bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer
Authors: Crown John P. , Diéras Véronique , Staroslawska Elzbieta , Yardley Denise A. , Bachelot Thomas , Davidson Neville , Wildiers Hans , Fasching Peter A. , Capitain Olivier , Ramos Manuel , Greil Richard , Cognetti Francesco , Fountzilas George , Blasinska-Morawiec Maria , Liedtke Cornelia , Kreienberg Rolf , Miller Wilson H. , Tassell Vanessa , Huang Xin , Paolini Jolanda , Kern Kenneth A. , Romieu Gilles
Published: July 2013

Purpose

Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC.

Patients and Methods

Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months).

Results

A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm.

Conclusion

The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.
Prospective Study of Tailoring Whole-Body Dual-Modality [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography With Plasma Epstein-Barr Virus DNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging
Authors: Tang Lin-Quan , Chen Qiu-Yan , Fan Wei , Liu Huai , Zhang Lu , Guo Ling , Luo Dong-Hua , Huang Pei-Yu , Zhang Xu , Lin Xiao-Ping , Mo Yun-Xian , Liu Li-Zhi , Mo Hao-Yuan , Li Jian , Zou Ru-Hai , Cao Yun , Xiang Yan-Qun , Qiu Fang , Sun Rui , Chen Ming-Yuan , Hua Yi-Jun , Lv Xing , Wang Lin , Zhao Chong , Guo Xiang , Cao Ka-Jia , Qian Chao-Nan , Zeng Mu-Sheng , Mai Hai-Qiang
Published: July 2013

Purpose

To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [18F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels.

Patients and Methods

Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared.

Results

Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low–risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively.

Conclusion

PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.
Prospective Multicenter Study Evaluating the Survival of Patients With Locally Advanced Cervical Cancer Undergoing Laparoscopic Para-Aortic Lymphadenectomy Before Chemoradiotherapy in the Era of Positron Emission Tomography Imaging
Authors: Gouy Sebastien , Morice Philippe , Narducci Fabrice , Uzan Catherine , Martinez Alejandra , Rey Annie , Bentivegna Enrica , Pautier Patricia , Deandreis Desiree , Querleu Denis , Haie-Meder Christine , Leblanc Eric
Published: July 2013

Purpose

The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy.

Patients and Methods

We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded.

Results

Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET–computed tomography [CT] results)—16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001).

Conclusion

To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.
TGF-β Induces Wnt10b in Osteoclasts From Female Mice to Enhance Coupling to Osteoblasts
Authors: Ota Kuniaki , Quint Patrick , Ruan Ming , Pederson Larry , Westendorf Jennifer J. , Khosla Sundeep , Oursler Merry Jo
Published: July 2013

In young adults, bone lost through osteoclast-mediated resorption is precisely replaced in both location and amount. Understanding how these two processes are coupled is crucial to advancing treatments for osteoporosis, a disease that progresses when the processes become uncoupled. We documented that osteoclasts secrete the mammalian integration 1 gene that is the homolog of Drosophila Wngless (Wnt) 10b, bone morphogenetic protein 6 (BMP6), and the chemokine sphingosin 1 phosphate (S1P) to promote mesenchymal cell mineralization in vitro. During bone resorption, TGF-β1 is released from the bone extracellular matrix and activated by osteoclasts. Thus, TGF-β1 levels are elevated during the resorption phase of bone turnover. We therefore investigated the influences of TGF-β1 on osteoclast-mediated support of mineralization. TGF-β1 increased osteoclast production of Wnt10b, but not BMP6 or S1P. Blocking Wnt10b activity with the Wnt signaling inhibitor Dickkoph-related protein 1 suppressed the ability of TGF-β–treated osteoclast-conditioned media to promote osteoblast mineralization. Examination of TGF-β signaling in osteoclasts revealed that induction of Wnt10b expression was dependent on Smad2/3 activation and independent from TGF-β1 stimulation of protein kinase B (AKT) or MAPK kinase. TGF-β1–treated osteoclast-conditioned media from cells with blocked Smad signaling exhibited a reduced ability to support mineralization, demonstrating the importance of Smad signaling in this response. Parallel cultures with suppressed TGF-β activation of AKT or MAPK kinase signaling retained their ability to elevate mineralization. These results demonstrate that TGF-β1 stimulates Wnt10b production in osteoclasts, which may enhance restoration of the bone lost during the resorptive phase of bone turnover.
The mechanical control of nervous system development
Authors: Franze Kristian
Published: July 2013

The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate
Authors: Mizeracka Karolina , DeMaso Christina R. , Cepko Constance L.
Published: July 2013

Several models of cell fate determination can be invoked to explain how single retinal progenitor cells (RPCs) produce different cell types in a terminal division. To gain insight into this process, the effects of the removal of a cell fate regulator, Notch1, were studied in newly postmitotic cells using a conditional allele of Notch1 (N1-CKO) in mice. Almost all newly postmitotic N1-CKO cells became rod photoreceptors, whereas wild-type (WT) cells achieved a variety of fates. Single cell profiling of wild-type and N1-CKO retinal cells transitioning from progenitor to differentiated states revealed differential expression of inhibitor of DNA binding factors Id1 and Id3, as well as Notch-regulated ankyrin repeat protein (Nrarp). Misexpression of Id1 and Id3 was found to be sufficient to drive production of Müller glial cells and/or RPCs. Moreover, Id1 and Id3 were shown to partially rescue the production of bipolar and Müller glial cells in the absence of Notch1 in mitotic and newly postmitotic cells. Misexpression of Nrarp, a downstream target gene and inhibitor of the Notch signaling pathway, resulted in the overproduction of rod photoreceptors at the expense of Müller glial cells. These data demonstrate that cell fate decisions can be made in newly postmitotic retinal cells, and reveal some of the regulators downstream of Notch1 that influence the choice of rod and non-rod fates. Taken together, our results begin to address how different signals downstream from a common pathway lead to different fate outcomes.
Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion
Authors: Inoue Naokazu , Hamada Daizo , Kamikubo Hironari , Hirata Kunio , Kataoka Mikio , Yamamoto Masaki , Ikawa Masahito , Okabe Masaru , Hagihara Yoshihisa
Published: July 2013

Although the membrane fusion of spermatozoon and egg cells is the central event of fertilization, the underlying molecular mechanism remains virtually unknown. Gene disruption studies have showed that IZUMO1 on spermatozoon and CD9 on oocyte are essential transmembrane proteins in sperm-egg fusion. In this study, we dissected IZUMO1 protein to determine the domains that were required for the function of sperm-egg fusion. We found that a fragment of the N terminus (Asp5 to Leu113) interacts with fertilization inhibitory antibodies. It also binds to the egg surface and effectively inhibits fusion in vitro. We named this fragment ‘IZUMO1 putative functional fragment (IZUMO1PFF)’. Surprisingly, IZUMO1PPF still maintains binding ability on the egg surface of Cd9-/- eggs. A series of biophysical measurements using circular dichroism, sedimentation equilibrium and small angle X-ray scattering revealed that IZUMO1PFF is composed of an N-terminal unfolded structure and a C-terminal ellipsoidal helix dimer. Egg binding and fusion inhibition were not observed in the IZUMO1PFF derivative, which was incapable of helix formation. These findings suggest that the formation of a helical dimer at the N-terminal region of IZUMO1 is required for its function. Cos-7 cells expressing the whole IZUMO1 molecule bound to eggs, and IZUMO1 accumulated at the interface between the two cells, but fusion was not observed. These observations suggest that IZUMO1 alone cannot promote sperm-egg membrane fusion, but it works as a factor that is related to the cellular surface interaction, such as the tethering of the membranes by a helical region corresponding to IZUMO1PFF-core.
Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition
Authors: Clay Matthew R. , Halloran Mary C.
Published: July 2013

Epithelial-to-mesenchymal transitions (EMTs) are crucial for morphogenesis and carcinoma metastasis, yet mechanisms controlling the underlying cell behaviors are poorly understood. RhoGTPase signaling has been implicated in EMT; however, previous studies have yielded conflicting results regarding Rho function, and its role in EMT remains poorly understood. Elucidation of precise Rho functions has been challenging because Rho signaling is highly context dependent and its activity is tightly regulated spatiotemporally within the cell. To date, few studies have examined how Rho affects cell motility in intact organisms, and the pattern of Rho activity during motile cell behaviors of EMT has not been determined in any system. Here, we image endogenous active Rho during EMT in vivo, and analyze effects of Rho and Rho-kinase (ROCK) manipulation on cell motility in vivo. We show that Rho is activated in a discrete apical region of premigratory neural crest cells during EMT, and Rho-ROCK signaling is essential for apical detachment and generation of motility within the neuroepithelium, a process that has been poorly understood. Furthermore, we find that Arhgap1 restricts Rho activation to apical areas, and this restriction is necessary for detachment. Our results provide new insight into mechanisms controlling local Rho activation and how it affects dynamic cell behaviors and actomyosin contraction during key steps of EMT in an intact living organism.
Systematic quantification of developmental phenotypes at single-cell resolution during embryogenesis
Authors: Moore Julia L. , Du Zhuo , Bao Zhirong
Published: July 2013

Current imaging technology provides an experimental platform in which complex developmental processes can be observed at cellular resolution over an extended time frame. New computational tools are essential to achieve a systems-level understanding of this high-content information. We have devised a structured approach to systematically analyze complex in vivo phenotypes at cellular resolution, which divides the task into a panel of statistical measurements of each cell in terms of cell differentiation, proliferation and morphogenesis, followed by their spatial and temporal organization in groups and the cohesion within the whole specimen. We demonstrate the approach to C. elegans embryogenesis with in toto imaging and automated cell lineage tracing. We define statistical distributions of the wild-type developmental behaviors at single-cell resolution based on over 50 embryos, cumulating in over 4000 distinct, developmentally based measurements per embryo. These methods enable statistical quantification of abnormalities in mutant or RNAi-treated embryos and a rigorous comparison of embryos by testing each measurement for the probability that it would occur in a wild-type embryo. We demonstrate the power of this structured approach by uncovering quantitative properties including subtle phenotypes in both wild-type and perturbed embryos, transient behaviors that lead to new insights into gene function and a previously undetected source of developmental noise and its subsequent correction.
Cell and tissue dynamics during Tribolium embryogenesis revealed by versatile fluorescence labeling approaches
Authors: Benton Matthew A. , Akam Michael , Pavlopoulos Anastasios
Published: July 2013

Studies on new arthropod models such as the beetle Tribolium castaneum are shifting our knowledge of embryonic patterning and morphogenesis beyond the Drosophila paradigm. In contrast to Drosophila, Tribolium embryos exhibit the short-germ type of development and become enveloped by extensive extra-embryonic membranes, the amnion and serosa. The genetic basis of these processes has been the focus of active research. Here, we complement genetic approaches with live fluorescence imaging of Tribolium embryos to make the link between gene function and morphogenetic cell behaviors during blastoderm formation and differentiation, germband condensation and elongation, and extra-embryonic development. We first show that transient labeling methods result in strong, homogeneous and persistent expression of fluorescent markers in Tribolium embryos, labeling the chromatin, membrane, cytoskeleton or combinations thereof. We then use co-injection of fluorescent markers with dsRNA for live imaging of embryos with disrupted caudal gene function caused by RNA interference. Using these approaches, we describe and compare cell and tissue dynamics in Tribolium embryos with wild-type and altered fate maps. We find that Tribolium germband condensation is effected by cell contraction and intercalation, with the latter being dependent on the anterior-posterior patterning system. We propose that germband condensation drives initiation of amnion folding, whereas expansion of the amniotic fold and closure of the amniotic cavity are likely driven by contraction of an actomyosin cable at the boundary between the amnion and serosa. Our methodology provides a comprehensive framework for testing quantitative models of patterning, growth and morphogenetic mechanisms in Tribolium and other arthropod species.
Maintenance of empathy levels among first and final year medical students: a cross sectional study
Authors: Bangash Areeb Sohail , Ali Nisreen Feroz , Shehzad Abdul Haseeb , Haqqi Sobia
Published: July 2013

Objectives:The purpose of this study was to quantifythe levels of empathy amongst medical students in the first year and final year of the medical curriculum at a medical university in Karachi, Pakistan.

Methods:A cross-sectional study, comprising of participating students in their first year and final year of the medical curriculum at Ziauddin University Medical College, was carried out, using the Empathy Quotient (EQ) scale consisting of 60 questions through a self-administered questionnaire. The results were collected anonymously over a time period of six months from a sample of 171 participants.

Results:According to our analysis, we found 82.67% of fifth year students and 80.21% of first years showing average or above average levels of empathy. Female mean scores were 42±9.60 while males were 38.7±9.358 (P=0.03). No association was found between empathy and age of the participants (p=0.77).

Conclusion:We found no significant difference in the levels of empathy between the first and fifth year medical students. However, it was shown that females exhibited higher levels of empathy than males.
Jenseits des Westens?
Authors: Nolte Paul
Published: July 2013

Vorspann

Alle reden von Demokratie - die Historiker nicht. Dabei ist der Bedarf nach historischer Einordnung riesengroß. Was hat es auf sich mit der oft beschworenen Krise der Demokratie in Deutschland? Sind die USA noch Vorbild oder folgen sie längst einem anderen Pfad als wir und die übrigen Europäer - einem Pfad voller Demokratiedevianz sogar? Was passiert in der arabischen Welt, in Indien und in Afrika? Klassische Demokratien gibt es dort nicht, die Entwicklung läuft auch nicht auf sie hinaus. Auf was aber dann? Paul Nolte, einer der einflussreichsten Historiker des Landes, appelliert an die Zunft, sich dieser brennenden Fragen anzunehmen und dabei die Zeitgeschichte der Demokratie als Globalgeschichte anzulegen.
Wiedergutmachung im 21. Jahrhundert
Authors: Lehnstaedt Stephan
Published: July 2013

Vorspann

Bei der Umsetzung des 2002 vom Bundestag einstimmig verabschiedeten so genannten Ghettorentengesetzes traten massive Probleme auf. Dass die meisten von Holocaust-Überlebenden gestellten Rentenanträge abgelehnt wurden, führte zu Nachfragen im Bundestag und Irritationen auf internationaler Ebene. Wie sich das zuständige Bundes- und das ebenfalls involvierte nordrhein-westfälische Arbeitsministerium hier positionierten, untersucht Stephan Lehnstaedt in seinem hoch aktuellen Beitrag. Er stützt sich dabei auf neueste Akten der beiden Ministerien, in die er auf der Grundlage des Informationsfreiheitsgesetzes Einblick erhalten konnte.
Der „Marsch für Gleichheit und gegen Rassismus“ von 1983
Authors: Garcia Marie-Carmen , Hajjat Abdellali , Mercader Patricia , Zancarini-Fournel Michelle
Published: July 2013

Vorspann

Der „Marsch für die Gleichheit und gegen den Rassismus“ von 1983 ist in die französische Geschichte eingegangen. Er begann in Marseille und endete sechs Wochen später in Paris - und bildete den Höhepunkt der antirassistischen Mobilisierung jenseits des Rheins. Nie zuvor waren nordafrikanische, aus den ehemaligen Kolonien stammende Immigranten in der Öffentlichkeit so präsent gewesen. Mittlerweile ranken sich zahlreiche Legenden um dieses historische Ereignis, das zum Gründungsmythos anderer antirassistischer Organisationen und zum Fluchtpunkt des Jugendprotests geworden ist. Vier französische Gelehrte erinnern an den historischen Marsch und analysieren seinen umkämpften Stellenwert im kollektiven Gedächtnis.
Der „Fall Theodor Eschenburg“
Authors: Wengst Udo
Published: July 2013

Vorspann

Theodor Eschenburg, imponierende Gründergestalt der Politikwissenschaft und zusammen mit Hans Rothfels erster Herausgeber dieser Zeitschrift, wird seit einiger Zeit wegen seiner Vergangenheit in der Weimarer Zeit und in der NS-Diktatur sowie wegen seines langen Schweigens danach kontrovers diskutiert. Die Debatte, die zunächst vor allem in der Deutschen Vereinigung für Politische Wissenschaft geführt wurde, hat nun auch die Vierteljahrshefte für Zeitgeschichte erreicht. Udo Wengst, der an einer Biographie Eschenburgs arbeitet, verteidigt seinen Protagonisten: Trotz mancher Inkonsistenzen in seinem Verhalten nach 1945 lasse sich Eschenburg bereits seit der späten Weimarer Republik als Demokrat charakterisieren; die gegenwärtige Kritik an ihm sei überzogen und entspringe einem Mangel an Verständnis für seine schwierige Situation während der NS-Diktatur. Die Diskussion über Eschenburg geht weiter. Schon in der nächsten Ausgabe der Vierteljahrshefte nehmen Hans Woller und Jürgen Zarusky dazu Stellung.
GENETICS IN ENDOCRINOLOGY: Genetic forms of severe insulin resistance: what endocrinologists should know
Authors: Parker Victoria E R , Semple Robert K
Published: July 2013

‘Insulin resistance’ (IR) is a widely used clinical term. It is usually defined as a state characterised by reduced glucose-lowering activity of insulin, but it is also sometimes used as a shorthand label for a clinical syndrome encompassing major pathologies such as type 2 diabetes, polycystic ovary syndrome, fatty liver disease and atherosclerosis. Nevertheless, the precise cellular origins of IR, the causal links among these phenomena and the mechanisms underlying them remain poorly understood or contentious. Prevalent IR usually results from a genetic predisposition interacting with acquired obesity; however, even in some lean individuals, very severe degrees of IR can be observed. It is important to identify these people as they often harbour identifiable single-gene defects and they may benefit from molecular diagnosis, genetic counselling and sometimes tailored therapies. Observation of people with known single-gene defects also offers the opportunity to make inferences about the mechanistic links between IR and common pathologies. Herein, we summarise the currently known monogenic forms of severe IR, with an emphasis on the practical aspects of their recognition, diagnosis and management. In particular, we draw distinctions among the biochemical subphenotypes of IR that arise from primary adipose tissue dysfunction or from primary insulin signalling defects and discuss the implications of this dichotomy for management.
Specific expression patterns and cell distribution of ancient and modern PAG in bovine placenta during pregnancy
Authors: Touzard Eve , Reinaud Pierrette , Dubois Olivier , Guyader-Joly Catherine , Humblot Patrice , Ponsart Claire , Charpigny Gilles
Published: July 2013

Pregnancy-associated glycoproteins (PAGs) constitute a multigenic family of aspartic proteinases expressed in the trophoblast of the ruminant placenta. InBos taurus, this family comprises 21 members segregated into ancient and modern phylogenetic groups. Ancient PAGs have been reported to be synthesized throughout the trophoblastic cell layer whereas modern PAGs are produced by binucleate cells of cotyledons. The aim of this study was to investigate modern and ancient PAGs during gestation in cotyledonary and intercotyledonary tissues. To obtain convincing and innovative results despite the high sequence identity shared between PAGs, we designed specific tools such as amplification primers and antibodies. Using real-time RT-PCR, we described the transcript expression of 16 bovine PAGs. Overall, PAGs are characterized by an increase in their expression during gestation. However, we demonstrated a segregation of modern PAGs in cotyledons and of ancient PAGs in the intercotyledonary chorion, except for the ancient PAG2 expressed in cotyledons. By raising specific antibodies against the modern PAG1 and ancient PAG11 and PAG2, we established the expression kinetics of the proteins using western blotting. Immunohistochemistry showed that PAGs were produced by specific cellular populations: PAG1 by binucleate cells in the whole trophoblastic layer, PAG11 was localized in binucleate cells of the intercotyledonary trophoblast and the chorionic plate of the cotyledon, while PAG2 was produced in mononucleate cells of the internal villi of the cotyledon. These results revealed a highly specific regulation of PAG expression and cell localization as a function of their phylogenetic status, suggesting distinct biological functions within placental tissues.
The ONE Step Initiative: Quality Improvement in a Pediatric Clinic for Secondhand Smoke Reduction
Authors: Bunik Maya , Cavanaugh Keith L. , Herrick Diane , Mehner Lauren , Venugopalakrishnan Janani , Crane Lori A. , Puma Jini
Published: July 2013

BACKGROUND AND OBJECTIVE:

Although comprehensive smoking counseling to limit secondhand smoke (SHS) is widely endorsed, it is often not done. Published evaluations of brief and practical systems that improve screening and counseling to reduce SHS are limited. Our objective was to determine if a quality improvement activity around smoking counseling leads to changes in (1) medical assistant and pediatric provider assessment of smoking history and (2) smoking or other behaviors affecting children’s SHS exposure.

METHODS:

In a large urban teaching clinic we assessed the ONE Step intervention, which included the following: (1) “Ask” (medical assistant asking whether caregivers smoke); (2) “Advise” (providers advising smoking outside and quitting if ready); (3) “Refer” (providers referring to the Colorado telephone QuitLine); and (4) electronic medical record prompts and required documentation regarding smoking. Medical assistant and provider assessments of smoking were evaluated with a chart review by using a pre-/posttest design. Caregiver behavior change was evaluated with a time-series survey that included assessment at baseline and follow-up via telephone at 6 and 12 months from study entry.

RESULTS:

ONE Step was associated with a statistically significant increase in Ask, Advise, and Refer documentation. Caregiver surveys showed that 97% found discussions of SHS with providers acceptable. Six- and 12-month follow-ups, respectively, showed that 14% and 13% of smokers reported quitting and that 63% and 70% of current smokers reported reduced SHS exposure.

CONCLUSIONS:

ONE Step was feasible to deliver in a busy outpatient setting, acceptable to families, and appears to have resulted in decreased exposure to SHS in our pediatric population.
Results From the New Jersey Statewide Critical Congenital Heart Defects Screening Program
Authors: Garg Lorraine F. , Van Naarden Braun Kim , Knapp Mary M. , Anderson Terry M. , Koppel Robert I. , Hirsch Daniel , Beres Leslie M. , Sweatlock Joseph , Olney Richard S. , Glidewell Jill , Hinton Cynthia F. , Kemper Alex R.
Published: July 2013

BACKGROUND AND OBJECTIVE:

New Jersey was the first state to implement legislatively mandated newborn pulse oximetry screening (POxS) in all licensed birthing facilities to detect critical congenital heart defects (CCHDs). The objective of this report was to evaluate implementation of New Jersey’s statewide POxS mandate.

METHODS:

A 2-pronged approach was used to collect data on infants screened in all New Jersey birthing facilities from August 31, 2011, through May 31, 2012. Aggregate screening results were submitted by each birthing facility. Data on failed screens and clinical characteristics of those newborns were reported to the New Jersey Birth Defects Registry (NJBDR). Three indicators were used to distinguish the added value of mandated POxS from standard clinical care: prenatal congenital heart defect diagnosis, cardiology consultation or echocardiogram indicated or performed before PoxS, or clinical findings at the time of POxS warranting a pulse oximetry measurement.

RESULTS:

Of 75 324 live births in licensed New Jersey birthing facilities, 73 320 were eligible for screening, of which 99% were screened. Forty-nine infants with failed POxS were reported to the NJBDR, 30 of whom had diagnostic evaluations solely attributable to the mandated screening. Three of the 30 infants had previously unsuspected CCHDs and 17 had other diagnoses or non-CCHD echocardiogram findings.

CONCLUSIONS:

In the first 9 months after implementation, New Jersey achieved a high statewide screening rate and established surveillance mechanisms to evaluate the unique contribution of POxS. The screening mandate identified 3 infants with previously unsuspected CCHDs that otherwise might have resulted in significant morbidity and mortality and also identified other significant secondary targets such as sepsis and pneumonia.
Lithium - the Metal of the Future?
Authors: Kunasz Ihor A.
Published: July 2013

The second half of the twentieth century saw a dramatic shift in lithium chemicals production from traditional pegmatite sources to brines. Today, the bulk of lithium carbonate, which serves as the raw material for various downstream lithium chemicals, including lithium metal for the lithium batteries, is produced from the brines of the Salar de Atacama, Chile, the Salar del Hombre Muerto, Argentina and Clayton Valley Nevada, U.S.A. There is minor production in Tibet and the People’s Republic of China (PRC). Australian spodumene concentrates are converted to lithium carbonate in the PRC.

The resurgence in the potential development of electric cars has resulted in the increased exploration for and identification of potential new lithium brine operations and the reassessment of some pegmatite deposits.

A number of predictions for a potentially large electric car market scenario have raised questions on the availability of sufficient lithium resources. However, since the original 1976 report on global lithium resources by the National Academies of Sciences and Engineering, newly identified deposits have almost quadrupled the total potentially available lithium resources. Based on the best predictions, the lithium supply is more than adequate to meet the demand for electric cars well into the 21st century.
Ultra-low Voltage, Self-aligned OTFTs for Frequency Applications
Authors: Lai Stefano , Cosseddu Piero , Gazzadi Gian Carlo , Martines Giovanni , Bonfiglio Annalisa , Barbaro Massimo
Published: July 2013

A novel structure for Organic Thin-Film Transistor (OTFT) is here presented. The devices are fabricated using a one-mask, photolithographic self-alignment technique which can be performed with standard photoresists and without further chemical treatments. This technique, combined with a novel technology for the realization of low voltage OTFTs, allows a dramatic reduction of the parasitic capacitances thus leading to a remarkable cut-off frequency. In this paper, the main electrical parameters of low voltage, self-aligned devices are reported, and a complete frequency characterization of the devices is given. These characteristics make the reported approach suitable for the development of basic circuitries for frequency applications.
Temperature Effect of Ionic Transition Metal Complex Light-Emitting Electrochemical Cells
Authors: Akatsuka Takeo , van Reenen Stephan , Bandiello Enrico , Bolink Henk J.
Published: July 2013

Light-Emitting Electrochemical Cells (LECs) consist of solution processable ionic light-emitting materials and use air stable electrodes. Their operational mechanism relies on both ionic and electronic conduction. The dynamic behavior is primarily determined by the ionic conductivity. Here, we demonstrate that with increasing temperature the LECs turn-on faster yet without decreasing the efficiency. This is due to the activation energy of ionic transport and the temperature independent photoluminescence quantum yields.
Comparação preliminar entre ultrassonografia quantitativa de falanges e densitometria óssea na avaliação da massa óssea em adolescentes
Authors: Duarte Stênio Bruno Leal , Carvalho Wellington Roberto Gomes de , Gonçalves Ezequiel Moreira , Ribeiro Roberto Regis , Farias Edson Santos , Magro Daniela de Oliveira , Oliveira Laís Mariana Ribeiro de , Guerra-Júnior Gil
Published: July 2013

OBJETIVO: Avaliar associação entre ultrassonografia quantitativa de falanges da mão (QUS) e a densitometria por absorção de raio-X de dupla energia (DXA) e desses com os históricos alimentar e de fraturas. SUJEITOS E MÉTODOS: Após dois anos de acompanhamento de 270 escolares, 10 com massa óssea por QUS abaixo de -2 DP foram incluídos no estudo e avaliados com DXA. RESULTADOS: A massa óssea por DXA de L1-L4 variou de -2,8 a -1,1 DP e de corpo inteiro -2,9 e -1,2. Três estudantes apresentaram fraturas. Baixa ingestão de cálcio foi observada nos 10 casos, de fósforo em 6 e de vitamina D em 8. Não houve diferença entre os casos com massa abaixo de -2 DP nos três métodos de avaliação. Não foi observada associação entre as fraturas e o histórico alimentar, nem com os valores de massa óssea. CONCLUSÃO: Neste pequeno grupo de adolescentes houve associação entre QUS e DXA, porém sem associação entre essas avaliações e as fraturas e a ingestão de cálcio, fósforo e vitamina D.
Avaliação do coeficiente de variação experimental para caracteres de frutos de pimenteiras
Authors: Silva Anderson Rodrigo da , Cecon Paulo Roberto , Rêgo Elizanilda Ramalho do , Nascimento Moysés
Published: July 2013

O objetivo deste estudo foi formular uma classificação para coeficientes de variação, de experimentos com pimentas do gênero Capsicum, para utilização em seis variáveis morfológicas do fruto. Foram selecionados 38 experimentos com resultados publicados, em que se constaram dados de caracterizações morfológicas do fruto e coeficientes de variação (CV) das seguintes variáveis respostas: peso médio do fruto, comprimento do fruto, comprimento do pedúnculo, maior e menor diâmetro do fruto e espessura do pericarpo. As faixas de classificação dos CV foram baseadas na metodologia proposta por Garcia (1989), que considera a propriedade da distribuição normal do CV. Pelo teste de Lilliefors, a 5% de probabilidade, todas as variáveis satisfizeram a pressuposição de distribuição normal do CV. As faixas de classificação do CV, obtidas para essas seis variáveis, foram distintas daquelas da classificação geral, proposta por Gomes (2000). Ademais, constatou-se que as classificações dos coeficientes de variação de variáveis morfológicas de pimenteiras do gênero Capsicum dependem da variável resposta, sendo que as maiores faixas de classificação de CV ocorreram para menor diâmetro do fruto, espessura do pericarpo e peso médio do fruto.
Análise histomorfométrica do músculo sóleo de ratos submetidos ao modelo animal de parkinsonismo induzido pelo MPTP
Authors: Loureiro Ana Paula Cunha , Niederheitmann Cecília Beatriz Helm , Gomes Anna Raquel Silveira , Loureiro Claudia da Cunha , Zotz Talita Gianello Gnoato
Published: July 2013

INTRODUÇÃO: Modelos experimentais da Doença de Parkinson (DP) que reproduzem a desnervação dopaminérgica têm sido desenvolvidos para estudar a patofisiologia desta doença e analisar a eficácia de novas terapêuticas. Dentre os sinais cardinais da DP temos a rigidez muscular, estudos sugerem que mudanças intrínsecas nas propriedades mecânicas do músculo podem ser responsáveis pelo aumento dessa alteração tônica. OBJETIVO: Analisar a morfologia geral e a histomorfometria do músculo sóleo de ratos Wistar induzidos ao Parkinsonismo por 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP). MATERIAIS E MÉTODOS: Utilizaram-se 24 ratos Wistar machos, com idade de 13 semanas e peso de 279 ± 13 g, divididos em quatro grupos: 1- controle-controle (n = 6): sham tratados com benserazida + salina; 2 - controle-L-DOPA (n = 6): sham tratados com benserazida + L-DOPA; 3 - MPTP- controle (n = 6): lesão na substância negra (SNc) por MPTP tratados com benserazida + salina; 4 - MPTP-L-DOPA (n = 6): lesão na SNc por MPTP tratados com benserazida + L-DOPA. Esses animais foram submetidos a eutanásia 35 dias após os procedimentos experimentais. Foram analisados: peso corporal, peso muscular, morfologia geral do músculo com microscopia de luz e mensuração da área de secção transversa das fibras musculares. Realizaram-se comparações com o teste t pareado entre o peso corporal inicial e final. A ANOVA post-hoc Tukey foi usada para comparações entre os grupos, sendo considerado significativo p ≤ 0,05. RESULTADOS: Não foram encontradas diferenças estatisticamente significativas nas variáveis analisadas. CONCLUSÃO: Os dados analisados não excluem a possibilidade de alterações ocorrerem no interior dessas células, nos tipos de fibras musculares ou em longo prazo.
Cognição e sustentabilidade: estudo de casos múltiplos no índice de sustentabilidade empresarial da BM&FBovespa
Authors: Nobre Farley Simon , Ribeiro Rhubens Ewald Moura
Published: July 2013

A busca da sustentabilidade nas organizações demanda de seus participantes uma complexidade cognitiva mais elevada devido às suas dimensões sistêmicas e aos seus múltiplos critérios associados à economia, à sociedade e ao meio ambiente. Este artigo estuda a relação entre Grau de Complexidade Cognitiva (GCC) e Sustentabilidade em Organizações (SEO) de empresas listadas no Índice de Sustentabilidade Empresarial (ISE) da Bolsa de Valores de São Paulo (BM&FBOVESPA). Como metodologia de pesquisa, adotou-se uma abordagem qualitativa, conduzida por meio de estudo de casos múltiplos. Utilizou-se pesquisa documental para levantar relatórios de sustentabilidade e questionários do ISE que foram submetidos à análise de conteúdo. A amostra intencional foi constituída por seis empresas que disponibilizaram por completo seus relatórios de sustentabilidade e questionários do ISE. As avaliações de GCC e SEO das empresas foram realizadas respectivamente sob as óticas do modelo de Criação de Valor Sustentável (CVS) e das dimensões, critérios e indicadores do ISE. Resultados de análises permitiram verificar similaridades e diferenças entre os casos estudados e confirmaram a existência de uma relação com tendência positiva entre GCC e SEO.
Nitrogen Removal from Wastewater by an Aerated Subsurface‐Flow Constructed Wetland in Cold Climates
Authors: Redmond Eric D. , Just Craig L. , Parkin Gene F.
Published: July 2013

The objective of this study was to assess the role of cyclic aeration, vegetation, and temperature on nitrogen removal by subsurface‐flow engineered wetlands. Aeration was shown to enhance total nitrogen and ammonia removal and to enhance removal of carbonaceous biochemical oxygen demand, chemical oxygen demand, and phosphorus. Effluent ammonia and total nitrogen concentrations were significantly lower in aerated wetland cells when compared with unaerated cells. There was no significant difference in nitrogen removal between planted and unplanted cells. Effluent total nitrogen concentrations ranged from 9 to 12 mg N/L in the aerated cells and from 23 to 24 mg N/L in unaerated cells. Effluent ammonia concentrations ranged from 3 to 7 mg N/L in aerated wetland cells and from 22 to 23 mg N/L in unaerated cells. For the conditions tested, temperature had only a minimal effect on effluent ammonia or total nitrogen concentrations. The tanks‐in‐series and the PkC* models predicted the general trends in effluent ammonia and total nitrogen concentrations, but did not do well predicting short‐term variability. Rate coefficients for aerated systems were 2 to 10 times greater than those for unaerated systems.
Nitrogen and Chemical Oxygen Demand Removal from Septic Tank Wastewater in Subsurface Flow Constructed Wetlands: Substrate (Cation Exchange Capacity) Effects
Authors: Collison Robert S. , Grismer Mark E.
Published: July 2013

The current article focuses on chemical oxygen demand (COD) and nitrogen (ammonium and nitrate) removal performance from synthetic human wastewater as affected by different substrate rocks having a range of porosities and cation exchange capacities (CECs). The aggregates included lava rock, lightweight expanded shale, meta‐basalt (control), and zeolite. The first three had CECs of 1 to 4 mequiv/100 gm, whereas the zeolite CEC was much greater (∼80 mequiv/100 gm). Synthetic wastewater was gravity fed to each constructed wetland system, resulting in a 4‐day retention time. Effluent samples were collected, and COD and nitrogen species concentrations measured regularly during four time periods from November 2008 through June 2009. Chemical oxygen demand and nitrogen removal fractions were not significantly different between the field and laboratory constructed wetland systems when corrected for temperature. Similarly, overall COD and nitrogen removal fractions were practically the same for the aggregate substrates. The important difference between aggregate effects was the zeolite's ammonia removal process, which was primarily by adsorption. The resulting single‐stage nitrogen removal process may be an alternative to nitrification and denitrification that may realize significant cost savings in practice.
Numerical study of the spreading and solidification of a molten particle impacting onto a rigid substrate under plasma spraying conditions
Authors: Oukach Soufiane , Hamdi Hassan , el Ganaoui , Pateyron Bernard
Published: July 2013

This paper deals with simulation of the spreading and solidification of a
fully molten particle impacting onto a preheated substrate under traditional
plasma spraying conditions. The multiphase problem governing equations of
mass, momentum and energy conservation taking into account heat transfer by
conduction, convection and phase change are solved by using a Finite Element
approach. The interface between molten particle and surrounding air, is
tracked using the Level Set method. The effect of the Reynolds number on the
droplet spreading and solidification, using a wide range of impact velocities
(40-250m/s), is reported. A new correlation that predicts the final spread
factor of splat as a function of Reynolds number is obtained. Thermal contact
resistance, viscous dissipation, wettability and surface tension forces
effects are taken into account.
Effect of applied moment on resistance to sliding among esthetic self-ligating brackets
Authors: Pliska Benjamin T. , Fuchs Rick W. , Beyer John P. , Larson Brent E.
Published: July 2013

Objective:

To determine the effect of mode of ligation and bracket material on resistance to sliding (RS) by comparing various esthetic brackets of conventionally ligated and self-ligating (SL) designs under an increasing applied moment in the second-order dimension.

Materials and Methods:

Eight different commercially available esthetic brackets of SL and conventional elastomeric-ligated (CL) designs were mounted on a testing apparatus to simulate canine retraction using sliding mechanics and the application of a moment on 0.019″×0.025″ stainless steel archwire. The samples examined were the CL brackets Clarity™, Inspire Ice™, SpiritMB™, and Mystique™, and the SL brackets ClaritySL™, In-OvationC™, In-OvationR™, and Smartclip™. The RS at calculated moments of 2000 g-mm and 4000 g-mm was determined and compared between the various brackets. Descriptive measures and one-way analysis of variance were used to calculate means and statistical differences among the bracket types.

Results:

The CL monocrystalline bracket displayed significantly greater (P < .05) RS than all other brackets tested. Among the other brackets, the range of RS values was 145.8–191.7 g and 291.9–389.2 g at moments of 2000 g-mm and 4000 g-mm, respectfully, though these differences were not significant (P < .05). All brackets tested displayed greater levels of RS (P < .05) at 4000 g-mm than at 2000 g-mm.

Conclusion:

With the exception of the CL monocrystalline bracket, all brackets displayed comparable amounts of RS regardless of mode of ligation or bracket slot material.
Persistence of Continuous Glucose Monitoring Use in a Community Setting 1 Year After Purchase
Authors: Chamberlain James , Dopita Dana , Gilgen Emily
Published: July 2013

IN BRIEF

Realization of the clinical benefits of continuous glucose monitoring (CGM) in diabetes management is dependent on the frequency with which patients use their CGM devices. This article describes an eight-item survey used to explore whether patients' frequency of CGM use is related to CGM technology in general or to differences among available CGM systems.
Predation on adult moose Alces alces by European brown bears Ursus arctos
Authors: Dahle Bj⊘rn , Wallin Kjell , Cederlund Göran , Persson Inga‐Lill , Selvaag Line Stabell , Swenson Jon E.
Published: July 2013

Several North American studies have reported significant predation rates on moose Alces alces by brown bears Ursus arctos. We documented predation on moose by brown bears in south‐central Sweden, where brown bears and moose occurred at estimated densities of 10‐30 and 400‐1,340/1,000 km2, respectively. Bears killed 0.8% of radio‐collared adult female moose (i.e. ≥ 1 year old) annually and no male moose (≥ 1 year old). Bear predation was the least important mortality factor we documented. Based on tracking brown bears on snow during spring we recorded one successful hunt for every 372 km of tracks and documented attacks only by adult bears and successful attacks only by adult males. Autopsy of moose older than calves that were killed by brown bears revealed that yearlings were more prone to predation than older moose, and that older (i.e. ≥ 2 years) cows were more vulnerable to predation than older bulls. Our study suggests a lower tendency for Scandinavian brown bears to prey on moose compared to most of the North American studies.