bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons from two high CO2 worlds – future oceans and intensive aquaculture
Authors: Ellis Robert P. , Urbina Mauricio A. , Wilson Rod W.
Published: October 2016

Exponentially rising CO2 (currently ~400 μatm) is driving climate change and causing acidification of both marine and freshwater environments. Physiologists have long known that CO2 directly affects acid–base and ion regulation, respiratory function and aerobic performance in aquatic animals. More recently, many studies have demonstrated that elevated CO2 projected for end of this century (e.g. 800–1000 μatm) can also impact physiology, and have substantial effects on behaviours linked to sensory stimuli (smell, hearing and vision) both having negative implications for fitness and survival. In contrast, the aquaculture industry was farming aquatic animals at CO2 levels that far exceed end‐of‐century climate change projections (sometimes >10 000 μatm) long before the term ‘ocean acidification’ was coined, with limited detrimental effects reported. It is therefore vital to understand the reasons behind this apparent discrepancy. Potential explanations include 1) the use of ‘control’ CO2 levels in aquaculture studies that go beyond 2100 projections in an ocean acidification context; 2) the relatively benign environment in aquaculture (abundant food, disease protection, absence of predators) compared to the wild; 3) aquaculture species having been chosen due to their natural tolerance to the intensive conditions, including CO2 levels; or 4) the breeding of species within intensive aquaculture having further selected traits that confer tolerance to elevated CO2. We highlight this issue and outline the insights that climate change and aquaculture science can offer for both marine and freshwater settings. Integrating these two fields will stimulate discussion on the direction of future cross‐disciplinary research. In doing so, this article aimed to optimize future research efforts and elucidate effective mitigation strategies for managing the negative impacts of elevated CO2 on future aquatic ecosystems and the sustainability of fish and shellfish aquaculture.
The Decolonization of Belief from a Native Perspective: Wak'as and Teología Andina in the Bolivian Highlands
Authors: Cuelenaere Laurence
Published: October 2016

Este artículo aborda dos aporías en los discursos descolonizadores en Bolivia. La primera se manifiesta en la distancia irreductible entre perspectivas coloniales y descoloniales sobre las creencias y la vivencia de los wak'as deidades, objetos sagrados, santuarios. La segunda reside en las contradicciones la Teología Andina incurre en sus pretensiones de descolonizar la teología entanto que llama a un saneamiento de las creencias para que sean aceptables al cristianismo y define prácticas para la neutralización de la furia de los wak'as. Exploro estas aporías a partir de testimonios y conversaciones con intelectuales de extracción aymara. La amplia gama de discursos descolonizadores que he tocado en este ensayo (no se pretende hacer una evaluación exhaustiva) acarrean posiciones contradictorias análogas al llamado al saneamiento y la neutralización por la teología andina.
Transitory cystic cavities in the developing mammalian brain – normal or anomalous?
Authors: Kaur Charanjit , Ling Eng‐Ang
Published: October 2016

Transitory cavities associated with the ventricular system represent probably one of the most unique features in the developing mammalian brain. In rodents, the cavities exist transiently in the developing brain and do not appear to be associated with any pathological events. Among the various cavities, the pyramidal‐shaped cavum septum pellucidum (CSP) located beneath the corpus callosum and between the lateral ventricles is most well defined. In addition to the CSP are the bilateral subependymal cysts that are consistently associated with the third and fourth ventricles as well as the aqueduct. The cavities/cysts contain a large number of amoeboid microglia expressing surface receptors and hydrolytic enzymes common to tissue macrophages. The significance of these cavities in the developing brain remains a conjecture. Firstly, the cavity walls are free of an apparent epithelial lining; hence, it is speculated that the cavities that appear to communicate with the widened neighboring interstitial tissue spaces may have resulted from physical traction due to the rapid growth of the perinatal brain. Secondly, the cavities contain prominent clusters of amoeboid microglia that may be involved in clearing the debris of degenerating axons and cells resulting from the early brain tissue remodeling. With the increase in brain tissue compactness following the beginning of myelination in the second postnatal week, all cavities are obliterated; concomitantly, the number of amoeboid microglia in them diminishes and all this might signal further maturation of the brain.
Treatment of erythematotelangiectatic rosacea with the fractionation of high‐fluence, long‐pulsed 595‐nm pulsed dye laser
Authors: Baek Jin Ok , Hur Hoon , Ryu Ha Ryeong , Kim Jeong Soo , Lee Kyung Real , Kim Yu Ri , Choi Kwang Ho
Published: October 2016

Various lasers have been used for the treatment of erythematotelangiectatic rosacea (ETR) that does not respond to systemic or topical therapy. The pulsed dye lasers (PDLs) are an effective option for ETR, and the purpuragenic fluence proved to be superior until now. Given that purpura and subsequent possible postinflammatory hyperpigmentation (PIH) are occasionally unbearable in some patients, and several studies using the low nonpurpuragenic fluence were reported. To deliver the sufficient high fluence of a PDL without generating purpura, we designed the fractionation of high fluence using five passes and longer pulse duration (6 milliseconds) of a PDL in succession. A total of eight patients with ETR were enrolled in this study; all patients were treated with PDL 10 times at 2‐week intervals. Erythema and telangiectasia scores, as well as improvement, were assessed by two physicians using the digital photographs. Moderate‐to‐marked improvement was achieved in most of the patients, and erythema and telangiectasia scores were significantly decreased. Purpura and PIH were not reported in all patients. The fractionation of high‐fluence, long‐pulsed 595 nm PDL is a very safe and effective treatment for ETR.
Value of brush cytology for optimal timing of liver transplantation in primary sclerosing cholangitis
Authors: Vannas Marko J. , Boyd Sonja , Färkkilä Martti A. , Arola Johanna , Isoniemi Helena
Published: October 2016

Background and Aims

Primary sclerosing cholangitis is associated with a high risk of cholangiocarcinoma. Here, we investigated the value of surveillance for dysplasia using brush cytology, to determine the optimal timing of liver transplantation in primary sclerosing cholangitis. We compared our preoperative findings, with the final explanted liver histopathology.

Methods

126 consecutive patients were transplanted for primary sclerosing cholangitis from 1984 to 2012. Patients were divided into two groups: symptomatic (n=91), and asymptomatic (n=35).

Results

Brush cytology was available for 101 patients; 66 symptomatic and 35 asymptomatic. Suspicious cytological findings were found in nine patients (14%) in the symptomatic group and 17 (49%) in the asymptomatic group. DNA flow cytometry was available for 49 patients (25 symptomatic, 24 asymptomatic), with aneuploidy detected in six patients (24%) in the symptomatic group and 15 (63%) in the asymptomatic group. Explanted liver histology showed biliary dysplasia or cholangiocarcinoma in 11 symptomatic patients (12%) and 15 asymptomatic patients (43%). A combination of cytological and DNA flow cytometry findings resulted in a test sensitivity of 68%, with a specificity of 86%. Ten‐year survival in the asymptomatic group was 91%.

Conclusions

Dysplasia surveillance using brush specimens may help to select those patients likely to benefit from early liver transplantation. It remains unclear as to whether surveillance with brush cytology improves long‐term survival, but there is presently no better method with which to predict transplantation timing.
Ovulation‐inducing factor (OIF/NGF) in seminal plasma: a review and update
Authors: Adams GP , Ratto MH , Silva ME , Carrasco RA
Published: October 2016

Contents

The ovulation‐inducing effect of seminal plasma was first reported in Bactrian camels over 30 years ago, and the entity responsible was dubbed ‘ovulation‐inducing factor’ (OIF). More recent studies, primarily in llamas and alpacas, characterized the biological and chemical properties ofOIFand ultimately identified it as βNGF. This recent discovery has allowed a convergence of knowledge previously separated by discipline and by mechanism; that is, neurobiology and reproductive biology, and autocrine/paracrine vs endocrine. To preserve this link, we have referred to the seminal factor asOIF/NGF. As a highly conserved protein, the implications of discoveries related toOIF/NGFin reproductive tissues extend beyond the camelid species, and results of recent studies show that the presence and function ofOIF/NGFin seminal plasma are conserved among species considered to be induced ovulators as well as those considered to be spontaneous ovulators. The abundance ofOIF/NGFin seminal plasma and the effects of seminal plasma on ovarian function strongly support the idea of an endocrine mode of action (i.e. systemic distribution with distant target tissues). This review is intended to provide an update on the progress in our understanding of the nature ofOIF/NGFin seminal plasma and its effects on reproductive function in the female, including the effects of dose and route of administration, evidence for ovarian effects in other species, tissue sources ofOIF/NGFand early findings related to the mechanism of action ofOIF.
Characterization of a novel HLA‐B*18 variant allele, HLA‐B*18:122, by genome sequencing
Authors: Sciarrino R. , De Donno M. , Biagini C. , Rombolà G. , Curcio M.
Published: October 2016

The HLA‐B*18:122 allele showed four nucleotide differences from HLA‐B*18:01:01:01.
Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort
Authors: Wilkinson A. L. , Pedersen S. H. , Urassa M. , Michael D. , Andreasen A. , Todd J. , Kinung'hi S. M. , Changalucha J. , McDermid J. M.
Published: October 2016

Objectives

HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort.

Methods

A 9‐plex panel of maternal plasma cytokines in HIV‐positive (n = 44) and HIV‐negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry.

Results

Health indicators (haemoglobin, mid‐upper‐arm circumference, body mass index) in HIV‐positive mothers without considerable immunosuppression did not differ from HIV‐negative women. Despite this, HIV‐exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF‐α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF‐α was associated with earlier delivery (−1.7 weeks, P = 0.039) and lower birthweights (−287 g; P = 0.020), while greater umbilical cord TNF‐α (−1.43 cm; P = 0.036) and IL‐12p70 (−2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL‐12p70 (−723 g; P = 0.001) and IFN‐γ (−482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery.

Conclusions

Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV‐exposed and HIV‐unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry.
Time dependent electromagnetic fields and 4-dimensional Stokes' theorem
Authors: Andosca Ryan , Singleton Douglas
Published: October 2016

Stokes' theorem is central to many aspects of physics—electromagnetism, the Aharonov-Bohm effect, and Wilson loops to name a few. However, the pedagogical examples and research work almost exclusively focus on situations where the fields are time-independent so that one need only deal with purely spatial line integrals (e.g., ∮A·dx) and purely spatial area integrals (e.g., ∫(∇×A)·da=∫B·da). Here, we address this gap by giving some explicit examples of how Stokes' theorem plays out with time-dependent fields in a full 4-dimensional spacetime context. We also discuss some unusual features of Stokes' theorem with time-dependent fields related to gauge transformations and non-simply connected topology.
Multiple-Choice Answers: To Change or Not to Change? Perhaps Not Such a Simple Question
Authors: Wainscott Heidi
Published: October 2016

When grading students’ quizzes and exams, I find that students are seemingly always changing their answers from the right answer to the wrong answer. In fact, I have cautioned students against changing their answer. Colleagues have made similar observations and some books on test-taking strategies advise against answer-changing. In an effort to find out how pervasive the answer-changing problem was, I collected some data and dug a little deeper into the research. My hypothesis was that students most frequently changed their answers from right to wrong. Have you made similar observations? If yes, then the results of this study may surprise you.
How to Drive a Car on a Snowy Slope
Authors: Ogawara Yasuo
Published: October 2016

When I was a freshman at Tokyo University of Science, my senpai (upper-class student mentor) took me to a certain skiing ground in his car, which was equipped with standard tires. He tried to enter the parking area there, but his car could not climb a short slope leading to the entrance. I would like to describe here how he dealt with the problem and present a physical analysis.
The business of doing good
Introduction to Social Entrepreneurship
Teresa Chahine
CRC Press, 2016. 299 pp.
Authors: Bagasra Omar
Published: October 2016

A guide for aspiring entrepreneurs offers a data-driven approach to making a difference
A plankton bloom shifts as the ocean warms
Authors: Worden Alexandra Z. , Wilken Susanne
Published: October 2016

Long-term data show how a widespread phytoplankton group responds to temperature changes
Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia
Authors: Hsu Li-Yang , Apisarnthanarak Anucha , Khan Erum , Suwantarat Nuntra , Ghafur Abdul , Tambyah Paul Anantharajah
Published: October 2016

Carbapenem-resistant Gram-negative bacteria, in particular theAcinetobacter baumannii-calcoaceticuscomplex andEnterobacteriaceae, are escalating global public health threats. We review the epidemiology and prevalence of these carbapenem-resistant Gram-negative bacteria among countries in South and Southeast Asia, where the rates of resistance are some of the highest in the world. These countries house more than a third of the world's population, and several are also major medical tourism destinations. There are significant data gaps, and the almost universal lack of comprehensive surveillance programs that include molecular epidemiologic testing has made it difficult to understand the origins and extent of the problem in depth. A complex combination of factors such as inappropriate prescription of antibiotics, overstretched health systems, and international travel (including the phenomenon of medical tourism) probably led to the rapid rise and spread of these bacteria in hospitals in South and Southeast Asia. In India, Pakistan, and Vietnam, carbapenem-resistantEnterobacteriaceaehave also been found in the environment and community, likely as a consequence of poor environmental hygiene and sanitation. Considerable political will and effort, including from countries outside these regions, are vital in order to reduce the prevalence of such bacteria in South and Southeast Asia and prevent their global spread.
Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases
Authors: Holcomb Zachary E. , Tsalik Ephraim L. , Woods Christopher W. , McClain Micah T.
Published: October 2016

Emerging pandemic infectious threats, inappropriate antibacterial use contributing to multidrug resistance, and increased morbidity and mortality from diagnostic delays all contribute to a need for improved diagnostics in the field of infectious diseases. Historically, diagnosis of infectious diseases has relied on pathogen detection; however, a novel concept to improve diagnostics in infectious diseases relies instead on the detection of changes in patterns of gene expression in circulating white blood cells in response to infection. Alterations in peripheral blood gene expression in the infected state are robust and reproducible, yielding diagnostic and prognostic information to help facilitate patient treatment decisions.
Comparison of MagPix Assays and Enzyme-Linked Immunosorbent Assay for Detection of Hemorrhagic Fever Viruses
Authors: Satterly Neal G. , Voorhees Matthew A. , Ames Abbe D. , Schoepp Randal J.
Published: October 2016

Viral hemorrhagic fevers, because of their high mortality rates, the lack of medical countermeasures, and their potential use as instruments of bioterrorism, pose a significant threat to the developed and the developing areas of the world. The key to preventing the spread of these diseases is early and accurate detection. For decades, the gold-standard immunoassay for hemorrhagic fever detection has been the enzyme-linked immunosorbent assay (ELISA); however, newer technologies are emerging with increased sensitivities. One such technology is the Luminex MagPix platform using xMAP microspheres. Here, we compare the MagPix platform with a traditional ELISA for IgM and antigen detection of infections from Lassa and Ebola viruses (LASV and EBOV, respectively). For IgM detection in nonhuman primate samples, the MagPix platform was 5 and 25 times more sensitive in detecting LASV and EBOV, respectively, compared to that with ELISA. For antigen detection in buffer, the MagPix platform was 25 and 2.5 times more sensitive in detecting lower levels of LASV and EBOV, respectively. In both IgM and antigen detection assays, the MagPix platform demonstrated excellent reproducibility at the lower limit of detection (LLOD). These findings demonstrate that the MagPix platform is a viable diagnostic replacement for the ELISA for viral hemorrhagic fevers.
Improved Detection of Respiratory Pathogens by Use of High-Quality Sputum with TaqMan Array Card Technology
Authors: Wolff Bernard J. , Bramley Anna M. , Thurman Kathleen A. , Whitney Cynthia G. , Whitaker Brett , Self Wesley H. , Arnold Sandra R. , Trabue Christopher , Wunderink Richard G. , McCullers Jon , Edwards Kathryn M. , Jain Seema , Winchell Jonas M.
Published: October 2016

New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with community-acquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (<18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as ≤10 epithelial cells/low-power field [lpf] and ≥25 white blood cells/lpf or a quality score [q-score] definition of 2+) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had ≥1 pathogen detected compared with NP/OP specimens in children (93% versus 68%;
P
< 0.0001) and adults (88% versus 61%;
P
< 0.0001); for each pathogen targeted, crossing threshold (

C
T

) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.
Identification of Novel Kaposi's Sarcoma-Associated HerpesvirusOrf50Transcripts: Discovery of New RTA Isoforms with Variable Transactivation Potential
Authors: Wakeman Brian S. , Izumiya Yoshihiro , Speck Samuel H.
Published: October 2016

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma and multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the geneOrf50. RTA is a known transactivator of multiple viral genes, allowing it to control the switch between latency and virus replication. We report here the identification of six alternatively splicedOrf50transcripts that are generated from four distinct promoters. These newly identified promoters are shown to be transcriptionally active in 293T (embryonic kidney), Vero (African-green monkey kidney epithelial), 3T12 (mouse fibroblast), and RAW 264.7 (mouse macrophage) cell lines. Notably, the newly identifiedOrf50transcripts are predicted to encode four different isoforms of the RTA which differ by 6 to 10 residues at the amino terminus of the protein. We show the global viral transactivation potential of all four RTA isoforms and demonstrate that all isoforms can transcriptionally activate an array of KSHV promoters to various levels. The pattern of transcriptional activation appears to support a transcriptional interference model within the Orf50 region, where silencing of previously expressed isoforms by transcription initiation from upstream Orf50 promoters has the potential to modulate the pattern of viral gene activation.

IMPORTANCEGammaherpesviruses are associated with the development of lymphomas and lymphoproliferative diseases, as well as several other types of cancer. The human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is tightly associated with the development of Kaposi's sarcoma and multicentric Castleman's disease, as well as a rare form of B cell lymphoma (primary effusion lymphoma) primarily observed in HIV-infected individuals. RTA is an essential viral gene product involved in the initiation of gammaherpesvirus replication and is conserved among all known gammaherpesviruses. We show here for KSHV that transcription of the gene encoding RTA is complex and leads to the expression of several isoforms of RTA with distinct functions. This observed complexity in KSHV RTA expression and function likely plays a critical role in the regulation of downstream viral and cellular gene expression, leading to the efficient production of mature virions.
JunD/AP-1 Antagonizes the Induction of
DAPK1
To Promote the Survival of v-Src-Transformed Cells
Authors: Maślikowski Bart M. , Wang Lizhen , Wu Ying , Fielding Ben , Bédard Pierre-André
Published: October 2016

The increase in AP-1 activity is a hallmark of cell transformation by tyrosine kinases. Previously, we reported that blocking AP-1 using the c-Jun dominant negative mutant TAM67 induced senescence, adipogenesis, or apoptosis in v-Src-transformed chicken embryo fibroblasts (CEFs) whereas inhibition of JunD by short hairpin RNA (shRNA) specifically induced apoptosis. To investigate the role of AP-1 in Src-mediated transformation, we undertook a gene profiling study to characterize the transcriptomes of v-Src-transformed CEFs expressing either TAM67 or the JunD shRNA. Our study revealed a cluster of 18 probe sets upregulated exclusively in response to AP-1/JunD impairment and v-Src transformation. Four of these probe sets correspond to genes involved in the interferon pathway. One gene in particular, death-associated protein kinase 1 (
DAPK1
), is a C/EBPβ-regulated mediator of apoptosis in gamma interferon (IFN-γ)-induced cell death. Here, we show that inhibition of DAPK1 abrogates cell death in v-Src-transformed cells expressing the JunD shRNA. Chromatin immunoprecipitation data indicated that C/EBPβ was recruited to the DAPK1 promoter while the expression of a dominant negative mutant of C/EBPβ abrogated the induction of DAPK1 in response to the inhibition of AP-1. In contrast, as determined by chromatin immunoprecipitation (ChIP) assays, JunD was not detected on the DAPK1 promoter under any conditions, suggesting that JunD promotes survival by indirectly antagonizing the expression of DAPK1 in v-Src transformed cells.

IMPORTANCE
Transformation by the v-Src oncoprotein causes extensive changes in gene expression in primary cells such as chicken embryo fibroblasts. These changes, determining the properties of transformed cells, are controlled in part at the transcriptional level. Much attention has been devoted to transcription factors such as AP-1 and NF-κB and the control of genes associated with a more aggressive phenotype. In this report, we describe a novel mechanism of action determined by the JunD component of AP-1, a factor enhancing cell survival in v-Src-transformed cells. We show that the loss of JunD results in the aberrant activation of a genetic program leading to cell death. This program requires the activation of the tumor suppressor death-associated protein kinase 1 (DAPK1). Since DAPK1 is phosphorylated and inhibited by v-Src, these results highlight the importance of this kinase and the multiple mechanisms controlled by v-Src to antagonize the tumor suppressor function of DAPK1.
Maternal perceptions of underweight and overweight for 6–8 years olds from a Canadian cohort: reporting weights, concerns and conversations with healthcare providers
Authors: McDonald Sheila W , Ginez Heather K , Vinturache Angela E , Tough Suzanne C
Published: October 2016

Objectives

The majority of mothers do not correctly identify their child's weight status. The reasons for the misperception are not well understood. This study's objective was to describe maternal perceptions of their child's body mass index (BMI) and maternal report of weight concerns raised by a health professional.

Design

Prospective, community-based cohort.

Participants

Data were collected in 2010 from 450 mothers previously included in a longitudinal birth cohort. Mothers of children aged 6–8 years reported their child's anthropometric measures and were surveyed concerning their opinion about their child's weight. They were also asked if a healthcare provider raised any concerns regarding their child's body weight. Child BMI was categorised according to the WHO Growth Charts adapted for Canada. Descriptive statistics and bivariate analyses were used to evaluate mothers' ability to correctly identify their children's body habitus.

Results

74% of children had a healthy BMI, 10% were underweight, 9% were overweight and 7% were obese. 80%, 89% and 62% of mothers with underweight, overweight and obese children, respectively, believed that their child was at the right weight. The proportion of mothers who recalled a health professional raising concerns about their child being underweight, overweight, and obese was low (12.5%).

Conclusions

The majority of mothers with children at unhealthy weights misclassified and normalised their child's weight status, and they did not recall a health professional raising concerns regarding their child's weight. The highest rates of child body weight misclassification occurred in overweight children. This suggests that there are missed opportunities for healthcare professionals to improve knowledge exchange and early interventions to assist parents to recognise and support healthy weights for their children.
BET 1: Tranexamic acid in epistaxis: who bloody nose?
Authors: Penrose Nicola , May Gabby
Published: October 2016

A shortcut review was carried out to establish whether tranexamic acid is effective in controlling epistaxis. Three studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these studies are tabulated. The clinical bottom line is that there is not enough evidence to recommend tranexamic acid in the standard management of epistaxis.
BET 2: Usefulness of IV lidocaine in the treatment of renal colic
Authors: Keller Duke , Seamon Jason , Jones JS
Published: October 2016

A shortcut review was carried out to establish whether intravenous lidocaine is effective in the management of renal colic. Two studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these studies are tabulated. The clinical bottom line is that intravenous lidocaine may be of some benefit in renal colic. However, there are other maybe more effective drugs available.
Lower and upper bounds on the mass of light quark–antiquark scalar resonance in the SVZ sum rules
Authors: Afonin S. S.
Published: October 2016

The calculation of the mass of light scalar isosinglet meson within the Shifman–Vainshtein–Zakharov (SVZ) sum rules is revisited. We develop simple analytical methods for estimation of hadron masses in the SVZ approach and try to reveal the origin of their numerical values. The calculations of hadron parameters in the SVZ sum rules are known to be heavily based on a choice of the perturbative threshold. This choice requires some important ad hoc information. We show analytically that the scalar mass under consideration has a lower and upper bound which are independent of this choice: [Formula: see text] GeV.
A Low Power Low-Pass Fourth-Order Filter for WiMAX/LTE Receiver in CMOS 45nm Technology
Authors: Niar Vida Orduee , Fatin Gholamreza Zare
Published: October 2016

In this paper, a [Formula: see text]-[Formula: see text] low-pass and low power filter with tunable in-band attenuation for WiMAX/LTE receiver is presented. The fourth-order filter consists of two cascaded biquad stages. The source-follower (SF) stage is used as a key building block in these biquads. In this paper, we have presented a circuit technique to reduce the nonlinearity of the SF stage resulting from unmatched signal swings at the gate and source terminals of the input transistor. The proposed SF stage, is used for design of a linear biquad which is then utilized in a fourth-order Butterworth low-pass filter. The simulation results of the filter for bandwidth of 10 MHz show that the IIP3 of the filter is equal to 8.22[Formula: see text]dBm, in-band noise density is 100[Formula: see text]nV/[Formula: see text]Hz and power consumption is 5.9[Formula: see text]mW. The supply voltage of the filter is equal to 1[Formula: see text]V.
Blood pressure reduction after gastric bypass surgery is explained by a decrease in cardiac output
Authors: van Brussel Peter M. , van den Bogaard Bas , de Weijer Barbara A. , Truijen Jasper , Krediet C.T. Paul , Janssen Ignace M. , van de Laar Arnold , Kaasjager Karin , Fliers Eric , van Lieshout Johannes J. , Serlie Mireille J. , van den Born Bert-Jan H.
Published: October 2016

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 ± 7 standard deviation (SD) yr, body mass index 45 ± 6 kg/m2] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 ± 5 kg (10%, P < 0.001). Office BP decreased from 137 ± 10/86 ± 6 to 128 ± 12/81 ± 9 mmHg ( P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 ± 14/80 ± 9 to 114 ± 10/73 ± 6 mmHg ( P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 ± 13/66 ± 7 to 102 ± 9/62 ± 7 mmHg ( P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 ± 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 ± 189 dyn·s·cm−5, 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4–14.3] to 13.8 [8.5–19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate ( R = −0.64, P = 0.02) and CO ( R = −0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control.

NEW & NOTEWORTHY The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients.
The Role of Parvalbumin, Sarcoplasmatic Reticulum Calcium Pump Rate, Rates of Cross-Bridge Dynamics, and Ryanodine Receptor Calcium Current on Peripheral Muscle Fatigue: A Simulation Study
Authors: Röhrle Oliver , Neumann Verena , Heidlauf Thomas
Published: October 2016

A biophysical model of the excitation-contraction pathway, which has previously been validated for slow-twitch and fast-twitch skeletal muscles, is employed to investigate key biophysical processes leading to peripheral muscle fatigue. Special emphasis hereby is on investigating how the model’s original parameter sets can be interpolated such that realistic behaviour with respect to contraction time and fatigue progression can be obtained for a continuous distribution of the model’s parameters across the muscle units, as found for the functional properties of muscles. The parameters are divided into 5 groups describing (i) the sarcoplasmatic reticulum calcium pump rate, (ii) the cross-bridge dynamics rates, (iii) the ryanodine receptor calcium current, (iv) the rates of binding of magnesium and calcium ions to parvalbumin and corresponding dissociations, and (v) the remaining processes. The simulations reveal that the first two parameter groups are sensitive to contraction time but not fatigue, the third parameter group affects both considered properties, and the fourth parameter group is only sensitive to fatigue progression. Hence, within the scope of the underlying model, further experimental studies should investigate parvalbumin dynamics and the ryanodine receptor calcium current to enhance the understanding of peripheral muscle fatigue.
Development of Shear Capacity Prediction Model for FRP-RC Beam without Web Reinforcement
Authors: Chowdhury Md. Arman , Ibna Zahid Zubayer , Islam Md. Mashfiqul
Published: October 2016

Available codes and models generally use partially modified shear design equation, developed earlier for steel reinforced concrete, for predicting the shear capacity of FRP-RC members. Consequently, calculated shear capacity shows under- or overestimation. Furthermore, in most models some affecting parameters of shear strength are overlooked. In this study, a new and simplified shear capacity prediction model is proposed considering all the parameters. A large database containing 157 experimental results of FRP-RC beams without shear reinforcement is assembled from the published literature. A parametric study is then performed to verify the accuracy of the proposed model. Again, a comprehensive review of 9 codes and 12 available models is done, published back from 1997 to date for comparison with the proposed model. Hence, it is observed that the proposed equation shows overall optimized performance compared to all the codes and models within the range of used experimental dataset.
Topological Entropy of One Type of Nonoriented Lorenz-Type Maps
Authors: Feng Guo
Published: October 2016

Constructing a Poincaré map is a method that is often used to study high-dimensional dynamical systems. In this paper, a geometric model of nonoriented Lorenz-type attractor is studied using this method, and its dynamical property is described. The topological entropy of one-dimensional nonoriented Lorenz-type maps is also computed in terms of their kneading sequences.
Management of Respiratory Syncytial Virus Bronchiolitis: 2015 Survey of Members of the European Society for Paediatric Infectious Diseases
Authors: Carande Elliott J. , Pollard Andrew J. , Drysdale Simon B.
Published: October 2016

In 1995, the European Society for Paediatric Infectious Diseases (ESPID) carried out a survey of its members to assess the variation in management of respiratory syncytial virus (RSV) bronchiolitis. The aim of the current study was to carry out a similar survey 20 years later to assess how the management had changed. An electronic, structured, English language survey, based on the United Kingdom National Institute for Health and Care Excellence (NICE) bronchiolitis draft guideline, was sent to ESPID members in March 2015. Questions asked included information on treatment practices of infants with bronchiolitis and doctor demographics. We received responses from 135 doctors (14% of the ESPID members) who worked in 115 hospitals. 56% of the doctors used a written guideline to manage bronchiolitic infants. All doctors stated that they isolated individually or in cohorts all hospitalised bronchiolitis infants. The level of oxygen saturation suggested as an indication to administer supplemental oxygen varied between <89% and <95%. We found significant reductions in the use of ribavirin, bronchodilators, and corticosteroids from 1995 to 2015 (ribavirin 57% to 13%,P<0.0001; bronchodilators 95% to 82%,P=0.0024; corticosteroids 81% to 45%,P<0.0001). Although variability in management remains high, encouragingly significantly fewer doctors are prescribing ribavirin, bronchodilators, and corticosteroids compared to 20 years ago.
Role of the Microenvironment in Liver Metastasis: From Pre- to Prometastatic Niches
Authors: Brodt Pnina
Published: October 2016

Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal tract but also for other malignancies, such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between tumor cells and different local resident subpopulations, including the sinusoidal endothelium, stellate, Kupffer, and inflammatory cells that are mediated through cell–cell and cell–extracellular matrix adhesion and the release of soluble factors. Cross-communication between different hepatic resident cells in response to local tissue damage and inflammation and the recruitment of bone marrow cells further enhance this intercellular communication network. Both resident and recruited cells can play opposing roles in the progression of metastasis, and the balance of these divergent effects determines whether the tumor cells will die, proliferate, and colonize the new site or enter a state of dormancy. Moreover, this delicate balance can be tilted in favor of metastasis, if factors produced by the primary tumor precondition the microenvironment to form niches of activated resident cells that promote tumor expansion. This review aims to summarize current knowledge on these diverse interactions and the impact they can have on the clinical management of hepatic metastases. Clin Cancer Res; 22(24); 5971–82. ©2016 AACR.
An Open-Label, Dose–Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma
Authors: Khalil Danny N. , Postow Michael A. , Ibrahim Nageatte , Ludwig Dale L. , Cosaert Jan , Kambhampati Siva Rama Prasad , Tang Shande , Grebennik Dmitri , Kauh John Sae Wook , Lenz Heinz-Josef , Flaherty Keith T. , Hodi F. Stephen , Lawrence Donald P. , Wolchok Jedd D.
Published: October 2016

Purpose: Tyrosinase-related protein-1 (TYRP1) is a transmembrane glycoprotein that is specifically expressed in melanocytes and melanoma cells. Preclinical data suggest that mAbs targeting TYRP1 confer antimelanoma activity. IMC-20D7S is a recombinant human IgG1 mAb targeting TYRP1. Here, we report the first-in-human phase I/Ib trial of IMC-20D7S.

Experimental Design: The primary objective of this study was to establish the safety profile and the MTD of IMC-20D7S. Patients with advanced melanoma who progressed after or during at least one line of treatment or for whom standard therapy was not indicated enrolled in this standard 3 + 3 dose–escalation, open-label study. IMC-20D7S was administered intravenously every 2 or 3 weeks.

Results: Twenty-seven patients were enrolled. The most common adverse events were fatigue and constipation experienced by nine (33%) and eight (30%) patients, respectively. There were no serious adverse events related to treatment, no discontinuations of treatment due to adverse events, and no treatment-related deaths. Given the absence of dose-limiting toxicities, an MTD was not defined, but a provisional MTD was established at the 20 mg/kg every 2-week dose based on serum concentration and safety data. One patient experienced a complete response. A disease control rate, defined as stable disease or better, of 41% was observed.

Conclusion: IMC-20D7S is well tolerated among patients with advanced melanoma with evidence of antitumor activity. Further investigation of this agent as monotherapy in selected patients or as part of combination regimens is warranted. Clin Cancer Res; 22(21); 5204–10. ©2016 AACR.
Significant Effect of Polymorphisms inCYP2D6on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study
Authors: Zembutsu Hitoshi , Nakamura Seigo , Akashi-Tanaka Sadako , Kuwayama Takashi , Watanabe Chie , Takamaru Tomoko , Takei Hiroyuki , Ishikawa Takashi , Miyahara Kana , Matsumoto Hiroshi , Hasegawa Yoshie , Kutomi Goro , Shima Hiroaki , Satomi Fukino , Okazaki Minoru , Zaha Hisamitsu , Onomura Mai , Matsukata Ayami , Sagara Yasuaki , Baba Shinichi , Yamada Akimitsu , Shimada Kazuhiro , Shimizu Daisuke , Tsugawa Koichiro , Shimo Arata , Tan Ern Yu , Hartman Mikael , Chan Ching-Wan , Lee Soo Chin , Nakamura Yusuke
Published: October 2016

Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, “endoxifen.” There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy.

Experimental Design: We enrolled 279 patients with hormone receptor–positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen. We prospectively investigated the effects of allelic variants of CYP2D6 on Ki-67 response, pathological response, and hot flushes.

Results: Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (P = 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor–positive cells in breast cancer tissues were significantly associated with Ki-67 response (P = 0.0076 and 0.0023, respectively). Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).

Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. Clin Cancer Res; 23(8); 2019–26. ©2016 AACR.
Preclinical Efficacy of an Antibody–Drug Conjugate Targeting Mesothelin Correlates with Quantitative 89Zr-ImmunoPET
Authors: Terwisscha van Scheltinga Anton G.T. , Ogasawara Annie , Pacheco Glenn , Vanderbilt Alexander N. , Tinianow Jeff N. , Gupta Nidhi , Li Dongwei , Firestein Ron , Marik Jan , Scales Suzie J. , Williams Simon-Peter
Published: October 2016

Antibody–drug conjugates (ADC) use monoclonal antibodies (mAb) as vehicles to deliver potent cytotoxic drugs selectively to tumor cells expressing the target. Molecular imaging with zirconium-89 (89Zr)-labeled mAbs recapitulates similar targeting biology and might help predict the efficacy of these ADCs. An anti-mesothelin antibody (AMA, MMOT0530A) was used to make comparisons between its efficacy as an ADC and its tumor uptake as measured by 89Zr immunoPET imaging. Mesothelin-targeted tumor growth inhibition by monomethyl auristatin E (MMAE), ADC AMA-MMAE (DMOT4039A), was measured in mice bearing xenografts of ovarian cancer OVCAR-3×2.1, pancreatic cancers Capan-2, HPAC, AsPC-1, and HPAF-II, or mesothelioma MSTO-211H. Ex vivo analysis of mesothelin expression was performed using immunohistochemistry. AMA-MMAE showed the greatest growth inhibition in OVCAR-3×2.1, Capan-2, and HPAC tumors, which showed target-specific tumor uptake of 89Zr-AMA. The less responsive xenografts (AsPC-1, HPAF-II, and MSTO-211H) did not show 89Zr-AMA uptake despite confirmed mesothelin expression. ImmunoPET can demonstrate the necessary delivery, binding, and internalization of an ADC antibody in vivo and this correlates with the efficacy of mesothelin-targeted ADC in tumors vulnerable to the cytotoxic drug delivered. Mol Cancer Ther; 16(1); 134–42. ©2016 AACR.