bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive Biology of Bothrops erythromelas from the Brazilian Caatinga
Authors: Alberto Barros Verônica , Rojas Claudio Augusto , Almeida-Santos Selma Maria
Published: December 2014

The reproductive biology of Bothrops erythromelas, a small pit viper from the Caatinga, a semiarid biome in Brazil, is described based on analysis of individuals deposited in zoological collections. Males are smaller and also attain sexual maturity at a smaller size than females. Female reproductive cycle is seasonal with an extended period of secondary vitellogenesis and births occurring in a restricted period from late spring to early summer. Sperm storage in females may probably occur in infundibular tubular glands and uterine muscular twisting (UMT), which is a polymorphic condition within B. erythromelas. Seasonal spermatogenesis in males is variable with some intraspecific variation regarding the male reproductive stage per season. Most males are reproductively active during spring/summer and reproductively quiescent during autumn/winter, although some individuals vary (e.g., show testicular spermatogenesis and active sexual segment of the kidneys (SSK) during winter). The SSK could be identified in every male. Most males showed highly hypertrophied SSK in spring/summer and moderately hypertrophied SSK in autumn/winter. The ampulla ductus deferentis was observed and histochemical reactions were conducted. We discuss the probable influence of the unique environmental conditions of the Caatinga region and phylogenetic inertia in the reproductive patterns of this snake species.
Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders
Authors: Rita Patrizia Aquino , Mariateresa Stigliani , Pasquale Del Gaudio , Teresa Mencherini , Francesca Sansone , Paola Russo
Published: December 2014

The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology), and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation.
Tumor-Associated Hyaluronan Limits Efficacy of Monoclonal Antibody Therapy
Authors: Singha Netai C. , Nekoroski Tara , Zhao Chunmei , Symons Rebecca , Jiang Ping , Frost Gregory I. , Huang Zhongdong , Shepard H. Michael
Published: December 2014

Despite tremendous progress in cancer immunotherapy for solid tumors, clinical success of monoclonal antibody (mAb) therapy is often limited by poorly understood mechanisms associated with the tumor microenvironment (TME). Accumulation of hyaluronan (HA), a major component of the TME, occurs in many solid tumor types, and is associated with poor prognosis and treatment resistance in multiple malignancies. In this study, we describe that a physical barrier associated with high levels of HA (HAhigh) in the TME restricts antibody and immune cell access to tumors, suggesting a novel mechanism of in vivo resistance to mAb therapy. We determined that approximately 60% of HER23+ primary breast tumors and approximately 40% of EGFR+ head and neck squamous cell carcinomas are HAhigh, and hypothesized that HAhigh tumors may be refractory to mAb therapy. We found that the pericellular matrix produced by HAhigh tumor cells inhibited both natural killer (NK) immune cell access to tumor cells and antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Depletion of HA by PEGPH20, a pegylated recombinant human PH20 hyaluronidase, resulted in increased NK cell access to HAhigh tumor cells, and greatly enhanced trastuzumab- or cetuximab-dependent ADCC in vitro. Furthermore, PEGPH20 treatment enhanced trastuzumab and NK cell access to HAhigh tumors, resulting in enhanced trastuzumab- and NK cell–mediated tumor growth inhibition in vivo. These results suggest that HAhigh matrix in vivo may form a barrier inhibiting access of both mAb and NK cells, and that PEGPH20 treatment in combination with anticancer mAbs may be an effective adjunctive therapy for HAhigh tumors. Mol Cancer Ther; 14(2); 523–32. ©2014 AACR.
The Allocation of Attention and Working Memory in Visual Crowding
Authors: Bacigalupo Felix , Luck Steven J.
Published: December 2014

When the distance between a visual target and nearby flankers falls below a critical distance, target discrimination declines precipitously. This is called “crowding.” Many researchers have proposed that selective attention plays a role in crowding. However, although some research has examined the effects of directing attention toward versus away from the targets, no previous research has assessed how attentional allocation varies as a function of target–flanker distance in crowding. Here, we used ERPs to assess the operation of attention during crowding, focusing on the attention-related N2pc component. We used a typical crowding task in which participants were asked to report the category (vowel/consonant) of a lateralized target letter flanked by distractor letters at different distances. We tested the hypothesis that attention fails when the target–flanker distance becomes too small for attention to operate effectively. Consistent with this hypothesis, we found that N2pc amplitude was maximal at intermediate target–flanker distances and decreased substantially when crowding became severe. In addition, we examined the sustained posterior contralateral negativity (SPCN), which reflects the amount of information being maintained in working memory. Unlike the N2pc component, the SPCN increased in amplitude at small target–flanker distances, suggesting that observers stored information about the target and flankers in working memory when attention failed to select the target. Together, the N2pc and SPCN results suggest that attention and working memory play distinctive roles in crowding: Attention operates to minimize interference from the flankers at intermediate target–flanker distances, whereas working memory may be recruited when attention fails to select the target at small target–flanker distances.
Short-term Motor Training, but Not Observational Training, Alters Neurocognitive Mechanisms of Action Processing in Infancy
Authors: Gerson Sarah A. , Bekkering Harold , Hunnius Sabine
Published: December 2014

The role of motor experience in the processing of perceived actions is hotly debated on both behavioral (e.g., action understanding) and neural (e.g., activation of the motor system) levels of interpretation. Whereas some researchers focus on the role of motor experience in the understanding of and motor activity associated with perceived actions, others emphasize the role of visual experience with the perceived actions. The question of whether prior firsthand motor experience is critical to motor system activation during perception of actions performed by others is best addressed through studies with infants who have a limited repertoire of motor actions. In this way, infants can receive motor or visual training with novel actions that are not mere recombinations of previously acquired actions. In this study, 10-month-old infants received active training with a motorically unfamiliar action that resulted in a distinct sound effect. They received observational experience with a second, similarly unfamiliar action. Following training, we assessed infants' neural motor activity via EEG while they listened to the sounds associated with the actions relative to a novel sound. We found a greater decrease in mu power to sounds associated with the motorically learned action than to those associated with the observed action that the infants had never produced. This effect was directly related to individual differences in the degree of motor learning via motor training. These findings indicate a unique effect of active experience on neural correlates of action perception.
Delay Period Activity of the Substantia Nigra during Proactive Control of Response Selection as Determined by a Novel fMRI Localization Method
Authors: Yoon Jong H. , Larson Paul , Grandelis Anthony , La Christian , Cui Edward , Carter Cameron S. , Minzenberg Michael J.
Published: December 2014

The ability to proactively control motor responses, particularly to overcome overlearned or automatic actions, is an essential prerequisite for adaptive, goal-oriented behavior. The substantia nigra (SN), an element of the BG, has figured prominently in current models of response selection. However, because of its small size and proximity to functionally distinct subcortical structures, it has been challenging to test the SN's involvement in response selection using conventional in vivo functional neuroimaging approaches. We developed a new fMRI localization method for directly distinguishing, on echo-planar images, the SN BOLD signal from that of neighboring structures, including the subthalamic nucleus (STN). Using this method, we tested the hypothesis that the SN supports the proactive control of response selection. We acquired high-resolution EPI volumes at 3 T from 16 healthy participants while they completed the Preparing to Overcome Prepotency task of proactive control. There was significantly elevated delay period signal selectively during high- compared with low-control trials in the SN. The STN did not show delay period activity in either condition. SN delay period signal was significantly inversely associated with task performance RTs across participants. These results suggest that our method offers a novel means for measuring SN BOLD responses, provides unique evidence of SN involvement in cognitive control in humans, and suggests a novel mechanism for proactive response selection.
Reliability of Information-Based Integration of EEG and fMRI Data: A Simulation Study
Authors: Assecondi Sara , Ostwald Dirk , Bagshaw Andrew P.
Published: December 2014

Most studies involving simultaneous electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data rely on the first-order, affine-linear correlation of EEG and fMRI features within the framework of the general linear model. An alternative is the use of information-based measures such as mutual information and entropy, which can also detect higher-order correlations present in the data. The estimate of information-theoretic quantities might be influenced by several parameters, such as the numerosity of the sample, the amount of correlation between variables, and the discretization (or binning) strategy of choice. While these issues have been investigated for invasive neurophysiological data and a number of bias-correction estimates have been developed, there has been no attempt to systematically examine the accuracy of information estimates for the multivariate distributions arising in the context of EEG-fMRI recordings. This is especially important given the differences between electrophysiological and EEG-fMRI recordings. In this study, we drew random samples from simulated bivariate and trivariate distributions, mimicking the statistical properties of EEG-fMRI data. We compared the estimated information shared by simulated random variables with its numerical value and found that the interaction between the binning strategy and the estimation method influences the accuracy of the estimate. Conditional on the simulation assumptions, we found that the equipopulated binning strategy yields the best and most consistent results across distributions and bias correction methods. We also found that within bias correction techniques, the asymptotically debiased (TPMC), the jackknife debiased (JD), and the best upper bound (BUB) approach give similar results, and those are consistent across distributions.
Mismatched Training and Test Distributions Can Outperform Matched
Ones
Authors: González Carlos R. , Abu-Mostafa Yaser S.
Published: December 2014

In learning theory, the training and test sets are assumed to be drawn from the same probability distribution. This assumption is also followed in practical situations, where matching the training and test distributions is considered desirable. Contrary to conventional wisdom, we show that mismatched training and test distributions in supervised learning can in fact outperform matched distributions in terms of the bottom line, the out-of-sample performance, independent of the target function in question. This surprising result has theoretical and algorithmic ramifications that we discuss.
Diabetes Educator Mentorship Program
Authors: Beck Joni K. , Traficano Sheryl E.
Published: December 2014

Purpose

The purpose of this article is to describe the Diabetes Educator Mentorship Program, communicate mentors’ experiences and perceptions during the first 3 years following implementation, and provide strategies to encourage mentoring.

Conclusions

Creation of this collaborative program has fostered successful attainment of additional certified diabetes educators who obtained diabetes self-management education and support (DSMES) practice requirement hours through a voluntary Diabetes Educator Mentorship Program. There is a significant need for additional mentors to meet the growing need for mentoring partnerships. Increasing the number of mentors will provide more opportunities to those seeking to gain DSMES experience and will ultimately expand the number of health professionals available to educate those with diabetes or prediabetes.
Information needs of male juvenile delinquents
Authors: Rafedzi E.R.K. , Abrizah A.
Published: December 2014

This qualitative study provides an overview of what we have learned so far about the information needs of Malaysian male juvenile offenders. This focus is important to consider when designing and delivering the best possible information services to this group. The study seeks to understand juvenile delinquents’ information needs in the prison environment, focusing on their educational needs; online information environment and with the use of electronic resources; their everyday life information seeking (ELIS) needs, in the use of personal sources and prison libraries; in the use of books and other reading materials, and for future life perspectives. Data were collected using unstructured interviews with 23 juveniles (13 to 21 years old) living in four correctional schools in Malaysia. The data analysis revealed a general theme of the purpose of information needs, the location, the information sources, preferred reading materials, preferred language and subjects read. Formal information channels such as the library may be perceived as ineffective by inmates, regardless of their types of information needs and its objective validity. The Internet and informal networks among inmates were the most preferred source of information. Delinquents in the initial stage of imprisonment had significantly greater need for information than those in the final stage. Current findings add to the limited literature the juvenile offenders’ information behavior and that of other youth.
Wipeout? The Gold Coast and Tweed surfboard manufacturing cluster and local economic development
Authors: Logue David , Argent Neil , Warren Andrew
Published: December 2014

The Gold Coast and Tweed coast region is an archetypal Australian high amenity coastal area. It is also home to a local surfboard manufacturing industry of international standing, with well over one hundred separate but frequently closely related firms located in this littoral zone. This paper explains the rise and enduring influence of the Gold Coast/Tweed surfboard manufacturing agglomeration through the conceptual lens of the new industrial districts literature. We explore the many multi-scalar challenges the local industry faces in order to remain viable in the longer term. Based on interviews with 19 active participants in the Gold Coast/Tweed surfboard and ancillary manufacturing industries during 2010, we find that a combination of high quality surf, an established surfing culture, local planning instruments, and ready accessibility to high quality material suppliers, have facilitated the emergence and subsequent evolution of the local surf industrial district. However, our research also finds this local cluster at a crossroad. International competition – exacerbated by Australia’s high exchange rate and cheap local ‘backyard producers’ – threaten cluster members’ already slim margins. The ongoing structural ageing of the cluster’s chief operators, driven in large part by an inability to attract younger workers/entrepreneurs, is at least partly explained by the precarious and penurious nature of employment and pay in the sector. The highly individualistic and independent nature of most surfboard manufacturers – once a key feature of the cluster’s ‘industrial atmosphere’ – has become something of a weakness with the industry unable to collectively agree on the creation of a formal government/peak industry organization to auspice accredited training and industry-specific lobbying.
Impaired Circadian Photosensitivity in Mice Lacking Glutamate Transmission from Retinal Melanopsin Cells
Authors: Gompf Heinrich S. , Fuller Patrick M. , Hattar Samer , Saper Clifford B. , Lu Jun
Published: December 2014

Intrinsically photoreceptive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and convey retinal light inputs to the circadian system via the retinohypothalamic tract (RHT) projection to the suprachiasmatic nucleus (SCN). The principal neurotransmitter of this projection is glutamate, and ipRGCs use the vesicular glutamate transporter 2 (VGLUT2) to package glutamate into synaptic vesicles. However, these neurons contain other potential neurotransmitters, such as pituitary adenylate cyclase activating polypeptide (PACAP). To test the role of glutamate in mediating ipRGC light inputs into the SCN, we crossed mice in which Cre-recombinase expression is driven by the melanopsin promotor (Opn4Cre/+) with mice in which the second exon of VGLUT2 is flanked by loxP sites (VGLUT2fl/fl), producing ipRGCs that are unable to package glutamate into synaptic vesicles. Such mice had free-running circadian rhythms that did not entrain to a 12:12 light-dark (12:12 LD) cycle, nor did they show a phase delay after a 45-min light pulse administered at circadian time (CT) 14. A small subset of the mice did appear to entrain to the 12:12 LD cycle with a positive phase angle to lights-off; a similar entrainment pattern could be achieved in free-running mice if they were exposed to a 12:12 LD cycle with light of a greater intensity. Glutamate transmission from the ipRGCs is necessary for normal light entrainment of the SCN at moderate (0.35 W/m2) light levels, but residual transmission (possibly by PACAP in ipRGCs or by other RGCs) can weakly entrain animals, particularly at very high (6.53 W/m2) light levels, although it may be less effective at suppressing locomotor activity (light masking).
Circadian Rhythms, the Molecular Clock, and Skeletal Muscle
Authors: Harfmann Brianna D. , Schroder Elizabeth A. , Esser Karyn A.
Published: December 2014

Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle.
Familial-Environmental Risk Factors in South African Children With Attention-Deficit Hyperactivity Disorder (ADHD)
Authors: van Dyk Leana , Springer Priscilla , Kidd Martin , Steyn Nellie , Solomons Regan , van Toorn Ronald
Published: December 2014

We investigated familial and environmental risk factors in a cohort of South African children diagnosed with attention-deficit hyperactivity disorder (ADHD). A prospective, hospital-based case control study was conducted comprising 50 children diagnosed with ADHD and 50 matched non-ADHD controls. The adjusted effect of familial-environmental risk factors on ADHD was determined by systematic assessment. Birth complications, parental psychiatric disorder, maternal ADHD, early childhood trauma, and nonmaternal child care were significant risk factors for ADHD. Prolonged breastfeeding was found to be protective. In a multivariable logistic regression model, 5 criteria (birth complications, breastfeeding <3 months, at least 1 parent with tertiary education, presence of parental psychiatric disorder, and nonmaternal primary caregiver) differentiated ADHD from non-ADHD controls with a sensitivity and specificity of 74% and 86%, respectively. We found a correlation between certain familial and environmental risk factors and ADHD. A 5-criterion multivariable logistic regression model may offer clinical guidance in ADHD diagnosis.
Compatibilizing effects of maleic anhydride-grafted-polypropylene (PP)on long carbon fiber-reinforced PP composites
Authors: Kim JS , Kim DH
Published: December 2014

We prepared long carbon fiber (LCF)-reinforced thermoplastic composites using a specially designed twin-screw system. To improve the interfacial adhesion strength between the matrix polypropylene (PP) and LCF, we used a compatibilizer (maleic anhydride-grafted PP (PPMA)). The fiber length of the composites was approximately 10–70 mm and influenced by the compatibilizer concentration. With an increase in the LCF and PPMA content, tensile strength, tensile modulus, flexural strength, and flexural modulus increase. We also investigated the thermal properties of the composites using thermogravimetric analysis and differential scanning calorimetry. The fractured surfaces of PP/PPMA/LCF composites exhibited higher wetting than those of PP/LCF composites. PPMA was found effective in improving the adhesion between fiber and matrix.
Structure–property relationship of polyetherimide based on aromatic dianhydride and long alkyl chain containing aromatic diamines
Authors: Balasubramanian R. , Jayaseeli X. , Sarojadevi M.
Published: December 2014

A series of new poly(ether imide)s (PEIs) were synthesized from different commercially available dianhydrides like 3,3′,4,4′-benzophenonetetracarboxylic dianyhride (BTDA) and pyromellitic dianhydride (PMDA) and diamines like 1,4-bis(4-aminophenoxy)propane, 1,4-bis(4-aminophenoxy)butane, 1,4-bis(4-aminophenoxy)pentane, and 1,4-bis(4-aminophenoxy)hexane by a typical two-step polymerization method. The structure of the monomers and PEIs prepared were confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance and carbon-13 nuclear magnetic resonance spectral analysis. Solubility of the PEIs was tested in various organic solvents. Thermal properties of the PEIs were investigated by thermogravimetric analysis and differential scanning calorimetry. The temperature corresponding to 5% ( T5%) and 10% ( T10%) weight loss are from 318°C to 418°C and from 380°C to 480°C, respectively. These PEIs exhibit glass transition temperature in the range of 195–245°C, very low water absorption (0.37–0.62%), and low dielectric constant (2.68–3.17) at 1 MHz. The PEIs film possessed good mechanical properties with tensile strength of 77–98 MPa, elongation at break of 8–13%, and tensile modulus of 1.5–2.2 GPa. These results imply that the synthesized PEIs are well suited to be used as dielectric materials. Based on these studies the structure–property relationships were established.
Effects of head deformation on aerodynamic characteristics of spinning vehicle
Authors: Wu Xiaosheng , Lu Tianyu , Lei Juanmian
Published: December 2014

Slight deformation of head influences the aerodynamic characteristics of head, after-body, and tail fins of spinning vehicle. The influence of head deformation was analyzed by the DES method. The results reveal that the frequency of interference on the after-body and fins caused by head deformation is different with the spin frequency of vehicle. It is more important that the interference caused by the head deformation has a lag phenomenon, which is related to the flow velocity and the spin rate of the vehicle. The normal force coefficient and side force coefficient of spinning vehicle with deformed head rise as the rotational speed of vehicle increases, and lag behind that in low spin rate conditions. In high Mach number conditions, the fluctuation magnitude of aerodynamic characteristics of spinning vehicle with deformed head is larger than those in low Mach number conditions.
Determinants of Mobility of Students in Europe
Authors: Caruso Raul , de Wit Hans
Published: December 2014

This article studies the economic determinants of intra-European student mobility. We constructed a panel of 33 European countries for the period 1998-2009. The dependent variable is the inflow of foreign students (International Standard Classification of Education [ISCED] 5-6) from European Union (EU)-27, European Economic Area (EEA), and candidate countries. Results show that (a) the expenditure per student appears to be a crucial determinant. It is reasonable to maintain that students are likely to choose countries where the students are granted with adequately funded services and perhaps monetary incentives. Eventually, other significant determinants are (a) the actual level of safety, (b) the degree of openness of host country, and (c) the GDP per capita of host country.
Effective Instructional Strategies for Kindergarten and First-Grade Students at Risk in Mathematics
Authors: Clarke Ben , Doabler Christian T. , Nelson Nancy J. , Shanley Caroline
Published: December 2014

This article provides an overview of effective instructional strategies and interventions for kindergarten and first-grade students at risk in mathematics. The article reviews instructional strategies and interventions within a multitier instructional model in order to provide a framework for teachers and schools looking to increase the effectiveness of their instructional support in the area of mathematics.
Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP)
Authors: Birtas Atesoglu Elif , Tarkun Pinar , Demirsoy Esra Terzi , Geduk Ayfer , Mehtap Ozgur , Batman Adnan , Kaya Fatih , Cekmen Mustafa Baki , Gulbas Zafer , Hacıhanefioglu Abdullah
Published: December 2014

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.
Analysis of Enoxaparin Dose Titration at a Large, Tertiary Teaching Facility
Authors: Freer J. Matt , Green Melissa S. , Iuppa Jennifer A. , Deal Eli N. , Thoelke Mark S.
Published: December 2014

Therapeutic drug monitoring of enoxaparin with antifactor Xa levels (AXALs) is recommended in some populations; however, the approach to dose titration is poorly described. Our study at a large, tertiary teaching facility examined the dose response to titration of enoxaparin based on AXAL. Patients from 2008 to 2012 receiving enoxaparin were included, provided 2 or more steady state AXAL were obtained within 30 days and that the enoxaparin was prescribed for treatment rather than prophylaxis. The primary outcome was the percentage of dose change required to obtain goal range AXAL following dose titration. Eighty-seven patients were available for analysis with the following key characteristics: renal dysfunction during treatment 72%, obesity 8%, and solid organ transplant 26%. Initial goal AXAL was attained in 27 (31%) patients, and ultimately 54 (62%) patients achieved goal AXAL. Of the 31 patients who had initial AXAL above goal, 13 (42%) patients reached goal with a median dose decrease of 24%. In the 29 patients who had an initial AXAL below goal, 11 (38%) achieved therapeutic AXAL with a median dose increase of 16%. The AXAL monitoring can guide enoxaparin titration with subtherapeutic or supratherapeutic AXAL and an increase or decrease of roughly 20% is suggested as an initial change.
Metering Self-Reported Adherence to Clinical Outcomes in Malaysian Patients With Hypertension
Authors: Karupaiah Tilakavati , Wong Kimberly , Chinna Karuthan , Arasu Kanimolli , Chee Winnie Siew Swee
Published: December 2014

The CORFIS ( Community-Based Cardiovascular Risk Factors Intervention Strategies) program was piloted in community clinics in Malaysia to address the lack of health education in chronic disease management. The stages of change model was applied in a multicenter quasi-experimental design to evaluate adherence to advocated behaviors in CORFIS patients with hypertension. Based on submitted diet and exercise records ( n = 209), adherence to sodium reduction, regular exercise, and increasing fruit and vegetable intake behaviors were quantified against weight, waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) changes. Patients were categorized at 6 months into nonadherent/N-A (Precontemplation, Contemplation, and Preparation), newly adherent/NA (Action) and totally adherent/TA (Maintenance) groups. Self-reported adherence records did not meet recommended targets for healthful behaviors, but clinical benefits were achieved by adherent groups as indicated by effect size (Cohen’s d) comparisons. SBP reduction was associated with adherence to sodium reduction in NA ( d = 0.60, p < .001) and TA ( d = 0.45, p < .001) compared to N-A ( d = 0.13, p > .05). Marginally increasing fruit and vegetable consumption (Δ = 0.41 servings) resulted in sizeable reductions in weight for NA ( d = 0.81, p < .001) > TA ( d = 0.54, p < .001) > N-A ( d = 0.21, p > .05) and in WC for NA ( d = 0.68, p < .00) > TA ( d = 0.53, p < .001) > N-A ( d = 0.52, p > .05). Exercise behavior was least successful as pedometer counting was below 10,000 steps but sizeable weight and WC reductions were largest for NA ( d = 0.71 and 0.79, respectively) > TA ( d = 0.60 and 0.53, respectively) > N-A ( d = 0.33 and 0.35, respectively). Patients reporting a shift to positive stages of change behaviors enjoyed clinically beneficial reductions in SBP, DBP, weight, and WC.
Gift solicitation and acceptance in journalism practice: An assessment of Kuwaiti journalists’ perspective
Authors: Onyebadi Uche , Alajmi Fawaz
Published: December 2014

Media ethics generally recommends that journalists should avoid accepting any form of gratification in order to maintain their objectivity and professional integrity. This study investigated the application of this ethical injunction in Kuwait. It surveyed and interviewed Kuwaiti journalists on their attitude toward gratification. Results indicate a breach of this ethical recommendation. Reasons for this include lack of media ethics education and training among journalists and the absence of ethical guidance by media owners. In addition, for a number of Kuwaiti reporters, journalism is a part-time job.
Design of a freeform reflector for LED sources based on a feedback method
Authors: Wu H , Luo C , Zhang X , Ge P , Zhang X
Published: December 2014

We propose a method for the design of a freeform reflector by means of feedback methods to create light-emitting diode (LED) sources with uniform illuminance. A reflector is first designed to obtain a uniform circular light distribution for a point source. Then the optical performance of the reflector is investigated for both the point sources and extended sources based on a Monte Carlo ray tracing method. Comparing the illumination differences, a new reflector is generated by adding feedback. Repeated iterations of feedback can improve the reflector performance. To validate the method, a reflector is designed for an extended LED source. The results demonstrate that the illuminance uniformity can reach 88% and system efficiency can reach 97.4% simultaneously, after six feedback cycles. These are certainly able to meet the needs of general lighting applications.
Investigating Factors Affecting Group Processes in Virtual Learning Environments
Authors: Hazari Sunil , Thompson Sandra
Published: December 2014

With the widespread popularity of distance learning, there is a need to investigate elements of online courses that continue to pose significant challenges for educators. One of the challenges relates to creating and managing group projects. This study investigated business students’ perceptions of group work in online classes. The constructs of learning and social interaction, process satisfaction, product satisfaction, and use of technology in the virtual learning environment were investigated. The use of social media networks by group participants was also examined. Recommendations are provided for business educators looking to develop or enhance teamwork in virtual learning environments.
Bimaxillary Protrusion in the Caucasian: A Cephalometric Study of the Morphological Features
Authors: Keating P. J.
Published: December 2014

The skeletal morphology of bimaxillary dental protrusion has been investigated in a comparative cephalometric study. Because this is considered a subset of Class I malocclusions, the null hypothesis is that there should be no significant skeletal differences between this group and a Class I control group.

There were 30 Caucasians in each group with no bias for age and sex differences between them. Eighteen radiographic landmarks were identified from which 33 skeletal, dental and soft tissue parameters were computed. The bimaxillary group had an average interincisal angle of 115° versus the controls 135°, and showed the following morphological features which persisted over a 5-year growth period: 1. A shorter posterior cranial base. 2. A longer and more prognathic maxilla. 3. Similar mandibular dimensions and prognathism. 4. A mild Class II skeletal pattern. 5. A smaller upper and posterior face height. 6. Diverging facial planes. 7. A procumbent soft tissue profile with a low lip line.

These findings indicate that there is a distinctive difference between the underlying skeletal patterns found in the two groups.
Cephalometric Analysis of Changes Produced by a Modified Herbst Appliance in the Treatment of Class II Division 1 Malocclusion
Authors: Sidhu Maninder S. , Kharbanda O. P. , Sidhu S. S.
Published: December 2014

This study investigated treatment changes produced by the Herbst appliance in a sample of severe Class II division 1 cases, over a period of 8 months. The sample consisted of 16 girls, of whom eight were treated by the Herbst appliance, whilst eight served as controls. All cases were matched with respect to age, sex, skeletofacial morphology, and length of treatment/observation period. Twenty-two skeletal and 19 dental parameters were recorded on pre- and post-treatment cephalograms. The net treatment effect of Herbst therapy was evaluated, taking into account the growth that occurred in the control sample.

The study revealed that during 8 months of Herbst therapy there was a significant increase in mandibular length, along with sagittal repositioning. The skeletal changes in the mandible were mainly responsible for overjet and molar relation correction. A slight, favourable forward rotation of the mandible was identified. Dentoalveolar features included flaring of lower incisors and distalization of upper molars. The appliance did not have any retrusive effect on the maxilla. The modified splint design differed from the original and was cemented rather than bonded.
Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
Authors: Wali Vikram B , Gilmore-Hebert Maureen , Mamillapalli Ramanaiah , Haskins Jonathan W , Kurppa Kari J , Elenius Klaus , Booth Carmen J , Stern David F
Published: December 2014

Introduction

Human Epidermal Growth Factor Receptor (ERBB4/HER4) belongs to the Epidermal Growth Factor receptor/ERBB family of receptor tyrosine kinases. While ERBB1, ERBB2 and ERBB3 are often overexpressed or activated in breast cancer, and are oncogenic, the role of ERBB4 in breast cancer is uncertain. Some studies suggest a tumor suppressor role of ERBB4, while other reports suggest an oncogenic potential. Alternative splicing of ERBB4 yields four major protein products, these spliced isoforms differ in the extracellular juxtamembrane domain (JM-a versus JM-b) and cytoplasmic domain (CYT-1 versus CYT-2). Two of these isoforms, JM-a CYT-1 and JM-a CYT-2, are expressed in the mammary gland. Failure to account for isoform-specific functions in previous studies may account for conflicting reports on the role of ERBB4 in breast cancer.

Methods

We have produced mouse mammary tumour virus (MMTV) -ERBB4 transgenic mice to evaluate potential developmental and carcinogenic changes associated with full length (FL) JM-a ERBB4 CYT-1 versus ERBB4 CYT-2. Mammary tissue was isolated from transgenic mice and sibling controls at various developmental stages for whole mount analysis, RNA extraction, and immunohistochemistry. To maintain maximal ERBB4 expression, transgenic mice were bred continuously for a year after which mammary glands were isolated and analyzed.

Results

Overexpressing FL CYT-1 isoform resulted in suppression of mammary ductal morphogenesis which was accompanied by decreased number of mammary terminal end buds (TEBs) and Ki-67 positive cells within TEBs, while FL CYT-2 isoform had no effect on ductal growth in pubescent mice. The suppressive ductal phenotype in CYT-1 mice disappeared after mid-pregnancy, and subsequent developmental stages showed no abnormality in mammary gland morphology or function in CYT-1 or CYT-2 transgenic mice. However, sustained expression of FL CYT-1 isoform resulted in formation of neoplastic mammary lesions, suggesting a potential oncogenic function for this isoform.

Conclusions

Together, we present isoform-specific roles of ERBB4 during puberty and early pregnancy, and reveal a novel oncogenic property of CYT-1 ERBB4. The results may be exploited to develop better therapeutic strategies in breast cancer.
TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning
Authors: Diermeier Sarah , Kolovos Petros , Heizinger Leonhard , Schwartz Uwe , Georgomanolis Theodore , Zirkel Anne , Wedemann Gero , Grosveld Frank , Knoch Tobias A , Merkl Rainer , Cook Peter R , Längst Gernot , Papantonis Argyris
Published: December 2014

Background

The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs.

Results

Using micrococcal nuclease treatment and high-throughput sequencing, we map genome-wide changes in nucleosome positioning in primary human endothelial cells stimulated with tumour necrosis factor alpha (TNFα) - a proinflammatory cytokine that signals through nuclear factor kappa-B (NF-κB). Within 10 min, nucleosomes reposition at regions both proximal and distal to NF-κB binding sites, before the transcription factor quantitatively binds thereon. Similarly, in long TNFα-responsive genes, repositioning precedes transcription by pioneering elongating polymerases and appears to nucleate from intragenic enhancer clusters resembling super-enhancers. By 30 min, widespread repositioning throughout megabase pair-long chromosomal segments, with consequential effects on three-dimensional structure (detected using chromosome conformation capture), is seen.

Conclusions

Whilst nucleosome repositioning is viewed as a local phenomenon, our results point to effects occurring over multiple scales. Here, we present data in support of a TNFα-induced priming mechanism, mostly independent of NF-κB binding and/or elongating RNA polymerases, leading to a plastic network of interactions that affects DNA accessibility over large domains.
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Authors: Love Michael I , Huber Wolfgang , Anders Simon
Published: December 2014

In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html.
Cyclosporin A, but not tacrolimus, negatively affects the hepatic extraction fraction of hepatobiliary scintigraphy in liver transplant recipients
Authors: Kaxiras Anastasios , Yamamoto Shinji , Söderdahl Gunnar , Wernerson Annika , Axelsson Rimma , Ericzon Bo-Göran
Published: December 2014

Background

Hepatobiliary scintigraphy using 99mTc-mebrofenin has been used as an investigation to study liver function after liver transplantation (LTx). Hepatic extraction fraction (HEF) is a measurement of the hepatic extraction efficiency and hepatic extraction rate. With the purpose of evaluating a possible diverging effect of cyclosporin A (CSA) and tacrolimus (TAC) on the HEF, we compared the HEF with biochemical and histological parameters in LTx patients receiving either CSA or TAC.

Methods

Thirty-nine adult patients who underwent LTx due to hepatitis C virus (HCV) cirrhosis were evaluated. All patients underwent a 3-month and 1-year follow-up that included hepatobiliary scintigraphy and biochemistry tests. Liver biopsy was performed at 1 year. These clinical parameters were compared between the two groups, TAC (n = 15) and CSA (n = 24).

Results

The average HEF was significantly lower in the CSA group compared to the TAC group both at 3 months and 1 year after LTx. The liver biochemistry tests, average donor and recipient age, average cold ischemia time (CIT), and a clearance were comparable in the two groups. The TAC group had more inflammation than the CSA group. Moreover, three patients who converted from CSA to TAC increased their HEF values.

Conclusions

CSA-treated patients presented a lower HEF value on hepatobiliary scintigraphy in spite of comparable liver function by traditional measurements indicating a decrease on HEF values by CSA.
Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach—The ALBI Grade
Authors: Johnson Philip J. , Berhane Sarah , Kagebayashi Chiaki , Satomura Shinji , Teng Mabel , Reeves Helen L. , O'Beirne James , Fox Richard , Skowronska Anna , Palmer Daniel , Yeo Winnie , Mo Frankie , Lai Paul , Iñarrairaegui Mercedes , Chan Stephen L. , Sangro Bruno , Miksad Rebecca , Tada Toshifumi , Kumada Takashi , Toyoda Hidenori
Published: December 2014

Purpose

Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade.

Patients and Methods

We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501).

Results

The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function.

Conclusion

The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade.