e calcificações periféricas. Foi decidido realizar pancreatectomia subtotal com linfadenectomia e optou-se pela esplenectomia com biópsia hepática intra-operatória. O anatomopatológico da ressecção cirúrgica do tumor pancreático revelou tumor pseudopapilar sólido compatível com o tumor de Frantz. A imuno-histoquímica confirmou os achados histopatológicos. Ela evoluiu com fístula pancreática e pancreatite resolvida após 15 dias. Atualmente, está sendo acompanhada ambulatorialmente em nosso serviço com remissão completa dos sintomas.
A viagem de Thomas Russel Ybarra (1938-1939): New York Times e a política da boa-vizinhança
Authors: Júnior Edson Bossonaro
Published: June 2018

O presente trabalho analisa as imagens produzidas pelo articulista e viajante do The New York Times (NYT), Thomas Russell Ybarra, enviado para a América Latina em 1938-1939, contexto da Política da Boa-Vizinhança, com o objetivo de averiguar o estado da penetração do nazi-fascismo e o grau de influência norte-americana naqueles países. Suas representações sobre os latino-americanos e a argumentação sobre as diferenças entre os EUA e os imperialismos europeus contribuíram para a concepção de um lugar distinto para o país no novo cenário mundial, que se abria diante da percepção de que se aproximava um conflito de grandes proporções, no qual os EUA, acreditava-se, desempenhariam papel central.
Uso de Ferramenta como Instrumento no Processo de Ensino-Aprendizagem
Authors: Munhoz Graziella Simeão , Lopes Andréa Cintra
Published: June 2018

Relatamos neste artigo o uso e a aplicação de uma ferramenta desenvolvida com o objetivo de acompanhar a aprendizagem, a evolução e a complexidade dos casos atendidos pelos alunos do terceiro ano de graduação do curso de Fonoaudiologia no Estágio Clínico da Disciplina de Diagnóstico Audiológico, oferecida pelo Departamento de Fonoaudiologia da Universidade de São Paulo, campus Bauru. A proposta do uso da avaliação somativa por meio da ferramenta formulário Controle dos Atendimentos: Clínica de Diagnóstico Audiológico no estágio clínico no terceiro ano busca auxiliar o professor na atribuição de notas, fornecer feedback ao estudante, comparar os resultados obtidos com diferentes graduandos e verificar a condução dos atendimentos, além de permitir ao docente acesso aos exames e às condutas audiológicas tomadas em cada caso.
Causes and Predictors of Readmission in Patients With Atrial Fibrillation Undergoing Catheter Ablation: A National Population‐Based Cohort Study
Authors: Arora Shilpkumar , Lahewala Sopan , Tripathi Byomesh , Mehta Varshil , Kumar Varun , Chandramohan Divya , Lemor Alejandro , Dave Mihir , Patel Nileshkumar , Patel Nilay V. , Palamaner Subash Shantha Ghanshyam , Viles‐Gonzalez Juan , Deshmukh Abhishek
Published: June 2018

Background

Reducing readmission after catheter ablation (
CA
) in atrial fibrillation (AF) is important.

Methods and Results

We utilized National Readmission Data (
NRD
) 2010–2014.
AF
was identified by
International Classification of Diseases, Ninth Edition, Clinical Modification (ICD‐9‐CM)
diagnostic code 427.31 in the primary field, while first
CA
of
AF
was identified via
ICD‐9
‐procedure code 37.34. Any admission within 30 or 90 days of index admission was considered a readmission. Cox proportional hazard regression was used to adjust for confounders. The primary outcomes were 30‐ and 90‐day readmissions and the secondary outcome was
AF
recurrence. In total, 1 128 372 patients with
AF
were identified from January 1, 2010 to September 30, 2014. Of which 37 360 (3.3%) underwent
CA
. Patients aged ≥65 years and female sex were less likely to receive
CA
for
AF
. Overall, 10.9% and 16.5% of
CA
patients were readmitted within 30 and 90 days post‐CA, respectively. Most common causes of readmissions were arrhythmia (
AF
, atrial flutter), heart failure, pulmonary causes (pneumonia, chronic obstructive pulmonary disease) and bleeding complications (gastrointestinal bleed, intracranial hemorrhage). Patients with diabetes mellitus, heart failure, coronary artery disease (
CAD
), chronic pulmonary and kidney disease, prior stroke/transient ischemic attack (TIA), female sex, length of stay ≥2 and disposition to the facility were prone to higher 30‐ and 90‐day readmissions post
‐CA
. Predictors of increase in
AF
recurrence post‐
CA
were female sex, diabetes mellitus, chronic pulmonary disease, and length of stay ≥2. Trends of 90‐day readmission and
AF
recurrence were found to improve over the study period.

Conclusions

We identified several demographic and clinical factors associated with the use of
CA
in
AF
, and short‐term outcomes of the same, which could potentially help in the patient selection and improve outcomes.
Gericault’s Fake-Gallop Horse Judged Speedy but Unrealistic
Authors: Mastandrea Stefano , Kennedy John M.
Published: June 2018

In two experiments, we tested pictures of horse gaits—alt (standing), walk, trot, gallop, and a fake gallop, a pose shown in a well-known Gericault painting. The pose was portrayed frequently in the nineteenth century, its features hotly debated. Fake gallop has legs extended fore and rear, close to parallel to the ground. Experiment 1 sampled real artworks depicting horses and Experiment 2 used silhouettes of horses. In both, reports of amount of movement increased from alt to fake gallop. In Experiment 1 similar results were obtained from novices and equestrians (‘experts’ familiar with horses). The extreme leg extension in fake gallop may suggest high speed, as Arnheim suggested. However, true gallop includes legs curled close together under the body—a ‘running pony’ pose—so both extremes of extension may suggest high speed. In Experiment 2, novices judged fake gallop unrealistic despite giving high movement scores. We suggest its depiction may be metaphoric, meaning a deliberately false item has relevant features of a referent. For the artworks, the amount of movement reported correlated positively but quite modestly with aesthetic appreciation, but for the silhouettes, the correlation was reversed. We suggest expression can be positive for many horse poses.
Checklist of the family Megalopodidae Latreille (Coleoptera: Chrysomeloidea); a synthesis of its diversity and distribution
Authors: RODRÍGUEZ-MIRÓN GEOVANNI M.
Published: June 2018

A checklist of the Megalopodidae of the world is presented. A total of 582 species in 29 genera and 11 subgenera are recognized belonging to the three subfamilies. The subfamilies, genera, and species are listed in alphabetical order. For each species, synonymous names and the geographical distribution by country is provided. The most diversified subfamily is Megalopodinae with 480 species and 24 genera. The Neotropical biogeographic region has the highest diversity of Megalopodidae, followed by the Ethiopian region. The knowledge of Megalopodidae is limited, and is remarkably biased by country. A significant increase in geographic and taxonomic information is needed in order to fill these knowledge gaps. The following taxonomic and nomenclatural changes are proposed: 1) type species are designated for the genera Macrolopha Weise and Falsomegalopus Pic. 2) Zeugophora novobicolor Rodríguez-Mirón is proposed as new replacement name of Zeugophora bicolor. 3) The following taxa are reinstated in the genera Temnaspis: T. speciosus Baly, T. arida Westwood, and T. nigriceps Baly. 4) Falsotemnaspis luteimembris Pic is proposed as new synonym (= F. lacordairei (Westwood)). 5) The next new combinations are proposed: Macrolopha bicolor (Jacoby), M. carinata (Bryant), M. centromaculata (Jacoby), M. costatipennis (Pic), M. dollmani (Bryant), M. hargreavesi (Bryan), M. mashuana (Jacoby), M. murrayi (Baly), M. neavei (Bryant), M. nyassae (Bryant), M. suturalis (Clavareau), M. variabilis (Westwood), M. aeneipennis (Weise), M. notaticollis (Pic), M. parvula (Weswood), M. theresae (Pic), M. tricoloripes (Pic) and Falsotemnaspis lacordairei (Westwood).
Neotype designation of Oribatula nativa Tseng, 1984 (Acari, Oribatida, Oribatulidae)
Authors: ERMILOV SERGEY G. , LIAO JHIH-RONG
Published: June 2018

The type material of oribatid mites (Acari, Oribatida) of Tseng’s collections were lost, therefore, designation of neotypes is necessary to ensure stability in zoological nomenclature. The neotype and paraneotypes of Oribatula nativa Tseng, 1984 (Oribatida, Oribatulidae) are designated. This species is redescribed based on adult material collected from Taiwan.
Linear Stability of Moist Convecting Atmospheres. Part I: From Linear Response Functions to a Simple Model and Applications to Convectively Coupled Waves
Authors: Kuang Zhiming
Published: June 2018

A procedure is presented to systematically construct simple models for the linear stability of moist convecting atmospheres. First, linear response functions of a cumulus ensemble constructed from cloud-system-resolving models are coupled with matrices expressing two-dimensional large-scale linear wave dynamics. For a radiative–convective equilibrium reference state, this model gives two branches of unstable modes: a propagating convectively coupled wave branch and a stationary branch related to storage of column-integrated moist static energy (MSE). The stationary branch is unstable only when radiative feedback is included, while the convectively coupled wave branch is less affected by radiative feedback. With a modular order-reduction procedure from control theory, the linear-response-function-based model is reduced to a system of six ordinary differential equations while still capturing the essential features of the unstable modes (eigenvalues and structures). The six-dimensional system is then split into a slow and a fast manifold. The slow manifold (again, reflecting column MSE storage) is essential for the stationary mode but not for the convectively coupled waves. The fast manifold is then transformed into a form similar to that of prior simple models of convectively coupled waves, thus placing those models and the insights derived from them on a firmer footing. The procedure also better quantifies the parameters of such simple models and allows the stability difference between different reference states to be better understood.
A Numerical Study on the Extreme Intensification of Hurricane Patricia (2015)
Authors: Fox K. Ryder , Judt Falko
Published: June 2018

In October 2015 Hurricane Patricia stormed through the eastern Pacific, taking its place as the strongest hurricane in recorded history when its intensity reached a record breaking 185 kt (1 kt = 0.51 m s−1). Operational models and the National Hurricane Center’s official forecast failed to predict Patricia’s unprecedented intensification, provoking questions as to whether such an extreme event can actually be forecast. This study reports on the successful simulation of Patricia using a state-of-the-art high-resolution numerical weather prediction model. It was found that high model resolution (Δx ≤ 1 km), vortex initialization, and the parameterization of dissipative heating were key factors in realistically simulating Patricia’s intensity evolution. The simulation was used to investigate Patricia’s environment in terms of sea surface temperature, vertical wind shear, and humidity, under the premise that a simulation able to capture Patricia’s peak intensity would also accurately represent Patricia’s environment. Compared with a climatology derived from the Statistical Hurricane Intensity Prediction Scheme dataset, sea surface temperature ranked in the 99th percentile and environmental vertical wind shear in the 83rd percentile (ordered from high to low). However, humidity ranked more moderately. Ensemble forecasts indicate that Patricia had relatively high predictability in comparison to other well-studied rapid intensification cases such as 2010’s Hurricane Earl. The results from this study imply that high-resolution models are in principle able to predict the intensity of extreme hurricanes like Patricia.