bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Vegetable Preparation Method and Taste-Test on Vegetable Preference for First Grade Children in the United States
Authors: Colas Marie Veronyck , Vaccaro Joan A. , Zarini Gustavo G. , Huffman Fatma G.
Published: November 2013

How children rate vegetables may be influenced by the preparation method. The primary objective of this study was for first grade students to be involved in a cooking demonstration and to taste and rate vegetables raw and cooked. First grade children of two classes (N= 52: 18 boys and 34 girls (approximately half Hispanic) that had assented and had signed parental consent participated in the study. The degree of liking a particular vegetable was recorded by the students using a hedonic scale of five commonly eaten vegetables tasted first raw (pre-demonstration) and then cooked (post-demonstration). A food habit questionnaire was filled out by parents to evaluate their mealtime practices and beliefs about their child’s eating habits. Paired sample t-tests revealed significant differences in preferences for vegetables in their raw and cooked states. Several mealtime characteristics were significantly associated with children’s vegetable preferences. Parents who reported being satisfied with how often the family eats evening meals together were more likely to report that their child eats adequate vegetables for their health (p=0.026). Parents who stated that they were satisfied with their child’s eating habits were more likely to report that their child was trying new foods (p<.001). Cooking demonstrations by nutrition professionals may be an important strategy that can be used by parents and teachers to promote vegetable intake. It is important that nutrition professionals provide guidance to encourage consumption of vegetables for parents so that they can model the behavior of healthy food consumption to their children.
The Child Health Scenario in India: An Application of Bayesian Approach
Authors: Bhattacharjee Atanu , Nath Dilip C. , Bhattacharjee Dibyojyoti
Published: November 2013

Background: The child mortality rate of a place is an indication of the basic health facility prevalent there. A place with better medical facility records low child mortality. The child mortality rate reduction is not as expected in many developing countries. In last two decades the child death rate has not been reduced significantly in India. The aim of this work is to explore the child death rate in different Indian states.
Materials and Methods: The Bayesian approach has been applied to control the over dispersion due to presence of zero (i.e. no-death count) in the data set. The Zero Inflated Poisson (ZIP) has been applied to control the presence of over the Zero Inflation Distribution. The data set has been considered from Indian National Health and Family Survey (NFHS-3) conducted during 2005-2006. The women having at least one living child of age less than five years has been selected as study subjects.
Production and Characterization of Bio-Chars and Bio-Oils Formed by Pyrolysis of Persian Hogweed (Heracleum persicum Desf.) in A Fixed-Bed Reactor
Authors: Aysu Tevfik
Published: November 2013

Pyrolysis of Persian Hogweed (Heracleum persicum Desf.) stalks were performed in a fixed-bed tubular reactor with (K2CO3, ZnCl2) and without catalyst at three different temperatures (400, 500 and 600 oC) with a constant heating rate of 50 oC/min. and with a constant sweeping gas (N2) flow rate of 100 cm3/min. The amounts of bio-char, bio-oil and gas produced were calculated and the compositions of the obtained bio-oils were characterized by GC-MS. The effects of pyrolysis parameters such as temperature and catalyst on the product yields were investigated. According to the results, both temperature and catalyst had significant effects on the conversion of Heracleum persicum Desf. into bio-chars, bio-oils and gaseous products. The highest bio-oil yield of 41.42% by weight including aqeous phase was achieved with 10% potassium carbonate catalyst at 500 oC. 71 different compounds were identified by GC-MS in the bio-oils obtained at 500 oC.
Phycocyanin as Potential Natural Dye for its Use in Photovoltaic Cells
Authors: Enciso Paula , Cabrerizo Franco M. , Gancheff Jorge S. , Denis Pablo A. , Cerdá María Fernanda
Published: November 2013

Phycocyanin, a blue protein extracted from Spirulina spp, shows promising characteristics that made it suitable for its use as natural dye in photovoltaic devices as the dye sensitized solar cells. In this work, a study of the aqueous solution-phase photochemistry, photophysics, spectroscopy, voltammetry and thermal stability of phycocyanin is presented. Suitable redox potentials (Eox = 1.2 V vs. Ag/AgCl) and a value of 1.96 V for E0,0 (i.e., the energy difference between the vibrationally relaxed levels of the first electronic excited state, S1, and the ground state, S0 of phycocyanin), allows the calculation of energetic profiles that in comparison with the conduction band of the anatase-TiO2 and I-/I3- electrolyte, could predict electron transfer with these components of the cell.
The data reported herein should not only help to evaluate the potential use of phycocyanin as sensitizer for solar cells, but should also help in the development of novel solar cells where the photoinduced behavior of this protein can be controlled.
Density Measurement for the Binary Mixtures of Ionic Liquid 1-ethyl- 3-methylimidazolium Diethylphosphate and Water (Methanol or Ethanol) at 1atm and (293.15 to 333.15) K
Authors: Gong Yin-Hui , Lu Ying-Zhou , Meng Hong , Li Chun-Xi
Published: November 2013

The density data for the binary mixtures of an ionic liquid (IL), 1-ethyl-3-methylimidazolium diethylphosphate [EMIM][DEP], and water (methanol or ethanol) were measured at 1 atm as a function of composition in the temperature range of (293.15 to 333.15) K using a vibrating-tube densimeter. The excess molar volumes (VE) and other thermodynamic properties were derived from the density data. All VE values are negative for the binary mixtures in the whole composition range, and reach to the maximum at the mole fraction of IL of ca. 0.3. The VE values decrease with increasing temperature for the aqueous solution of ILs, but increase with the increasing temperature for the IL solutions of methanol or ethanol. The excess molar volumes were correlated successfully by an empirical equation with the maximum average absolute relative deviation within 0.02%.
L’étude des identités dans l’Antiquité est-elle utopique ?
Authors: Bélanger Steeve
Published: November 2013

Au cours des dernières décennies, la recherche en histoire ancienne a connu un important renouvellement historiographique, méthodologique et thématique ayant permis d’aborder sous des angles novateurs d’importants acquis et présupposés de la recherche et de leur apporter de riches nuances. Les multiples enquêtes sur les constructions, déconstructions et reconstructions des identités anciennes ont grandement contribué à ce renouvellement de la recherche. Loin d’être utopiques et anachroniques, les recherches sur les phénomènes identitaires dans l’Antiquité ouvrent sur des perspectives nouvelles qu’il convient désormais de prendre en considération en histoire ancienne.
Repenser le rapport entre loi et famille dans la Grèce archaïque et classique : l’exemple de la descendance dans les inscriptions à caractère législatif
Authors: Lajeunesse Maude
Published: November 2013

Cet article s’intéresse à la mention des enfants et des descendants dans les inscriptions législatives grecques des époques archaïque et classique. Les documents préservés réglementaient l’inclusion sociale et civique des enfants, l’exclusion civique des descendants d’individus subversifs, le rôle de l’enfant comme héritier principal et certains des autres rôles que l’enfant devait jouer au sein de sa famille et de sa patrie. Généralement, même lorsque l’enfant était nommé à titre individuel, c’est toute la lignée qui était concernée par les dispositions légales, qui visaient, d’une part, à contrôler la composition du corps civique et, d’autre part, à promouvoir la régulation interne des familles1.
Peer Review Guidance: How Do You Write a Good Review?
Authors: Allen Thomas Wesley
Published: November 2013

Peer review is essential to the quality of scientific publications. As the volume of submissions to these journals increases, the need for an expanding cadre of trained reviewers also increases. Many reviewers do not receive formal training on conducting a peer review or education on the peer review process, however. The author presents an overview of the peer review process and provides guidance for conducting high-quality reviews of manuscripts submitted to The Journal of the American Osteopathic Association and other scientific journals.
Third‐Trimester Abnormal Uterine Artery Doppler Findings Are Associated With Adverse Pregnancy Outcomes
Authors: Shwarzman Polina , Waintraub Adi Y. , Frieger Michael , Bashiri Asher , Mazor Moshe , Hershkovitz Reli
Published: November 2013

Objectives

To evaluate the association between third‐trimester abnormal uterine artery Doppler findings and pregnancy outcomes.

Methods

A prospective study was designed, including 198 consecutive singleton pregnancies between 27 and 41 weeks' gestation. In the study population, 144 had normal uterine artery Doppler waveforms, 37 had unilateral pathologic waveforms, and 17 had bilateral pathologic waveforms. Eighty patients had intrauterine growth restriction (IUGR), preeclampsia toxemia, or both, and 118 had no complications and served as a control group. The uterine artery Doppler waveform was considered abnormal when a notch or pulsatility index above the 90th percentile was noted.

Results

In patients with bilateral pathologic uterine artery Doppler waveforms, the rates of cesarean delivery, small‐for‐gestational‐age (SGA) neonates, preterm delivery, and low Apgar scores were increased compared to patients with normal or pathologic unilateral waveforms (P = .009; P > .001; P = .007; P > .001, respectively). The incidence rates for SGA neonates, cesarean delivery, and preterm delivery were significantly higher among patients without IUGR or preeclampsia toxemia when associated with pathologic bilateral waveforms in comparison to normal waveforms (P = .01 for all). A bilateral pathologic waveform was found to be an independent risk factor for cesarean delivery and SGA neonates. The incidence rates for SGA neonates and preterm delivery were significantly higher among patients with IUGR and/or preeclampsia toxemia when associated with bilateral abnormalities in comparison to normal waveforms (P = .01 for both).

Conclusions

Third‐trimester abnormal uterine artery Doppler findings are associated with worse perinatal outcomes among patients both with and without pregnancy complications.
Twin Reversed Arterial Perfusion Sequence
Authors: Oliver Edward R. , Coleman Beverly G. , Goff Donna A. , Horii Steven C. , Howell Lori J. , Rychik Jack , Bebbington Michael W. , Johnson Mark P.
Published: November 2013

Objectives

The purpose of this study was to test the hypothesis that using the formula of a prolate ellipsoid to estimate parabiotic twin mass correlates better with findings of pump twin compromise than using the sonographic method of Moore et al (Am J Obstet Gynecol 1990; 163:907–912).

Methods

A 10‐year retrospective review was performed to identify all cases of the suspected twin reversed arterial perfusion (TRAP) sequence. Parabiotic twin mass was estimated by summing body and extremity volumes calculated using the prolate ellipsoid formula (width × height × length × 0.523). Parabiotic twin mass was also estimated using the sonographic Moore method [1.21 × length2 − (1.66 × length)]. Parabiotic twin mass estimated by both methods was correlated with sonographic findings associated with increased risk of pump twin compromise.

Results

Fifty‐nine pregnancies complicated by TRAP were identified. Using the prolate ellipsoid formula, the parabiotic twin mean sizes ± SD (as a percentage of pump twin weight) were 103.0% ± 52.0% and 56.9% ± 44.3% in cases with and without pump twin compromise (P = .0005), respectively. Using the sonographic Moore method, the mean parabiotic twin sizes were 122.9% ± 54.3% and 99.6% ± 62.8% in cases with and without pump twin compromise (P = .14). The median estimated masses of the parabiotic twin were 197 ± 219 g using the prolate ellipsoid formula and 310 ± 212 g using the sonographic Moore method (P = .0001). A parabiotic twin size greater than 70% of the pump twin correlated with findings associated with increased risk of pump twin compromise when using the prolate ellipsoid formula (P = .002) but not the sonographic Moore method (P = .09).

Conclusions

Sonographic findings associated with increased risk of pump twin compromise correlate better with prolate ellipsoid estimates of parabiotic twin mass. The median estimated mass of the parabiotic twin was statistically larger when calculated by the sonographic Moore method than by the prolate ellipsoid formula.
Low Nondiagnostic Rate for Fine‐Needle Capillary Sampling Biopsy of Thyroid Nodules
Authors: Mahony Gregory T. , Mahony Barry S.
Published: November 2013

Objectives

This study examined the hypothesis that sonographically guided fine‐needle capillary thyroid biopsies performed by an experienced operator and with constant technique on nodules that meet the Society of Radiologists in Ultrasound criteria warranting biopsy can result in a nondiagnostic rate that is significantly lower than prior published reports.

Methods

We retrospectively reviewed the sonographic and pathologic reports from 228 consecutive sonographically guided fine‐needle capillary thyroid biopsies performed during a 3‐year interval by a single operator with more than 15 years of experience performing fine‐needle capillary thyroid biopsies. There were no exclusion criteria. Sonographic and pathologic reports from all nodules biopsied were included in the analysis. The radiologist's protocol included 6 fine‐needle capillary biopsies, each with 20 passes of the needle into the periphery and/or solid components of the nodule. The cytologic specimens were reviewed off‐site in adherence with the Bethesda system for reporting thyroid cytopathologic findings and classified as diagnostic or nondiagnostic. The nondiagnostic rate in this study was compared with the nondiagnostic rates in prior published reports.

Results

Among the 228 fine‐needle capillary thyroid biopsies performed during the study interval, cytologic analysis showed 1 nondiagnostic biopsy, yielding a nondiagnostic rate of 0.4%. This rate was significantly lower than previously published reports (P < .001).

Conclusions

Sonographically guided fine‐needle capillary biopsies of the thyroid performed by an experienced radiologist can result in a nondiagnostic rate of less than 1%. This finding warrants further investigation into the reasons for the discrepancy between the results of this study and other previous reports.
Sonographically Guided Lumbar Puncture in Pediatric Patients
Authors: Wang Page I. , Wang Anthony C. , Naidu Jennifer O. , DiPietro Michael A. , Sundgren Pia C. , Quint Douglas J. , Parmar Hemant A. , Shah Gaurang V. , Muraszko Karin M. , Srinivasan Ashok
Published: November 2013

Our aim with this study was to develop a user‐friendly method for pediatric sonographically guided lumbar punctures so that we can visualize intrathecal anatomy, confirm intrathecal injection at the time of injection, and, most importantly, avoid ionizing radiation to a child's already radiosensitive pelvis. Sonographically guided lumbar puncture was prospectively performed in children aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to identify relevant anatomy (including the conus in children 10 years and younger), confirm intrathecal injection, visualize intrathecal hematoma, and avoid radiation. Sonography is a promising modality for image‐guided lumbar punctures without radiation in children.
Sternal Pseudotumor of Childhood
Authors: Ilivitzki Anat , Sweed Yechiel , Beck Nira , Militianu Daniela
Published: November 2013

The common approach to rapidly growing peristernal lesions in young infants is oncologic consultation, imaging, and early tissue diagnosis. We represent 3 such cases with unique sonographic findings favoring nonaggressive lesions named self‐limiting sternal tumors of childhood, in which a conservative approach of sonographic follow‐up was chosen. We review the typical sonographic characteristics in this rather new and rare entity, separating it from the more aggressive group of lesions in this location and age group, and suggest that the classic appearance should imply a wait‐and‐see approach, with sonographic follow‐up studies rather than invasive intervention.
On fitting a triangle into a circle: A study on employment outcomes of adults with Fetal Alcohol Spectrum Disorder who attended postsecondary institutions
Authors: Duquette Cheryll , Orders Shari
Published: November 2013

Duquette, C., & Orders, S. (2013). On fitting a triangle into a circle: A study on employment outcomes of adults with Fetal Alcohol Spectrum Disorder who attended postsecondary institutions. The International Journal Of Alcohol And Drug Research, 2(3), 27-36. doi:10.7895/ijadr.v2i3.105 (http://dx.doi.org/10.7895/ijadr.v2i3.105)Aim: This study examined the employment outcomes of individuals with FASD who had undertaken postsecondary studies.Design: A qualitative research design using inductive thematic analysis and descriptive statistics was employed.Setting: The study took place in the United States and Canada.Participants: Ten adoptive mothers, one birth mother, one step-mother and one mother-in-law (N=13), representing 17 adult children, responded to the survey. Four adults with FASD who had undertaken postsecondary studies each participated in an individual interview.Measures: An electronic survey consisting mostly of open-ended items was used to obtain data on the postsecondary and employment experiences of adults with FASD from the perspectives of their relatives. Adults with FASD participated in individual interviews in which they elaborated on their experiences.Findings: More than half of the adults with FASD were employed, albeit mostly in the service sector and on a part-time basis. Four of the adults had received an early diagnosis, and these individuals were all employed; two were working in the area of their postsecondary studies. Six of the adults with FASD who had completed their college programs were working at the time of the research.Conclusions: For those individuals who did not graduate or were not employed, symptoms of FASD and other disabilities (e.g., substance abuse and mental health problems) were related to these negative outcomes. However, a supportive network of friends and family contributed to success in postsecondary studies and employment.
Exploring the prevention of Fetal Alcohol Spectrum Disorder in the Northwest Territories of Canada: Brightening our home fires
Authors: Badry Dorothy , Felske Aileen
Published: November 2013

Badry, D., & Felske, A. (2013). Exploring the prevention of Fetal Alcohol Spectrum Disorder in the Northwest Territories of Canada: Brightening our home fires. The International Journal Of Alcohol And Drug Research, 2(3), 7-15. doi:10.7895/ijadr.v2i3.125 (http://dx.doi.org/10.7895/ijadr.v2i3.125)Aims: The prevention of Fetal Alcohol Spectrum Disorder (FASD) in a Northern context from a woman’s health perspective was explored in the qualitative research study, Brightening Our Home Fires (BOHF). It is recognized that research on the prevention of FASD is a sensitive topic due to stigma associated with alcohol use during pregnancy. Women’s health and FASD prevention were identified as the focus of the research, as they are deeply intertwined topics.Design: The BOHF project was designed as a participation action research project that utilized Photovoice as a primary methodology to approach the topic of FASD prevention in the Northwest Territories (NT) from a women’s health lens.Setting: This research took place in Yellowknife, NT. Participants included both Dene and Inuit women.Participants: Eight women living in a homeless centre in Yellowknife, Northwest Territories.Measures: This was a qualitative research study that utilized Participatory Action Research (PAR) to explore women’s health in the North. Photovoice was the primary methodology. The analysis of this research focused on both image and text, and a depth analysis of text led to theme identification.Findings: Findings included the importance, to women participants, of housing, access to treatment resources for alcohol, and engagement with health-related resources, and the challenges they experience that are related to their histories of trauma.Conclusions: Engagement with women in the NT on FASD prevention was important in broadly identifying the linkages between trauma and alcohol use while respecting context and stigma around alcohol use and pregnancy.
Subsurface methane sources and migration pathways within a gas hydrate mound system, Gulf of Mexico
Authors: Wilson Rachel M. , Macelloni Leonardo , Simonetti Antonello , Lapham Laura , Lutken Carol , Sleeper Ken , D'Emidio Marco , Pizzi Marco , Knapp James , Chanton Jeff
Published: November 2013

Geochemical profiles were coupled with seismic information to examine subsurface hydrocarbon source, migration, and fate at a Gulf of Mexico carbonate‐gas hydrate mound (Woolsey Mound). Three seafloor features were investigated in detail: (1) major faults resulting from a rising salt body, (2) an acoustic backscatter anomaly, and (3) a pockmark associated with a major fault. We analyzed sulfate, chloride, dissolved inorganic carbon, and hydrocarbon concentrations, and carbon isotopes in pore water extracted from 20 m piston cores to characterize gas source and calculate methane flux. Dissolved biogenic methane dominated the off‐fault sites, while the contribution of thermogenic methane increased near a major fault where thermogenic gas hydrates were recovered. Within the pockmark, methane concentrations were low and isotopes indicated a biogenic source. Since pockmarks are typically formed from expulsive fluid flow, this suggests that either the pockmark is the legacy of a conduit that has become plugged or that the expulsed fluid is confined within the fault walls. At the acoustic anomaly, nonsteady state sulfate profiles suggested temporal variability in methane flux. Estimates from >75 gravity cores collected across Woolsey Mound since 2002 were mapped to display the spatial variability in methane flux relative to the faults. Methane flux to the seafloor was generally low, but increased several fold near the faults suggesting that the faults may provide conduits for hydrocarbons to bypass the “microbial biofilter” and cross the sediment water interface.
Summer melt regulates winter glacier flow speeds throughout Alaska
Authors: Burgess Evan W. , Larsen Christopher F. , Forster Richard R.
Published: November 2013

Predicting how climate change will affect glacier and ice sheet flow speeds remains a large hurdle toward accurate sea level rise forecasting. Increases in surface melt rates are known to accelerate glacier flow in summer, whereas in winter, flow speeds are believed to be relatively invariant. Here we show that wintertime flow speeds on nearly all major glaciers throughout Alaska are not only variable but are inversely related to melt from preceding summers. For each additional meter of summertime melt, we observe an 11% decrease in wintertime velocity on glaciers of all sizes, geometries, climates, and bed types. This dynamic occurs because interannual differences in summertime melt affect how much water is retained in the subglacial system during winter. The ubiquity of the dynamic indicates it occurs globally on glaciers and ice sheets not frozen to their beds and thus constitutes a new mechanism affecting sea level rise projections.
Greenland subglacial lakes detected by radar
Authors: Palmer Steven J. , Dowdeswell Julian A. , Christoffersen Poul , Young Duncan A. , Blankenship Donald D. , Greenbaum Jamin S. , Benham Toby , Bamber Jonathan , Siegert Martin J.
Published: November 2013

Subglacial lakes are an established and important component of the basal hydrological system of the Antarctic ice sheets, but none have been reported from Greenland. Here we present airborne radio echo sounder (RES) measurements that provide the first clear evidence for the existence of subglacial lakes in Greenland. Two lakes, with areas ~8 and ~10 km2, are found in the northwest sector of the ice sheet, ~40 km from the ice margin, and below 757 and 809 m of ice, respectively. The setting of the Greenland lakes differs from those of Antarctic subglacial lakes, being beneath relatively thin and cold ice, pointing to a fundamental difference in their nature and genesis. Possibilities that the lakes consist of either ancient saline water in a closed system or are part of a fresh, modern open hydrological system are discussed, with the latter interpretation considered more likely.
The effect of geomagnetic‐storm‐induced enhancements to ionospheric emissions on the interpretation of the TIMED/GUVI O/N2 ratio
Authors: Lee Woo Kyoung , Kil Hyosub , Paxton Larry J. , Zhang Yongliang , Shim Ja Soon
Published: November 2013

We examine the consequence of enhanced atomic oxygen (OI) 135.6 nm emissions due to the recombination of O+ with electrons on the column number density ratio of atomic oxygen to molecular nitrogen (O/N2 ratio) provided by Global Ultraviolet Imager (GUVI) on board the Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics satellite. GUVI O/N2 ratio is derived from the measurements of OI 135.6 nm and N2 Lyman‐Birge‐Hopfield airglow emissions. The OI 135.6 nm emission arises from two sources: photoelectron impact excitation of neutral atomic oxygen and the radiative recombination of O+ with electrons. We estimate the O/N2 ratio disturbance associated with the O+ density enhancement during geomagnetic storms through the case study of the storms on 20 November 2003 and 8 November 2004. The OI 135.6 nm emission enhancement originating from the ionosphere is derived using the Utah State University Global Assimilation of Ionospheric Measurements model ionosphere. Our results show that the O/N2 ratio increase from the equator to middle latitudes during the storm periods is primarily associated with thermospheric neutral composition disturbances. However, the contribution of the OI 135.6 nm emission originating from the ionosphere to the storm time O/N2 ratio increase is substantial in the northern low‐middle latitude regions where severe plasma density enhancements occur during the main phase of the storms. Therefore, the ionospheric contribution should be considered for an accurate assessment of the storm time O/N2 ratio increase at low‐middle latitudes during these large storm events.
Plasma in the near Venus tail: Venus Express observations
Authors: Dubinin E. , Fraenz M. , Zhang T. L. , Woch J. , Wei Y. , Fedorov A. , Barabash S. , Lundin R.
Published: November 2013

Although Venus has no global intrinsic magnetic fields, it possesses a long magnetotail of induced origin. The topology of the tail is determined by the interplanetary magnetic field orientation. We present recent plasma and magnetic field observations in the near Venus tail (X≥−3RV) made by the Venus Express spacecraft. We show that ion acceleration in the Venus plasma sheet is produced by the slingshot effect of the draping magnetic field lines, though some features as differential streaming of different ion species point to the existence of other forces. We explain a bell shape of ion spectrograms while the spacecraft crosses the current sheet. The absence of a balance between the lobe magnetic pressure and thermal pressure of plasma in the plasma sheet indicates a dynamic rather than a static equilibrium in the Venus magnetotail. A strong asymmetry of the plasma sheet is controlled by the direction of the motional electric field in the upstream solar wind. In the hemisphere pointed in the direction of the motional electric field, the j×B force accelerates plasma tailward supplying the plasma sheet, while in the opposite hemisphere, the flow pattern occurs less regularly with smaller speeds but higher number densities.
Temperature trends in the midlatitude summer mesosphere
Authors: Lübken F.‐J. , Berger U. , Baumgarten G.
Published: November 2013

We have performed trend studies in the mesosphere in the period 1961–2009 with Leibniz‐Institute Middle Atmosphere (LIMA) model driven by European Centre for Medium‐Range Weather Forecasts reanalysis below approximately 40 km and adapts temporal variations of CO2 and O3 according to observations. Temperatures in the mesosphere/lower thermosphere vary nonuniformly with time, mainly due to the influence of O3. Here we analyze the contribution of varying concentrations of CO2 and O3 to the temperature trend in the mesosphere. It is important to distinguish between trends on pressure altitudes, zp, and geometrical altitudes, zgeo, where the latter includes the effect of shrinking due to cooling at lower heights. For the period 1961–2009, temperature trends on geometrical and pressure altitudes can differ by as much as −0.9 K/dec in the mesosphere. Temperature trends reach approximately −1.3±0.11 K/dec at zp∼60 km and −1.8±0.18 K/dec at zgeo∼70 km, respectively. CO2 is the main driver of these trends in the mesosphere, whereas O3 contributes approximately one third, both on geometrical and pressure heights. Depending on the time period chosen, linear temperature trends can vary substantially. Altitudes of pressure levels in the mesosphere decrease by up to several hundred meters. We have performed long‐term runs with LIMA applying twentieth century reanalysis dating back to 1871. Again, trends are nonuniform with time. Since the late nineteenth century, temperatures in the mesosphere have dropped by approximately 5–7 K on pressure altitudes and up to 10–12 K on geometrical altitudes.
Radiative‐convective instability
Authors: Emanuel Kerry , Wing Allison A. , Vincent Emmanuel M.
Published: November 2013

Radiative‐moist‐convective equilibrium (RCE) is a simple paradigm for the statistical equilibrium the earth's climate would exhibit in the absence of lateral energy transport. It has generally been assumed that for a given solar forcing and long‐lived greenhouse gas concentration, such a state would be unique, but recent work suggests that more than one stable equilibrium may be possible. Here we show that above a critical specified sea surface temperature, the ordinary RCE state becomes linearly unstable to large‐scale overturning circulations. The instability migrates the RCE state toward one of the two stable equilibria first found by Raymond and Zeng (2000). It occurs when the clear‐sky infrared opacity of the lower troposphere becomes so large, owing to high water vapor concentration, that variations of the radiative cooling of the lower troposphere are governed principally by variations in upper tropospheric water vapor. We show that the instability represents a subcritical bifurcation of the ordinary RCE state, leading to either a dry state with large‐scale descent, or to a moist state with mean ascent; these states may be accessed by finite amplitude perturbations to ordinary RCE in the subcritical state, or spontaneously in the supercritical state. As first suggested by Raymond (2000) and Sobel et al. (2007), the latter corresponds to the phenomenon of self‐aggregation of moist convection, taking the form of cloud clusters or tropical cyclones. We argue that the nonrobustness of self‐aggregation in cloud system resolving models may be an artifact of running such models close to the critical temperature for instability.
An Overview of the Discovery and Development Process for Biologics
Authors: Shih Heather H. , Miller Paula , Harnish Douglas C.
Published: November 2013

This chapter will focus on protein‐based biologics, particularly mAbs as they represent the largest class of biologic drugs. By the end of 2011, the US Food and Drug Administration (FDA) had approved close to 40 mAbs and antibody variants. We will provide an overview of the discovery and development process for protein therapeutics with a primary focus on mAbs.Additionally, we will summarize the current status of the protein‐based biologics field and discuss several future trends.
Clinical Assessment of Biologic Agents
Authors: Saketkoo Lesley Ann , Mittoo Shikha , Espinoza Luis R.
Published: November 2013

Biologic agents have become a powerful armament in the treatment of immune‐mediated diseases, although long‐term data are still being collected. It seems biologics may have favorably altered outcomes in mortality and disability in recalcitrant and life‐threatening diseases. At the same time, these “miraculous” agents come with important and potentially life‐threatening concerns related to immune suppression that can give rise to serious infection, heart failure, demyelinating neural disease, and malignancy.Therefore, continued assessment of efficacy and adverse effects are central to the management of patients treated with biologics. The following chapter outlines important considerations in the clinical assessment during and after a biologic clinical trial. This chapter will cover structural aspects of clinical trial design, surveillance for adverse effects, provide an overview of endpoints in clinical trials design, and discuss the basis for generic (not disease‐specific) and disease‐specific instruments (aka outcome measures and endpoints) used in trials. This chapter will also provide information on novel forms of developing clinical endpoints from the patient's perspective.
Landscape and Consideration of Intellectual Property for Development of Biosimilars
Authors: Melethil Srikumaran
Published: November 2013

This chapter will introduce the recently passed Biologics Price Competition and Innovation Act of 2009 (BPCI Act) with special emphasis on the intellectual property (IP) provisions of the law, especially as they relate to patents and trade secrets.It begins with a brief legislative history to provide the reader with an overview of the scientific, legal, economic, and political debate prior to the passage of the BPCI Act. It is followed by a limited presentation of approval guidelines for biosimilarity to enable the reader to obtain a better understanding of the scientific challenges associated with manufacturing biosimilars. Next, key intellectual property provisions under the BPCI Act for innovator and generic manufacturers are presented.This is followed by certain legal issues that have been raised, such as challenges to the U.S. Food and Drug Administration's (FDA's) use of innovator data and postapproval applicability of safe harbor provisions.This chapter concludes with a future perspective that draws the attention of the reader to certain widely debated intellectual property and regulatory issues that will soon be or can be expected to be decided by the FDA and the Supreme Court. These decisions will likely have a major impact on the intellectual property landscape and dialogue for biosimilars.
Protein and Peptide Purification
Authors: Nfor Beckley K. , Freydell Esteban J. , Ottens Marcel
Published: November 2013

The objective of this chapter is to present a comprehensive overview of the key aspects of downstream process (DSP) development of proteins and peptides. The chapter opens with a general description of the DSP steps and highlights their objectives and the basic bioseparation techniques employed. After introducing the reader to the general aspects of DSP, recent developments in inclusion bodies refolding are presented. There are several challenges facing downstream process development, and strategies for protein/peptide purification process development and how each tries to address/overcome the DSP challenges are reviewed. Finally, expert views on future directions of purification process development efforts are presented.
Analytical Characterization of Proteins and Peptides
Authors: Wang Yajun Jennifer , Hosken Brian
Published: November 2013

This chapter describes protein therapeutics, including monoclonal antibodies (mAbs), in terms of their expected protein structure and their commonly encountered variants. Current methods and strategies used for the physicochemical characterization of protein therapeutics and their variants will be discussed.
Protein and Peptide Formulation Development
Authors: Ohtake Satoshi , Wang Wei
Published: November 2013

Proteins/peptides are generally much more sensitive to process‐ or storage‐induced degradations than small synthetic molecules. Therefore, significant efforts are needed to formulate these protein/peptide drug candidates into viable commercial products.This chapter reviews the degradation processes in proteins/peptides, describes factors affecting protein/peptide stability, and discusses strategies in the successful development and manufacturing of protein/peptide commercial products.
Vaccine Development: History, Current Status, and Future Trends
Authors: van der Pol Leo , Amorij Jean‐Pierre
Published: November 2013

Vaccines consists of a heterogeneous group of biopharmaceuticals that show little synergy to allow a standardized approach for product and process development. For a more homogeneous group of recombinant protein biopharmaceuticals, such as monoclonal antibodies, a modular approach has been accomplished that reduces the risk and required time for a new development project. These protein products are well characterized, facilitating a Quality by design (QbD) approach. For vaccines, a prospective design approach is complicated by the limited knowledge on host‐pathogen interaction, in particular the responses of the human immune system, and the great variability of many pathogens.This frustrates the formulation of product quality features of a vaccine in order to guarantee the exertion of the desired (protecting) effect. The classic trial‐and‐error approach for vaccine development is often insufficient to combat variable and immune deceiving pathogens and generates limited scientific understanding for the present‐day desired level of control on process and product. Therefore, it seems promising that progress in scientific understanding of, in particular, the innate immune system enables tailored vaccine design. Knowledge‐based adjuvant design, and the upcoming recombinant subunit vaccines, conjugate vaccines, and virus‐like particle (VLP) vaccines, is expected to facilitate a vaccine design based on a structure‐function relationship in the future. This chapter presents an overview of vaccine development with special attention on process development and the route toward quality by design for vaccines.
The State of the Art and Future of Gene Medicines
Authors: Jacobs Frank , Gordts Stephanie C. , De De Geest Bart
Published: November 2013

In this chapter, we will discuss the significant technological progress that has been made in the development of gene therapy strategies and the application of these strategies in specific therapeutic niches. More specifically, we aim to provide an overview of selected highlights from the past (preclinical development), current (first‐in‐man clinical trials), and future (remaining hurdles and regulatory aspects) of different gene therapy approaches. In these discussions, we will focus on gene therapy approaches using viral vectors because they are generally considered to be more efficacious and have yielded the most prominent clinical successes.
Nucleic Acid Vaccines
Authors: Buglione‐Corbett Rachel , Suschak John , Wang Shixia , Lu Shan
Published: November 2013

The use of safe and effective vaccines has become a fundamental aspect of global health.To this end, immunization with a nucleic‐acid‐based vaccine has led to new considerations in vaccination strategies.At least in preclinical studies, antigen‐encoding DNA plasmids are capable of eliciting a broad spectrum of immune responses against antigens from a variety of pathogens. As shown in this chapter, while DNA vaccination provides several advantages over other established vaccination strategies, further optimization is necessary before it becomes the predominant strategy in human patients.DNA vaccination has shown great promise in prime‐boost strategies and may provide a solution for pathogens that were previously thought unpreventable or untreatable.Their adaptability and ease of manipulation may prove to be the aspect that pushes them to the front line of vaccination.It appears that DNA vaccines are on the precipice of redefining the field of vaccinology.
Multifunctional Polymeric Nanosystems forRNAInterference Therapy
Authors: Iyer Arun , Ganesh Shanthi , Zhou Qiong L. , Amiji Mansoor
Published: November 2013

RNA interference (RNAi) is one of the most powerful tools for selective silencing of specific aberrant genes for therapeutic management of diseases such as cancer, diabetes, and inflammatory disorders. However, the labile nature of nucleic acid constructs coupled with the difficulty in selectively delivering them to the target tissues, cells, and the intracellular cellular machinery within the cells has been a primary hindrance for the clinical translation of RNAi. Multifunctional nano‐systems provide distinct advantages over other delivery strategies based on their ability to selectively target diseased tissues, such as solid tumors based on passive and active targeting principles. Such nano‐systems can incorporate multiple therapeutic payloads, such as small molecule drugs, small interfering RNAs (siRNAs), and micro RNAs (miRNAs) as well as imaging/contrast agents for simultaneous disease detection, quantifying siRNA/miRNA gene expression/knockdown, examining in vivo fate and sites of localization/excretion, as well as exploring therapeutic potentials in vivo. In this chapter, we have described the principles and mechanisms based on RNA interference phenomenon and the barriers to its successful clinical translation. Furthermore, we have discussed the modes of delivery that have been employed including the advantages of multifunctional polymeric nano‐systems with illustrative examples covering their utility in the management of diseases such as cancer, inflammation, and other chronic diseases.
Advent and Maturation of Regenerative Medicine
Authors: Mhashilkar Abner M. , Atala Anthony
Published: November 2013

The goals for regenerative medicine (RM) are focused on developing innovative tools in modern medicine. Recent progress has led to the development and clinical implementation of newer technologies, ranging from diagnostics to therapeutics for a wide variety of metabolic, degenerative, and infectious diseases.These include specific applications toward age‐ and genetic‐related human and animal dysfunctions and disorders. The focus of this review is to present, in a nutshell, the current status of adult stem cell therapy (CT) and tissue engineering (TE), including the challenges faced, progresses attained, and an optimistic view of the future. We will also provide our views on how the next 20+ years will potentially affect these RM‐driven innovations and how they are applied toward a variety of disease treatments, cures, and diagnostics.
Conventional and Novel Container Closure and Delivery Systems
Authors: Wong Joseph , Chaubal Mahesh V.
Published: November 2013

Recent years have seen continued growth in the area of biologics with a majority of pharmaceutical companies developing a pipeline in next‐generation biologic products. Most biologics are administered via injectable routes of administration and often require frequent injections. Hence, delivery devices that can reduce discomfort associated with injectable delivery (both to the caregiver and the patient) are of interest as part of lifecycle management of biologic products. This chapter attempts to discuss some key features of these delivery devices for biologics (both conventional and novel) that are important for consideration in product development.
Growth of Monodisperse Gold Nanospheres with Diameters from 20 nm to 220 nm and Their Core/Satellite Nanostructures
Authors: Ruan Qifeng , Shao Lei , Shu Yiwei , Wang Jianfang , Wu Hongkai
Published: November 2013

Gold nanocrystals and nanoassemblies have attracted extensive attention for various applications, including chemical and biological sensing, solar energy harvesting, and plasmon‐enhanced spectroscopies, due to their unique plasmonic properties. It is of great importance to prepare shape‐controlled Au nanocrystals with high monodispersity over a large range of sizes. In this work, Au nanospheres with sizes ranging from 20 nm to 220 nm are prepared using a simple seed‐mediated growth method aided with mild oxidation. As‐prepared Au nanospheres are remarkably uniform in size. The resultant Au nanospheres of different sizes are ideal building blocks for constructing plasmonic nanoassemblies. Core/satellite nanostructures are assembled out of differently sized Au nanospheres with molecular linkers. The core/satellite nanostructures show a red‐shifted plasmon resonance peak in comparison to that of the Au cores, which is consistent with the results calculated according to Mie theory. As predicted by finite‐difference time‐domain simulations, the assembled core/satellite nanostructures exhibit strongly enhance Raman signals. This facile growth of Au nanospheres and assembly of core/satellite nanostructures are expected to facilitate the design of new nanoassemblies with desired plasmonic properties and functions.
Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies
Authors: Minden Mark D. , Hogge Donna E. , Weir Scott J. , Kasper Jim , Webster Debra A. , Patton Lavonne , Jitkova Yulia , Hurren Rose , Gronda Marcela , Goard Carolyn A. , Rajewski Lian G. , Haslam John L. , Heppert Kathleen E. , Schorno Kevin , Chang Hong , Brandwein Joseph M. , Gupta Vikas , Schuh Andre C. , Trudel Suzanne , Yee Karen W. L. , Reed Gregory A. , Schimmer Aaron D.
Published: November 2013

The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first‐in‐human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5–80 mg/m2 oral ciclopirox olamine once daily for five days in 21‐day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half‐life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m2 ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty‐three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half‐life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m2, demonstrating biological activity of the drug. Dose‐limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m2 four times daily, and no dose limiting toxicity was observed at 40 mg/m2 once daily. Hematologic improvement was observed in two patients. Once‐daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population. Am. J. Hematol. 89:363–368, 2014. © 2013 Wiley Periodicals, Inc.