bluuebunny/crossref_metadata_2025 huggingface dataset:
The quasi‐6 day wave and its interactions with solar tides
Authors: Forbes Jeffrey M. , Zhang Xiaoli
Published: March 2017

Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) temperature measurements between 20 and 110 km altitude and ±50° latitude during 2002–2015 are employed to reveal the climatological characteristics of the quasi‐6 day wave (Q6DW) and evidence for secondary waves (SW) resulting from its nonlinear interactions with solar tides. The mean period is 6.14d with a standard deviation (σ) of 0.26d. Multiyear‐mean maximum amplitudes (3–5 K, σ ∼ 4 K) occur within the mesosphere‐lower thermosphere (MLT) region between 75 and 100 km during day of year (DOY) 60–120 and 180–300 in the Northern Hemisphere and DOY 0–110 and 200–300 in the Southern Hemisphere. Amplitudes approach 10 K in some individual years. At midlatitudes downward phase progression exists from 100 to 35 km with a mean vertical wavelength of about 70 km. Signatures of SW due to Q6DW‐tide interactions appear at distinct space‐based zonal wave numbers (ks) in temperature spectra constructed in the reference frame of the TIMED orbit. However, SW produced by several different tides can collapse onto the same (ks) value, rendering their relative contributions indistinguishable. Nevertheless, by determining the space‐based wave amplitudes attached to these values of (ks), and demonstrating that they are a large fraction of the interacting wave amplitudes, we conclude that the aggregate contributions of the SW to the overall wave spectrum must be significant. Because the SW have periods, zonal wave numbers, and latitude‐height structures different from those of the primary waves, they contribute additionally to the complexity of the wave spectrum. This complexity is communicated to the ionosphere through collisions or through the dynamo electric fields generated by the total wave spectrum.
Formation of plasma around a small meteoroid: 1. Kinetic theory
Authors: Dimant Y. S. , Oppenheim M. M.
Published: March 2017

Every second, millions of submilligram meteoroids enter the Earth's atmosphere producing dense plasmas. Radars easily detect these plasmas, and researchers use this data to characterize both the meteoroids and the atmosphere. This paper develops a first‐principle kinetic theory describing the behavior of particles ablated from a small fast‐moving meteoroid and then colliding with atmospheric molecules. These collisions result in partial ionization of the ablated particles and formation of a dense plasma around the meteoroid. This theory produces analytic expressions describing the spatial structure and velocity distributions of ions and neutrals near the ablating meteoroid. The analytical model will serve as a basis for a more accurate quantitative interpretation of radar measurements and should help calculate meteoroid and atmosphere parameters from radar head‐echo observations.
Cardinal Manifestations of Cancer
Authors: Holland James F. , Hong Waun Ki , Kufe Donald W. , Bast Robert C. , Hait William N. , Pollock Raphael E. , Weichselbaum Ralph R.
Published: March 2017

Overview

Cancer is asymptomatic at its initiation. Symptoms arise when a conduit is impaired, when cancer cells impinge on nerve fibers causing pain or dysfunction, when secretory products of the tumor cause systemic symptoms such as fever, weight loss, or fatigue, when ulceration and bleeding occur, or upon recognition of a mass. Indeed any symptom that lasts two weeks, even intermittently, could be a symptom of cancer, the great imitator. Cancer always belongs in the differential diagnosis.
Tumor Angiogenesis
Authors: Heymach John V. , Zurita‐Saavedra Amado , Kopetz Scott , Cascone Tina , Nilsson Monique
Published: March 2017

Overview

Angiogenesis, the growth of new capillary blood vessels, is central to cancer growth and metastasis and is recognized to be a potential therapeutic target for the treatment of cancer. Antiangiogenic agents have become part of the standard treatment armamentarium for many solid tumors, providing significant clinical benefits for some cancers (e.g., renal cell, colorectal) and modest or no benefit for others. This chapter is focused on principles of tumor angiogenesis that are intrinsic to the behavior of human cancer, and lessons that can be gleaned from the clinical testing and use of angiogenesis inhibitors to date.
Hepatitis Viruses and Hepatoma
Authors: Wang Hongyang , Cao Guangwen , Fu Jing , Lv Guishuai
Published: March 2017

Overview

Hepatitis is an inflammation of the liver, occurring as the result of a viral infection or the exposure of liver to toxic substances such as alcohol or aflatoxin B. Hepatitis viruses are the most common cause of hepatitis in the world, of which HBV and HCV can cause persistent liver infection, frequently resulting in chronic hepatitis, liver cirrhosis, and eventually hepatocellular carcinoma (HCC). HBV belongs to the genus
Orthohepadnavirus
of the
Hepadnaviridae
with a circular incomplete double‐stranded DNA genome, containing four overlapping open reading frames (ORFs) that encode the surface envelope protein (HBsAg), the core protein (HBcAg and HBeAg), a polymerase, and a multifunctional nonstructural protein termed X (HBx), respectively. HBV genotypes and subgenotypes have distinct geographical distributions. In East Asia, HBV genotypes B and C are endemic. Accordingly, any differences in its global incidence may be explained by differences in the HCV and HBV prevalence. It has been estimated that 57% of cirrhosis is attributable to either HBV (30%) or HCV (27%) and 78% of HCC is attributable to HBV (53%) or HCV (25%). In China, up to 80% of HCC cases are attributable to HBV, and approximately 20% of HCC patients test positive for HCV‐RNA. Besides the oncogenic function of HBV‐encoding protein, the HBV infection‐induced virus or host DNA mutation has been found contribution for HCC development. Unlike to HBV, HCV belongs to the genus
Hepacivirus
of the Flaviviridae family, with a single‐stranded positive‐sense RNA genome. There is no host genome integration, nor does HCV contain any known oncogenes. The major mechanisms of HCV‐induced hepatocarcinogenesis include the oncogenic effect of HCV viral proteins, steatosis and insulin resistance, chronic inflammation and fibrosis, oxidative stress, and chromosomal instability. This chapter exclusively focuses on hepatitis and hepatoma caused mainly by HBV and HCV infection, discussing epidemiologic considerations, construction and genotype, role of virus in performing HCC, and early diagnosis and prophylaxis. Still, viruses that selectively infect endemic host predispose patients to malignant hepatoma, to some extent, placing a burden on the healthcare worldwide. Therefore, an upturn in morbidity of hepatitis and hepatoma will be of great importance in public health.
Behavioral Approaches to Cancer Prevention
Authors: Philip Errol J. , Ostroff Jamie S.
Published: March 2017

Overview

Certain health behaviors increase the risk of being diagnosed with cancer. It has been estimated that 35% of cancer deaths throughout the world could be avoided through adoption of health promoting behaviors. This chapter summarizes research on the effects of behavioral risk factors on cancer incidence and behavioral interventions for cancer prevention. Several behavioral risk factors—tobacco use, unhealthy diet, sedentary lifestyle and obesity, sun and UV exposure—have all been associated with cancer etiology, and clinical recommendations for health promoting behavior change interventions have been developed. Physician recommendations and delivery of health promotion counseling are essential for effective dissemination of cancer prevention efforts.
Diet and Nutrition in the Etiology and Prevention of Cancer
Authors: Clinton Steven K. , Grainger Elizabeth M. , Giovannucci Edward L.
Published: March 2017

Overview

Associations between nutrients, foods, dietary patterns, and cancer risk have been the source of substantial scientific inquiry as improved tools to assess dietary exposures and cancer outcomes have emerged for different populations around the globe. Research includes observational studies, epidemiologic cohort studies, and some human intervention trials that are supported by mechanistic laboratory investigations. These efforts strongly implicate dietary patterns as a major risk factor in the global cancer burden and have resulted in the formulation of dietary guidelines for prevention of cancer by several public health organizations. The dietary recommendations, which also include maintaining a healthy weight and participating in regular physical activity, are interrelated and are intended to guide the development of behavior patterns regarding diet orchestration and exercise that are consistent with reducing the risk of cancer. Those undergoing cancer treatment with diverse therapeutic interventions require personalized consultations with nutrition professionals, such as registered dietitians, in order to maintain optimal health while reducing toxicity and enhancing efficacy of therapy. Increasingly, the role of diet and physical activity in cancer survivorship is being addressed, and the future will likely include more specific survivorship guidelines, personalized for individuals, that reduce the risk of cancer recurrence, lower the long‐term consequences of cancer therapy, and promote health and quality of life.
Monoclonal Serotherapy
Authors: Bast Robert C. , Zalutsky Michael R. , Frankel Arthur E.
Published: March 2017

Overview

Monoclonal antibodies have impacted significantly the care of patients with cancer. Some 22 monoclonal antibodies, cytotoxic drug conjugates, radionuclide conjugates, and targeted toxins have been approved by the US FDA for the treatment of a dozen different malignancies, although three of these biologicals are no longer marketed. Useful monoclonal antibodies have targeted proteins on the cancer cell surface most frequently (CD20 by rituximab and HER2 by trastuzumab and pertuzumab), inhibiting growth, inducing apoptosis, and enhancing chemotherapy, but some have targeted cytokines (IL‐6 by siltuximab), growth factors [vascular endothelial growth factor (VEGF) by bevacizumab], and growth factor receptors (VEGFR2 by ramucirumab) that can affect endothelial cells in tumor vessels, or have altered the immune response by neutralizing checkpoint inhibitors (CTLA4 by ipilimumab and PD1 by nivolumab or pembrolizumab). In the case of trastuzumab and pertuzumab, binding of the two antibodies to different sites on HER2 cell surface receptors has produced greater antitumor activity than either alone. Enhanced cancer cell killing has also been achieved by conjugation of antibodies with cytotoxic drugs (emtansine to anti‐HER2 trastuzumab and vedotin to anti‐CD30 brentuximab) or radionuclide conjugates (90Y to anti‐CD20 ibritumomab tiuxetan) permitting effective treatment for patients who had failed therapy with unconjugated antibodies. There are several barriers to effective therapy with monoclonal antibodies including antigen specificity, antigenic modulation, heterogeneity of antigen expression, effective delivery of antibodies to cancer cells, potency of effector mechanisms, and response to foreign globulin. The latter problem has been circumvented with the use of chimeric constructs, humanization of murine antibodies, and developing genetically engineered mice with the ability to develop fully human antibodies. Use of unconjugated antibodies is likely to improve as our knowledge of tumor biology and immunology grows, identifying targets such as OX‐40 ligand. Use of smaller molecularly engineered binding constructs may improve pharmacokinetics and pharmacodynamics of serotherapy. Combinations of antibodies may be required to compensate for antigenic heterogeneity. Development of antibody drug conjugates will require the identification of monoclonal reagents that target tumor initiating stem cells. Pretargeting and the use of α‐emitters are promising approaches to improving antibody‐radionuclide conjugates. Development of targeted toxins must be further explored.
Neoplasms of the Eye
Authors: Francis Jasmine H. , Schefler Amy C. , Abramson David H.
Published: March 2017

Overview

Cancers involving the eye are less common compared to lung, prostate and breast cancer. However, they pose a special challenge because they can influence both life and vision. The field of ophthalmic oncology focuses on these two elements: improving efficacy to treat the disease and save life, and limiting the consequence of treatment to maintain vision. The eye itself is composed of a variety of distinct tissues and ophthalmic malignancies can affect a number of these anatomical areas. This makes the topic of neoplasms of the eye heterogeneous in origin, pathogenesis, prognosis, and treatment.
Urologic Complications
Authors: Sanford Rachel A. , Abudayyeh Ala , Logothetis Christopher J. , Tannir Nizar M.
Published: March 2017

Overview

The management of patients with cancer requires anticipation and timely intervention for urologic complications including urinary tract obstruction, cystitis, nephritis, and nephrotoxicity from chemotherapeutic agents. In patients with limited‐stage disease receiving therapy with curative intent, skilled management of urologic complications is crucial for delivering adequate doses of chemotherapy and avoiding dose reductions that may compromise the likelihood of cure. In the metastatic setting, skillful management of urologic complications including urinary obstruction can provide significant palliation of symptoms. This chapter reviews the diagnosis and management of urinary tract obstruction occurring at the level of the ureters, the bladder, and the urethra. Mechanisms of chemotherapy‐ and radiation‐induced cystitis and nephritis and their management are reviewed. Finally, an overview of the most commonly used potentially nephrotoxic therapeutic agents is provided, with an emphasis on diagnosis, treatment, and prevention. In addition to cytotoxic chemotherapy, the nephrotoxicity caused by targeted therapies is discussed, and emerging insights into immune‐related adverse events (irAE) that may affect the kidney are reviewed.
Respiratory Complications
Authors: Shannon Vickie R. , Eapen George A. , Jimenez Carlos A. , Grosu Horiana B. , Morice Rodolfo C. , Bashoura Lara , Evans Scott E. , Adachi Roberto , Kroll Michael , Faiz Saadia A. , Balachandran Diwakar D. , Pravinkumar Selvaraj E. , Dickey Burton F.
Published: March 2017

Overview

The respiratory system is particularly susceptible to complications of cancer and cancer therapy. This vulnerability arises from the stringent architectural requirements for gas exchange, the continuous exposure of the respiratory tract to the external environment, and the severe symptoms that can accompany respiratory compromise. Gas exchange requires patent airways, an effective musculoskeletal ventilatory pump, a thin alveolocapillary membrane, and adequate blood flow through the pulmonary circulation. In cancer patients, primary and metastatic tumors of the chest compromise major airways; pleural effusions externally compress the lungs and impair diaphragmatic function; direct, hematogenous, or lymphangitic spread of tumor replaces functioning lung parenchyma; resectional surgery reduces parenchymal volume; nonresectional surgery can transiently impair lung function; radiotherapy, chemotherapy, stem cell therapy, and infection injure the vulnerable alveolocapillary membrane; tumors directly or indirectly compromise the musculoskeletal pump; and venous thromboembolism (VTE) and pulmonary vasculopathy obstruct pulmonary blood flow.

The normal respiratory system contains considerable physiologic reserve, such that surgical loss of one lung is generally well tolerated. However, in cancer patients, insults to multiple components of the respiratory system may result in progressive loss of physiologic reserve and increasing dyspnea. Dyspnea, cough, wheezing, stridor, chest pain, and hemoptysis are common symptoms in the cancer setting that lead to pulmonary consultation.

In this chapter, we will discuss the pathophysiology, diagnosis, and management of the major respiratory complications of cancer and its therapy. We begin with the direct effects of cancer and cancer therapies on the lungs, review major indirect effects of cancer on the lungs, and end with respiratory failure in the cancer patient.
Oncologic Emergencies
Authors: Yeung Sai‐Ching Jim , Escalante Carmen P.
Published: March 2017

Overview

Cancer and its treatment can lead to oncologic emergencies. This chapter discusses the approach to acute emergency problems in cancer patients. A list of emergent problems has been selected for focused discussion. Sudden cardiopulmonary arrest is discussed along with special consideration in resuscitation of cancer patients. Arrhythmia, superior vena caval syndrome, pericardial tamponade, and acute hemorrhage are important cardiovascular emergencies. Tumor lysis syndrome can be rapidly fatal, and early recognition and treatment are very important in preventing disastrous outcomes. Pulmonary problems include airway obstruction, pleural effusion, hemoptysis, pneumothorax, and pulmonary embolism. Neurological emergencies include spinal cord compression, brain herniation, and status epilepticus. Neutropenic fever is perhaps the most frequently discussed important topic in oncologic emergency. Other important issues such as perforated viscus, anaphylaxis, and cytokine release syndrome are also discussed. Oncologists and emergency physicians must be aware of these potentially serious acute complications of cancer patients in order to initiate appropriate treatments in a timely manner.
Energy dependence and angular dependence of an optically stimulated luminescence dosimeter in the mammography energy range
Authors: Kawaguchi Ai , Matsunaga Yuta , Suzuki Shoichi , Chida Koichi
Published: March 2017

This study aimed to investigate the energy dependence and the angular dependence of commercially available optically stimulated luminescence (OSL) point dosimeters in the mammography energy range. The energy dependence was evaluated to calculate calibration factors (CFs). The half‐value layer range was 0.31–0.60 mmAl (Mo/Mo 22–28 kV, Mo/Rh 28–32 kV, and W/Rh 30–34 kV at 2‐kV intervals). Mo/Rh 28 kV was the reference condition. Angular dependence was tested by rotating the X‐ray tube from −90° to 90° in 30° increments, and signal counts from angled nanoDots were normalized to the 0° signal counts. Angular dependence was compared with three tube voltage and target/filter combinations (Mo/Mo 26 kV, Mo/Rh 28 kV and W/Rh 32 kV). The CFs of energy dependence were 0.94–1.06. In Mo/Mo 26–28 kV and Mo/Rh 28–32 kV, the range of CF was 0.99–1.01, which was very similar. For angular dependence, the most deteriorated normalized values (Mo/Mo, 0.37; Mo/Rh, 0.43; and W/Rh, 0.58) were observed when the X‐ray tube was rotated at a 90° angle, compared to 0°. The most angular dependences of ± 30°, 60°, and 90° decreased by approximately 4%, 14%, and 63% respectively. The mean deteriorated measurement 30° intervals from 0° to ± 30° was 2%, from ± 30° to ± 60° was 8%, and from ± 60° to ± 90° was 40%. The range of energy dependence in typical mammography energy range was not as much as that in general radiography and computed tomography. For accurate measurement using nanoDot, the tilt needs to be under 30°.
Quantum Conductance Probing of Oxygen Vacancies in SrTiO3 Epitaxial Thin Film using Graphene
Authors: Kang Kyeong Tae , Kang Haeyong , Park Jeongmin , Suh Dongseok , Choi Woo Seok
Published: March 2017

Quantum Hall conductance in monolayer graphene on an epitaxial SrTiO3 (STO) thin film is studied to understand the role of oxygen vacancies in determining the dielectric properties of STO. As the gate‐voltage sweep range is gradually increased in the device, systematic generation and annihilation of oxygen vacancies, evidenced from the hysteretic conductance behavior in the graphene, are observed. Furthermore, based on the experimentally observed linear scaling relation between the effective capacitance and the voltage sweep range, a simple model is constructed to manifest the relationship among the dielectric properties of STO with oxygen vacancies. The inherent quantum Hall conductance in graphene can be considered as a sensitive, robust, and noninvasive probe for understanding the electronic and ionic phenomena in complex transition‐metal oxides without impairing the oxide layer underneath.
Synthesis of Fluoromethyl‐Substituted Isoxazolines via Transition Metal‐Free Oxyfluorination of Alkenyl Oximes
Authors: Zhao Juan , Jiang Min , Liu Jin‐Tao
Published: March 2017

A mild and efficient transition metal‐free intramolecular oxyfluorination of alkenyl oximes is demonstrated. The reaction tolerates a range of substrates to give a series of monofluoromethylated isoxazoline derivatives with good yields. The possible pathways are proposed based on the reaction results and control experiments.

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Factors associated with employment status before and during pregnancy: Implications for studies of pregnancy outcomes
Authors: Rocheleau Carissa M. , Bertke Stephen J. , Lawson Christina C. , Romitti Paul A. , Desrosiers Tania A. , Agopian A.J. , Bell Erin , Gilboa Suzanne M. ,   The National Birth Defects Prevention Study
Published: March 2017

Background

Potential confounding or effect modification by employment status is frequently overlooked in pregnancy outcome studies.

Methods

To characterize how employed and non‐employed women differ, we compared demographics, behaviors, and reproductive histories by maternal employment status for 8,343 mothers of control (non‐malformed) infants in the National Birth Defects Prevention Study (1997–2007) and developed a multivariable model for employment status anytime during pregnancy and the 3 months before conception.

Results

Sixteen factors were independently associated with employment before or during pregnancy, including: maternal age, pre‐pregnancy body mass index, pregnancy intention, periconceptional/first trimester smoking and alcohol consumption, and household income.

Conclusions

Employment status was significantly associated with many common risk factors for adverse pregnancy outcomes. Pregnancy outcome studies should consider adjustment or stratification by employment status. In studies of occupational exposures, these differences may cause uncontrollable confounding if non‐employed women are treated as unexposed instead of excluded from analysis. Am. J. Ind. Med. 60:329–341, 2017. © 2017 Wiley Periodicals, Inc.
Hydrophobic Water Probed Experimentally at the Gold Electrode/Aqueous Interface
Authors: Tong Yujin , Lapointe François , Thämer Martin , Wolf Martin , Campen R. Kramer
Published: March 2017

Quantitative description of reaction mechanisms in aqueous phase electrochemistry requires experimental characterization of local water structure at the electrode/aqueous interface and its evolution with changing potential. Gaining such insight experimentally under electrochemical conditions is a formidable task. The potential‐dependent structure of a subpopulation of interfacial water with one OH group pointing towards a gold working electrode is characterized using interface specific vibrational spectroscopy in a thin film electrochemical cell. Such free‐OH groups are the molecular level observable of an extended hydrophobic interface. This free‐OH interacts only weakly with the Au surface at all potentials, has an orientational distribution that narrows approaching the potential of zero charge, and disappears on oxidation of the gold electrode.
A Stable, Soluble, and Crystalline Supramolecular System with a Triplet Ground State
Authors: Futagoishi Tsukasa , Aharen Tomoko , Kato Tatsuhisa , Kato Azusa , Ihara Toshiyuki , Tada Tomofumi , Murata Michihisa , Wakamiya Atsushi , Kageyama Hiroshi , Kanemitsu Yoshihiko , Murata Yasujiro
Published: March 2017

A supramolecular complex was constructed by encapsulation of a 3O2 molecule inside an open‐cage C60 derivative. Its single‐crystal X‐ray diffraction analysis revealed the presence of the 3O2 at the center of the fullerene cage. The CV measurements suggested that unprecedented dehydrogenation was promoted by the encapsulated 3O2 after two‐electron reduction. The ESR measurements displayed the triplet character as well as the anisotropy of the 3O2. Additionally, the SQUID measurements also demonstrated the paramagnetic behavior above 3 K without an antiferromagnetic transition. Upon photoirradiation with visible light, three phosphorescent bands at the NIR region were observed, arising from the exited 1O2 generated by self‐sensitization with the outer cage, whose lifetimes were not affected by the environments. These studies confirmed that the complex is a crystalline triplet system with incompatible “high spin density” but “small interspin interaction” properties.
Mastering the structure of PLA foams made with extrusion assisted by supercritical CO2
Authors: Chauvet Margot , Sauceau Martial , Baillon Fabien , Fages Jacques
Published: March 2017

In this study, the outcome of operating conditions of extrusion assisted by supercritical CO2 for the manufacture of poly(lactic acid) foams was investigated. It was found that the temperature before and inside the die was the most prominent parameter to tune the foam properties. Foam porosity as high as 96% could be obtained (for die temperature between 109 and 112 °C), representing a total expansion exceeding 30. In this temperature range, low crystallinity (≈6%) was induced giving foams with high radial expansion i.e., large diameters and open porosity. At 112 °C, the CO2 was able to greatly expand the foams, providing 73% of its potential blowing effect. On the other hand, a low die temperature (below a die temperature of 107 °C) induces a significantly higher level of crystallinity resulting in foams with closed‐porosity and a large longitudinal expansion due to higher strength of the polymer melt. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45067.
CH3NH3PbBr3 Perovskite Nanocrystals as Efficient Light‐Harvesting Antenna for Fluorescence Resonance Energy Transfer
Authors: Muthu Chinnadurai , Vijayan Anuja , Nair Vijayakumar C.
Published: March 2017

Hybrid perovskites have created enormous research interest as a low‐cost material for high‐performance photovoltaic devices, light‐emitting diodes, photodetectors, memory devices and sensors. Perovskite materials in nanocrystal form that display intense luminescence due to the quantum confinement effect were found to be particularly suitable for most of these applications. However, the potential use of perovskite nanocrystals as a light‐harvesting antenna for possible applications in artificial photosynthesis systems is not yet explored. In the present work, we study the light‐harvesting antenna properties of luminescent methylammonium lead bromide (CH3NH3PbBr3)‐based perovskite nanocrystals using fluorescent dyes (rhodamine B, rhodamine 101, and nile red) as energy acceptors. Our studies revealed that CH3NH3PbBr3 nanocrystals are an excellent light‐harvesting antenna, and efficient fluorescence resonance energy transfer occurs from the nanocrystals to fluorescent dyes. Further, the energy transfer efficiency is found to be highly dependent on the number of anchoring groups and binding ability of the dyes to the surface of the nanocrystals. These observations may have significant implications for perovskite‐based light‐harvesting devices and their possible use in artificial photosynthesis systems.
X‐ray studies of solar system objects: Past, present, and the next decade
Authors: Branduardi‐Raymont G.
Published: March 2017

This paper presents an overview of the remarkable progress that X‐ray studies of solar system objects have delivered over the past three decades, covering research that encompasses remote observations with XMM‐Newton and Chandra, in situ measurements by planetary missions, and models of solar wind propagation from 1 AU. The future of X‐ray exploration of the solar system in the next decade is bright, counting on the continuing excellent imaging and spectral performance of XMM‐Newton instruments, which is most effective when combined with the outstanding spatial resolution of Chandra and in particular while planetary missions are making in situ measurements of solar wind and local conditions.
Relationship between early motor milestones and severity of restricted and repetitive behaviors in children and adolescents with autism spectrum disorder
Authors: Uljarević Mirko , Hedley Darren , Alvares Gail A. , Varcin Kandice J. , Whitehouse Andrew J. O.
Published: March 2017

This study explored the relationships between the later age of achievement of early motor milestones, current motor atypicalities (toe walking), and the severity of restricted and repetitive behaviors (RRBs) in individuals with autism spectrum disorder (ASD). Parents of 147 children and adolescents with ASD (Mage = 8.09 years, SD = 4.28; 119 males) completed an early developmental milestones questionnaire and the Social Responsiveness Scale as a measure of Insistence on Sameness (IS) and Repetitive Mannerisms (RM). Two hierarchical regression analyses were conducted to test whether RM and IS behaviors were predicted by early motor milestones, or current toe walking. The final model predicting RM accounted for 15% of the variance (F = 3.02, p = .009), with toe walking as a unique and independent predictor of RM scores (t = 3.568, p = .001). The final model predicting IS accounted for 19.1% of variance in IS scores (F = 4.045, p = .001), with chronological age (CA) (t = 2.92, p = .004), age when first standing (t = 2.09, p = .038), and toe walking (t = 2.53, p = .013) as unique independent predictors. Toe walking (t = 2.4, p = .018) and age when first sitting (t = 2.08, p = .04) predicted the severity of RRBs on the Autism Diagnostic Observation Schedule (F = 2.334, p = .036). Our study replicates previous findings on the relationship between concurrent motor impairments and RRBs, and provides the first evidence for the association between RRBs and age of attainment of early motor milestones. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1163–1168. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Response to changing contingencies in infants at high and low risk for autism spectrum disorder
Authors: Northrup Jessie B. , Libertus Klaus , Iverson Jana M.
Published: March 2017

One recently proposed theory of autism spectrum disorder (ASD) hypothesizes that individuals with the disorder may have difficulty using prior experiences to predict future events [Hellendoorn et al., 2015; Northrup, 2016; Sinha et al., 2014]. To date, this theory has not been tested in infancy. The current study analyzed how young infants at heightened (HR; older sibling with ASD) vs. low risk (LR; no first degree relatives with ASD) for ASD responded to changing contingencies when interacting with two visually identical rattles—one that produced sounds during shaking (Sound), and one that did not (Silent). Infants were given the rattles in a Sound‐Silent‐Sound order at 6 and 10 months, and shaking behavior was coded. Results indicated that LR and HR infants (regardless of ASD diagnosis) did not differ from each other in shaking behavior at 6 months. However, by 10 months, LR infants demonstrated high initial shaking with all three rattles, indicating expectations for rattle affordances, while HR infants did not. Significantly, HR infants, and particularly those with an eventual ASD diagnosis, did not demonstrate an “extinction burst”—or high level of shaking—in the first 10 sec with the “silent” rattle, indicating that they may have difficulty generalizing learning from one interaction to the next. Further, individual differences in the strength of this “extinction burst” predicted cognitive development in toddlerhood among HR infants. Difficulty forming expectations for new interactions based on previous experiences could impact learning and behavior in a number of domains.Autism Res2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Autism Res2017, 10: 1239–1248. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
High‐throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis
Authors: Tripolszki Kornélia , Török Dóra , Goudenège David , Farkas Katalin , Sulák Adrienn , Török Nóra , Engelhardt József I. , Klivényi Péter , Procaccio Vincent , Nagy Nikoletta , Széll Márta
Published: March 2017

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of the motor neurons. To date, 126 genes have been implicated in ALS. Therefore, the heterogenous genetic background of ALS requires comprehensive genetic investigative approaches.

Methods

In this study, DNA from 28 Hungarian ALS patients was subjected to targeted high‐throughput sequencing of the coding regions of three Mendelian ALS genes: FUS, SETX, and C9ORF72.

Results

A novel heterozygous missense mutation (c.791A>G, p.N264S) of the SETX gene was identified in a female patient presenting an atypical ALS phenotype, including adult onset and lower motor neuron impairment. No further mutations were detected in the other Mendelian ALS genes investigated.

Conclusion

Our study contributes to the understanding of the genetic and phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest that the elucidation of the genetic background of MNDs requires a complex approach, including the screening of both Mendelian and non‐Mendelian genes.
Synthesis and Superpotent Anticancer Activity of Tubulysins Carrying Non‐hydrolysable N‐Substituents on Tubuvaline
Authors: Sani Monica , Lazzari Paolo , Folini Marco , Spiga Marco , Zuco Valentina , De Cesare Michelandrea , Manca Ilaria , Dall'Angelo Sergio , Frigerio Massimo , Usai Igor , Testa Andrea , Zaffaroni Nadia , Zanda Matteo
Published: March 2017

Synthetic tubulysins 24 a–m, containing non‐hydrolysable N‐substituents on tubuvaline (Tuv), were obtained in high purity and good overall yields using a multistep synthesis. A key step was the formation of differently N‐substituted Ile‐Tuv fragments 10 by using an aza‐Michael reaction of azido‐Ile derivatives 8 with the α,β‐unsaturated oxo‐thiazole 5. A structure–activity relationship study using a panel of human tumour cell lines showed strong anti‐proliferative activity for all compounds 24 a–m, with IC50 values in the sub‐nanomolar range, which were distinctly lower than those of tubulysin A, vinorelbine and paclitaxel. Furthermore, 24 a–m were able to overcome cross‐resistance to paclitaxel and vinorelbine in two tumour cell lines with acquired resistance to doxorubicin. Compounds 24 e and 24 g were selected as leads to evaluate their mechanism of action. In vitro assays showed that both 24 e and 24 g interfere with tubulin polymerization in a vinca alkaloid‐like manner and prevent paclitaxel‐induced assembly of tubulin polymers. Both compounds exerted antimitotic activity and induced apoptosis in cancer cells at very low concentrations. Compound 24 e also exhibited potent antitumor activity at well tolerated doses on in vivo models of diffuse malignant peritoneal mesothelioma, such as MESOII peritoneal mesothelioma xenografts, the growth of which was not significantly affected by vinorelbine. These results indicate that synthetic tubulysins 24 could be used as standalone chemotherapeutic agents in difficult‐to‐treat cancers.
Coronary artery calcification is common on nongated chest computed tomography imaging
Authors: Balakrishnan Revathi , Nguyen Brian , Raad Roy , Donnino Robert , Naidich David P. , Jacobs Jill E. , Reynolds Harmony R.
Published: March 2017

Background

Coronary artery calcification as assessed by computed tomography (CT) is a validated predictor of cardiovascular risk, whether identified on a dedicated cardiac study or on a routine non‐gated chest CT. The prevalence of incidentally detected coronary artery calcification on non‐gated chest CT imaging and consistency of reporting have not been well characterized.

Hypothesis

Coronary calcification is present on chest CT in some patients not taking statin therapy and may be under‐reported.

Methods

Non‐gated chest CT images dated 1/1/2012 to 1/1/2013 were retrospectively reviewed. Demographics and medical history were obtained from charts. Patients with known history of coronary revascularization and/or pacemaker/defibrillator were excluded. Two independent readers with cardiac CT expertise evaluated images for the presence and anatomical distribution of any coronary calcification, blinded to all clinical information including CT reports. Original clinical CT reports were subsequently reviewed.

Results

Coronary calcification was identified in 204/304 (68%) chest CTs. Patients with calcification were older and had more hyperlipidemia, smoking history, and known coronary artery disease. Of patients with calcification, 43% were on aspirin and 62% were on statin medication at the time of CT. Coronary calcification was identified in 69% of reports when present.

Conclusions

A high prevalence of coronary calcification was found in non‐gated chest CT scans performed for non‐cardiac indications. In one‐third, coronary calcification was not mentioned in the clinical report when actually present. In this population of patients with cardiac risk factors, standard reporting of the presence of coronary calcification may provide an opportunity for risk factor modification.
Predictors and variability of drug‐eluting vs bare‐metal stent selection in contemporary percutaneous coronary intervention: Insights from the PRISM study
Authors: Shafiq Ali , Gosch Kensey , Amin Amit P. , Ting Henry H. , Spertus John A. , Salisbury Adam C.
Published: March 2017

Drug‐eluting stents (DES) reduce risk of in‐stent restenosis after percutaneous coronary intervention (PCI) but require dual antiplatelet therapy (DAPT) for a longer term than bare‐metal stents (BMS). Few studies have examined clinical predictors of DES vs BMS, and variability in provider selection between DES and BMS in clinical practice has not been well described. These insights can inform our understanding of current practice and may identify opportunities to improve decision‐making stent selection decinsion‐making. In a multicenter registry, 3295 consecutive patients underwent PCI by 158 interventional cardiologists across 10 US sites. Eighty percent of patients with treated with DES. Using hierarchical regression, diabetes mellitus, multivessel disease, health insurance, and white race were independently associated with greater DES use, whereas increasing age, history of hypertension, anticipated surgery, use of warfarin, lower hemoglobin, prior history of bleeding, and treatment of right coronary and left circumflex artery lesions as compared with PCI of left anterior descending artery were associated with lower likelihood of receiving DES. Adjusted rates of DES use across providers varied from 52.3% to 94.6%, and adjusted median odds ratio for DES selection was 1.69. DES selection appeared to reflect physicians’ attempts to balance benefits of DES against risks of prolonged DAPT. Nevertheless, marked residual variability in DES selection across providers persisted after adjusting for predictors of restenosis, bleeding, and other factors. Further studies are needed to better understand drivers of this variability and identify the impact of patient and provider preferences on stent selection at the time of PCI.
Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long‐term outcomes of a prospective randomized trial
Authors: Chang Ying‐Jun , Wang Yu , Mo Xiao‐Dong , Zhang Xiao‐Hui , Xu Lan‐Ping , Yan Chen‐Hua , Chen Huan , Chen Yu‐Hong , Chen Yao , Han Wei , Wang Feng‐Rong , Wang Jing‐Zhi , Liu Kai‐Yan , Huang Xiao‐Jun
Published: March 2017

BACKGROUND

Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft‐versus‐host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo‐SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown.

METHODS

In this prospective, randomized trial, the authors compared the long‐term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo‐HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG‐10) or 6 mg/kg (ATG‐6) of ATG. Analysis of disease‐free survival, GVHD‐free/recurrence‐free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease‐free patients who had survived for at least 6 months and had received regular follow‐up evaluations.

RESULTS

A total of 224 patients were recruited. The median follow‐up period was 1614 days (range, 28‐1929 days). The rate of infection‐related deaths in ATG‐10 arm was double that of the ATG‐6 arm (14.3% vs 7.1%;P = .084). The 5‐year cumulative incidence was comparable between the ATG‐6 and ATG‐10 groups for disease recurrence (12.8% vs 13.4%;P = .832) and nonrecurrence mortality (11.6% vs 17.0%;P = .263). The 5‐year probability of disease‐free survival was comparable between the groups (75.6% vs 69.6%;P = .283). The 5‐year cumulative incidence of cGVHD was found to be higher with ATG‐6 (75.0% vs 56.3% [P = .007] and moderate‐to‐severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%;P = .043). The 5‐year probability of GRFS was higher in the ATG‐10 group (41.0% vs 26.8%;P = .008). In the multivariate analysis, ATG‐10 was found to be associated with a lower risk of cGVHD and improved GRFS.

CONCLUSIONS

ATG‐10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection‐related deaths.Cancer2017;123:2881–92.©2017 American Cancer Society.
Irreversible Bleaching of Donor–Acceptor Stenhouse Adducts on the Surfaces of Magnetite Nanoparticles
Authors: Ahrens Johannes , Bian Tong , Vexler Tom , Klajn Rafal
Published: March 2017

Two novel donor–acceptor Stenhouse adducts (DASAs) featuring the catechol moiety were synthesized and characterized. Both compounds bind strongly to the surfaces of magnetite nanoparticles. An adrenaline‐derived DASA renders the particles insoluble in all common solvents, likely because of poor solvation of the zwitterionic isomer generated on the nanoparticle surfaces. Well‐soluble nanoparticles were successfully obtained using dopamine‐derived DASA equipped with a long alkyl chain. Upon its attachment to nanoparticles, this DASA undergoes an irreversible decoloration reaction owing to the formation of the zwitterionic form. The reaction follows first‐order kinetics and proceeds more rapidly on large nanoparticles. Interestingly, decoloration can be suppressed in the presence of free DASA molecules in solution or at high nanoparticle concentrations.
Quantum imaging of high‐dimensional Hilbert spaces with Radon transform
Authors: Gyongyosi Laszlo
Published: March 2017

High‐dimensional Hilbert spaces possess large information encoding and transmission capabilities. Characterizing exactly the real potential of high‐dimensional entangled systems is a cornerstone of tomography and quantum imaging. The accuracy of the measurement apparatus and devices used in quantum imaging is physically limited, which allows no further improvements to be made. To extend the possibilities, we introduce a post‐processing method for quantum imaging that is based on the Radon transform and the projection‐slice theorem. The proposed solution leads to an enhanced precision and a deeper parameterization of the information conveying capabilities of high‐dimensional Hilbert spaces. We demonstrate the method for the analysis of high‐dimensional position–momentum photonic entanglement. We show that the entropic separability bound in terms of standard deviations is violated considerably more strongly in comparison to the standard setting and current data processing. The results indicate that the possibilities of the quantum imaging of high‐dimensional Hilbert spaces can be extended by applying appropriate calculations in the post‐processing phase. Copyright © 2017 John Wiley & Sons, Ltd.
Extending the Scope of Bis(acyl)phosphane Oxides: Additional Derivatives
Authors: Eibel Anna , Schmallegger Max , Zalibera Michal , Huber Alex , Bürkl Yasmin , Grützmacher Hansjörg , Gescheidt Georg
Published: March 2017

A series of new bis(acyl)phosphane oxide (BAPO) photoinitiators has been synthesized and tested with respect to their efficiency in the initiation step of radical photopolymerizations. The transient absorption spectra of the phosphanoyl radicals obtained upon laser‐flash photolysis reveal maxima at ca. 450–460 nm. Rate constants for the addition of these radicals to the double bonds of butyl acrylate, methyl methacrylate, 1‐vinyl‐2‐pyrrolidone, and styrene have been determined. All phosphanoyl radicals have been found to react the most rapidly with styrene and the most slowly with butyl acrylate. Low fluorescence quantum yields of 0.1–0.3 % reveal that the studied BAPOs undergo efficient intersystem crossing, followed by α‐cleavage. The heat profiles of selected photopolymerizations have been observed using a high‐resolution infrared camera. Thermal‐imaging experiments show substantial monomer‐dependent exothermicity. All BAPO derivatives can additionally act as electron acceptors, as indicated by cyclic voltammetry and EPR spectroscopy.
Iridium(III)‐Catalyzed Selective Sulfonamidation of o‐Carborane with Sulfonyl Azide by Carboxylic Acid‐Assisted B(4)–H Bond Activation
Authors: Li Huanhuan , Bai Fan , Yan Hong , Lu Changsheng , Bregadze Vladimir I.
Published: March 2017

An iridium‐catalyzed cage B–H sulfonamidation of o‐carborane directed by a carboxylic acid group is reported that proceeds in the absence of ligands or external oxidants. A series of sulfonyl azides can be selectively sulfonamidated at the B(4) site in high yields with excellent functional group tolerance. This approach can also be applied to aryl and aliphatic azides. Innocuous CO2 and N2 were released as byproducts. In addition, the carboxylic acid group can be easily removed under mild conditions.
Protecting‐Group‐Free Total Syntheses of Rubrolide R and S
Authors: Schacht Mathias , Boehlich Gordon Jacob , de Vries Jessica , Bertram Stephanie , Gabriel Gülsah , Zimmermann Phyllis , Heisig Peter , Schützenmeister Nina
Published: March 2017

The two marine natural products rubrolide R (1) and S (2) were synthesised in only three linear steps starting from commercially available tetronic acid without using protecting‐group chemistry. Key steps in the syntheses were the Pd‐catalysed Suzuki–Miyaura cross‐coupling followed by a vinylogous aldol condensation. Both compounds have been tested for their antibiotic and antiviral activities. At a concentration of 10 µm rubrolide R (1) and S (2), a 2‐log and 1.5‐log reduction in virus titre has been detected for a seasonal influenza virus (H3N2) and the pandemic swine influenza virus (pH1N1), respectively.
The Clue
Authors: Tate Tyler
Published: March 2017

As I stood outside of Carlos's room, I felt caught on the horns of a dilemma. It seemed impossible to truly “be there” for Carlos without sacrificing my other intern duties. This tension pervaded much of my residency training, as I often found myself spending more time completing chart notes, answering pages, and giving sign out than I did at the bedside with my patients. I knew I had a duty to “do my job”—I could not let my team down. But what about my duty to Carlos, a duty to act on my intuition and try to “get to the bottom” of his illness, if that was even possible? And what about my thirteen other patients? Wasn't I was their doctor as well? I have spent countless hours studying the ethical frameworks for medical rationing. And yet no framework could have told me how to weigh my intuition in that crucial moment of decision‐making, or when it was okay to leave a few notes unfinished in order to have the time to talk with Carlos.

Suddenly, I knew what I had to do.